Industrial chemistry and chemical engineering Books

Book SynopsisThis readily comprehensible book explains the identification of molecular targets via cellular assays, reporter genes or transgenic models, as well as surveying recent advances in the synthesis, separation and analysis of drugs. A special section is devoted to molecular genetics methods. With its examination of these novel methods and generous practical advice, this is essential reading for all pharmaceutical chemists, molecular biologists and medical researchers using molecular methods to study drugs and their action.Trade Review"...a welcome addition to the library of anyone seeking to build a multidisciplinary group" Applied Organometallic Chemistry, June 2004 "In all, the book touches on some of the trendiest subjects that interface to form the frontier of modern medicinal chemistry." Kevin G. Rice, Division of Medicinal and Natural Products Chemistry, College of Pharmacy, The University of Iowa, Iowa City, Journal of Medicinal Chemistry, Vol. 47, No. 26, 2004 "Molecular Biology in Medicinal Chemistry ist eine exzellente Einführung in einige wichtige Aspekte der pharmazeutischen Forschung und der Chemischen Biologie. Jeder Wissenschaftler, der sich für diese Gebiete interessiert, sollte über seine Bibliothek Zugriff auf dieses Buch haben." Rolf Breinbauer Angewandte Chemie "It is not the book "screening for beginners" but, thanks to the wide range of topics, every reader will find several very interesting chapters in it. The readership is addressed in the title: medicinal chemists in industry and academia. I, for my part, found far more in it than I expected." Boris Schmidt ChemBioChem 8/2004 "Das von Dingermann, Steinhilber und Folkers zusammengestellte Autorenteam beleuchtet in kompetenter und aufschlußreicher Weise den gegenwärtigen Stand und Stellenwert der molekularebiologischer Methoden und Techniken im Bereich der pharmazeutischen Chemie. ... Mit dem Themenblock Kinetik, Metabolismus und Toxikologie schließt das Buch ab. Diese hervorragende Zusammenstellung über den aktuellen Stand von Pharmacogenomics und Toxicogenomics sowie die umfassende und detaillierte Referenzliste setzt Maßstäbe und wäre allein schon Grund genug das Buch zu erwerben." Stefan Müller, Köln, Arzneimittel-Forschung/Drug Research, 1/05Table of ContentsMOLECULAR TARGETS Cellular Assays in Drug Discovery Gene Knockout Models Reporter Gene Assay Systems for the Investigation of GPCRs From the Human Genome to New Drugs: The Potential of Orphan GPCRs SYNTHESIS Stereoselective Synthesis with the Help of Recombinant Enzymes Nucleic Acid Drugs ANALYSIS Recent Trends in Enantioseparation of Chiral Drugs Affinity Chromatography NMR-based Drug Discovery 13C- and 15N-Isotopic Labeling of Proteins Antibody Fragments as Crystallization Enhancers KINETICS, METABOLISM AND TOXICOLOGY Pharmacogenetics: The Effect of Inherited Genetic Variation on Drug Disposition and Drug Response Pharmacogenomics of Bioavaliability and Elimination Toxicogenomics: Integration of New Molecular Biological Tools in Toxicology

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Book SynopsisUm solide, langzeitbeständige und stoffgerechte Klebungen im industriellen oder handwerklichen Bereich herzustellen, sind sowohl gute Grundlagenkenntnisse als auch fachlich fundiertes Wissen von Nöten. Die einzelnen Informationen in der vorhandenen Fachliteratur aufzuspüren, ist äußerst mühsam und zeitraubend. Das vorliegende Handbuch - geschrieben von Spezialisten verschiedener Fachbereiche in Forschung und Industrie - vermittelt das vollständige klebtechnische Wissen in kompakter und übersichtlicher Form: Neben klassischen Gebieten wie Adhäsion, Chemie und charakteristischem Verhalten von Klebstoffen und Klebverbindungen werden insbesondere auch aktuelle praxisrelevante Fragestellungen und die sehr verschiedenartigen Anwendungsmöglichkeiten des Klebens umfassend behandelt - erstmalig in der Literatur.Trade Review"Fachleute mit langjähriger Erfahrung aus dem breiten Bereich der Klebetechnik, haben sich zu einer wirklich hervorragenden Arbeit zusammengefunden, wie dieses Buch mit jeder Seite beweist. Das zur Zeit verfügbare wissenschaftlich fundierte Fachwissen über die Klebtechnik und deren Anwendungsmöglichkeiten wird in sehr einfacher und leicht verständlicher aber fundierter Weise in diesem Buch in allen Teilbereichen dargelegt. (...) Großer Wert wurde auf die Veranschaulichung durch viele Abbildungen gelegt, welche die Arbeit und das Verständnis zu manch schwierigen Themen erleichtern sollen und dieser Aufgabe auch gerecht werden. Die systematische und übersichtliche Gliederung des Buches ermöglichen dem Leser eine klare Orientierung und ein schnelles Auffinden des gesuchten Fachgebietes. Ein wirklich hervorragendes und gut verständliches Fachbuch am letzten Stand der Technik, das ich ruhigen Gewissens jedem interessierten Leser weiterempfehlen möchte." Buchkritik.at Aus Beurteilungen zur Projektidee: "Ich bin davon überzeugt, dass Herr Professor Walter Brockmann, auf Grund seiner jahrzehntelangen Erfahrung sicherlich wie Wenige einen exzellenten Überblick der gesamten Entwicklung erreicht hat, ein Buch vorstellen wird, das in der Fachwelt breite Anerkennung finden dürfte." Dr. Gierenz, Solingen "Es gibt kaum aktuelle klebtechnische Literatur, welche praxisorientiert informiert." "Sämtliche relevanten Themen und Aspekte werden berücksichtigt." "Renommee des Autors (...) sehr hoch!" Industrieverband Klebstoffe "KT ist eine Querschnittstechnologie und entspricht modernsten Entwicklungen der Materialwissenschaften und ist damit für Innovationen unerlässlich. Die KT gilt als universelle Fügetechnik, damit sind alle techn. Bereiche davon betroffen." "Der Autor Brockmann genießt ein sehr hohes Renommee insbesondere auch wegen seiner umfassenden Erfahrungen auf diesem Gebiet." "In dem neuen, jetzt bei Wiley-VCH erschienenen Buch "Klebtechnik" berichten Brockmann et al. von modernen Verfahren und Technologien." Welt der Farben "Der Preis ist gemessen an Umfang und Ausstattung akzeptabel. Dieses Buch kann deshalb allen, die sich für die Klebtechnik interessieren, empfohlen werden." Materials and Corrosion "... das in kompakter und leicht verständlicher Weise zeigt, was die Klebtechnik heute und in Zukunft in den verschiedenartigen Anwendungsbereichen leisten kann. ... Beschrieben werden u.a. praxisrelevante Fragestellungen... Außerdem erhält der Leser Einblicke in raffinierte Klebtechniken der Natur und viele alltägliche Kleblösungen. ...erfährt in diesem Buch, dass die oft skeptisch betrachtete Klebtechnik bei richtiger Entwicklung und Ausführung der Klebungen eine sehr leistungsfähige Fügetechnik ist und bekommt Hilfestellung, klebtechnische Aufgaben erfolgreich zu bearbeiten." adhäsion - kleben & dichten (Das Fachmagazin für industrielle Kleb- und Dichttechnik) "Den Herausgebern und den weiteren Mitautoren ist es gelungen, die fachlichen Begründungen verständlich zu interpretieren, damit auch ein 'Newcomer' bei seinen Aufgabenstellungen diese umsetzen kann. (...) Deshalb ist die 'Klebtechnik' ein wichtiger Begleiter für den Ingenieur und Chemiker aus der adhäsiven Füge- und Verbindungstechnik, um tägliche Aufgabenstellungen in der Praxis der Klebtechnik fachgerecht bearbeiten zu lassen. Es werden nicht nur die vielfältigen Klebstoffbasen, die Qualitätssicherungen und die Prüfverfahren von Klebverbindungen diskutiert, was der Praktiker besonders schätzen wird..." Klebstoff-Dokumentum "...ein höchst erfreulich und außerordentlich gelungenes Werk... Nur selten gelingt eine derart vorbehaltlose Empfehlung." Chemie Ingenieur Technik Table of ContentsDIE POSITION DER KLEBTECHNIK IM BEREICH DER VERBINDUNGSVERFAHREN DIE GESCHICHTLICHR ENTWICKLUNG DER KLEBTECHNIK ADHÄSION UND DIE QUALIFIZIERUNG VON KLEBSTOFFEN Adhäsion Die Klassifizierung von Klebstoffen Physikalisch härtende Klebstoffe Chemisch härtende Klebstoffe Allgemeine Verarbeitungshinweise AUFBAU UND EIGENSCHAFTEN DER KLEBSTOFFE Haftklebstoffe Kontaktklebstoffe Schmelzklebstoffe Phenolharz-Klebstoffe Epoxidharz-Klebstoffe Polyurethan-Klebstoffe Acrylatklebstoffe Silikone Füllstoffe und Additive Lösbare Klebverbindungen VORBEREITUNG, HERSTELLUNG, CHARAKTERISIERUNG UND QUALITÄTSSICHERUNG VON KLEBVERBUNDEN Oberflächenvorbehandlung Applikationsverfahren Mechanisches Verhalten von Klebverbindungen Langzeitverhalten von Klebverbindungen Qualitätssicherung ANWENDUNGEN DER KLEBTECHNIK Transportwesen (Flugzeugbau, Kraftfahrzeugbau, Eisenbahnwesen, Schiffbau) Bauwesen Holzbau Papier und Verpackungsindustrie Kleinindustrie und Handwerk Elektronikindustrie Optische Industrie Maschinen- und Apparatebau Textilindustrie Schuhindustrie Straßenwesen Oberflächendesign Do It Yourself Medizin Kleben in der Natur WENIGER BEKANNTE KLEBANWENDUNGEN Folien (PU) für Windkraftrotoren Drag Reduction Film für Flugzeuge Schwingungsdämpfer Verbundglas Ski Glühbirnen Archäologie Schmuckindustrie ZUKUNFTSTRENDS Wirtschaftliche Trends Technische Trends F&E Aktivitäten in der Klebtechnik

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Book SynopsisThe first authoritative overview of past and current strategies for successful drug development by analog generation, this unique resource spans all important drug classes and all major therapeutic fields, including histamine antagonists, ACE inhibitors, beta blockers, opioids, quinolone antibiotics, steroids and anticancer platinum compounds. Of the 19 analog classes presented in detail, 9 are described by the scientists who discoverd them. The book includes a table of the most successful drug analogs as based on the IMS ranking and compares them in terms of chemical structure, mode of action and patentability.Trade Review"This book is eminently capable of educating both newcomers and experienced practitioners to the fields of medicinal chemistry and pharmacology, and it is highly recommended as an addition to the personal collection of the practicing drug designer and as a reference volume for institutional use as well." Journal of Medicinal Chemistry "Overall the book is of interest for medicinal chemists who already have a sound knowledge of aspects of analogue-based drug design." ChemMedChemTable of ContentsIntroduction GENERAL ASPECTS OF ANALOGUE-BASED DRUG DISCOVERY Analogues as a Means of Discovering New Drugs Drug Likeness and Analogue-Based Drug Discovery Privileged Structures and Analog-Based Drug Discovery SELECTED EXAMPLES FROM THE ANALOGUE-BASED DRUG DISCOVERIES Development of Anti-Ulcer H2-Receptor Histamine Antagonists Esomeprazole in the Framework of Proton-Pump Inhibitor Development The Development of a New Proton-Pump Inhibitor: The Case History of Pantoprazole Optimizing the Clinical Pharmacologic Properties of the HMG-CoA Reductase Inhibitors Optimizing Antihypertensive Therapy by Angiotensin Receptor Blockers Optimizing Antihypertensive Therapy by Angiotensin-Converting Enzyme Inhibitors Case Study of Lacidipine in the Research of New Calcium Antagonists Selective Beta-Adrenergic Receptor-Blocking Agents Case Study: "Esmolol Stat" [1] Development of Organic Nitrates for Coronary Heart Disease Development of Opioid Receptor Ligands Stigmines Structural Analogues of Clozapine Quinolone Antibiotics: The Development of Moxifloxacin The Development of Bisphosphonates as Drugs Cisplatin and its Analogs for Cancer Chemotherapy The History of Drospirenone Histamine H1 Blockers: From Relative Failures to Blockbusters Within Series of Analogues Corticosteroids: From Natural Products to Useful Analogues

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Book SynopsisThis first book to concentrate on providing a concise, representative overview of polymer microencapsulation for novel organic coatings and all its chemical and engineering aspects collates the literature hitherto spread out among journals in various disciplines. It covers all the important methods for carrying out microencapsulations, including in situ polymerization, phase separation, emulsification, grinding and spray drying. The result is a solid, introduction from first-hand practitioners working in industry and research institutions for newcomers to the field. It is equally vital reading for professionals already active in the area needing to stay abreast of developments.Trade Review"FC is a largely qualitative and descriptive book which makes it quiet readable." (Journal of Metals, July 20, 2008) "The graphics are of high quality and this applies to the general appearance of the whole book. Impressive is the very comprehensive coverage of the relevant literature." (ChemPhysChem, 2008)"...Functional Coatings ist stattdessen eine eindrucksvolle Sammlung von Forschungsergebnissen zahlreicher Expertengruppen und somit ein ausgezeichnetes Nachschlagewerk für Wissenschaftler, die sich für dieses Gebiet interessieren. Die Themen sind dank des ausführlichen Inhalts- und Sachwortverzeichnisses leicht zu finden. Fazit: Das Buch ist Interessierten an Hochschulen und in der Industrie sehr zu empfehlen." Angewandte Chemie, 05/2007Table of ContentsFunctional Coatings And Microencapsulation: A General Perspective Encapsulation Through (Mini)emulsion Polymerization Microcapsules Through Layer-by-Layer Assembly Technique Polymer Encapsulation of Inorganic Particles Microencapsulation Of Liquid Active Agents Polymer Encapsulation and Conductive Coatings Smart Textiles using The Micro Encapsulation Technology Encapsulation Through Sol-gel Technique and Their Applications in Functional Coatings Electrolytic Co-deposition of Microencapsulated Particles

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Book SynopsisMembrane Technology - a clean and energy saving alternative to traditional/conventional processes. Developed from a useful laboratory technique to a commercial separation technology, today it has widespread and rapidly expanding use in the chemical industry. It has established applications in areas such as hydrogen separation and recovery of organic vapors from process gas streams, and selective transport of organic solvents, and it is opening new perspectives for catalytic conversion in membrane reactors. Membrane technology provides a unique solution for industrial waste treatment and for controlled production of valuable chemicals. This book outlines several established applications of membranes in the chemical industry, reviews the available membranes and membrane processes for the field, and discusses the huge potential of this technology in chemical processes. Each chapter has been written by an international leading expert with extensive industrial experience in the field.Trade Review'Several of my students have also reviewed the book and commented on the value they see that it provides in showing the considerable extent that membranes have managed to invade diverse application areas. Therefore, when all is said and done, the question of whether I would recommend buying the book gets a strong YES as an answer.' Professor William Koros, Georgia Institute of Technology, Atlanta, USA, for Journal of Membrane Science, Elsevier "...an updated and practice-oriented overview of membrane processes adressed to process engineers, material scientists and to environmental specialists working in the chemical industry." Environmental Engineering and Management JournalTable of ContentsPART I: MEMBRANES FOR THE CHEMICAL INDUSTRY Introduction Membrane Market Membrane Preparation Presently Available Membranes for Liquid Separation Surface Modification of Membranes Membranes for Fuel Cells Gas Separation with Membranes PART II: CURRENT APPLICATIONS AND PERSPECTIVES The Separation of Organic Vapors from Gas Streams by Means of Membranes Gas Separation Membrane Application State-of-art of Pervaporation Processes in the Chemical Industry Organic Solvent Nanofiltration Industrial Membrane Reactors Electromembrane Processes Membrane Technology in the Chemical Industry: Future Directions

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Book SynopsisThis authoritative work represents a broad treatment of the field, including the basic principles of membrane reactors, a comparative study of these and conventional fixed-bed reactors or multi-tube reactors, modeling, industrial applications, and emerging applications -- all based on case studies and model reactions with a stringent mathematical framework. The significant progress made over the last few years in this inherently hot multidisciplinary field is summarized in a competent manner, such that the novice can grasp the elementary concepts, while professionals can familiarize themselves with the latest developments in the area. For the industrial practitioner, this practical book covers all important current and potential future applications.Table of ContentsPreface BASIC PROBLEMS OF CHEMICAL REACTION ENGINEERING AND POTENTIAL OF MEMBRANE REACTORS Challenges in Chemical Reaction Engineering Concepts of Membrane Reactors Available Membranes Illustration of the Selectivity Problem Reaction Rate, Conversion, Selectivity and Yield Distributed Dosing in Packed-Bed and Membrane Reactors Kinetic Compatibility in Membrane Reactors Current Status of Membrane Reactors of the Distributor Type MODELING OF MEMBRANE REACTORS Introduction Momentum, Mass and Heat Balances Transport Kinetics Reduced Models Solvability, Discretization Methods and Fast Solution Implementation in FLUENT, MooNMD, COMSOL and ProMoT Conclusion CATALYSIS AND REACTION KINETICS OF A MODEL REACTION Introduction The Reaction Network of the Oxidative Dehydrogenation of Ethane Catalysts and Structure-Activity Relations Derivation of a Kinetic Model TRANSPORT PHENOMENA IN POROUS MEMBRANES AND MEMBRANE REACTORS Introduction Aspects of Discretizing Convection-Diffusion Equations Velocity Fields in Membrane Reactors Determination of Transport Coefficients and Validation of Models Analysis of Convective and Diffusive Transport Phenomena in a CMR Parametric Study of a CMR Conclusion PACKED-BED MEMBRANE REACTORS Introduction Principles and Modeling Model-Based Analysis of a Distributed Dosing via Membranes Experimental Results for the Oxidative Dehydrogenation of Ethane to Ethylene Results for the Oxidative Dehydrogenation of Propane Summary and Conclusions FLUIDIZED-BED MEMBRANE REACTORS Introduction Modeling of the Distributed Reactant Dosage in Fluidized Beds Experimental Conclusions SOLID ELECTROLYTE MEMBRANE REACTORS Introduction Operational and Material Aspects in Solid Electrolyte Membrane Reactors Modeling of Solid Electrolyte Membrane Reactors Membrane Reactors Applying Ion-Conducting Materials Conclusions NONLINEAR DYNAMICS OF MEMBRANE REACTORS Introduction Limit of Chemical Equilibrium Pattern Formation Conclusions COMPARISON OF DIFFERENT MEMBRANE REACTORS General Aspects Regarding Membrane Reactors of the Distributor Type Oxidative Dehydrogenation of Ethane in Different Types of Membrane Reactors General Conclusion

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Book SynopsisThis topical reference and handbook addresses the chemistry, pharmacology, toxicology and the patentability of prodrugs, perfectly mirroring the integrated approach prevalent in today's drug design. It summarizes current experiences and strategies for the rational design of prodrugs, beginning at the early stages of the development process, as well as discussing organ- and site-selective prodrugs. Every company employing medicinal chemists will be interested in this practice-oriented overview of a key strategy in modern drug discovery and development.Trade Review"The book captures all the important aspects of prodrugs. It is well organized in that each chapter presents a specific topic with very little duplication of contents between chapters . . . Given the fact that prodrugs are now increasingly integrated into early drug discovery, this type of book would be a valuable addition to the library of any drug discovery institution." (Journal of Medicinal Chemistry, 8 August 2011) "Every company employing medicinal chemists will be interested in this practice-oriented overview of a key strategy in modern drug discovery and development." (Pharmiweb, 16 February 2011)Table of ContentsList of Contributors XVII Preface XXI A Personal Foreword XXIII Part One Prodrug Design and Intellectual Property 1 1 Prodrug Strategies in Drug Design 3Jarkko Rautio 1.1 Prodrug Concept 3 1.2 Basics of Prodrug Design 4 1.3 Rationale for Prodrug Design 5 1.3.1 Overcoming Formulation and Administration Problems 6 1.3.2 Overcoming Absorption Barriers 8 1.3.3 Overcoming Distribution Problems 9 1.3.4 Overcoming Metabolism and Excretion Problems 10 1.3.5 Overcoming Toxicity Problems 10 1.3.6 Life Cycle Management 13 1.4 History of Prodrug Design 14 1.5 Recently Marketed Prodrugs 17 1.5.1 Prodrug Prevalence 17 1.5.2 Recent Prodrug Approvals 17 1.6 Concluding Remarks 25 References 26 2 The Molecular Design of Prodrugs by Functional Group 31Victor R. Guarino 2.1 Introduction 31 2.2 The Prodrug Concept and Basics of Design 32 2.3 Common Functional Group Approaches in Prodrug Design 34 2.3.1 Aliphatic and Aromatic Alcohols 34 2.3.1.1 Phosphate Monoesters 35 2.3.1.2 Simple Acyl Esters 37 2.3.1.3 Amino Acid Esters 38 2.3.1.4 Other Ester-Based Approaches 39 2.3.2 Carboxylic Acids 40 2.3.2.1 Alkyl Esters 41 2.3.2.2 Aminoalkyl Esters 42 2.3.2.3 Spacer Groups to Alleviate Steric Hindrance 42 2.3.3 Imides, Amides, and Other NH Acids 43 2.3.3.1 Imide-Type NH Acids 44 2.3.3.2 Amide-Type NH Acids 44 2.3.3.3 Sulfonamide NH Acids 48 2.3.4 Phosphates, Phosphonates, and Phosphinates 49 2.3.4.1 Simple Alkyl and Aryl Esters 49 2.3.4.2 Acyloxyalkyl and Alkoxycarbonyloxyalkyl Esters 50 2.3.4.3 Aryl Phospho(n/r)amidates and Phospho(n/r)diamides 51 2.3.4.4 HepDirect Technology 53 2.3.5 Amines and Benzamidines 53 2.3.5.1 N-Acyloxyalkoxycarbonyl Prodrugs 54 2.3.5.2 N-Mannich Bases 55 2.3.5.3 N-Acyloxyalkyl and N-Phosphoryloxyalkyl Prodrugs of Tertiary Amines 55 2.3.5.4 N-Hydroxy and Other Modifications for Benzamidines 56 2.4 Conclusions 56 References 57 3 Intellectual Property Primer on Pharmaceutical Patents with a Special Emphasis on Prodrugs and Metabolites 61Eyal H. Barash 3.1 Introduction 61 3.2 Patents and FDA Approval Process 61 3.3 Obtaining a Patent 65 3.3.1 Utility 66 3.3.2 Novelty 67 3.3.3 Nonobviousness 71 3.4 Conclusion 78 Part Two Prodrugs Addressing ADMET Issues 79 4 Increasing Lipophilicity for Oral Drug Delivery 81Majid Y. Moridani 4.1 Introduction 81 4.2 pKa, Degree of Ionization, Partition Coefficient, and Distribution Coefficient 81 4.3 Prodrug Strategies to Enhance Lipid Solubility 85 4.4 Prodrug Examples for Antibiotics 87 4.4.1 Bacampicillin 87 4.4.2 Carindacillin 88 4.4.3 Cefditoren Pivoxil 89 4.4.4 Cefuroxime Axetil 90 4.4.5 Cefpodoxime Proxetil 91 4.5 Antiviral Related Prodrugs 92 4.5.1 Oseltamivir 92 4.5.2 Famciclovir 92 4.5.3 Adefovir Dipivoxil 93 4.5.4 Tenofovir Disoproxil 94 4.6 Cardiovascular Related Prodrugs 95 4.6.1 Enalapril 95 4.6.2 Fosinopril 96 4.6.3 Olmesartan Medoxomil 97 4.7 Lipophilic Prodrugs of Benzamidine Drugs 98 4.7.1 Ximelagatran 98 4.7.2 Dabigatran Etexilate 99 4.8 Miscellaneous Examples 100 4.8.1 Capecitabine 100 4.8.2 Mycophenolate Mofetil 101 4.8.3 Misoprostol 102 4.8.4 Additional Examples 102 4.9 Summary and Conclusion 104 References 106 5 Modulating Solubility Through Prodrugs for Oral and IV Drug Delivery 111Victor R. Guarino 5.1 Introduction 111 5.2 Basics of Solubility and Oral/IV Drug Delivery 112 5.2.1 Some Basic Fundamentals of Solubility 112 5.2.2 Some General Comments on IV Drug Delivery 114 5.2.3 Some General Comments on Oral Drug Delivery 116 5.3 Prodrug Applications for Enhanced Aqueous Solubility 117 5.3.1 Prodrug Concept 117 5.3.2 Examples of Prodrugs to Enhance Aqueous Solubility for IV Administration 118 5.3.2.1 Fosphenytoin 118 5.3.2.2 Fospropofol 119 5.3.2.3 Parecoxib 120 5.3.2.4 Irinotecan 120 5.3.3 Prodrugs to Enhance Aqueous Solubility for Oral Administration 121 5.3.3.1 Fosamprenavir 121 5.3.3.2 Valganciclovir 122 5.4 Challenges with Solubilizing Prodrugs of Insoluble Drugs 123 5.4.1 Challenges with Solubilizing Prodrug Strategies for IV Administration 123 5.4.2 Challenges with Solubilizing Prodrug Strategies for Oral Administration 124 5.5 Additional Applications of Prodrugs for Modulating Solubility 125 5.5.1 Alleviating pH-Dependent Oral Bioavailability of Weakly Basic Drugs 126 5.5.2 Aligning pH-Solubility and pH-Stability Relationships for IV Products 126 5.5.3 Modulating Solubility in Negative Direction 127 5.6 Parallel Exploration of Analogues and Prodrugs in Drug Discovery (Commentary) 128 5.7 Conclusions 129 References 129 6 Prodrugs Designed to Target Transporters for Oral Drug Delivery 133Mark S. Warren and Jarkko Rautio 6.1 Introduction 133 6.2 Serendipity: An Actively Transported Prodrug 133 6.3 Requirements for Actively Transported Prodrugs 135 6.4 Peptide Transporters: PEPT1 and PEPT2 135 6.5 Monocarboxylate Transporters 140 6.6 Bile Acid Transporters 143 6.7 Conclusions 147 References 147 7 Topical and Transdermal Delivery Using Prodrugs: Mechanism of Enhancement 153Kenneth Sloan, Scott C. Wasdo, and Susruta Majumdar 7.1 Introduction 153 7.2 Arrangement of Water in the Stratum Corneum 155 7.3 A New Model for Diffusion Through the Stratum Corneum: The Biphasic Solubility Model 156 7.4 Equations for Quantifying Effects of Solubility on Diffusion Through the Stratum Corneum 158 7.4.1 The Roberts–Sloan Equation When the Vehicle is Water 159 7.4.2 The Roberts–Sloan Equation When the Vehicle is a Lipid 160 7.4.3 The Series/Parallel Equation When the Vehicle is a Lipid 161 7.5 Design of Prodrugs for Topical and Transdermal Delivery Based on the Biphasic Solubility Model 162 7.5.1 5-Fluorouracil Prodrugs 164 7.5.1.1 N-Acyl 5-FU Prodrugs 165 7.5.1.2 N-Soft Alkyl 5-FU Prodrugs 166 7.5.2 Acetaminophen (APAP) Prodrugs 167 7.5.2.1 O-Acyl APAP Prodrugs 168 7.5.2.2 O-Soft Alkyl APAP Prodrugs 170 7.5.3 S-Soft Alkyl Prodrugs of 6-Mercaptopurine 170 7.5.3.1 Effect of Vehicles on Topical and Transdermal Delivery 171 7.6 Comparison of Human and Mouse Skin Experiments 172 7.7 Summary 174 References 175 8 Ocular Delivery Using Prodrugs 181Deep Kwatra, Ravi Vaishya, Ripal Gaudana, Jwala Jwala, and Ashim K. Mitra 8.1 Introduction 181 8.2 Criteria for an Ideal Ophthalmic Prodrug 181 8.3 Anatomy and Physiology of the Eye 182 8.3.1 Anterior Chamber 183 8.3.2 Posterior Chamber 183 8.4 Barriers to Ocular Drug Delivery 184 8.4.1 Tear Film 184 8.4.2 Corneal Epithelium 184 8.4.3 Aqueous Humor and BAB 184 8.4.4 Conjunctiva 184 8.4.5 Blood–Retinal Barrier 185 8.5 Influx and Efflux Transporters on the Eye 185 8.6 Transporter-Targeted Prodrug Approach 186 8.6.1 Acyclovir 186 8.6.2 Ganciclovir 188 8.6.3 Quinidine 188 8.7 Drug Disposition in Ocular Delivery 189 8.8 Effect of Physiochemical Factors on Drug Disposition in Eye 190 8.9 Prodrug Strategy to Improve Ocular Bioavailability (Nontransporter-Targeted Approach) 192 8.9.1 Epinephrine 192 8.9.2 Phenylephrine 192 8.9.3 Pilocarpine 193 8.9.4 Timolol 195 8.9.5 Prostaglandin F2a 197 8.10 Recent Patents and Marketed Ocular Prodrugs 198 8.11 Novel Formulation Approaches for Sustained Delivery of Prodrugs 201 8.12 Conclusion 201 References 202 9 Reducing Presystemic Drug Metabolism 207Majid Y. Moridani 9.1 Introduction 207 9.2 Presystemic Metabolic Barriers 209 9.2.1 Esterases 209 9.2.2 Cytochrome P450 Enzymes 212 9.2.3 Phase II Drug Metabolizing Enzymes 214 9.2.4 Peptidases 215 9.2.5 Other Oxidative Metabolizing Enzymes 216 9.3 Prodrug Approaches to Reduce Presystemic Drug Metabolism 217 9.4 Targeting Colon 220 9.5 Targeting Lymphatic Route 221 9.6 Conclusion 225 References 226 10 Enzyme-Activated Prodrug Strategies for Site-Selective Drug Delivery 231Krista Laine and Kristiina Huttunen 10.1 Introduction 231 10.2 General Requirements for Enzyme-Activated Targeted Prodrug Strategy 232 10.3 Examples of Targeted Prodrug Strategies 232 10.3.1 Tumor-Selective Prodrugs 232 10.3.1.1 Prodrugs Activated by Hypoxia-Associated Reductive Enzymes 233 10.3.1.2 Prodrugs Activated by Glutathione S-Transferase 236 10.3.1.3 Prodrugs Activated by Thymidine Phosphorylase 237 10.3.2 Organ-Selective Prodrugs 239 10.3.2.1 Liver-Targeted Prodrugs 239 10.3.2.2 Kidney-Targeted Prodrugs 242 10.3.2.3 Colon-Targeted Prodrugs 243 10.3.3 Virus-Selective Prodrugs 244 10.4 Summary 245 References 246 11 Prodrug Approaches for Central Nervous System Delivery 253Quentin R. Smith and Paul R. Lockman 11.1 Blood–Brain Barrier in CNS Drug Development 253 11.2 Prodrug Strategies 255 11.3 Prodrug Strategies Based Upon BBB Nutrient Transporters 257 11.4 Prodrug Strategies Based Upon BBB Receptors 263 11.5 CNS Prodrug Summary 264 References 266 12 Directed Enzyme Prodrug Therapies 271Dan Niculescu-Duvaz, Gabriel Negoita-Giras, Ion Niculescu-Duvaz, Douglas Hedley, and Caroline J. Springer 12.1 Introduction 271 12.2 Theoretical Background of DEPT 271 12.2.1 ADEPT and Other Enzyme–Conjugates Approaches 272 12.2.2 LIDEPT 273 12.2.3 GDEPT and Other Gene Delivery Approaches 273 12.2.4 BDEPT 275 12.3 Comparison of ADEPT and GDEPT 275 12.4 Enzymes in ADEPT and GDEPT 278 12.5 Design of Prodrugs 282 12.5.1 Mechanisms of Prodrug Activation 282 12.5.1.1 Electronic Switch 282 12.5.1.2 Cell Exclusion 285 12.5.1.3 Blockage of the Pharmacophore 285 12.5.1.4 Conversion to Substrate for Endogenous Enzymes 287 12.5.1.5 Formation of a Reactive Moiety 287 12.5.1.6 Formation of a Second Interactive Group 288 12.5.2 Enzymatic Reactions Activating the Prodrug. The Trigger 288 12.5.2.1 Reactions Catalyzed by Hydrolases: Hydrolytic Cleavage 289 12.5.2.2 Activation by Nucleotide Phosphorylation 290 12.5.2.3 Activation by Reductases 290 12.5.2.4 Activation by Oxidases 291 12.5.2.5 (Deoxy)Ribosyl Transfer 291 12.5.3 The Linker. Self-Immolative Prodrugs 292 12.5.3.1 Self-Immolative Prodrugs Fragmenting by Elimination 293 12.5.3.2 Linker–Drug Connection 293 12.5.3.3 Self-Immolative Prodrugs Fragmenting Following Cyclization 296 12.6 Strategies Used for the Improvement of DEPT Systems 296 12.6.1 Improvement of the Prodrug 296 12.6.1.1 Cytotoxicity Differential 297 12.6.1.2 Stability of Prodrugs 298 12.6.1.3 Cytotoxicity and Mechanism of Action of the Released Drug 299 12.6.1.4 Stability of the Released Drug 299 12.6.1.5 Resistance (Prodrug Related) 300 12.6.1.6 Kinetics of Activation 300 12.6.1.7 Physicochemical Properties 302 12.6.1.8 Pharmacokinetics 303 12.6.1.9 Specificity of Enzyme Activation 304 12.6.2 Improving the Enzymes 304 12.6.3 The Multigene Approach 305 12.6.4 Enhancing the Immune Response 307 12.7 Biological Data for ADEPT and GDEPT 307 12.7.1 Bacteria 308 12.7.2 Viruses 308 12.7.3 Adenoviral Vectors 308 12.7.4 Pox Viral Vectors 309 12.7.5 Adeno-Associated Viral Vectors 309 12.7.6 Retroviral Vectors 309 12.7.7 Lentiviral Vectors 310 12.7.8 Measles Viral Vectors 310 12.7.9 Herpes Simplex Viral Vectors 311 12.7.10 Neural Stem Cells/Progenitor Cells 311 12.7.11 Liposomes 311 12.7.12 ADEPT Vectors 312 12.7.13 Vectors for Prodrugs 312 12.7.14 Clinical Studies 316 12.8 Conclusions 316 References 318 Part Three Codrugs and Soft Drugs 345 13 Improving the Use of Drug Combinations Through the Codrug Approach 347Peter A. Crooks, Harpreet K. Dhooper, and Ujjwal Chakraborty 13.1 Codrugs and Codrug Strategy 347 13.2 Ideal Codrug Characteristics 348 13.3 Examples of Marketed Codrugs 349 13.4 Topical Codrug Therapy for the Treatment of Ophthalmic Diseases 351 13.4.1 Codrugs for the Treatment of Diabetic Retinopathy 351 13.4.2 Codrugs Containing Corticosteroids for Proliferative Vitreoretinopathy 353 13.4.3 Codrugs Containing Nonsteroidal Anti-Inflammatory Agents for Treatment of Proliferative Vitreoretinopathy 355 13.4.4 Codrugs Containing Ethacrynic Acid for Treatment of Elevated Intraocular Pressure 356 13.5 Codrugs for Transdermal Delivery 357 13.5.1 Codrugs for the Treatment of Alcohol Abuse and Tobacco Dependence 357 13.5.2 Duplex Codrugs of Naltrexone for Transdermal Delivery 362 13.5.3 Codrugs Containing a-Tocopherol for Skin Hydration 362 13.6 Codrugs of L-DOPA for the Treatment of Parkinson’s Disease 363 13.6.1 L-DOPA Codrugs that Incorporate Inhibitors of L-DOPA Metabolism 363 13.6.2 L-DOPA–Antioxidant Codrugs 364 13.7 Analgesic Codrugs Containing Nonsteroidal Anti-Inflammatory Agents 367 13.7.1 Flurbiprofen–Histamine H2 Antagonist Codrugs 367 13.7.2 NSAID–Acetaminophen Codrugs 368 13.7.3 Naproxen–Propyphenazone Codrugs 370 13.7.4 Flurbiprofen–Amino Acid Codrugs 371 13.7.5 NSAID–Chlorzoxazone Codrugs 372 13.7.6 Acetaminophen–Chlorzoxazone Codrug 373 13.8 Analgesic Codrugs of Opioids and Cannabinoids 373 13.9 Codrugs Containing Anti-HIV Drugs 375 13.9.1 AZT–Retinoic Acid Codrug 377 References 378 14 Soft Drugs 385Paul W. Erhardt and Michael D. Reese 14.1 Introduction 385 14.1.1 Definition 385 14.1.2 Prototypical Agent 386 14.1.2.1 Backdrop 386 14.1.2.2 Clinical Challenge 386 14.1.2.3 Pharmacological Target 388 14.1.2.4 Pharmacology, Human Pharmacokinetic Profile, and Clinical Deployment 389 14.2 Indications 390 14.2.1 A Huge Potential 391 14.2.2 ‘‘To Market, To Market’’ 392 14.3 Design Considerations 396 14.3.1 General Requirements 396 14.3.2 Enzymatic Aspects 397 14.3.3 Chemical Structural Aspects 397 14.4 Case Study: The Discovery of Esmolol 400 14.4.1 Internal Esters 400 14.4.2 External Esters 402 14.4.3 ‘‘Square Pegs and Round Holes’’ 402 14.4.4 Surrogate Scaffolds for Testing Purposes and a ‘‘Glimmer of Hope’’ 403 14.4.5 A ‘‘Goldilocks’’ Compound Called Esmolol 404 14.4.6 ‘‘Esmolol Stat’’ 406 14.4.7 Case Study Summary and Some Take-Home Lessons for Today 407 14.4.7.1 Compound Libraries 407 14.4.7.2 Biological Testing 408 14.4.7.3 SAR 408 14.5 Summary 408 References 409 Part Four Preclinical and Clinical Consideration for Prodrugs 415 15 Pharmacokinetic and Biopharmaceutical Considerations in Prodrug Discovery and Development 417John P. O’Donnell 15.1 Introduction 417 15.2 Understanding Pharmacokinetic/Pharmacodynamic Relationships 417 15.3 Pharmacokinetics 418 15.4 Tools for the Prodrug Scientist 421 15.4.1 Bioanalytical Assay Development 421 15.4.2 Use of Radiolabel 422 15.5 Enzymes Involved with Prodrug Conversion 423 15.5.1 Carboxylesterases 423 15.5.2 Alkaline Phosphatase 426 15.5.3 Cytochrome P450 428 15.6 Use of the Caco-2 System for Permeability and Active Transport Evaluation 428 15.7 XP13512: Improving PK Performance by Targeting Active Transport 432 15.8 Prodrug Absorption: Transport/Metabolic Conversion Interplay 434 15.8.1 Pivampicillin 434 15.8.2 Valacyclovir 436 15.9 Preabsorptive Degradation 438 15.9.1 Cephalosporin Prodrugs 438 15.9.2 Sulopenem Prodrugs PF-00398899, PF-03709270, and PF-04064900 439 15.10 Biopharmaceutical-Based PK Modeling for Prodrug Design 440 15.11 Conclusions 447 References 447 16 The Impact of Pharmacogenetics on the Clinical Outcomes of Prodrugs 453Jane P.F. Bai, Mike Pacanowski, Atiqur Rahman, and Lawrence L. Lesko 16.1 Introduction 453 16.2 Clopidogrel and CYP2C19 454 16.2.1 Summary 457 16.3 Codeine and CYP2D6 457 16.3.1 Summary 460 16.4 Tamoxifen and CYP2D6 460 16.4.1 Summary 463 16.5 Fluorouracil Prodrugs and Carboxylesterase 464 16.5.1 Capecitabine and Carboxylesterase 465 16.5.1.1 Summary 467 16.5.2 Tegafur and CYP2A6 467 16.5.2.1 Summary 468 16.6 Irinotecan and Carboxylesterase 2 468 16.6.1 Summary 469 16.7 Others 470 16.7.1 ACE Inhibitors and CES 470 16.7.2 Cyclophosphamide and CYP2B6/CYP2C19 470 16.7.2.1 Summary 471 16.8 Drug Development Implication 471 16.9 Conclusions 473 References 473 Index 483

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Book SynopsisAdopting a didactic approach at an advanced, masters level, this concise textbook provides an array of questions & answers and features numerous industrial case studies and examples, with references for further, more detailed reading and to the latest peer-reviewed articles at the end of each chapter. A significant feature is the book's treatment of more recently developed catalytic processes and their applications in the pharmaceutical and fine chemical industries, with an indication of their present and future commercial impact. Written by a dedicated lecturer with a wealth of experience in industry, this is an invaluable tool for practicing chemical engineers and chemists who need to advance their education in this vibrant and expanding field.Trade Review“High recommended and excellent value in the paperback format.” (Organic Process Research and Development Journal, 2012) Table of ContentsFOREWORD PREFACE PART I CHEMICAL BASICS DEFINITION, OPTIONS, AND EXAMPLES: WHAT ACTUALLY IS CATALYSIS? Definition of Catalysis The Different Varieties of Catalysis The Directing Effect of the Catalyst Catalysis as a Part of "Green Chemistry" Sources of Information about Catalysis A BRIEF HISTORY: HOMOGENEOUS TRANSITION METAL CATALYSIS: A YOUNG SCIENCE A Brief History INDUSTRIAL HOMOGENEOUS CATALYSIS: WHAT IS THE ECONOMIC IMPORTANCE? Application Areas of Catalysis Important Homogeneous Catalyzed Processes Synthesis of Fine Chemicals by Homogeneous Catalysis DEFINITIONS OF IMPORTANT TERMS: SELECTIVITY, STY, TON, TOF, AND MORE. . . Conversion Yield Selectivity Other Important Target Values The Choice is Yours! BONDS, ELEMENTAL STEPS, AND CATALYST CYCLES: BASICS OF ORGANOMETALLIC CHEMISTRY Ligands Change in Oxidation State Changing of Coordination Number (CN) and Coordination Geometry The Elementary Steps Catalytic Cycles TRANSITION METAL COMPLEXES: THE "CAPTAINS" OF HOMOGENEOUS CATALYSIS Group IIIB Metals and Lanthanides Metals of Group IVB Metals of Groups VB to VIIB The "Iron Metals" of Group VIII The Noble Metals from Group VIII Gold: A Noble Metal from Group IB The Cost of Catalyst Metals The Availability of Transition Metal Catalysts A Typical Experiment: Synthesis of Pd(acac)2 THE COMPLEX LIGANDS: THE "MATES" OF HOMOGENEOUS CATALYSIS Monodentate Ligand or Chelate? Basicity of Ligands Cone Angle ("Tolman Cone Angle") The Bite Angle Costs and Accessibility of Ligands A Typical Experiment: The Synthesis of Biphephos Stability of Ligands THE SOLVENTS: THE REACTION MEDIUM Criteria for Choosing Solvents Miscibility of Solvents Solvents as Activators Solvents as Deactivators Availability and Purity of Solvents Special Solvents ASYMMETRIC CATALYSIS: THE "SPECIAL CASE" A Glossary of Asymmetric Catalysis A Quick Look Back Mechanistic Considerations Chiral Ligands Overview on Homogeneous Catalyzed Asymmetric Syntheses Industrial Applications THERMODYNAMICS OF HOMOGENEOUS CATALYSIS: WHEN DOES A CHEMICAL REACTION RUN? Gibbs Energy and Energy Plot Calculation or Assessment of the Free Reaction Enthalpy Thermodynamic Analysis of Complex Reaction Systems KINETICS OF HOMOGENEOUS CATALYSIS: HOW DOES THE REACTION PROCEED? Frequently Occurring Kinetics The Energy Diagram for Explaining Regioselectivity The Energy Diagram for Explaining Enantioselectivity Execution of Kinetic Measurements A Concrete Example: The (Isomerizing) Hydroformylation of Octenes Possible Failures in Kinetic Measurements OVERVIEW ON SPECTROSCOPIC METHODS: CAN WE SEE INTO HOMOGENEOUS CATALYSIS? UV/Visible Spectroscopy IR Spectroscopy NMR Spectroscopy Mass Spectroscopy Extended X-Ray Absorption Fine Structure Analysis Inductively Coupled Plasma Optical Emission Spectroscopy (ICP-OES) PART II PROCESS ENGINEERING FUNDAMENTALS REACTOR TYPES: WHERE DOES CATALYSIS OCCUR? Reactions in Homogeneous Liquid Phase Fluid-Fluid Systems The "Embarras de Richesses" Pressure Reactors New Trends OVERVIEW ON CATALYST RECYCLING METHODS: IS MY CATALYST ECONOMICAL? The Principles of Separation Precipitation Crystallization Adsorption THERMAL SEPARATION: THE SIMPLEST REMOVAL OF VOLATILE PRODUCTS The Basics Example: Hydroformylation Example: Oxidation of Ethene to Acetaldehyde Example: Carbonylation of Methanol to Acetic Acid IMMOBILIZATION ON SOLID SUPPORTS: FROM HOMOGENEOUS TO HETEROGENEOUS The Basic Principle Organic Supports Inorganic Supports LIQUID-LIQUID MULTIPHASE SYSTEMS: THE SMART APPROACH TO CATALYST SEPARATION Variants of Liquid?Liquid Biphasic (LLB) Systems Reaction and Separation Reactions with In-Situ Extraction Reactions with Post Extraction THERMOMORPHIC SOLVENT SYSTEMS: CLEVER ENHANCEMENTS Thermoregulated Phase-Transfer Catalysis Thermoregulated Microemulsions Thermoregulated Fluorous Solvent Systems Thermoregulated Polymer-Bound Catalysts Thermomorphic Multicomponent Solvent Systems A Retrospective Look at Catalyst Recycling Methods PART III HOMOGENEOUS CATALYZED REACTION TYPES AN OVERVIEW OF C?C-BONDING REACTIONS: A GUIDE THROUGH THE JUNGLE HYDROFORMYLATIONS: THE INDUSTRIAL ROUTE TO ALDEHYDES AND ALCOHOLS Substrates Catalysts Mechanisms Industrial Processes Asymmetric Hydroformylation A Typical Experiment: Hydroformylation of 1-Octene CARBONYLATIONS: THE VERSATILE INSERTIONS OF CARBON MONOXIDE Reactions between CO and Hydrogen Reactions of CO with Alkenes and Vinyl Arenes Reactions of CO with Dienes Reactions of CO with Alkynes Reactions of CO with Alcohols A Typical Experiment OLIGOMERIZATION AND CYCLOOLIGOMERIZATION: THE CONVERSION OF UNSATURATED ALIPHATICS INTO SHORT CHAINS OR MEDIUM-SIZED RINGS Oligomerization of Alkenes Dienes Alkynes Cooligomerizations A Typical Experiment METATHESIS: A "CHANGE-YOUR-PARTNERS" DANCE Mechanism and Catalysts Industrial Applications A Typical Experiment: Self Metathesis of 1-Octene POLYMERIZATIONS: THE PURPOSEFUL ASSEMBLY OF MACROMOLECULES Polyethylene and Ziegler Catalysts Polypropylene and Metallocene Catalysis Further Polyolefins Polydienes Polyketones Polyalkynes Post-Metallocenes Current Topics in Polymer Research A Typical Experiment TELOMERIZATIONS: THE CONSTRUCTION OF C8 AND C10 CHAINS Reactions, Mechanisms, and Catalysts Butadiene Telomerizations Telomerizations with Isoprene Telomerizations in Liquid?Liquid Biphasic Systems A Typical Experiment REACTIONS WITH CARBON DIOXIDE: THE ACTIVATION OF AN "INACTIVE" MOLECULE Carbon Dioxide and Alkanes Carbon Dioxide and Alkenes Carbon Dioxide and Dienes Carbon Dioxide and Alkynes Carbon Dioxide and Aromatics Carbon Dioxide and Hydrogen Carbon Dioxide and Epoxides Carbon Dioxide and Amines Carbon Dioxide-Containing Polymers A Typical Experiment CARBON-CARBON COUPLING WITH AROMATICS: NEW NAME REACTIONS Mizoroki-Heck Reactions Sonogashira-Hagihara Reactions Suzuki-Miyaura Reaction Cross-Couplings with Metal Organyles A Typical Experiment HYDROGENATIONS: C-H BOND FORMATION Catalysts and Mechanisms Asymmetric Hydrogenation Hydrogenation of Various Functional Groups Technical Applications A Typical Experiment OXIDATIONS: FORMATION OF C-O BONDS Wacker Oxidations Epoxidations Asymmetric Dihydroxylations Oxidative Cleavage of C=C Double Bonds Oxidations of Alkyl Aromatics A Typical Experiment AMINATIONS: FORMATION OF C-N BONDS Amination of Aryl Halides Hydroamination of Alkenes Hydroaminations of Dienes Hydroamination of Alkynes Amination of Functional Groups . . .Some More Aminations A Typical Experiment ISOMERIZATIONS: MIGRATION OF DOUBLE BONDS AND REARRANGEMENT OF THE CARBON BACKBONE Isomerization of Alkenes Isomerization of Substituted Alkenes Rearrangement of the Backbone A Typical Experiment PART IV NEW TRENDS TANDEM REACTIONS: MULTIPLE SYNTHESIS STEPS IN ONE POT Multicomponent Reactions Multifunctional Catalysis Tandem and Related Reactions A Typical Experiment COMBINATORIAL CHEMISTRY AND HIGH-THROUGHPUT CATALYST SCREENING: THE FAST WAY TO OPTIMUM RESULTS Basics and Definitions Parallel Reactor Systems Sequential Reactor Systems GREEN SOLVENTS: WORKING WITH ECO-FRIENDLY SOLVENTS Ionic Liquids Supercritical Fluids Fluorous Solvents Polyethers Conclusions ALKANE ACTIVATIONS: ACQUISITIONS OF NEW FEEDSTOCKS Mechanistic Considerations Alkane Oxidations Alkane Carbonylations Alkane Metathesis Alkane Hydrogenolysis Alkane Borylation Alkane Sulfonation A Look Back MORE EFFICIENT LIGANDS: THE BEST IS THE ENEMY OF THE GOOD Nitrogen-Containing Ligands Unusual Phosphorus Ligands Ligands Containing Elements from Group VIA Ligands Containing Elements from Group IVA NANOCATALYSIS: BETWEEN HOMOGENEOUS AND HETEROGENEOUS CATALYSIS Synthesis and Properties of Nanocatalysts Stabilization of Nanoparticles Heterogenization of Nanoparticles on Solid Supports Catalysis Involving Metal Nanoparticles HOMOGENEOUS CATALYSIS WITH RENEWABLES: USING NATURE.S TREASURES Catalytic Conversion of Fatty Compounds Catalytic Reactions of Carbohydrates Catalytic Reactions of Terpenes ELECTROCATALYSIS/SONOCATALYSIS/PHOTOCATALYSIS/MICROWAVE/EXTREME PRESSURE: ALTERNATIVE METHODS OF ACTIVATION Electrocatalysis Photocatalysis Sonocatalysis Microwave Catalysis Extreme High-Pressure Catalysis PROCESS DEVELOPMENT IN MINIPLANTS: FROM LABORATORY TO PRODUCTION Miniplant with Continuously Stirred-Tank Reactor (Miniplant I) Miniplant with Loop Reactor and Phase Separator (Miniplant II) Miniplant with Jetloop Reactor and Phase Separator (Miniplant III) Miniplant with a Mixer?Settler Battery (Miniplant IV) THE FUTURE OF HOMOGENEOUS CATALYSIS: A LOOK AHEAD New Resources New Reactions New Catalysts New Methods ANSWERS TO THE QUICKIES

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Book SynopsisAn exploration of current and possible future hydrogen storage technologies, written from an industrial perspective. The book describes the fundamentals, taking into consideration environmental, economic and safety aspects, as well as presenting infrastructure requirements, with a special focus on hydrogen applications in production, transportation, military, stationary and mobile storage. A comparison of the different storage technologies is also included, ranging from storage of pure hydrogen in different states, via chemical storage right up to new materials already under development. Throughout, emphasis is placed on those technologies with the potential for commercialization.Table of ContentsIntroduction FUNDAMENTALS Phase Diagram Energy Density Safety Aspects Production of hydrogen (reforming, water electrolysis, gasification, biomass conversion, biological production - bacteria, fermentation,photosynthesis; photo dissociation, splitting of water) HYDROGEN APPLICATIONS / INFRASTRUCTURE REQUIREMENT Production Transportation Filling station Stationary Military (portables, submarines, balloons?) Portable STORAGE OF PURE HYROGEN IN DIFFERENT STATES Compressed Hydrogen Liquid / Slush Hydrogen Metal Hydrides CHEMICAL STORAGE Hydrocarbons Ammonia Borates HYDROGEN STORAGE OPTIONS - COMPARISON Economic Considerations Safety Considerations Environmental Considerations / Waste, Hazardous Materials Dimension Considerations Sociological Considerations NEW MATERIALS / OUTLOOK Hydropolysilane (HPS) Storage in Carbon Materials Storage in Micro Spheres Other Materials Outlook

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Book SynopsisKraft-Wärme-Kopplung in Heizkraftwerken, Wärmerückgewinnung aus Abluft oder aus Abwasserströmen - wo immer ein hoher energetischer Wirkungsgrad gefragt ist, müssen Verfahren und Prozesse in geeigneter Form miteinander gekoppelt werden. Verlustenergien, wie sie bei konventionellen Prozessen anfallen, lassen sich auf diese Weise nutzen, was Energie einspart und Ressourcen schont. Damit das angestrebte Ziel nicht nur für einzelne Spezialisten erreichbar ist, werden gewonnene Erfahrungen verallgemeinert und in Empfehlungen, den verfahrens- und energietechnischen Kompositionsregeln, zusammengefasst. Praxisnah zeigt dieses Buch, wie energieeffiziente Verfahren und Prozesse aufgebaut beziehungsweise aufzubauen sind, und erläutert die komplexen thermodynamischen Aspekte der Energieumwandlung bei Entwurf und Optimierung verfahrenstechnischer und verwandter Systeme. Zusammenhänge werden erkennbar und helfen, eine eigene Systematik zu entwickeln. Mit Beispielen, die sich am beruflichen Alltag der Verfahrenstechniker ausrichten, wird jede Regel veranschaulicht. Eine umfassende Einführung für Studenten der Verfahrenstechnik, Energietechnik, Heizungs- und Klimatechnik und anderer Ingenieurwissenschaften sowie das ideale Werkzeug für den beruflichen Alltag von Ingenieuren der Verfahrens- und Wärmetechnik sowie von Chemieingenieuren.Trade Review"Ein geeignetes Kreativ-Werkzeug für den beruflichen Alltag von Ingenieuren." KI - Kälte Luft Klimatechnik (7-8/2012, 01.08.2012) "Der Autor, der Chemie- und Wärmetechnikingenieur Herbert Müller, beleuchtet intensiv die Thermodynamik bei Energiegewinnung und -umwandlung. Das liegt dem ehemaligen Lehrstuhlinhaber der Hochschule Wismar angesichts der zunehmenden Bedeutung der Kraft-Wärme-Kopplung am Herzen. Gedacht ist sein Buch für Studierende und als Nachschlagewerk." VDI Nachrichten (23.12.2011) "Es gibt zur Lösung des Energieproblems nur eine Strategie mit Erfolgsaussichten, nämlich die Nutzung erneuerbarer Energien gekoppelt mit einer Erhöhung der Energieeffizienz. (...) Im vorliegenden Buch (werden) diesbezüglich gewonnenen Erfahrungen verallgemeinert und in Empfehlungen, den verfahrens- und energietechnischen Kompositionsregeln, zusammengestellt." Hlh.de (19.09.2011)Table of ContentsVorwort XI 1 Das Umfeld der Aufstellung und Nutzung von Kompositionsregeln 1 1.1 Kosten und Kostenreduzierung in verfahrenstechnischen Systemen 1 1.2 Strategische Orientierungen und Maßnahmeklassen der Rationalisierung 2 1.3 Funktions- und Prinzipstrukturen 6 2 Allgemeine Kompositionsregeln 13 2.1 Überblick und Wiederverwertungsregel 13 2.2 Regeln, die sich unmittelbar aus den Rationalisierungs-Maßnahmeklassen ableiten 15 2.2.1 Anergienutzungsregel 15 2.2.1.1 Beispiel: Wärmepumpeneinsatz (betrifft Nr. 9 und Nr. 11 nach Abb. 1.4) 16 2.2.1.2 Beispiel: Kühlung warmer Stoffe (Nr. S2 nach Abb. 1.4) 18 2.2.2 Intervallteilungsregel 20 2.2.2.1 Beispiele zur Anwendung der Intervallteilungsregel in ihrer direkten Form 22 2.2.2.2 Beispiele zur Anwendung der Intervallteilungsregel in ihrer Umkehrform 33 2.2.2.3 Zusammenfassung 38 2.2.3 Exergiekonzentrierungsregel 38 2.2.3.1 Beispiel: Wärmetrafoeinsatz bei der Klärschlammtrocknung 38 2.2.4 Temperaturwechselungsregel 41 2.2.4.1 Beispiel: Flüssigkeitsunterkühlung in Kälteprozessen 42 2.2.4.2 Beispiel: Regenerative Speisewasservorwärmung im Dampfkraftprozess 43 2.2.5 Beimischregel 44 2.2.5.1 Beispiel: Beimischregelung in der Heizungs- und Feuerungstechnik 44 2.2.5.2 Beispiel: Kondensationswärmerückgewinnung mittels sog. „Dampfpumpe“ 45 2.2.6 Splittungsregel 46 2.2.6.1 Beispiel: Verdichtersatz für Wärmepumpen 47 2.2.6.2 Beispiel: Kapazitätsquantelung bei Pumpensystemen 48 2.2.6.3 Beispiel: Werkhallenbeheizung und Kaltwärmezufuhr von Wärmepumpen 48 2.2.7 Partnerwahlregel 49 2.2.7.1 Beispiel: Kraft-Wärme-Kälte-Kopplung KWKK 50 2.2.7.2 Beispiel: Wärmerückgewinnung bei thermischen Prozessen mit stückigen Gütern 51 2.2.7.3 Beispiel: Anlagenkomposition nach der Pinch-Point-Methode 53 2.2.7.4 Beispiel: Gekoppelte Kompressions-/Absorptionskühlanlage 56 2.2.7.5 Beispiel: Rückgewinnung mechanischer Energie – Umkehrosmose 56 2.3 Regeln, die die Wahl der Arbeits- oder Hilfsstoffe betreffen 57 2.3.1 Zusatzstoffregel 57 2.3.1.1 Beispiel: Sorptionskreisprozesse 59 2.3.1.2 Beispiel: Platen-Munters-Prinzip 65 2.3.1.3 Beispiel: Führen von Phasenwandlungsprozessen in einem Trägergas zur Potentialverschiebung – Verdunstung 65 2.3.1.4 Beispiel: Klimatisierung und verbesserte Wärmerückgewinnung durch Hinzunahme von Sorbentien 68 2.3.1.5 Beispiel: Cheng- oder STIG-Prozess (Steam Injected Gas Turbine) 70 2.3.1.6 Beispiel: Ausfrieren 71 2.3.1.7 Beispiel: „Schleppmittel“-Rektifikation 72 2.3.1.8 Beispiel: Regenerative Wärmeübertragung 72 2.3.1.9 Zusammenfassende Bemerkung 73 2.3.2 Gleichstoffregel 73 2.3.2.1 Beispiel: WDK-Prozess 73 2.3.2.2 Beispiel: Brüdenverdichtung (andere Bezeichnung: Thermokompression) 74 2.3.2.3 Beispiel: Hochtemperatur-Gasexpansion zur Effektivierung der Wiederverdampfung von verflüssigtem Methan – Fortsetzung des Beispiels in Abschnitt 2.2.2.2.2 76 2.3.2.4 Beispiel: Ruths-Dampfspeicher 77 2.4 Regeln, die die Strukturbildung direkt betreffen 77 2.4.1 Überlagerungsregel 77 2.4.1.1 Beispiel: Lüftungs- und Heizungsanlagen – vgl. Abb. 2.34 78 2.4.2 Diversifizierungsregel 80 2.4.2.1 Beispiel: Hintereinandergeschaltete Kraftprozesse 80 2.4.3 Stufenbildungsregel 82 2.4.3.1 Beispiel: Mehrstufige Kompressionskälteanlagen 82 2.4.3.2 Beispiel: Arbeitsmittelgemische in der Tieftemperatur-Kältetechnik 83 2.4.3.3 Beispiel: Rektifikation 83 2.4.3.4 Beispiel: Partielle Kaskadenschaltung – Wärmepumpe mit Hilfskreislauf 84 2.4.4 Kompaktierungsregel 85 2.4.4.1 Beispiel: Flexibilisierung des Sorptions-BHKW 85 2.4.4.2 Beispiel: Kombinierte Kompressions-Absorptionswärmepumpe 86 2.4.4.3 Beispiel: Multi-effect- und Multi-lift-Überlagerung – Teil I 87 2.4.5 Substitutions- und Kompensationsregel 92 2.4.5.1 Beispiel: Kreisprozess-Elementar- und -Kombifälle 93 2.4.5.2 Beispiel: Multi-effect- und Multi-lift-Überlagerung – Teil II 93 2.4.5.3 Beispiel: Wärmerückgewinnung bei Druckluft 96 2.4.6 Ortsänderungsregel 97 2.4.6.1 Beispiel: Kalte Fernwärmeversorgung 98 2.5 Regeln, die das Zeitverhalten betreffen 100 2.5.1 Funktionsumkehrregel 100 2.5.1.1 Beispiel: Zeitgleiche Wärme-Kältekopplung (bei Druckluftkühlung, Trocknung, Lebensmittelmärkten) 102 2.5.1.2 Beispiel: Wärmeübertrager als Heizer und Kühler 103 2.5.1.3 Beispiel: Zeitlich alternierende Wärme-Kälte-Kopplung 103 2.5.1.4 Beispiel: Adsorptive Kühlung 105 2.5.1.5 Beispiel: Alternierend Kraft- und Arbeitsmaschine 108 2.5.1.6 Beispiel: Thermodiffusions-Intervalltrocknungsverfahren 108 2.5.1.7 Beispiel: Absorptionskälteanlagen als Wärmetransformator in verfahren-/verarbeitungstechnischen Prozessen 109 2.5.2 Flexibilitätsregel 110 2.5.2.1 Beispiel: Direktantrieb von Arbeitsmaschinen u. ä. 110 2.5.2.2 Beispiel: Zusatzfeuerung beim GuD-Prozess 111 2.5.2.3 Beispiel: Großkälteanlage zum Heizen und Kühlen in Helsinki/Finnland 111 2.5.2.4 Beispiel: Bypassverwendung 112 2.5.2.5 Beispiel: Flexible Raumklimatisierung bei Wärme-Kälte-Kopplung 114 2.5.3 Ausgleichungsregel 115 2.5.3.1 Beispiel: Netzarten 115 2.5.3.2 Beispiel: Energiespeicherung 119 2.5.3.3 Beispiel: „Multifunktionales“ Fernwärmenetz 124 2.6 Weitere allgemeine Regeln, die sich keiner bisherigen Gruppe zwanglos zuordnen lassen 125 2.6.1 Zeit-und-Ort-Regel 125 2.6.1.1 Beispiel: Thermowechselspeicher 126 2.6.1.2 Beispiel: Mehrkolbenverbundtechnik 128 2.6.2 Ausgewogenheitsregel 129 2.6.2.1 Beispiel: Funktionsdifferenzierte Dieselmotorenanlage – der „Isomotor“ 130 2.6.2.2 Beispiel: Funktionsintegrierte Bauelemente 131 2.6.3 Von-Selbst-Regel 132 2.6.3.1 Beispiel: Passive Kühlung durch Nachtlüftung 135 2.6.3.2 Beispiel: Schwerkraftbedingte Von-Selbst-Lösungen 136 2.6.3.3 Beispiel: „Von-Selbst“-Drucklufttrocknung 138 2.6.4 Öffnungsregel 139 2.6.4.1 Beispiel: Geschlossene und offene Heizungssysteme 140 2.6.4.2 Beispiel: Hochtemperaturbrennwertnutzung 141 2.6.4.3 Beispiel: Offene Geschlossenheit 144 2.6.4.4 Beispiel: Gasturbine – Schließen bisher offener Systeme 145 2.6.5 WEPOL-Regel 146 2.6.5.1 Beispiel: Katalyse 148 2.6.5.2 Beispiel: Schutzgasmoduliertes Schweißen 148 2.6.6 Prioritätsregel 150 2.6.6.1 Beispiel: Integrierte Energieversorgung eines Krankenhauskomplexes 150 3 Spezielle Kompositionsregeln für ausgewählte Prozesse 153 3.1 Überblick 153 3.2 Kreisprozesse 155 3.3 Wärmeübertragung (bzw. Wärmeübertrager) 157 3.3.1 Beispiel zu Regel WÜ 11: Wärmerückgewinnung aus Schlachtbetrieb-Abwasser 160 3.4 Verdampfung 161 3.4.1 Beispiel: Wasserentsalzung 167 3.5 Kristallisation 168 3.6 Trocknung 170 3.6.1 Beispiel zu den TR-Regeln: Trocknung eines organischen Breis zu Pulver 173 3.7 Sorption 175 3.8 Extraktion und Destillation/Rektifikation 180 3.9 Chemische Reaktionstechnik 182 3.9.1 Beispiel: Verknüpfung exo- und endothermer Reaktionen 184 4 Nutzung der Regeln für Anlagenanalysen 187 4.1 Beispiel: Perpetuum mobile II. Art 188 5 Komplexe Beispiele 191 5.1 Offene Kaltluftmaschine 191 5.2 Energetische Verbesserung der Trinkwassergewinnung aus feuchter Luft 193 5.3 Energierückgewinnung aus Trocknerabluft mit Kondensationswärmenutzung 195 5.4 Integrierte thermische Solarenergienutzung 201 5.5 Energieautarke Verarbeitungstechnik in landwirtschaftlichen Kooperativen 208 5.5.1 Kooperativen auf einer energetischen Basis ohne Biobrennstoffe 208 5.5.2 Kooperativen auf einer energetischen Basis mit Biobrennstoffen 213 5.6 Druckzellenmotor 216 6 Ausblick 221 Literaturverzeichnis 223 Anhang 1: Übersicht über die allgemeinen Kompositionsregeln 231 Anhang 2: Verzeichnis der Einzelbeispiele in den Kapiteln 2 bis 4 237 Stichwortverzeichnis 241

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Book SynopsisTeaching the fundamental knowledge required for successful dispersion of powders in a liquid, this book covers a host of topics -- from recent advances to industrial applications. In 15 chapters it supports formulation chemists in preparing a suspension in a more rational way, by applying the principles of colloid and interface science, while at the same time enabling the research scientist to discover new methods for preparing stable suspensions. Essential reading for those working in the pharmaceutical, cosmetic, food, paint, ceramic and agricultural industries.Trade Review“Therefore, it is an essential and interdisciplinary guideline, and warmly recommended not only to those working in the field of dispersions/suspensions in pharmaceutical, cosmetic, food, paint, ceramic and agricultural industries but also to students, scientists and practitioners in other scientific fields (chemistry/food science & technology/food processing, production, etc).” (Advances in Food Science, 1 January 2013)Table of ContentsPreface GENERAL INTRODUCTION Fundamental Knowledge Required for Successful Dispersions of Powders into Liquids Particle Dimensions in Suspensions Concentration Range of Suspensions Outline of the Book FUNDAMENTALS OF WETTING AND SPREADING Introduction The Concept of the Contact Angle Adhesion Tension Work of Adhesion Wa Work of Cohesion Calculation of Surface Tension and Contact Angle The Spreading of Liquids on Surfaces Contact Angle Hysteresis THE CRITICAL SURFACE TENSION OF WETTING AND THE ROLE OF SURFACTANTS IN POWDER WETTING The Critical Surface Tension of Wetting Theoretical Basis of the Critical Surface Tension Effect of Surfactant Adsorption Dynamic Processes of Adsorption and Wetting Wetting of Powders by Liquids STRUCTURE OF THE SOLID-LIQUID INTERFACE AND ELECTROSTATIC STABILIZATION Structure of the Solid-Liquid Interface Structure of the Electrical Double Layer Distinction between Specific and Nonspecific Adsorbed Ions Electrical Double-Layer Repulsion van der Waals Attraction Total Energy of Interaction Flocculation of Suspensions Criteria for Stabilization of Dispersions with Double-Layer Interaction ELECTROKINETIC PHENOMENA AND ZETA POTENTIAL Stern-Grahame Model of the Double Layer Calculation of Zeta Potential from Particle Mobility Measurement of Electrophoretic Mobility and Zeta Potential Electroacoustic Methods GENERAL CLASSIFICATION OF DISPERSING AGENTS AND ADSORPTION OF SURFACTANTS AT THE SOLID/LIQUID INTERFACE Classification of Dispersing Agents ADSORPTION AND CONFORMATION OF POLYMERIC SURFACTANTS AT THE SOLID-LIQUID INTERFACE Theories of Polymer Adsorption Experimental Techniques for Studying Polymeric Adsorption Measurement of the Adsorption Isotherm Measurement of the Fraction of Segments p Determination of the Segment Density Distribution p(z) and Adsorbed Layer Thickness delta h Examples of the Adsorption Isotherms of Nonionic Polymeric Surfactants Adsorbed Layer Thickness Results Kinetics of Polymer Adsorption STABILIZATION AND DESTABILIZATION OF SUSPENSIONS USING POLYMERIC SURFACTANTS AND THE THEORY OF STERIC STABILIZATION Introduction Interaction between Particles Containing Adsorbed Polymeric Surfactant Layers (Steric Stabilization) Flocculation of Sterically Stabilized Dispersions Bridging Flocculation by Polymers and Polyelectrolytes Examples for Suspension Stabilization Using Polymeric Surfactants Polymeric Surfactants for Stabilization of Preformed Latex Dispersions PROPERTIES OF CONCENTRATED SUSPENSIONS Interparticle Interactions and Their Combination Definition of "Dilute", "Concentrated", and "Solid" Suspensions States of Suspension on Standing SEDIMENTATION OF SUSPENSIONS AND PREVENTION OF FORMATION OF DILATANT SEDIMENTS Sedimentation Rate of Suspensions Prevention of Sedimentation and Formation of Dilatant Sediments CHARACTERIZATION OF SUSPENSIONS AND ASSESSMENT OF THEIR STABILITY Introduction Assessment of the Structure of the Solid/Liquid Interface Assessment of Sedimentation of Suspensions Assessment of Flocculation and Ostwald Ripening (Crystal Growth) Scattering Techniques Measurement of Rate of Flocculation Measurement of Incipient Flocculation Measurement of Crystal Growth (Ostwald Ripening) Bulk Properties of Suspensions: Equilibrium Sediment Volume (or Height) and Redispersion RHEOLOGICAL TECHNIQUES FOR ASSESSMENT OF STABILITY OF SUSPENSIONS Introduction Steady-State Measurements Constant Stress (Creep) Measurements Dynamic (Oscillatory) Measurements RHEOLOGY OF CONCENTRATED SUSPENSIONS Introduction

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Book SynopsisIn this new edition of a bestseller, all the contents have been brought upto-date by addressing current standards and best practices in the assessment and prediction of ADMET properties. Although the previous chapter layout has been retained, substantial revisions have been made, with new topics such as pro-drugs, active metabolites and transporters covered in detail in a manner useful to the Drug Discovery scientist. The authors discuss the parameters and processes important for the absorption, distribution and retention of drug compounds in the body, plus the potential problems created by their transformation into toxic byproducts. While aimed at all those dealing professionally with the development and application of pharmaceutical substances, the readily comprehensible style makes this book equally suitable for students of pharmacy and related subjects. Uniquely comprehensive, the book relates physicochemistry and chemical structure to pharmacokinetic properties and ultimately drug efficacy and safety.Table of ContentsPHYSICOCHEMISTRY Physicochemistry and Pharmacokinetics Partition and Distribution Coefficients as Measures of Lipophilicity Limitations on the Use of 1-Octanol Further Understanding of logP Alternative Lipophilicity Scales Computational Systems to Determine Lipophilicity Membrane Systems to Study Drug Behavior Dissolution and Solubility The BCS Classification and Central Role of Permeability PHARMACOKINETICS Setting the Scene Intravenous Administration: Volume of Distribution Intravenous Administration: Clearance Intravenous Administration: Clearance and Half-life Intravenous Administration: Infusion Oral Administration Repeated Doses Development of the Unbound (Free) Drug Model Unbound Drug and Drug Action Unbound Drug Model and Barriers to Equilibrium Pharmacodynamic Models Slow Offset Compounds Factors Governing Unbound Drug Concentration ABSORPTION The Absorption Process Dissolution Membrane Transfer Barriers to Membrane Transfer Prodrugs to Increase Oral Absorption Active Transport Models for Absorption Estimation Estimation of Absorption Potential and other Computational DISTRIBUTION Membrane Transfer Access to the Target Brain Penetration CLEARANCE The Clearance Processes Role of Transport Proteins in Drug Clearance Interplay Between Metabolic and Renal Clearance Role of Lipophilicity in Drug Clearance Active Metabolites Balancing the Rate of Renal and Metabolic clearance and Potency RENAL CLEARANCE Kidney Anatomy and Function Lipophilicity and Reabsorption by the Kidney Effect of Charge on Renal Clearance Plasma Protein Binding and Renal Clearance Balancing Renal Clearance and Absorption Renal Clearance and Drug Design METABOLIC (HEPATIC) CLEARANCE Symbols Function of Metabolism (Biotransformation) Cytochrome P450 Other Oxidative Metabolism Processes Oxidative Metabolism and Drug Design Nonspecific Esterases Prodrugs to Aid Membrane Transfer Enzymes Catalyzing Drug Conjugation Stability to Conjugation Processes Pharmacodynamics and Conjugation TOXICITY Toxicity Findings Structure - Toxicity Analyses Reactive Metabolite Screening in Drug Discovery Structural Alerts/Toxicophores in Drug Design Dealing with Reactive Metabolite Positives in Drug Discovery: Risk Assessment Strategies - Effect of Daily Dose Dealing with Reactive Metabolite Positives in Drug Discovery: Risk Assessment Strategies - Competing Detoxication Pathways Stratification of Toxicity Toxicity Prediction: Computational Toxicology Toxicogenomics Pharmacogenomics Enzyme Induction and Drug Design Enzyme Inhibition and Drug Design PREDICTING HUMAN PHARMACOKINETICS Objectives of Predicting Human Pharmacokinetics Allometric Scaling of Preclinical In Vivo PK Parameters Prediction of Human PK Parameters Using In Vitro Data Elimination Half-Life Moving Forward ADME SCREENING The High-Throughput Synthesis and Screening Trend The Concept of ADME Space Drug Metabolism and Discovery Screening Sequences Physicochemistry Absorption/Permeability Metabolism, Induction, and Inhibition Transporters Protein Binding Pharmacokinetics

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Book SynopsisThis second edition of a very successful book is thoroughly updated with existing chapters completely rewritten while the content has more than doubled from 16 to 36 chapters. As with the first edition, the focus is on industrial pharmaceutical research, written by a team of industry experts from around the world, while quality and safety management, drug approval and regulation, patenting issues, and biotechnology fundamentals are also covered. In addition, this new edition now not only includes biotech drug development but also the use of biopharmaceuticals in diagnostics and vaccinations. With a foreword by Robert Langer, Kenneth J Germeshausen Professor of Chemical and Biomedical Engineering at MIT and member of the National Academy of Engineering and the National Academy of Sciences.Trade Review"This textbook provides a concise overview of pharmaceutical biotechnology focusing on the industrial needs of recombinant drugs, processes, and clinical use." E-STREAMS "... international experts ... have provided precise and valuable information for the industrial experts, scientists, pharmacists, research managers..." American Journal of Therapeutics Table of Contents Preface PART I: CONCEPTS AND METHODS FOR RECOMBINANT DRUG PRODUCTION Pharmaceutical Biotechnology and Industrial Applications: Learning Lessons from Molecular Biology (Oliver Kayser, Heribert Warzecha) Procaryotic Cells in Biotech Production (Andriy Luzhetskyy, Gabriele Weitnauer, Andreas Bechtold) Mammalian Cells in Biotech Production (Maria J. De Jesus and Florian M. Wurm) Biopharmaceuticals from Plants (Heribert Warzecha) The Production of Biopharmaceuticals in Transgenic Animals (Heiner Niemann, Alexander Kind, Angelika Schnieke) Translation of New Technologies in Biomedicines: Shaping the Road from Basic Research to Drug Development and Clinical Application - and Back Again (Michael Balls, Andrew Bennett, David Kendall) PART II: BRINGING THE DRUG INTO ACTION - FROM DOWNSTREAMING TO APPROVAL Overview and Classification of Approved Recombinant Drugs (Theo Dingermann, I. Zundorf) Downstream Processing (Uwe Gottschalk) Characterization of Recombinant Proteins (Christoph Giese, Henning von Horsten, Stefan Zietze) Formulation Strategies for Recombinant Protein and Related Biotech Drugs (Gerhard Winter, Julia Myschik) Drug Approval in the European Union and United States (Gary Walsh) Patents in the Pharmaceutical Biotechnology Industry: Legal and Ethical Issues (David B. Resnick) Biosimilar Drugs (Walter Hinderer) Pharmacokinetics and Pharmacodynamics of Therapeutic Peptides and Proteins (Yi Zhang, Bernd Meibohm) PART III: VACCINES Scientific, Technical and Economic Aspects of Vaccine Research and Development (Jens Peter Gregersen) New Nanobiotechnological Strategies for the Development of Vectors for Cancer Vaccines (Sean M. Geary, Caitlin D. Lemke, Yogita Krishnamachari, Aliasger K. Salem) Recombinant Vaccines: Development, Production and Application (Luke Richard Le Grand Michaela White, Evan B. Siegel, Ross Thomas Barnard) PART IV: RECENT APPLICATIONS IN PHARMACEUTICAL BIOTECHNOLOGY In Silico and Ultra-high Throughput Screenings (uHTS) in Drug Discovery: An Overview (Debmalya Barh, Shoaib Ahmad, Atanu Bhattacharjee) Metabolic Engineering of Medicinal Plants and Microorganisms for the Production of Natural Products (O Kayser, J Hille, HJ Woerdenbag) Metabolomics as Bioanalytical Tool for Characterization of Medicinal Plants and their Phytomedical Preparations (Nizar Happyana, Remco Muntendam, Oliver Kayser) Integration of Biotechnologies for the Development of Personalized Medicine (Kewal Jain) Xenotransplantation in Pharmaceutical Biotechnology (Gregory J. Brunn and Jeffrey L. Platt) Nutraceuticals/Functional Foods for Improving Health and Preventing Disease (Jian Zhao) Index

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Book SynopsisMit einem neuen Herausgeberteam wird das Buch "Industrielle Anorganische Chemie" grundlegend überarbeitet weitergeführt. Das Lehrwerk bietet in hervorragend übersichtlicher, knapp und präzise gehaltener Form eine aktuelle Bestandsaufnahme der industriellen anorganischen Chemie. Zu Herstellungsverfahren, wirtschaftlicher Bedeutung und Verwendung der Produkte, sowie zu ökologischen Konsequenzen, Energie- und Rohstoffve brauch bieten die Autoren einen fundierten Überblick. Hierfür werden die bewährten Prinzipien hinsichtlich der Beiträge von Vertretern aus der Industrie sowie des generellen Aufbaus beibehalten. Inhaltlich werden Neugewichtungen vorgenommen: l Aufnahme hochaktueller Themen wie Lithium und seine Verbindungen und Seltenerdmetalle l Aufnahme bislang vernachlässigter Themen wie technische Gase, Halbleiter- und Elektronikmaterialien, Hochofenprozess sowie Edelmetalle l Straffung aus industriell-anorganischer Sicht weniger relevanter Themen z.B. in den Bereichen Baustoffe oder Kernbrennstoffe l Ergänzungen in der Systematik hinsichtlich bislang nicht behandelter Alkali- und Erdalkalimetalle und ihre Bedeutung in der industriellen anorganischen Chemie l Betrachtung der jeweiligen Rohstoffsituation Begleitmaterial für Dozenten verfügbar unter: www.wiley-vch.de/textbooks "Von den Praktikern der industriellen Chemie verfasst, füllt dieser Band eine Lücke im Fachbuchangebot. Das Buch sollte von jedem fortgeschrittenen Chemiestudenten und auch von Studierenden an Fachhochschulen technischchemischer Richtungen gelesen werden. Dem in der Industrie tätigen Chemiker schließlich bietet es einen lohnenden Blick über den Zaun seines engen Arbeitsgebietes.... Die Autoren haben ein Buch vorgelegt, dem man eine weite Verbreitung wünschen und vorhersagen kann." GIT "Das Buch kann uneingeschränkt empfohlen werden." Nachrichten aus Chemie Technik und Laboratorium "sein besonderer Wert liegt in der anschaulichen Darstellung und in der Verknüpfung technischer und wirtschaftlicher Fakten." chemie-anlagen + verfahrenTrade Review"Ein sehr gelungenes, aktuelles und praxisnahes Werk, dem neben dem Fachwissen der Autoren auch die Mitarbeit von Kollegen aus der Industrie anzumerken ist." Lebensmittelchemiker Mitteilungen (01.03.2014) "Das Buch macht beim Blättern und Lesen schlicht Spaß" Tu-Chemnitz.de (25.02.2014) "Ein Bindeglied zwischen den eher theoretischen Lehrbüchern der anorganischen Chemie und denen der chemischen Verfahrenstechnik." BG RCI.magazin (01.01.2014) "hervorragend übersichtlich und präzise" CHEManager-online.com (20.12.2013) "hervorragendes Nachschlagewerk" app.uni-regensburg.de - Fachschaft Chemie (15.10.2013) "kompakt und gut verständlich" ZfP-Zeitung (Oktober 2013, 11.10.2013) "eine aktuelle Bestandsaufnahme der industriellen anorganischen Chemie" PROCESS (9/2013, 01.09.2013) Aus Rezensionen der zweiten Auflage: 'Von den Praktikern der industriellen Chemie verfaßt, füllt dieser Band eine Lücke im Fachbuchangebot.... Das Buch sollte von jedem fortgeschrittenen Chemiestudenten und auch von Studierenden an Fachochschulen technisch-chemischer Richtungen gelesen werden.... Dem in der Industrie tätigen Chemiker schließlich bietet es einen lohnenden Blick über den Zaun seines engen Arbeitsgebietes.... Die Autoren haben ein Buch vorgelegt, dem man eine weite Verbreitung wünschen und vorhersagen kann...' (GIT) '... Der kurzgefaßte Text erlaubt es schnell die wesentlichen Fakten zu erkennen. Dem raschen Auffinden einer gesuchten Information ist dienlich, daß etwa ein Drittel jeder Seite als Rand reserviert ist, auf dem - neben dem entsprechenden Text angeordnet - die wichtigsten Schlagworte und Zahlen noch einmal zusammengefaßt sind. Hilfreich ist auch die optische Hervorhebung der Reaktionsgleichungen.... Die entscheidenden Fakten sind so schnell wie in einem Lexikon, aber ausführlicher und trotzden übersichtlich zu finden. Für die erste Information bietet es gegenüber den bekannten großen Enzyklopädien den Vorteil der Auswahl des Wesentlichen, das somit griffbereit, preisgünstig und auf den neuesten Stand zur Verfügung steht. Das Buch kann uneingeschränkt empfohlen werden...' (Nachrichten aus Chemie Technik und Laboratorium) '... Sein besonderer Wert liegt in der anschaulichen Darstellung und in der Verknüpfung technischer und wirtschaftlicher Fakten...' (chemie-anlagen + verfahren)Table of ContentsVorwort zur 4. Auflage XIX Kurzbiografien der Autoren XXI Geleitwort XXIII 1 Anorganische Grundprodukte 1 1.1 Wasserstoff und seine Verbindungen 1 1.1.1 Wasserstoff 1 1.1.1.1 Allgemeines 1 1.1.1.2 Wirtschaftliche Bedeutung und Verwendung 1 1.1.1.3 Vorkommen und Rohstoffe 3 1.1.1.4 Herstellung von Wasserstoff 3 1.1.1.5 Neue Trends zur Synthese von Wasserstoff 6 1.1.2 Wasser 8 1.1.2.1 Allgemeines 9 1.1.2.2 Wirtschaftliche Bedeutung und Verwendung 9 1.1.2.3 Vorkommen und Rohstoffe 10 1.1.2.4 Aufbereitung von Wasser 11 1.1.3 Wasserstoffperoxid und anorganische Peroxoverbindungen 20 1.1.3.1 Allgemeines 21 1.1.3.2 Wirtschaftliche Bedeutung und Verwendung 22 1.1.3.3 Wasserstoffperoxid 24 1.1.3.4 Peroxoverbindungen 28 1.2 Stickstoff und Stickstoffverbindungen 31 1.2.1 Allgemeines 32 1.2.2 Wirtschaftliche Bedeutung und Verwendung 33 1.2.3 Vorkommen und Rohstoffe 37 1.2.4 Stickstoffverbindungen 38 1.3 Phosphor und seine Verbindungen 50 1.3.1 Allgemeines 50 1.3.2 Wirtschaftliche Bedeutung und Verwendung 51 1.3.3 Vorkommen und Rohstoffe für Phosphor und anorganische Phosphorverbindungen 56 1.3.4 Herstellung von Phosphor 59 1.3.4.1 Herstellung von weißem Phosphor 59 1.3.4.2 Herstellung von rotem Phosphor 61 1.3.5 Herstellung von Phosphorverbindungen 62 1.3.5.1 Phosphorsäure 62 1.3.5.2 Phosphorpentoxid 71 1.3.5.3 Phosphorpentasulfid 72 1.3.5.4 Halogenide des Phosphors 72 1.3.5.5 Säuren und Salze des Phosphors mit P<5+ 74 1.3.5.6 Organische Verbindungen des Phosphors 75 1.4 Schwefel und Schwefelverbindungen 79 1.4.1 Allgemeines 80 1.4.2 Wirtschaftliche Bedeutung und Verwendung 80 1.4.3 Vorkommen und Rohstoffe 81 1.4.4 Herstellung von Schwefel 82 1.4.4.1 Schwefel aus Elementarschwefelvorkommen 82 1.4.4.2 Schwefel aus Schwefelwasserstoff und Schwefeldioxid 82 1.4.4.3 Schwefel aus Pyrit 83 1.4.5 Herstellung und Verwendung von Schwefelverbindungen 83 1.4.5.1 Schwefeldioxid, 100 %ig 83 1.4.5.2 Schwefeltrioxid, 100 %ig 84 1.4.5.3 Schwefelsäure 85 1.4.5.4 Dischwefeldichlorid 95 1.4.5.5 Schwefeldichlorid 95 1.4.5.6 Thionylchlorid 95 1.4.5.7 Sulfurylchlorid 96 1.4.5.8 Chlorsulfonsäure 96 1.4.5.9 Fluorsulfonsäure 97 1.4.5.10 Salze der Schwefligen Säure 97 1.4.5.11 Natriumthiosulfat und Ammoniumthiosulfat 97 1.4.5.12 Natriumdithionit und Natriumhydroxymethansulfinat 98 1.4.5.13 Schwefelwasserstoff 99 1.4.5.14 Natriumsulfid 100 1.4.5.15 Natriumhydrogensulfid 100 1.4.5.16 Schwefelkohlenstoff 100 1.5 Halogene und Halogenverbindungen 101 1.5.1 Fluor und Fluorverbindungen 101 1.5.1.1 Allgemeines 102 1.5.1.2 Wirtschaftliche Bedeutung und Verwendung von Fluor 102 1.5.1.3 Vorkommen und Rohstoffe 103 1.5.1.4 Herstellung von Fluor 105 1.5.1.5 Herstellung und Verwendung von Fluorverbindungen 107 1.5.2 Chlor und Chlorverbindungen 117 1.5.2.1 Allgemeines 118 1.5.2.2 Wirtschaftliche Bedeutung und Verwendung 118 1.5.2.3 Vorkommen und Rohstoffe 120 1.5.2.4 Herstellung von Chlor 120 1.5.2.5 Herstellung und Verwendung von Chlorverbindungen 131 1.5.3 Brom und Bromverbindungen 141 1.5.3.1 Allgemeines 142 1.5.3.2 Wirtschaftliche Bedeutung und Verwendung 142 1.5.3.3 Vorkommen und Rohstoffe 144 1.5.3.4 Herstellung von Brom 144 1.5.3.5 Herstellung von Bromverbindungen 146 1.5.4 Iod und Iodverbindungen 147 1.5.4.1 Allgemeines 147 1.5.4.2 Wirtschaftliche Bedeutung und Verwendung 148 1.5.4.3 Vorkommen und Rohstoffe 149 1.5.4.4 Herstellung von Iod 149 1.5.4.5 Herstellung von Iodverbindungen 150 1.6 Technische Gase 151 1.6.1 Allgemeines 151 1.6.2 Wirtschaftliche Bedeutung und Verwendung 153 1.6.3 Herstellung 155 1.6.3.1 Sauerstoff und Stickstoff 155 1.6.3.2 Edelgase 156 1.6.3.3 Kohlenstoffmonoxid 160 1.6.3.4 Kohlenstoffdioxid 163 2 Mineralische Dünger 171 2.1 Phosphorhaltige Düngemittel 171 2.1.1 Wirtschaftliche Bedeutung 172 2.1.1.1 Gesamtphosphordünger 172 2.1.1.2 Superphosphat 173 2.1.1.3 Tripelsuperphosphat 173 2.1.1.4 Ammoniumphosphate 174 2.1.1.5 Thomasphosphate 174 2.1.2 Rohstoffe 174 2.1.3 Gewinnung der Phosphate 175 2.1.3.1 Schwefelsäureaufschluss zur Herstellung von Superphosphat 175 2.1.3.2 Phosphorsäureaufschluss 176 2.1.3.3 Salpetersäureaufschluss 176 2.1.3.4 Aufschluss durch Glühverfahren 177 2.1.3.5 Thomasphosphat 177 2.1.3.6 Ammoniumphosphate 177 2.1.3.7 Nitrophosphate 179 2.2 Stickstoffhaltige Düngemittel 180 2.2.1 Wirtschaftliche Bedeutung 180 2.2.1.1 Ammoniumsulfat 181 2.2.1.2 Ammoniumnitrat 182 2.2.1.3 Harnstoff 182 2.2.2 Herstellung von stickstoffhaltigen Düngemitteln 183 2.2.2.1 Ammoniumsulfat 184 2.2.2.2 Harnstoff 184 2.2.2.3 Ammoniumnitrat 187 2.3 Kaliumhaltige Düngemittel 189 2.3.1 Vorkommen von Kalisalzen 189 2.3.2 Wirtschaftliche Bedeutung von kaliumhaltigen Düngemitteln 190 2.3.3 Herstellung von kaliumhaltigen Düngemitteln 191 2.3.3.1 Kaliumchlorid 191 2.3.3.2 Kaliumsulfat 193 2.3.3.3 Kaliumnitrat 194 3 Metalle und ihre Verbindungen 197 3.1 Alkali- und Erdalkalimetalle und ihre Verbindungen 197 3.1.1 Alkalimetalle und ihre Verbindungen 197 3.1.1.1 Lithium und seine Verbindungen 198 3.1.1.2 Natrium und seine Verbindungen 206 3.1.1.3 Kalium und seine Verbindungen 217 3.1.1.4 Rubidium und seine Verbindungen 220 3.1.1.5 Caesium und seine Verbindungen 221 3.1.2 Erdalkalimetalle und ihre Verbindungen 223 3.1.2.1 Allgemeines 223 3.1.2.2 Beryllium und seine Verbindungen 223 3.1.2.3 Magnesium und seine Verbindungen 225 3.1.2.4 Calcium und seine Verbindungen 230 3.1.2.5 Strontium und seine Verbindungen 234 3.1.2.6 Barium und seine Verbindungen 237 3.2 Aluminium und seine Verbindungen 240 3.2.1 Allgemeines 241 3.2.2 Wirtschaftliche Bedeutung und Verwendung 241 3.2.2.1 Aluminiummetall 241 3.2.2.2 Aluminiumverbindungen 242 3.2.3 Vorkommen und Rohstoffe 244 3.2.4 Herstellung von Aluminium 245 3.2.4.1 Recycling 246 3.2.5 Herstellung von Aluminiumverbindungen 246 3.3 Eisen und Stahl 248 3.3.1 Allgemeines 249 3.3.2 Wirtschaftliche Bedeutung und Verwendung 249 3.3.3 Vorkommen und Rohstoffe 251 3.3.4 Eisen, metallisch 252 3.3.4.1 Hochofenprozess 253 3.3.5 Stahl 256 3.3.5.1 Wind- und Herdfrischverfahren 256 3.3.5.2 Elektroschmelzverfahren 257 3.3.5.3 Edelstahl 258 3.3.6 Eisenverbindungen 258 3.4 Kupfer 260 3.4.1 Allgemeines 260 3.4.2 Wirtschaftliche Bedeutung und Verwendung 261 3.4.2.1 Kupfermetall 261 3.4.2.2 Kupferverbindungen 261 3.4.3 Vorkommen und Rohstoffe 262 3.4.3.1 Sekundärrohstoffe 263 3.4.4 Herstellung von Kupfer 264 3.4.4.1 Pyrometallurgische Herstellung von Kupfer 264 3.4.4.2 Kupferraffination 267 3.4.4.3 Hydrometallurgische Kupfergewinnung 269 3.4.5 Herstellung von Kupferverbindungen 273 3.5 Silicium und seine anorganischen Verbindungen 275 3.5.1 Allgemeines 275 3.5.2 Wirtschaftliche Bedeutung und Verwendung 276 3.5.3 Vorkommen und Rohstoffe 277 3.5.4 Herstellung von Ferrosilicium und technischem Silicium 277 3.5.5 Herstellung von anorganischen Siliciumverbindungen 279 3.5.5.1 Siliciumhalogenide 280 3.5.5.2 Kieselsäureester Si(OR)4 281 3.6 Blei und seine Verbindungen 281 3.6.1 Allgemeines 281 3.6.2 Wirtschaftliche Bedeutung 282 3.6.3 Vorkommen 283 3.6.4 Herstellung 284 3.6.5 Bleiverbindungen 287 3.6.5.1 Bleiacetate, -carbonate 287 3.6.5.2 Bleihalogenide 288 3.6.5.3 Bleioxide 288 3.6.5.4 Bleipigmente 291 3.6.5.5 Bleisulfate 291 3.6.5.6 Organische Bleiverbindungen 291 3.7 Zinn und seine Verbindungen 293 3.7.1 Allgemeines 293 3.7.2 Wirtschaftliche Bedeutung und Verwendung 293 3.7.3 Vorkommen und Rohstoffe 294 3.7.4 Herstellung von Zinn 295 3.7.5 Herstellung und Verwendung von Zinnverbindungen 295 3.8 Buntmetalle 296 3.8.1 Titan und seine Verbindungen 296 3.8.1.1 Allgemeines 296 3.8.1.2 Wirtschaftliche Bedeutung und Verwendung 296 3.8.1.3 Vorkommen und Rohstoffe 297 3.8.1.4 Herstellung von Titan 297 3.8.2 Vanadium 298 3.8.2.1 Allgemeines 298 3.8.2.2 Wirtschaftliche Bedeutung und Verwendung 298 3.8.2.3 Vorkommen und Rohstoffe 299 3.8.2.4 Vanadium, metallisch 300 3.8.2.5 Ferrovanadium 300 3.8.2.6 Vanadiumverbindungen 301 3.8.3 Chrom und seine Verbindungen 301 3.8.3.1 Vorkommen 302 3.8.3.2 Herstellung 302 3.8.3.3 Wirtschaftliche Bedeutung 304 3.8.3.4 Chromverbindungen 306 3.8.4 Wolfram und seine Verbindungen 313 3.8.4.1 Allgemeines 313 3.8.4.2 Wirtschaftliche Bedeutung und Verwendung 314 3.8.4.3 Vorkommen und Rohstoffe 315 3.8.4.4 Gewinnung von Wolfram 316 3.8.4.5 Gewinnung von Wolframverbindungen 317 3.8.5 Mangan und Manganverbindungen 317 3.8.5.1 Allgemeines 317 3.8.5.2 Wirtschaftliche Bedeutung und Verwendung 318 3.8.5.3 Vorkommen und Rohstoffe 319 3.8.5.4 Herstellung von Mangan 320 3.8.5.5 Herstellung von Manganverbindungen 321 3.8.6 Molybdän und seine Verbindungen 326 3.8.6.1 Wirtschaftliche Bedeutung und Verwendung 327 3.8.6.2 Vorkommen und Rohstoffe 328 3.8.6.3 Gewinnung von Molybdän 329 3.8.6.4 Ferromolybdän 329 3.8.6.5 Gewinnung der Molybdänverbindungen 330 3.8.7 Cobalt 330 3.8.7.1 Allgemeines 330 3.8.7.2 Wirtschaftliche Bedeutung und Verwendung 331 3.8.7.3 Vorkommen und Rohstoffe 333 3.8.7.4 Herstellung von Cobalt 334 3.8.7.5 Herstellung von Cobaltverbindungen 338 3.8.8 Nickel 339 3.8.8.1 Allgemeines 339 3.8.8.2 Wirtschaftliche Bedeutung und Verwendung 340 3.8.8.3 Vorkommen und Rohstoffe 341 3.8.8.4 Herstellung von Nickel 342 3.8.8.5 Herstellung von Nickelverbindungen 348 3.8.9 Zink und seine Verbindungen 350 3.8.9.1 Allgemeines 350 3.8.9.2 Wirtschaftliche Bedeutung und Verwendung 350 3.8.9.3 Vorkommen und Rohstoffe 351 3.8.9.4 Herstellung von Zink 351 3.8.9.5 Herstellung und Verwendung von Zinkverbindungen 352 3.9 Edelmetalle 352 3.9.1 Gold und seine Verbindungen 352 3.9.1.1 Allgemeines 353 3.9.1.2 Wirtschaftliche Bedeutung und Verwendung 353 3.9.1.3 Vorkommen und Rohstoffe 354 3.9.1.4 Gewinnung und Herstellung von Gold 356 3.9.1.5 Herstellung von Goldverbindungen 357 3.9.2 Silber und seine Verbindungen 358 3.9.2.1 Allgemeines 358 3.9.2.2 Wirtschaftliche Bedeutung und Verwendung 359 3.9.2.3 Vorkommen und Rohstoffe 359 3.9.2.4 Herstellung von Silber 360 3.9.2.5 Herstellung und Verwendung von Silberverbindungen 362 3.9.3 Platin, Palladium und seine Verbindungen 363 3.9.3.1 Allgemeines 364 3.9.3.2 Wirtschaftliche Bedeutung und Verwendung 364 3.9.3.3 Vorkommen und Rohstoffe 366 3.9.3.4 Herstellung von Platin und Palladium 367 3.9.3.5 Herstellung und Verwendung von Platin- und Palladiumverbindungen 369 3.9.4 Osmium und seine Verbindungen 371 3.9.4.1 Allgemeines 371 3.9.4.2 Wirtschaftliche Bedeutung und Verwendung 372 3.9.4.3 Vorkommen und Rohstoffe 372 3.9.4.4 Herstellung und Verwendung von Osmiumverbindungen 373 3.9.5 Iridium und seine Verbindungen 373 3.9.5.1 Allgemeines 373 3.9.5.2 Wirtschaftliche Bedeutung und Verwendung 374 3.9.5.3 Vorkommen und Rohstoffe 375 3.9.5.4 Herstellung von Iridium 375 3.9.5.5 Herstellung und Verwendung von Iridiumverbindungen 375 3.9.6 Rhodium und seine Verbindungen 376 3.9.6.1 Allgemeines 376 3.9.6.2 Wirtschaftliche Bedeutung und Verwendung 377 3.9.6.3 Vorkommen und Rohstoffe 378 3.9.6.4 Herstellung von Rhodium 378 3.9.6.5 Herstellung und Verwendung von Rhodiumverbindungen 378 3.9.7 Rhenium und seine Verbindungen 379 3.9.7.1 Allgemeines 379 3.9.7.2 Wirtschaftliche Bedeutung und Verwendung 380 3.9.7.3 Vorkommen und Rohstoffe 380 3.9.7.4 Herstellung von Rhenium 381 3.9.7.5 Herstellung und Verwendung von Rhenium(VII)-Verbindungen 381 3.9.8 Quecksilber und seine Verbindungen 382 3.9.8.1 Allgemeines 383 3.9.8.2 Wirtschaftliche Bedeutung und Verwendung 383 3.9.8.3 Vorkommen und Rohstoffe 385 3.9.8.4 Herstellung von Quecksilber 385 3.9.8.5 Herstellung und Verwendung von Quecksilberverbindungen 386 3.10 Anhang 392 4 Halbleiter- und Technologiematerialien 395 4.1 Silicium als Halbleiter 395 4.1.1 Allgemeines 396 4.1.2 Wirtschaftliche Bedeutung und Verwendung 397 4.1.3 Vorkommen und Rohstoffe 398 4.1.4 Herstellung von Reinstsilicium 399 4.2 Germanium 407 4.2.1 Allgemeines 408 4.2.2 Wirtschaftliche Bedeutung und Verwendung 408 4.2.3 Vorkommen und Rohstoffe 409 4.2.4 Herstellung von Germanium 409 4.3 Gallium 409 4.3.1 Allgemeines 410 4.3.2 Wirtschaftliche Bedeutung und Verwendung 410 4.3.3 Vorkommen und Rohstoffe 410 4.3.4 Herstellung von Gallium 411 4.4 Indium 411 4.4.1 Allgemeines 412 4.4.2 Wirtschaftliche Bedeutung und Verwendung 412 4.4.3 Vorkommen und Rohstoffe 413 4.4.4 Herstellung von Indium 413 4.5 Bor 414 4.5.1 Allgemeines 414 4.5.2 Wirtschaftliche Bedeutung und Verwendung 414 4.5.3 Vorkommen und Rohstoffe 415 4.5.4 Herstellung von Bor 415 4.6 Arsen 416 4.6.1 Allgemeines 416 4.6.2 Wirtschaftliche Bedeutung und Verwendung 416 4.6.3 Vorkommen und Rohstoffe 417 4.6.4 Herstellung von Arsen 417 4.7 Antimon 418 4.7.1 Allgemeines 418 4.7.2 Wirtschaftliche Bedeutung und Verwendung 419 4.7.3 Vorkommen und Rohstoffe 419 4.7.4 Herstellung von Antimon 420 4.8 Seltene Erden 420 4.8.1 Allgemeines 421 4.8.2 Wirtschaftliche Bedeutung und Verwendung 422 4.8.3 Vorkommen und Rohstoffe 422 4.8.4 Herstellung der Seltenen Erden 423 4.8.4.1 Scandium 423 4.8.4.2 Yttrium, Lanthan und Lanthanoide 423 4.9 Niob 425 4.9.1 Allgemeines 425 4.9.2 Wirtschaftliche Bedeutung und Verwendung 426 4.9.3 Vorkommen und Rohstoffe 426 4.9.4 Herstellung 427 4.10 Tantal 427 4.10.1 Allgemeines 428 4.10.2 Wirtschaftliche Bedeutung und Verwendung 428 4.10.3 Vorkommen und Rohstoffe 429 4.10.4 Herstellung von Tantal 430 4.11 Verbindungshalbleiter 430 5 Organosiliciumverbindungen 433 5.1 Industriell bedeutende Organosiliciumverbindungen 433 5.1.1 Nomenklatur 433 5.2 Technisch bedeutende Silane 434 5.2.1 Unsubstituierte Silane 434 5.2.2 Halogensilane 434 5.2.3 Organosilane 436 5.3 Siloxane/Silicone 439 5.3.1 Allgemeines 439 5.3.2 Nomenklatur 439 5.3.3 Wirtschaftliche Situation 440 5.3.4 Herstellung 441 5.3.5 Technische Durchführung der Polymerisation 445 5.3.6 Herstellung verzweigter Polysiloxane 446 5.4 Technische Siliconprodukte 447 5.4.1 Siliconöle 447 5.4.2 Siliconölfolgeprodukte 449 5.4.3 Siliconkautschuke 450 5.4.3.1 Kaltvulkanisierender Einkomponenten-Siliconkautschuk 450 5.4.3.2 Kaltvulkanisierender Zweikomponentensiliconkautschuk 450 5.4.3.3 Heißvulkanisierender, peroxidisch vernetzender Siliconkautschuk 451 5.4.3.4 Heißvulkanisierender, additionsvernetzender Siliconkautschuk 452 5.4.3.5 Eigenschaften von Silicongummi 453 5.4.4 Siliconharze 453 5.4.5 Silicon-Copolymere, -Blockcopolymere und -Pfropfcopolymere 454 6 Anorganische Festkörper 457 6.1 Silikatische Erzeugnisse 457 6.1.1 Glas 457 6.1.1.1 Allgemeines 457 6.1.1.2 Wirtschaftliche Bedeutung und Verwendung 460 6.1.1.3 Vorkommen und Rohstoffe 461 6.1.1.4 Herstellung von Glas 463 6.1.1.5 Glaseigenschaften und Verwendung 468 6.1.1.6 Herstellung von Alkalisilikaten 469 6.1.2 Zeolithe 470 6.1.2.1 Allgemeines 470 6.1.2.2 Wirtschaftliche Bedeutung und Verwendung 473 6.1.2.3 Vorkommen und Rohstoffe 475 6.1.2.4 Herstellung von synthetischen Zeolithen 475 6.2 Anorganische Fasern 478 6.2.1 Einführung 479 6.2.2 Verfahren zur Herstellung von anorganischen Fasern 481 6.2.2.1 Natürliche Mineralfasern 481 6.2.2.2 Künstliche Mineralfasern 482 6.2.2.3 Synthetische keramische Fasern 496 6.2.2.4 Kohlenstofffasern 502 6.2.2.5 Metallfasern 504 6.2.3 Ausgewählte Fasereigenschaften und Anwendungsfelder 505 6.2.3.1 Einführung 505 6.2.3.2 Natürliche Mineralwollen 508 6.2.3.3 Künstliche Mineralwollen 509 6.2.3.4 Textilglasfasern 511 6.2.3.5 Polykieselsäurefasern 513 6.2.3.6 Synthetische keramische Fasern 516 6.2.3.7 Kohlenstofffasern 518 6.2.3.8 Metallfasern 520 6.2.3.9 Faser-Verbundwerkstoffe 522 6.2.4 Physiologische und legislative Aspekte 526 6.3 Baustoffe 527 6.3.1 Allgemeines 528 6.3.2 Kalk 529 6.3.2.1 Allgemeines 529 6.3.2.2 Wirtschaftliche Bedeutung und Verwendung 529 6.3.2.3 Vorkommen und Rohstoffe 530 6.3.2.4 Gebrannter Kalk 530 6.3.2.5 Gelöschter Kalk 531 6.3.2.6 Dampfgehärtete Baustoffe 533 6.3.3 Zement 533 6.3.3.1 Allgemeines 533 6.3.3.2 Wirtschaftliche Bedeutung und Verwendung 535 6.3.3.3 Rohstoffe 535 6.3.3.4 Portlandzement 535 6.3.3.5 Hüttenzemente 539 6.3.3.6 Puzzolanzemente 539 6.3.3.7 Tonerdezement 541 6.3.3.8 Asbestzement 541 6.3.3.9 Sonstige Zementarten 542 6.3.3.10 Vorgänge beim Erstarren von Zement 542 6.3.4 Gips 544 6.3.4.1 Allgemeines 544 6.3.4.2 Wirtschaftliche Bedeutung und Verwendung 547 6.3.4.3 Vorkommen und Rohstoffe 548 6.3.4.4 Chemieanhydrit aus der Flusssäureherstellung 550 6.3.4.5 Chemiegips 550 6.3.5 Grobkeramische Produkte für die Bauindustrie 552 6.3.6 Blähprodukte 553 6.3.6.1 Allgemeines 553 6.3.6.2 Vorkommen und Rohstoffe 554 6.3.6.3 Wirtschaftliche Bedeutung und Verwendung 556 6.3.6.4 Herstellung von Blähprodukten 556 6.3.6.5 Blähprodukte aus Gläsern (Foam-glass) 558 6.3.7 Geopolymere 558 6.3.7.1 Allgemeines 558 6.3.7.2 Verwendung und wirtschaftliche Bedeutung 559 6.3.7.3 Vorkommen und Rohstoffe 559 6.3.7.4 Reaktion 560 6.3.7.5 Eigenschaften 561 6.4 Keramik 562 6.4.1 Allgemeines 563 6.4.2 Einteilung der keramischen Erzeugnisse 563 6.4.3 Allgemeine Verfahrensschritte zur Herstellung von Keramiken 565 6.4.4 Tonkeramische Erzeugnisse 565 6.4.4.1 Zusammensetzung und Rohstoffe 567 6.4.4.2 Abbau und Aufbereitung von Rohkaolin 569 6.4.4.3 Herstellung tonkeramischer Massen 569 6.4.4.4 Formgebungsverfahren 570 6.4.4.5 Trocknungsverfahren 574 6.4.4.6 Keramischer Brand 574 6.4.4.7 Eigenschaften und Anwendung tonkeramischer Produkte 577 6.4.5 Sonderkeramische Erzeugnisse 579 6.4.5.1 Oxidkeramik 579 6.4.5.2 Elektro- und Magnetokeramik 585 6.4.5.3 Feuerfeste Keramik 591 6.4.5.4 Nichtoxidkeramik 599 6.5 Hartstoffe 609 6.5.1 Allgemeines 609 6.5.2 Wirtschaftliche Bedeutung und Verwendung 610 6.5.3 Allgemeine Herstellungsverfahren und Eigenschaften von Metallcarbiden 610 6.5.4 Carbide der IV. Nebengruppe 611 6.5.4.1 Titancarbid 611 6.5.4.2 Zirconiumcarbid und Hafniumcarbid 613 6.5.5 Carbide der V. Nebengruppe 613 6.5.5.1 Vanadiumcarbid 613 6.5.5.2 Niobcarbid und Tantalcarbid 613 6.5.6 Carbide der VI. Nebengruppe 613 6.5.6.1 Chromcarbid 613 6.5.6.2 Molybdäncarbid 614 6.5.6.3 Wolframcarbid 614 6.5.6.4 Hartmetalllegierungen auf Basis von Wolframcarbid 615 6.5.7 Thoriumcarbid und Urancarbid 616 6.5.8 Metallnitride 617 6.5.9 Metallboride 618 6.5.10 Metallsilicide 619 6.6 Kohlenstoffmodifikationen 620 6.6.1 Allgemeine Vorbemerkungen 620 6.6.2 Diamant 620 6.6.2.1 Allgemeines 621 6.6.2.2 Wirtschaftliche Bedeutung und Verwendung 622 6.6.2.3 Gewinnung natürlicher Diamanten 623 6.6.2.4 Herstellung synthetischer Diamanten 624 6.6.3 Natürlicher Graphit 626 6.6.3.1 Allgemeines 627 6.6.3.2 Wirtschaftliche Bedeutung und Verwendung 627 6.6.3.3 Vorkommen, Rohstoffe und Gewinnung 629 6.6.4 Synthetischer Kohlenstoff und synthetischer Graphit 630 6.6.4.1 Allgemeines 633 6.6.4.2 Wirtschaftliche Bedeutung und Verwendung 633 6.6.4.3 Vorkommen und Rohstoffe 634 6.6.4.4 Herstellung von synthetischem Kohlenstoff und synthetischem Graphit 635 6.6.5 Spezielle Kohlenstoff- und Graphitarten 640 6.6.5.1 Allgemeines 641 6.6.5.2 Pyrokohlenstoff und Pyrographit 642 6.6.5.3 Glaskohlenstoff und Schaumkohlenstoff 643 6.6.5.4 Graphitfolien und -membranen 644 6.6.6 Carbon Black 645 6.6.6.1 Allgemeines 647 6.6.6.2 Wirtschaftliche Bedeutung und Verwendung 647 6.6.6.3 Herstellung von Carbon Black 651 6.6.7 Aktivkohle 656 6.6.7.1 Allgemeines 657 6.6.7.2 Wirtschaftliche Bedeutung und Verwendung 657 6.6.7.3 Vorkommen und Rohstoffe 659 6.6.7.4 Herstellung von Aktivkohle 659 6.7 Füllstoffe 662 6.7.1 Allgemeines 665 6.7.2 Wirtschaftliche Bedeutung und Verwendung 666 6.7.3 Vorkommen, Rohstoffe und Herstellung von Füllstoffen 668 6.7.3.1 Natürliche Füllstoffe 668 6.7.3.2 Synthetische Füllstoffe 670 6.8 Anorganische Pigmente 675 6.8.1 Allgemeines 676 6.8.2 Weißpigmente 680 6.8.2.1 Titandioxid 682 6.8.2.2 Lithopone und Zinksulfidpigmente 688 6.8.2.3 Zinkoxid-Weißpigmente 689 6.8.3 Buntpigmente 690 6.8.3.1 Eisenoxidpigmente 694 6.8.3.2 Chrom(III)-oxidpigmente 699 6.8.3.3 Chromat- und Molybdatpigmente 701 6.8.3.4 Mischphasenpigmente und keramische Farbkörper 702 6.8.3.5 Cadmiumpigmente 704 6.8.3.6 Bismutvanadatpigmente 705 6.8.3.7 Eisenblaupigmente 706 6.8.3.8 Ultramarinpigmente 707 6.8.4 Spezialpigmente 708 6.8.4.1 Korrosionsschutzpigmente 709 6.8.4.2 Effektpigmente 711 6.8.4.3 Lumineszenzpigmente 713 6.8.4.4 Magnetpigmente 713 7 Kernbrennstoffkreislauf 721 7.1 Die Bedeutung der Kernenergie in der Energiewirtschaft 721 7.2 Allgemeines zum Brennstoffkreislauf 725 7.3 Verfügbarkeit von Uran 726 7.4 Kernreaktortypen 728 7.4.1 Allgemeines 729 7.4.2 Leichtwasserreaktoren 729 7.4.2.1 Siedewasserreaktoren 729 7.4.2.2 Druckwasserreaktoren 730 7.4.3 Graphitmoderierte Reaktoren 730 7.4.3.1 Gasgekühlte Reaktoren 730 7.4.3.2 Leichtwassergekühlte Reaktoren 731 7.4.4 Schwerwasserreaktoren 732 7.4.5 Schnellbrutreaktoren 732 7.5 Kernbrennstoffgewinnung 733 7.5.1 Urankonzentrat-(„Yellow-cake“-)Gewinnung 736 7.5.1.1 Uran aus Uranerzen 736 7.5.1.2 Uran aus Phosphaterzen bzw. Nassphosphorsäure 740 7.5.1.3 Uran aus Meerwasser 741 7.5.2 Konversion von Urankonzentrat zu Uranhexafluorid 741 7.5.2.1 Allgemeines 741 7.5.2.2 Nassverfahren zur Herstellung von UF6 741 7.5.2.3 Trockenverfahren zur Herstellung von UF6 742 7.5.3 235U-Anreicherung 743 7.5.4 Rekonversion von UF6 in Kernbrennstoffe 744 7.5.4.1 In Urandioxid 744 7.5.5 Andere Urankernbrennstoffe 746 7.5.5.1 Uranmetall 746 7.5.5.2 Uran-Plutonium-Mischoxide 746 7.5.6 Herstellung der Brennelemente 747 7.6 Entsorgung von Kernkraftwerken 747 7.6.1 Allgemeines 750 7.6.2 Teilschritte der Entsorgung 752 7.6.2.1 Zwischenlagerung abgebrannter Brennelemente 752 7.6.2.2 Wiederaufarbeitung abgebrannter Brennelemente 752 7.6.2.3 Weiterverarbeitung der Uran- bzw. Plutoniumlösungen 754 7.6.2.4 Konditionierung der radioaktiven Abfälle 755 7.6.2.5 Endlagerung radioaktiver Abfälle 757 Stichwortverzeichnis 761

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Book SynopsisA one-stop resource for researchers, developers, and post graduate students in pharmaceutical science. This handbook and ready reference provides detailed, but not overloaded information -- presenting the topic without unnecessarily complex formalism. As such, it gives a systematic and coherent overview of disordered materials for pharmaceutical applications, covering fundamental aspects, as well as preparation and characterization techniques for the target-oriented development of drug delivery systems based on disordered crystals and amorphous solids. Special attention is paid to examine the different facets and levels of disorder in their structural and dynamic aspects as well as the effect of disorder on dissolution and stability. Chapters on processing induced disorder and on patenting issues round off the book. As a result the book helps overcoming the challenges of using these materials in the pharmaceutical industry. For pharmaceutical and medicinal chemists, materials scientists, clinical physicists, and pharmaceutical laboratories looking to make better and more potent pharmaceuticals.Table of Contents1 Some Facets of Molecular Disorder in Crystalline and Amorphous Pharmaceuticals 1 Marc Descamps and Jean-François Willart 1.1 The Crystal/Amorph Alternative 2 1.2 Characteristics of the Disorder in Glass Formers 28 Acknowledgments 51 References 51 2 Influence of Disorder on Dissolution 57 Khushboo Kothari and Raj Suryanarayanan 2.1 Introduction 57 2.2 Approaches to Enhance Solubility 59 2.3 Measuring the Solubility Advantage of Amorphous Compounds 64 2.4 Solid Dispersions 66 2.5 Polymer Properties 67 2.6 Drug?Polymer Interactions 70 2.7 Polymer Concentration 71 2.8 Other Formulation Components 73 2.9 Formulation Variables 74 2.10 Reliable Measurement of Supersaturation 75 2.11 Conclusion 76 References 77 3 Crystal Imperfections in Molecular Crystals: Physical and Chemical Consequences 85 William Jones and Mark D. Eddleston 3.1 Introduction 85 3.2 General Aspects of Defects in Crystals 87 3.3 Role of Imperfections in Reactivity and Stability ? Chemistry in the Perfect and Imperfect Lattice 92 3.4 Role in Physical Processes 96 3.5 Concluding Remarks 99 References 99 4 Observation and Characterization of Crystal Defects in Pharmaceutical Solids 103 Mark D. Eddleston andWilliam Jones 4.1 Introduction 103 4.2 Techniques for Characterizing Defects within Crystals 104 4.3 Techniques for Characterizing Defects Emergent at Crystal Surfaces 119 4.4 Techniques for Quantifying Defect Densities within Crystals 125 4.5 The Complementarity of Techniques for Characterizing Defects 126 4.6 Summary and Outlook 127 Acknowledgment 128 References 128 5 "Enantiomeric Disorder" Pharmaceutically Oriented 135 Gerard Coquerel and Rui Tamura 5.1 Introduction 135 5.2 Introduction and Lexicon of Specific Terms Used among Chiral Molecules and Chiral Molecular Associations 135 5.3 Restrictions in Symmetry Operations Inside Crystal Lattices with an Enantiomeric Excess Different from Zero 136 5.4 Impact of Chirality on Phase Diagrams and the Gibbs?Scott Phase Rule 137 5.5 Competitions between Solid Solutions (Impact of Polymorphism on Solid Solutions) Application: Preferential Enrichment 149 5.6 Disorder at Level 3 Multiepitaxy between Enantiomers 154 5.7 Conclusion and Perspectives 156 Acknowledgments 157 References 157 6 Conformational Disorder and Atropisomerism in Pharmaceutical Compounds 161 Attilio Cesàro, Barbara Bellich, Giovanna Giannini, and Alessandro Maiocchi 6.1 Premise: Conformational Energy Barriers in FlexibleMolecules 161 6.2 Conformational Topology and Crystallization of Chain Molecules 162 6.3 Conformational Polymorphism and Crystallization of Flexible Molecules 165 6.4 Conformational Flexibility of Ring Molecules: Carbohydrates 170 6.5 Hindered Conformational Isomerism: Atropisomerism 172 6.6 Conclusion 178 Acknowledgments 180 References 180 7 Tautomerism in Drug Delivery 183 Zaneta Wojnarowska and Marian Paluch 7.1 Broadband Dielectric Spectroscopy as a Powerful Tool for Investigating the Tautomerization Process in Condensed Materials 187 7.2 Tautomerization Kinetics of Supercooled Pharmaceuticals 190 Acknowledgment 197 References 198 8 Disorders in Pharmaceutical Polymers 201 Emeline Dudognon and Sheng Qi 8.1 Polymers Architectures - Structural Disorders 202 8.2 Structural States and Phases Transitions 205 8.3 Dynamic Disorders 213 8.4 Blends of Polymer and Small Molecules 221 8.5 Effect of the Structural Properties of Pharmaceutical Polymers on Their Physical Behavior 224 8.6 Concluding Remarks 234 References 235 9 Polymer Gels, Hydrogels, and Scaffolds ? An Overview 241 Madeleine Djabourov and Kawthar Bouchemal 9.1 Introduction 241 9.2 Gels and Hydrogels 243 9.3 Scaffolds 268 9.4 Conclusion 275 References 276 10 Use of the Pair Distribution Function Analysis in the Context of Pharmaceutical Materials 283 Pierre Bordet and PaulineMartinetto 10.1 Introduction 283 10.2 What Is the PDF? 284 10.3 How to Measure the PDF 288 10.4 Modeling of the PDF 290 10.5 Applications of PDF Analysis to Molecular and Pharmaceutical Compounds 292 10.6 Conclusion 297 Acknowledgments 298 References 298 11 Application of Broadband Dielectric Spectroscopy to Study Molecular Mobility in Pharmaceutical Systems 301 Katarzyna Grzybowska, Karolina Adrjanowicz, and Marian Paluch 11.1 Introduction to Broadband Dielectric Spectroscopy 301 11.2 Molecular Dynamics in Amorphous Pharmaceutical Systems 316 11.3 Molecular Mobility and Dielectric Response in Partially Ordered Pharmaceutical Systems 346 Acknowledgment 353 References 353 12 Raman Spectroscopy in Disordered Molecular Compounds: Application to Pharmaceuticals 361 Alain Hedoux 12.1 Introduction 361 12.2 Raman Spectroscopy 362 12.3 Analysis of Molecular Compounds by Raman Spectroscopy 370 12.4 Conclusion 388 References 388 XII Contents 13 Study of Disordered Materials by Terahertz Spectroscopy 393 Juraj Sibik and J. Axel Zeitler 13.1 Introduction 393 13.2 Exploration of Terahertz Dynamics Prior to THz-TDS 394 13.3 Response of Supercooled Liquids and Glasses at Terahertz Frequencies 397 13.4 Terahertz Studies of Disordered Molecular Solids 400 13.5 Organic Glass-Forming Liquids 404 13.6 Characterization of Disordered Biological and Pharmaceutical Systems 410 13.7 Outlook 416 References 418 14 Study of Disorder by Solid-State NMR Spectroscopy 427 Marco Geppi, Silvia Borsacchi, and Elisa Carignani 14.1 Introduction 427 14.2 Basics of Solid-State NMR 428 14.3 Static Disorder 433 14.4 Dynamic Disorder 448 14.5 A Case Study 458 14.6 Final Remarks and Future Perspectives 462 References 464 15 Processing-Induced Disorder in Pharmaceutical Materials 467 Sheng Qi 15.1 Introduction 467 15.2 Pharmaceutical Processing 468 15.3 Conclusion 484 References 485 16 Patenting of Inventions Relating to Solid Forms, with Special Considerations on Disordered Forms 491 Bertrand Gellie 16.1 Patentability of Disordered Crystals 493 16.2 Patentability of Co-crystals 496 16.3 Patentability of Amorphous Forms 500 16.4 Patenting (Disordered) Nanocrystals 509 16.5 Conclusions 511 Index 513

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Book SynopsisFaster, cheaper and environmentally friendly, these are the criteria for designing new reactions and this is the challenge faced by many chemical engineers today. Based on courses thaught by the authors, this advanced textbook discusses opportunities for carrying out reactions on an industrial level in a technically controllable, sustainable, costeffective and safe manner. Adopting a practical approach, it describes how miniaturized devices (mixers, reactors, heat exchangers, and separators) are used successfully for process intensification, focusing on the engineering aspects of microstrctured devices, such as their design and main chracteristics for homogeneous and multiphase reactions. It adresses the conditions under which microstructured devices are beneficial, how they should be designed, and how such devices can be integrated in an existing chemical process. Case studies show how the knowledge gained can be applied for particular processes. The textbook is essential for master and doctoral students, as well as for professional chemists and chemical engineers working in this area.Table of ContentsPreface XI List of Symbols XIII 1 Overview of Micro Reaction Engineering 1 1.1 Introduction 1 1.2 What are Microstructured Devices? 2 1.3 Advantages of Microstructured Devices 2 1.3.1 Enhancement of Transfer Rates 2 1.3.2 Enhanced Process Safety 5 1.3.3 Novel OperatingWindow 7 1.3.4 Numbering-Up Instead of Scale-Up 7 1.4 Materials and Methods for Fabrication of Microstructured Devices 9 1.5 Applications of Microstructured Devices 10 1.5.1 Microstructured Reactors as Research Tool 11 1.5.2 Industrial/Commercial Applications 11 1.6 Structure of the Book 13 1.7 Summary 13 References 14 2 Basis of Chemical Reactor Design and Engineering 19 2.1 Mass and Energy Balance 19 2.2 Formal Kinetics of Homogenous Reactions 21 2.2.1 Formal Kinetics of Single Homogenous Reactions 22 2.2.2 Formal Kinetics of Multiple Homogenous Reactions 24 2.2.3 Reaction Mechanism 25 2.2.4 Homogenous Catalytic Reactions 26 2.3 Ideal Reactors andTheir Design Equations 29 2.3.1 Performance Parameters 29 2.3.2 BatchWise-Operated Stirred Tank Reactor (BSTR) 30 2.3.3 Continuous Stirred Tank Reactor (CSTR) 35 2.3.4 Plug Flow or Ideal Tubular Reactor (PFR) 39 2.4 Homogenous Catalytic Reactions in Biphasic Systems 452.5 Heterogenous Catalytic Reactions 49 2.5.1 Rate Equations for Intrinsic Surface Reactions 50 2.5.2 Deactivation of Heterogenous Catalysts 57 2.6 Mass and Heat Transfer Effects on Heterogenous Catalytic Reactions 59 2.6.1 External Mass and Heat Transfer 60 2.6.2 Internal Mass and Heat Transfer 69 2.6.3 Criteria for the Estimation of Transport Effects 83 2.7 Summary 84 2.8 List of Symbols 86 References 87 3 Real Reactors and Residence Time Distribution (RTD) 89 3.1 Nonideal Flow Pattern and Definition of RTD 89 3.2 Experimental Determination of RTD in Flow Reactors 91 3.2.1 Step Function Stimulus-Response Method 92 3.2.2 Pulse Function Stimulus-Response Method 93 3.3 RTD in Ideal Homogenous Reactors 95 3.3.1 Ideal Plug Flow Reactor 95 3.3.2 Ideal Continuously Operated Stirred Tank Reactor (CSTR) 95 3.3.3 Cascade of Ideal CSTR 96 3.4 RTD in Nonideal Homogeneous Reactors 98 3.4.1 Laminar Flow Tubular Reactors 98 3.4.2 RTD Models for Real Reactors 100 3.4.3 Estimation of RTD in Tubular Reactors 105 3.5 Influence of RTDon the Reactor Performance 107 3.5.1 Performance Estimation Based on Measured RTD 108 3.5.2 Performance Estimation Based on RTD Models 110 3.6 RTD in Microchannel Reactors 115 3.6.1 RTD of Gas Flow in Microchannels 117 3.6.2 RTD of Liquid Flow in Microchannels 118 3.6.3 RTD of Multiphase Flow in Microchannels 122 3.7 List of Symbols 126 References 127 4 Micromixing Devices 129 4.1 Role of Mixing for the Performance of Chemical Reactors 129 4.2 Flow Pattern and Mixing in Microchannel Reactors 136 4.3 Theory of Mixing in Microchannels with Laminar Flow 137 4.4 Types of Micromixers and Mixing Principles 143 4.4.1 Passive Micromixer 144 4.4.2 Active Micromixers 154 4.5 Experimental Characterization of Mixing Efficiency 158 4.5.1 Physical Methods 158 4.5.2 Chemical Methods 159 4.6 Mixer Efficiency and Energy Consumption 171 4.7 Summary 172 4.8 List of Symbols 173 References 1735 Heat Management by Microdevices 179 5.1 Introduction 179 5.2 Heat Transfer in Microstructured Devices 181 5.2.1 Straight Microchannels 181 5.2.2 Curved Channel Geometry 189 5.2.3 Complex Channel Geometries 191 5.2.4 Multichannel Micro Heat Exchanger 191 5.2.5 Microchannels with Two Phase Flow 193 5.3 Temperature Control in Chemical Microstructured Reactors 195 5.3.1 Axial Temperature Profiles in Microchannel Reactors 197 5.3.2 Parametric Sensitivity 201 5.3.3 Multi-injection Microstructured Reactors 212 5.4 Case Studies 221 5.4.1 Synthesis of 1,3-Dimethylimidazolium-Triflate 221 5.4.2 Nitration of Dialkyl-Substituted Thioureas 222 5.4.3 Reduction of Methyl Butyrate 223 5.4.4 Reactions with Grignard Reagent in Multi-injection Reactor 224 5.5 Summary 226 5.6 List of Symbols 226 References 228 6 Microstructured Reactors for Fluid–Solid Systems 231 6.1 Introduction 231 6.2 Microstructured Reactors for Fluid–Solid Reactions 232 6.3 Microstructured Reactors for Catalytic Gas-Phase Reactions 233 6.3.1 Randomly Micro Packed Beds 233 6.3.2 Structured Catalytic Micro-Beds 235 6.3.3 CatalyticWall Microstructured Reactors 238 6.4 Hydrodynamics in Fluid–Solid Microstructured Reactors 239 6.5 Mass Transfer in Catalytic Microstructured Reactors 243 6.5.1 Randomly Packed Bed Catalytic Microstructured Reactors 244 6.5.2 Catalytic Foam Microstructured Reactors 245 6.5.3 CatalyticWall Microstructured Reactors 246 6.5.4 Choice of Catalytic Microstructured Reactors 253 6.6 Case Studies 255 6.6.1 Catalytic Partial Oxidations 255 6.6.2 Selective (De)Hydrogenations 257 6.6.3 Catalytic Dehydration 259 6.6.4 Ethylene Oxide Synthesis 259 6.6.5 Steam Reforming 260 6.6.6 Fischer–Tropsch Synthesis 261 6.7 Summary 261 6.8 List of Symbols 262 References 262 7 Microstructured Reactors for Fluid–Fluid Reactions 267 7.1 Conventional Equipment for Fluid–Fluid Systems 267 7.2 Microstructured Devices for Fluid–Fluid Systems 268 7.2.1 Micromixers 269 7.2.2 Microchannels 271 7.2.3 Microstructured Falling Film Reactor for Gas–Liquid Reactions 272 7.3 Flow Patterns in Fluid–Fluid Systems 273 7.3.1 Gas–Liquid Flow Patterns 273 7.3.2 Liquid–Liquid Flow Patterns 280 7.4 Mass Transfer 284 7.4.1 Mass Transfer Models 285 7.4.2 Characterization of Mass Transfer in Fluid–Fluid Systems 286 7.4.3 Mass Transfer in Gas–Liquid Microstructured Devices 287 7.4.4 Mass Transfer in Liquid–Liquid Microstructured Devices 296 7.4.5 Comparison with Conventional Contactors 299 7.5 Pressure Drop in Fluid–Fluid Microstructured Channels 300 7.5.1 Pressure Drop in Gas–Liquid Flow 301 7.5.2 Pressure Drop in Liquid–Liquid Flow 304 7.6 Flow Separation in Liquid–Liquid Microstructured Reactors 307 7.6.1 Conventional Separators 308 7.6.2 Types of Microstructured Separators 308 7.6.3 Conventional Separator Adapted for Microstructured Devices 315 7.7 Fluid–Fluid Reactions in Microstructured Devices 315 7.7.1 Examples of Gas–Liquid Reactions 317 7.7.2 Examples of Liquid–Liquid Reactions 319 7.8 Summary 323 7.9 List of Symbols 324 References 325 8 Three-Phase Systems 331 8.1 Introduction 331 8.2 Gas–Liquid–Solid Systems 331 8.2.1 Conventional Gas–Liquid–Solid Reactors 331 8.2.2 Microstructured Gas–Liquid–Solid Reactors 333 8.3 Gas–Liquid–Liquid Systems 346 8.4 Summary 347 8.5 List of Symbols 347 References 348 Index 351

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Book SynopsisFilling a gap in the literature for a hands-on guide focusing on everyday laboratory challenges, this English edition has been expanded and revised using the feedback received on the successful German precursor. Throughout the book, Professor Mascher draws on his 30 years of experience and provides abundant practical advice, troubleshooting and other hints highlighted in boxes, as well as a broad selection of walkthrough case studies. Based on a course taught by the author, the first part of the book intuitively explains all steps of routine bioanalysis and explains how to set up a robust, inexpensive and effi cient method for a given substance. In the second part he includes 20 worked example cases that highlight common challenges and how to overcome them. With its appendix containing tried-and-tested analytical methods for 100 clinically relevant substances from the author`s own laboratory, complete with spectral and MS data as well as literature references and basic pharmacokinetic information, this is a life-long companion for everyone working in clinical, pharmaceutical and biochemical analysis. Comments to the German book: "The book comes to life through its examples, showing not only what did work in the author's laboratory, but also what didn't." ChemieReport "Indispensable for novices, while even old hands will be able to expand their knowledge. A collection of analytical data for ca. 100 substances completes the book's offering, leaving almost nothing to be desired." pharmindTrade Review"The book is clearly written and comprehensive. A lot of practical advice and tips makes it helpful for any practically oriented clinical laboratory and it can be counted as a valuable source for everyone working with chromatographic techniques in a bioanalytical laboratory." (Analytical and Bioanalytical Chemistry, 13 November 2012) “This book is more than a very successful and useful user guide, and is a valuable tool for the laboratorywork, not only for clinical analysts, but also for biochemists, pharmacists, etc. In addition to a compact targeted representation of the most important theoretical foundations for the planning and execution of (clinical) analysis (sample preparation, HPLC separation, usage of different modes, detection capabilities, derivatization techniques to the point of validation), the readers receive valuable information for their work, which are explained on the basis of practical examples [pages 1–64].” (ChemMedChem, 1 November 2012)Table of ContentsPreface INTRODUCTION First Question: Determination of Ibuprofen in Plasma Second Question: Determination of Tryptophan in Urine Third Question: Determination of Paclitaxel in Tissue PLANNING OF ANALYSES Introduction Limit of Detection (LOD) and Determination (LLOQ) Detectors Structure of the Analyte Solubility of an Analyte Selection of the Detector SAMPLE PREPARATION Dilution Protein Precipitation, Overview Extraction HPLC SEPARATION HPLC Pumps Degassers Injector HPLC Columns DETECTION Detection in the Pharmaceutical/Bioanalytical Area Detection in the "Clinical Area" (Therapy Control/Compliance) CHEMICAL DERIVATISATION FOR DETECTION ENHANCEMENT VALIDATION CONCEPTS Introduction Realisation of the FDA Guideline PRACTICAL HINTS CONCERNING STABILITY, DESTRUCTION AND DEGRADATION PRODUCTS METABOLITES INTERNAL STANDARDS CASE STUDIES WITH INTENSIVE DISCUSSION FOR EACH SUBSTANCE Acetylcarnitine in Plasma Acetylcysteine in Plasma Acyclovir in Plasma and Urine Caffeine in Plasma Diazepam in Plasma Diclofenac in Plasma Dihydralazine in Plasma Duramycin (Moli1901) in Plasma Fluticasone Propionate in Plasma Hydroxytriamterene Sulfate and Triamterene in Plasma and Urine Ibuprofen in Plasma (also Enantiomeric Separation) Minocycline in plasma Norfloxacine in Plasma and Urine Paclitaxel in Plasma, Urine, and Tissue Paracetamol (Acetaminophen) in Plasma Pimelic Acid in Plasma and Urine 8-Prenylnaringenin in Plasma and in Different Types of Tissues Silibinin in Plasma Valnemulin in Plasma, Different Tissue Types and Animal Feed Vitamin B1 (Total Thiamine) in Plasma APPENDIX Short Description of Determination for about 100 Substances Substances listed in the Appendix A Short Explanation of Tables Presented in the Appendix

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Book SynopsisGreen, clean and renewable are the hottest keywords for catalysis and industry. This handbook and ready reference is the first to combine the fields of advanced experimentation and catalytic process development for biobased materials in industry. It describes the entire workflow from idea, approach, research, and process development, right up to commercialization. A large part of the book is devoted to the use of advanced technologies and methodologies like high throughput experimentation, as well as reactor and process design models, with a wide selection of real-life examples included at each stage. The contributions are from authors at leading companies and institutes, providing firsthand information and knowledge that is hard to find elsewhere. This work is aimed at decision makers, engineers and chemists in industry, chemists and engineers working with/on renewables, chemists in the field of catalysis, and chemical engineers.Trade Review“Overall, especially for an edited book, this is a well organized book showing the overall story, rather than giving only pieces of a puzzle . . . It makes for an entertaining read. The book is certainly more suited to researchers in the field or at least with some background information.” (Green Processing and Synthesis, 1 August 2013) Table of ContentsTHE NEXT FEEDSTOCK TRANSITION PREFACE THE INDUSTRIAL PLAYING FIELD FOR THE CONVERSION OF BIOMASS TO RENEWABLE FUELS AND CHEMICALS Introduction The Renewables Arena Renewable Fuels Renewable Chemicals Conclusions SELECTING TARGETS Introduction Target Selection Can Focus on Specific Structures or General Technologies Previous Selection Efforts Corroboration of the Value of Screening Studies The Importance of Outcomes and Comparisons of Outcomes Evaluation Processes Can be Comprised of a Variety of Criteria Catalysis Aspects Conclusions THE DEVELOPMENT OF CATALYTIC PROCESSES FROM TERPENES TO CHEMICALS Introduction Strain Engineering for the Production of Terpenes Terpene Building Blocks of Commercial Interest Sesquiterpenes as Chemical Building Blocks: ß-Farnesene Polymers Lubricants Conclusions FURAN-BASED BUILDING BLOCKS FROM CARBOHYDRATES Importance of Furans as Building Blocks Sources of Carbohydrates Carbohydrate Dehydration Conclusions and Further Perspectives A WORKFLOW FOR PROCESS DESIGN - USING PARALLEL REACTOR EQUIPMENT BEYOND SCREENING Introduction The Evolution of Parallel Reactor Equipment The Evolution of Research Methodology - Conceptual Process Design Essential Workflow Elements Other Examples of Parallel Reactor Equipment Applied Beyond Screening - Long-Term Catalyst Performance Concluding Remarks BRASKEM'S ETHANOL TO POLYETHYLENE PROCESS DEVELOPMENT Introduction Ethanol and Brazil Commercial Plants for Ethanol Dehydration Legislation and Certification Process Description Polymerization Conclusion FATS AND OILS AS RAW MATERIAL FOR THE CHEMICAL INDUSTRY Introduction - Setting the Scene, Definitions Why Fats and Oils Need Catalytic Transformation Catalytic Process Development - Conceptual Fatty Alcohols: Then and Now, a Case Study Conclusion and Outlook: Development Challenges for the Future PRODUCTION OF AROMATIC CHEMICALS FROM BIOBASED FEEDSTOCK Introduction Chemical Routes to Aromatic Chemicals from Biomass Biological Routes to Specific Aromatic Chemicals Lignin - The Last Frontier Considerations for Scale-Up and Commercialization Conclusion ORGANOSOLV BIOREFI NING: CREATING HIGHER VALUE FROM BIOMASS Introduction Concepts and Principles of Biorefinery Technologies Catalytic Processes Employed in Biorefining An Organosolv Biorefinery Process for High-Value Products Conclusions BIOMASS-TO-LIQUIDS BY THE FISCHER - TROPSCH PROCESS Basics of Fischer - Tropsch Chemistry and BTL Cobalt Fischer - Tropsch Catalysis Fischer - Tropsch Reactors Biomass Pretreatment and Gasification Biomass-to-Liquids Process Concepts BTL Pilot and Demonstration Plants XTL Energy and Carbon Efficiencies BTL Summary and Outlook CATALYTIC TRANSFORMATION OF EXTRACTIVES Introduction Fine and Special Chemicals from Crude Tall Oil Compounds Fine and Special Chemicals from Turpentine Compounds Conclusions Acknowledgment ENVIRONMENTAL ASSESSMENT OF NOVEL CATALYTIC PROCESSES BASED ON RENEWABLE RAW MATERIALS - CASE STUDY FOR FURANICS Introduction Energy Savings by Catalytic Processes LCA Methodology Case Study: Energy Analysis and GHG Balance of Polyethylene Furandicarboxylate (PEF) as a Potential Replacement for Polyethylene Terephthalate (PET) Discussion and Conclusions CARBON DIOXIDE: A VALUABLE SOURCE OF CARBON FOR CHEMICALS, FUELS AND MATERIALS Introduction The Conditions for Industrial Use of CO2 Carbon Dioxide Conversion Energy Products from CO2 Production of Inorganic Carbonates Enhanced Fixation of CO2 into Aquatic Biomass Conclusion and Future Outlook INDEX

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Book SynopsisDer unentbehrliche Begleiter für Studium und Beruf liegt jetzt in seiner aktualisierten und erweiterten dritten Auflage vor. Das Buch behandelt die physikalischen und chemischen Grundlagen der Verfahrenstechnik anhand von Beispielen und Fallstudien. In anschaulicher Weise werden Themen wie Fluidmechanik, Mehrstoffthermodynamik, Stoffaustausch, Wärmeübertragung und Reaktionskinetik erläutert, ohne hierbei den Bezug zur Praxis zu verlieren. Zahlreiche Aufgaben und ausführlich beschriebene Lösungswege, die auf einen maximalen Lerneffekt abzielen, runden das Werk ab. Gerichtet an Verfahrenstechniker, Ingenieure, Chemiker, Umweltwissenschaftler, Biotechnologen und alle Verfahrenstechnik-Interessierte.Trade Review"Alles in einem: das Wissen der Verfahrenstechnik wird in umfassender und zusammenhängender Form dargestellt und anwendungsbezogene Fragen und Antworten werden detailliert behandelt." Chemie Ingenieur Technik. CIT-Journal (04/2018) "ermöglicht eine praxisausgerichtete Weiterbildung" Materials and Corrosion (3/2013) "ein[...] ständige[r] Begleiter für Verfahrenstechniker." solidbau.at (11.10.2012) / industriemagazin.net (10.10.2012) "Das neue Werk bietet alles in einem: Das Wissen der Verfahrenstechnik wird in umfassender und zusammenhängender Form dargestellt und anwendungsbezogene Fragen und Antworten werden detailliert behandelt." PROCESS (4/2012) "Klar und übersichtlich [...] Das Buch ist eine bewährte Kombination aus Lehrbuch plus praxisnaher Anwendungsentwicklung durch Fallstudien." PROCESS online (20.03.2012) "stellt das Wissen der Verfahrenstechnik in umfassender und zusammenhängender Form dar. [...] Nutzen kann man das Fachbuch einerseits als Lehrbuch, andererseits auch als Praxisbuch. Es ermöglicht eine industrienahe, praktisch orientierte Weiterbildung." PROCESS (01.02.2012) "Neben der prägnanten und überschaubaren Darstellung der verfahrenstechnischen Grundlagen, wird besonderer Wert auf anwendungsbezogene Aufgaben gelegt. Damit ist es als Fachbuch für die Praxis ebenso geeignet wie als Lehrbuch." PROCESS online (13.01.2012)Table of ContentsEinleitung XI 1 Ähnlichkeitstheorie und Dimensionsanalyse 1 1.1 Grundprinzipien 1 1.2 Physikalische Ähnlichkeit 4 1.3 Modelltheorie 7 1.4 Möglichkeiten der Kennzahlbestimmung 11 2 Chemische Thermodynamik 17 2.1 Grundbegriffe 17 2.1.1 Abgrenzung der chemischen Thermodynamik 17 2.1.2 Größen der chemischen Thermodynamik 19 2.1.3 Thermische Zustandsgleichung 21 2.2 Hauptsätze 25 2.2.1 Innere Energie und 1. Hauptsatz 25 2.2.2 Entropie, 2. und 3. Hauptsatz 29 2.3 Abgeleitete Zustandsgrößen und Gleichgewichtsbedingungen 32 2.4 Mischphasen und Mehrphasen-Systeme 35 2.4.1 Mischphasen 35 2.4.2 Mehrphasengleichgewichte und das Einkomponenten-System 40 2.4.3 Zweiphasen-Systeme mit mehreren Komponenten 42 2.5 Reaktionssysteme 48 2.5.1 Reaktionsenergie 48 2.5.2 Reaktionsgleichgewicht 51 2.5.3 Reaktionskinetik 54 3 Grenzflächen und Partikel 61 3.1 Thermodynamik der Grenzflächen 61 3.2 Zweiphasen-Systeme 64 3.3 Dreiphasen-Systeme 65 3.4 Partikel 66 4 Fluiddynamik 73 4.1 Grundlagen 73 4.1.1 Strömungslehre und Rheologie 73 4.1.2 Differenzielle Form der Grundgleichungen 78 4.1.3 Integrale Form der Grundgleichungen 82 4.1.4 Bernoulli’sche Gleichung 87 4.2 Laminarströmung und Turbulenz 91 4.3 Integration der Grundgleichungen 94 4.3.1 Exakte Integration 94 4.3.2 Integration bei Vernachlässigung einzelner Terme 97 4.3.3 Teilintegration durch Dimensionsanalyse 100 4.4 Einige Anwendungen der Strömungslehre 101 4.4.1 Widerstand von Körpern in Strömungen 101 4.4.2 Druckverluste in Leitungen und Apparaten 105 4.4.3 Durchflussmessungen über Druckverluste 107 4.4.4 Druckverluste in Haufwerken 110 4.4.5 Zweiphasen-Strömungen 112 4.4.5.1 Wirbelschicht 112 4.4.5.2 Blasensäulen 113 4.4.5.3 Rieselfilme 114 5 Wärmedurchgangsprozesse 119 5.1 Grundbeziehungen für den Wärmetransport 119 5.1.1 Transportmechanismen 119 5.1.2 Wärmeleitung 120 5.1.3 Konvektiver Wärmetransport 125 5.1.4 Wärmestrahlung 127 5.2 Wärmeübergang und ‑durchgang 129 5.2.1 Ansatz für den Wärmeübergang 129 5.2.2 Wärmeübergang an einphasige Fluide 131 5.2.2.1 Wärmeübergangszahl bei erzwungener Konvektion 131 5.2.2.2 Längsströmung bei Rohren 133 5.2.2.3 Queranströmung von Rohren 136 5.2.2.4 Strömung längs ebener oder leicht gekrümmter Flächen 137 5.2.2.5 Wärmeübergangszahl bei freier Konvektion 137 5.2.3 Wärmeübergang bei Phasenumwandlungen 140 5.2.4 Wärmedurchgang 144 5.3 Berechnung von Wärmetauschern 146 5.3.1 Kalorische Apparate 146 5.3.2 Treibendes Temperaturgefälle 149 5.3.3 Auslegung und Optimierung 157 6 Stoffaustauschprozesse 161 6.1 Grundbeziehungen für den Stoffaustausch 161 6.1.1 Transportmechanismen 161 6.1.2 Stoffübergang 165 6.1.3 Stoffdurchgang 169 6.2 Berechnung von Stoffaustauschapparaten 173 6.3 Berechnung über die Stoffdurchgangszahl 173 6.3.1 Rektifikation 176 6.3.2 Absorption und Extraktion 177 6.4 Berechnung über die Trennstufe 181 6.4.1 Grundbeziehungen 181 6.4.2 Rektifikation binärer Mischungen 184 6.4.3 Absorption und Extraktion 190 6.4.4 Vielstoffsysteme 195 6.5 Optimierung von Stoffaustauschapparaten 196 7 Technische Reaktionsführung 199 7.1 Bedeutung der technischen Reaktionsführung 199 7.2 Chemische Reaktion 201 7.2.1 Stöchiometrie 201 7.2.2 Reaktionstechnische Begriffe 202 7.2.3 Makroreaktionskinetik 204 7.3 Reaktionsapparate 206 7.4 Ideale Reaktoren 208 7.4.1 Diskontinuierlich betriebener Rührkessel 208 7.4.2 Kontinuierlich betriebener Rührkessel 209 7.4.3 Strömungsrohr 210 7.4.4 Verweilzeiten 210 7.5 Kombination und Optimierung idealer Reaktoren 212 7.6 Rückführung nicht umgesetzter Komponenten 216 7.7 Verweilzeitverteilung 217 7.7.1 Grundbegriffe 217 7.7.2 Umsatzgrad und Verweilzeitspektrum 220 7.8 Kalorische Effekte 223 7.9 Stabilität 225 8 Mathematischer Anhang 229 8.1 Koordinatennetze 229 8.1.1 Funktionsleitern und rechtwinklige Netze 229 8.1.2 Dreiecksnetz (Gibbs’sche Koordinaten) 234 8.2 Partielle Differenzialquotienten und das totale Differenzial 239 8.3 Häufigkeitsverteilungen 243 8.3.1 Relative Häufigkeit und Summenhäufigkeit 243 8.3.2 Mittel- und Streuwerte 246 8.3.3 Spezielle Häufigkeitsverteilungen 249 9 Lösungen der Aufgaben 253 10 Literatur 293 Index 297

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Book SynopsisPropellants and Explosives Explosives and propellants are termed energetic materials for containing considerable chemical energy which can be converted into rapid expansion. In contrast to simple burning of a fuel, explosives and propellants are self-contained and do not need external supply of oxygen via air. Since their energy content thus inherently creates the risk of accidental triggering of the explosive reaction, proper synthesis, formulation, and handling during production and use are of utmost importance for safety and necessitate specialist knowledge on energetic materials, their characteristics, handling, and applications. Now in its third edition, the classic on the thermochemical aspects of the combustion of propellants and explosives is completely revised and updated and includes green propellants as new topic. The combustion processes of typical energetic crystalline and polymeric materials and various types of propellants and pyrolants are presented to provide an informative, generalized approach for the understanding of the combustion mechanisms of those materials. The first half of the book represents an introductory text on pyrodynamics, describing fundamental aspects of the combustion of energetic materials. The second half highlights applications of energetic materials as propellants, explosives and pyrolants with focus on phenomena occurring in rocket motors. In addition, the appendix gives a brief overview of the fundamentals of aerodynamics and heat transfer, which is a prerequisite for the study of pyrodynamics. A detailed reference for readers interested in rocketry or explosives technology.Table of ContentsPreface xix Preface to the Second Edition xxi Preface to the First Edition xxiii 1 Foundations of Pyrodynamics 1 1.1 Heat and Pressure 1 1.1.1 First Law of Thermodynamics 1 1.1.2 Specific Heat 2 1.1.3 Entropy Change 4 1.2 Thermodynamics in a Flow Field 5 1.2.1 One-Dimensional Steady-State Flow 5 1.2.1.1 Sonic Velocity and Mach Number 5 1.2.1.2 Conservation Equations in a Flow Field 6 1.2.1.3 Stagnation Point 6 1.2.2 Formation of Shock Waves 7 1.2.3 Supersonic Nozzle Flow 10 1.3 Formation of Propulsive Forces 12 1.3.1 Momentum Change and Thrust 12 1.3.2 Rocket Propulsion 14 1.3.2.1 Thrust Coefficient 15 1.3.2.2 Characteristic Velocity 15 1.3.2.3 Specific Impulse 16 1.3.3 Gun Propulsion 17 1.3.3.1 Thermochemical Process of Gun Propulsion 17 1.3.3.2 Internal Ballistics 18 1.4 Formation of Destructive Forces 20 1.4.1 Pressure and Shock Wave 20 1.4.2 Shock Wave Propagation and Reflection in Solid Materials 21 References 21 2 Thermochemistry of Combustion 23 2.1 Generation of Heat Energy 23 2.1.1 Chemical Bond Energy 23 2.1.2 Heat of Formation and Heat of Explosion 24 2.1.3 Thermal Equilibrium 25 2.2 Adiabatic Flame Temperature 26 2.3 Chemical Reaction 31 2.3.1 Thermal Dissociation 31 2.3.2 Reaction Rate 31 2.4 Evaluation of Chemical Energy 32 2.4.1 Heats of Formation of Reactants and Products 33 2.4.2 Oxygen Balance 33 2.4.3 Thermodynamic Energy 36 References 39 3 Combustion Wave Propagation 41 3.1 Combustion Reactions 41 3.1.1 Ignition and Combustion 41 3.1.2 Premixed and Diffusion Flames 42 3.1.3 Laminar and Turbulent Flames 42 3.2 Combustion Wave of a Premixed Gas 43 3.2.1 Governing Equations for the Combustion Wave 43 3.2.2 Rankine–Hugoniot Relationships 44 3.2.3 Chapman–Jouguet Points 46 3.3 Structures of Combustion Waves 49 3.3.1 Detonation Wave 49 3.3.2 Deflagration Wave 52 3.4 Ignition Reactions 54 3.4.1 The Ignition Process 54 3.4.2 Thermal Theory of Ignition 54 3.4.3 Flammability Limit 55 3.5 Combustion Waves of Energetic Materials 56 3.5.1 Thermal Theory of Burning Rate 56 3.5.1.1 Thermal Model of Combustion Wave Structure 56 3.5.1.2 Thermal Structure in the Condensed Phase 59 3.5.1.3 Thermal Structure in the Gas Phase 59 3.5.1.4 Burning Rate Model 62 3.5.2 Flame Stand-Off Distance 64 3.5.3 Burning Rate Characteristics of Energetic Materials 66 3.5.3.1 Pressure Exponent of Burning Rate 66 3.5.3.2 Temperature Sensitivity of Burning Rate 66 3.5.4 Analysis of Temperature Sensitivity of Burning Rate 66 3.5.5 Chemical Reaction Rate in Combustion Wave 69 References 71 4 Energetics of Propellants and Explosives 73 4.1 Crystalline Materials 73 4.1.1 Physicochemical Properties of Crystalline Materials 73 4.1.2 Perchlorates 76 4.1.2.1 Ammonium Perchlorate 77 4.1.2.2 Nitronium Perchlorate 77 4.1.2.3 Potassium Perchlorate 78 4.1.3 Nitrates 78 4.1.3.1 Ammonium Nitrate 78 4.1.3.2 Potassium Nitrate and Sodium Nitrate 79 4.1.3.3 Pentaerythrol Tetranitrate 79 4.1.3.4 Triaminoguanidine Nitrate 80 4.1.4 Nitro Compounds 80 4.1.5 Nitramines 80 4.2 Polymeric Materials 82 4.2.1 Physicochemical Properties of Polymeric Materials 82 4.2.2 Nitrate Esters 82 4.2.3 Inert Polymers 84 4.2.4 Azide Polymers 87 4.2.4.1 GAP 88 4.2.4.2 BAMO 90 4.3 Classification of Propellants and Explosives 91 4.4 Formulation of Propellants 94 4.5 Nitropolymer Propellants 96 4.5.1 Single-Base Propellants 96 4.5.2 Double-Base Propellants 96 4.5.2.1 NC–NG Propellants 97 4.5.2.2 NC–TMETN Propellants 99 4.5.2.3 Nitro-Azide Polymer Propellants 99 4.5.2.4 Chemical Materials of Double-Base Propellants 100 4.6 Composite Propellants 100 4.6.1 AP Composite Propellants 101 4.6.1.1 AP–HTPB Propellants 101 4.6.1.2 AP–GAP Propellants 103 4.6.1.3 Chemical Materials of AP Composite Propellants 104 4.6.2 AN Composite Propellants 104 4.6.3 Nitramine Composite Propellants 104 4.6.4 HNF Composite Propellants 106 4.6.5 TAGN Composite Propellants 108 4.7 Composite-Modified Double-Base Propellants 108 4.7.1 AP–CMDB Propellants 110 4.7.2 Nitramine CMDB Propellants 110 4.7.3 Triple-Base Propellants 112 4.8 Black Powder 113 4.9 Formulation of Explosives 114 4.9.1 Industrial Explosives 114 4.9.1.1 ANFO Explosives 114 4.9.1.2 Slurry Explosives 114 4.9.2 Military Explosives 115 4.9.2.1 TNT-Based Explosives 115 4.9.2.2 Plastic-Bonded Explosives 115 References 116 5 Combustion of Crystalline and Polymeric Materials 119 5.1 Combustion of Crystalline Materials 119 5.1.1 Ammonium Perchlorate (AP) 119 5.1.1.1 Thermal Decomposition 119 5.1.1.2 Burning Rate 120 5.1.1.3 Combustion Wave Structure 121 5.1.2 Ammonium Nitrate (AN) 121 5.1.2.1 Thermal Decomposition 121 5.1.3 HMX 122 5.1.3.1 Thermal Decomposition 122 5.1.3.2 Burning Rate 122 5.1.3.3 Gas-Phase Reaction 123 5.1.3.4 Combustion Wave Structure and Heat Transfer 124 5.1.4 Triaminoguanidine Nitrate (TAGN) 126 5.1.4.1 Thermal Decomposition 126 5.1.4.2 Burning Rate 130 5.1.4.3 Combustion Wave Structure and Heat Transfer 130 5.1.5 ADN (Ammonium Dinitramide) 132 5.1.6 HNF (Hydrazinium Nitroformate) 134 5.2 Combustion of Polymeric Materials 135 5.2.1 Nitrate Esters 135 5.2.1.1 Decomposition of Methyl Nitrate 136 5.2.1.2 Decomposition of Ethyl Nitrate 136 5.2.1.3 Overall Decomposition Process of Nitrate Esters 137 5.2.1.4 Gas-Phase Reactions of NO2 and NO 137 5.2.2 Glycidyl Azide Polymer (GAP) 139 5.2.2.1 Thermal Decomposition and Burning Rate 139 5.2.2.2 Combustion Wave Structure 142 5.2.3 Bis-azide Methyl Oxetane (BAMO) 142 5.2.3.1 Thermal Decomposition and Burning Rate 142 5.2.3.2 Combustion Wave Structure and Heat Transfer 146 References 148 6 Combustion of Double-Base Propellants 151 6.1 Combustion of NC-NG Propellants 151 6.1.1 Burning Rate Characteristics 151 6.1.2 Combustion Wave Structure 152 6.1.2.1 Gas-Phase Reaction Zones 156 6.1.2.2 A Simplified Reaction Model in Fizz Zone 157 6.1.3 Burning Rate Model 160 6.1.3.1 Model for Heat Feedback from the Gas Phase to the Condensed Phase 160 6.1.3.2 Burning Rate Calculated by a Simplified Gas-Phase Model 160 6.1.4 Energetics of the Gas Phase and Burning Rate 162 6.1.5 Temperature Sensitivity of Burning Rate 168 6.2 Combustion of NC-TMETN Propellants 171 6.2.1 Burning Rate Characteristics 171 6.2.2 Combustion Wave Structure 173 6.3 Combustion of Nitro-Azide Propellants 173 6.3.1 Burning Rate Characteristics 173 6.3.2 Combustion Wave Structure 174 6.4 Catalyzed Double-Base Propellants 176 6.4.1 Super-Rate, Plateau, and Mesa Burning 176 6.4.2 Effects of Lead Catalysts 177 6.4.2.1 Burning Rate Behavior of Catalyzed Liquid Nitrate Esters 177 6.4.2.2 Effect of Lead Compounds on Gas-Phase Reactions 178 6.4.3 Combustion of Catalyzed Double-Base Propellants 179 6.4.3.1 Burning Rate Characteristics 179 6.4.3.2 Reaction Mechanism in the Dark Zone 182 6.4.3.3 Reaction Mechanism in the Fizz Zone Structure 184 6.4.4 Combustion Models of Super-Rate, Plateau, and Mesa Burning 184 6.4.5 LiF-Catalyzed Double-Base Propellants 187 6.4.6 Ni-Catalyzed Double-Base Propellants 189 6.4.7 Suppression of Super-Rate and Plateau Burning 191 References 193 7 Combustion of Composite Propellants 195 7.1 AP Composite Propellants 195 7.1.1 Combustion Wave Structure 195 7.1.1.1 Premixed Flame of AP Particles and Diffusion Flame 195 7.1.1.2 Burning Rate Model of Granular Diffusion Theory 199 7.1.1.3 Combustion Wave Structure of Oxidizer-Rich AP Propellants 200 7.1.2 Burning Rate Characteristics 203 7.1.2.1 Effect of AP Particle Size 203 7.1.2.2 Effect of the Binder 205 7.1.2.3 Temperature Sensitivity 208 7.1.3 Catalyzed AP Composite Propellants 210 7.1.3.1 Positive Catalysts 211 7.1.3.2 LiF Negative Catalyst 213 7.1.3.3 SrCO3 Negative Catalyst 216 7.2 Nitramine Composite Propellants 219 7.2.1 Burning Rate Characteristics 220 7.2.1.1 Effect of Nitramine Particle Size 220 7.2.1.2 Effect of Binder 220 7.2.2 Combustion Wave Structure 221 7.2.3 HMX-GAP Propellants 224 7.2.3.1 Physicochemical Properties of Propellants 224 7.2.3.2 Burning Rate and Combustion Wave Structure 224 7.2.4 Catalyzed Nitramine Composite Propellants 227 7.2.4.1 Super-Rate Burning of HMX Composite Propellants 227 7.2.4.2 Super-Rate Burning of HMX-GAP Propellants 228 7.2.4.3 LiF Catalysts for Super-Rate Burning 230 7.2.4.4 Catalyst Action of LiF on Combustion Wave 232 7.3 AP-Nitramine Composite Propellants 235 7.3.1 Theoretical Performance 235 7.3.2 Burning Rate 236 7.3.2.1 Effects of AP/RDX Mixture Ratio and Particle Size 236 7.3.2.2 Effect of Binder 238 7.4 TAGN-GAP Composite Propellants 241 7.4.1 Physicochemical Characteristics 241 7.4.2 Burning Rate and Combustion Wave Structure 242 7.5 AN-Azide Polymer Composite Propellants 243 7.5.1 AN-GAP Composite Propellants 243 7.5.2 AN-(BAMO-AMMO)-HMX Composite Propellants 246 7.6 AP-GAP Composite Propellants 247 7.7 ADN, HNF, and HNIW Composite Propellants 249 References 250 8 Combustion of CMDB Propellants 253 8.1 Characteristics of CMDB Propellants 253 8.2 AP-CMDB Propellants 253 8.2.1 Flame Structure and Combustion Mode 253 8.2.2 Burning Rate Models 255 8.3 Nitramine-CMDB Propellants 258 8.3.1 Flame Structure and Combustion Mode 258 8.3.2 Burning Rate Characteristics 261 8.3.3 Thermal Wave Structure 262 8.3.4 Burning Rate Model 267 8.4 Plateau Burning of Catalyzed HMX-CMDB Propellants 269 8.4.1 Burning Rate Characteristics 269 8.4.2 Combustion Wave Structure 270 8.4.2.1 Flame Stand-Off Distance 270 8.4.2.2 Catalyst Activity 271 8.4.2.3 Heat Transfer at the Burning Surface 273 References 275 9 Combustion of Explosives 277 9.1 Detonation Characteristics 277 9.1.1 Detonation Velocity and Pressure 277 9.1.2 Estimation of Detonation Velocity of CHNO Explosives 279 9.1.3 Equation of State for Detonation of Explosives 280 9.2 Density and Detonation Velocity 280 9.2.1 Energetic Explosive Materials 280 9.2.2 Industrial Explosives 281 9.2.2.1 ANFO Explosives 282 9.2.2.2 Slurry and Emulsion Explosives 282 9.2.3 Military Explosives 283 9.2.3.1 TNT-Based Explosives 283 9.2.3.2 Plastic-Bonded Explosives 284 9.3 Critical Diameter 285 9.4 Applications of Detonation Phenomena 285 9.4.1 Formation of a Flat Detonation Wave 285 9.4.2 Munroe Effect 287 9.4.3 Hopkinnson Effect 288 9.4.4 Underwater Explosion 289 References 292 10 Formation of Energetic Pyrolants 293 10.1 Differentiation of Propellants, Explosives, and Pyrolants 293 10.1.1 Thermodynamic Energy of Pyrolants 294 10.1.2 Thermodynamic Properties 295 10.2 Energetics of Pyrolants 296 10.2.1 Reactants and Products 296 10.2.2 Generation of Heat and Products 297 10.3 Energetics of Elements 297 10.3.1 Physicochemical Properties of Elements 297 10.3.2 Heats of Combustion of Elements 299 10.4 Selection Criteria of Chemicals 300 10.4.1 Characteristics of Pyrolants 300 10.4.2 Physicochemical Properties of Pyrolants 304 10.4.3 Formulations of Pyrolants 306 10.5 Oxidizer Components 309 10.5.1 Metallic Crystalline Oxidizers 310 10.5.1.1 Potassium Nitrate 310 10.5.1.2 Potassium Perchlorate 311 10.5.1.3 Potassium Chlorate 311 10.5.1.4 Barium Nitrate 311 10.5.1.5 Barium Chlorate 311 10.5.1.6 Strontium Nitrate 312 10.5.1.7 Sodium Nitrate 312 10.5.2 Metallic Oxides 312 10.5.3 Metallic Sulfides 313 10.5.4 Fluorine Compounds 313 10.6 Fuel Components 314 10.6.1 Metallic Fuels 314 10.6.2 Nonmetallic Solid Fuels 316 10.6.2.1 Boron 316 10.6.2.2 Carbon 316 10.6.2.3 Silicon 317 10.6.2.4 Sulfur 317 10.6.3 Polymeric Fuels 317 10.6.3.1 Nitropolymers 317 10.6.3.2 Polymeric Azides 318 10.6.3.3 Hydrocarbon Polymers 318 10.7 Metal Azides 318 References 319 11 Combustion Propagation of Pyrolants 321 11.1 Physicochemical Structures of Combustion Waves 321 11.1.1 Thermal Decomposition and Heat Release Process 321 11.1.2 Homogeneous Pyrolants 322 11.1.3 Heterogeneous Pyrolants 322 11.1.4 Pyrolants as Igniters 323 11.2 Combustion of Metal Particles 324 11.2.1 Oxidation and Combustion Processes 325 11.2.1.1 Aluminum Particles 325 11.2.1.2 Magnesium Particles 325 11.2.1.3 Boron Particles 326 11.2.1.4 Zirconium Particles 326 11.3 Black Powder 326 11.3.1 Physicochemical Properties 326 11.3.2 Reaction Process and Burning Rate 327 11.4 Li–SF6 Pyrolants 327 11.4.1 Reactivity of Lithium 327 11.4.2 Chemical Characteristics of SF6 328 11.5 Zr Pyrolants 328 11.5.1 Reactivity with BaCrO4 328 11.5.2 Reactivity with Fe2O3 329 11.6 Mg-Tf Pyrolants 329 11.6.1 Thermochemical Properties and Energetics 329 11.6.2 Reactivity of Mg and Tf 331 11.6.3 Burning Rate Characteristics 331 11.6.4 Combustion Wave Structure 334 11.7 B - KNO3 Pyrolants 336 11.7.1 Thermochemical Properties and Energetics 336 11.7.2 Burning Rate Characteristics 336 11.8 Ti - KNO3 and Zr - KNO3 Pyrolants 338 11.8.1 Oxidation Process 338 11.8.2 Burning Rate Characteristics 338 11.9 Metal-GAP Pyrolants 339 11.9.1 Flame Temperature and Combustion Products 339 11.9.2 Thermal Decomposition Process 340 11.9.3 Burning Rate Characteristics 340 11.10 Ti-C Pyrolants 341 11.10.1 Thermochemical Properties of Titanium and Carbon 341 11.10.2 Reactivity of Tf with Ti-C Pyrolants 341 11.10.3 Burning Rate Characteristics 342 11.11 NaN3 Pyrolants 342 11.11.1 Thermochemical Properties of NaN3 Pyrolants 342 11.11.2 NaN3 Pyrolant Formulations 343 11.11.3 Burning Rate Characteristics 344 11.11.4 Combustion Residue Analysis 344 11.12 GAP-AN Pyrolants 345 11.12.1 Thermochemical Characteristics 345 11.12.2 Burning Rate Characteristics 345 11.12.3 Combustion Wave Structure and Heat Transfer 345 11.13 Nitramine Pyrolants 346 11.13.1 Physicochemical Properties 346 11.13.2 Combustion Wave Structures 346 11.14 B-AP Pyrolants 347 11.14.1 Thermochemical Characteristics 347 11.14.2 Burning Rate Characteristics 348 11.14.3 Burning Rate Analysis 350 11.14.4 Site and Mode of Boron Combustion in the Combustion Wave 352 11.15 Friction Sensitivity of Pyrolants 353 11.15.1 Definition of Friction Energy 353 11.15.2 Effect of Organic Iron and Boron Compounds 354 References 357 12 Emission from Combustion Products 359 12.1 Fundamentals of Light Emission 359 12.1.1 Nature of Light Emission 359 12.1.2 Black-Body Radiation 360 12.1.3 Emission and Absorption by Gases 361 12.2 Light Emission from Flames 362 12.2.1 Emission from Gaseous Flames 362 12.2.2 Continuous Emission from Hot Particles 362 12.2.3 Colored Light Emitters 362 12.3 Smoke Emission 363 12.3.1 Physical Smoke and Chemical Smoke 363 12.3.2 White Smoke Emitters 364 12.3.3 Black Smoke Emitters 365 12.4 Smokeless Pyrolants 366 12.4.1 Nitropolymer Pyrolants 366 12.4.2 Ammonium Nitrate Pyrolants 367 12.5 Smoke Characteristics of Pyrolants 368 12.6 Smoke and Flame Characteristics of Rocket Motors 374 12.6.1 Smokeless and Reduced Smoke 374 12.6.2 Suppression of Rocket Plume 376 12.6.2.1 Effect of Chemical Reaction Suppression 379 12.6.2.2 Effect of Nozzle Expansion 380 12.7 HCl Reduction from AP Propellants 383 12.7.1 Background of HCl Reduction 383 12.7.2 Reduction of HCl by the Formation of Metal Chlorides 385 12.8 Reduction of Infrared Emission from Combustion Products 387 12.9 Green Propellants 388 12.9.1 AN-Composite Propellants 389 12.9.2 ADN- and HNF-Composite Propellants 390 12.9.3 Nitramine Composite Propellants 390 12.9.4 TAGN-GAP Composite Propellants 391 12.9.5 NP Propellants 391 References 392 13 Transient Combustion of Propellants and Pyrolants 393 13.1 Ignition Transient 393 13.1.1 Convective and Conductive Ignition 393 13.1.2 Radiative Ignition 396 13.2 Ignition for Combustion 398 13.2.1 Description of the Ignition Process 398 13.2.2 Ignition Process 400 13.3 Erosive Burning Phenomena 402 13.3.1 Threshold Velocity 402 13.3.2 Effect of Cross-Flow 404 13.3.3 Heat Transfer through a Boundary Layer 404 13.3.4 Determination of Lenoir–Robilard Parameters 406 13.4 Combustion Instability 409 13.4.1 T∗ Combustion Instability 409 13.4.2 L∗ Combustion Instability 411 13.4.3 Acoustic Combustion Instability 414 13.4.3.1 Nature of Oscillatory Combustion 414 13.4.3.2 Combustion Instability Test 415 13.4.3.3 Model for Suppression of Combustion Instability 423 13.5 Combustion under Acceleration 424 13.5.1 Burning Rate Augmentation 424 13.5.2 Effect of Aluminum Particles 425 13.6 Wired Propellant Burning 426 13.6.1 Heat-Transfer Process 426 13.6.2 Burning-Rate Augmentation 428 References 432 14 Rocket Thrust Modulation 435 14.1 Combustion Phenomena in a Rocket Motor 435 14.1.1 Thrust and Burning Time 435 14.1.2 Combustion Efficiency in a Rocket Motor 437 14.1.3 Stability Criteria for a Rocket Motor 440 14.1.4 Temperature Sensitivity of Pressure in a Rocket Motor 442 14.2 Dual-Thrust Motor 444 14.2.1 Principles of a Dual-Thrust Motor 444 14.2.2 Single-Grain Dual-Thrust Motor 445 14.2.3 Dual-Grain Dual-Thrust Motor 446 14.2.3.1 Mass Generation Rate and Mass Discharge Rate 446 14.2.3.2 Determination of Design Parameters 448 14.2.4 Thrust Modulator 451 14.3 Pulse Rocket Motor 451 14.3.1 Design Concept of Pulse Motor 451 14.3.2 Operational Flight Design of Pulse Motor 452 14.3.3 Combustion Test Results of a Two-Pulse Rocket Motor 454 14.4 Erosive Burning in a Rocket Motor 455 14.4.1 Head-End Pressure 455 14.4.2 Determination of Erosive-Burning Effect 456 14.5 Nozzleless Rocket Motor 459 14.5.1 Principles of the Nozzleless Rocket Motor 459 14.5.2 Flow Characteristics in a Nozzleless Rocket 460 14.5.3 Combustion Performance Analysis 462 14.6 Gas-Hybrid Rockets 463 14.6.1 Principles of the Gas-Hybrid Rocket 463 14.6.2 Thrust and Combustion Pressure 466 14.6.3 Pyrolants Used as Gas Generators 466 References 469 15 Ducted Rocket Propulsion 471 15.1 Fundamentals of Ducted Rocket Propulsion 471 15.1.1 Solid Rockets, Liquid Ramjets, and Ducted Rockets 471 15.1.2 Structure and Operational Process 472 15.2 Design Parameters of Ducted Rockets 473 15.2.1 Thrust and Drag 473 15.2.2 Determination of Design Parameters 474 15.2.3 Optimum Flight Envelope 475 15.2.4 Specific Impulse of Flight Mach Number 476 15.3 Performance Analysis of Ducted Rockets 477 15.3.1 Fuel-Flow System 477 15.3.1.1 Non-choked Fuel-Flow System 478 15.3.1.2 Fixed Fuel-Flow System 478 15.3.1.3 Variable Fuel-Flow System 478 15.4 Principle of the Variable Fuel-Flow Ducted Rocket 479 15.4.1 Optimization of Energy Conversion 479 15.4.2 Control of Fuel-Flow Rate 479 15.5 Energetics of Gas-Generating Pyrolants 482 15.5.1 Required Physicochemical Properties 482 15.5.2 Burning Rate Characteristics of Gas-Generating Pyrolants 483 15.5.2.1 Burning Rate and Pressure Exponent 483 15.5.2.2 Wired Gas-Generating Pyrolants 484 15.5.3 Pyrolants for Variable Fuel-Flow Ducted Rockets 485 15.5.4 GAP Pyrolants 486 15.5.5 Metal Particles as Fuel Components 487 15.5.6 GAP-B Pyrolants 488 15.5.7 AP Composite Pyrolants 490 15.5.8 Effect of Metal Particles on Combustion Stability 490 15.6 Combustion Tests for Ducted Rockets 491 15.6.1 Combustion Test Facility 491 15.6.2 Combustion of Variable-Flow Gas Generator 493 15.6.3 Combustion Efficiency of Multiport Air Intake 497 References 500 A Appendix A: List of Abbreviations of Energetic Materials 503 B Appendix B: Mass and Heat Transfer in a Combustion Wave 505 B.1 Conservation Equations at a Steady State in a One-Dimensional Flow Field 505 B.1.1 Mass Conservation Equation 505 B.1.2 Momentum Conservation Equation 506 B.1.3 Energy Conservation Equation 506 B.1.4 Conservation Equations of Chemical Species 507 B.2 Generalized Conservation Equations at a Steady State in a Flow Field 508 C Appendix C: Shock Wave Propagation in a Two-Dimensional Flow Field 509 C.1 Oblique Shock Wave 509 C.2 Expansion Wave 513 C.3 Diamond Shock Wave 514 References 515 D Appendix D: Supersonic Air Intake 517 D.1 Compression Characteristics of Diffusers 517 D.1.1 Principles of a Diffuser 517 D.1.2 Pressure Recovery 518 D.2 Air Intake System 521 D.2.1 External Compression System 521 D.2.2 Internal Compression System 522 D.2.3 Air Intake Design 522 References 524 E Appendix E: Measurements of Burning Rate and Combustion Wave Structure 525 Index 527

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Book SynopsisWritten by the pioneers of Viagra, the first blockbuster PDE inhibitor drug. Beginning with a review of the first wave of phosphodiesterase (PDE) inhibitors, this book focuses on new and emerging PDE targets and their inhibitors. Drug development options for all major human PDE families are discussed and cover diverse therapeutic fields, such as neurological/psychiatric, cardiovascular/metabolic, pain, and allergy/respiratory diseases. Finally, emerging chemotherapeutic applications of PDE inhibitors against malaria and other tropical diseases are discussed.Table of ContentsList of Contributors XI Preface XV A Personal Foreword XVII 1 Introduction 1Andrew S. Bell and Spiros Liras 2 Toward a New Generation of PDE5 Inhibitors through Advances in Medicinal Chemistry 9Dafydd R. Owen 2.1 Introduction 9 2.2 The First-Generation Agents 10 2.3 PDE5 as a Mechanism and Alternative Indications Beyond MED 11 2.4 A Summary of PDE5 Chemotypes Reported Post-2010 11 2.5 Second-Generation PDE5 Inhibitors from Pfizer: Pyrazolopyrimidines 12 2.6 Second-Generation PDE5 Inhibitors from Pfizer: Pyridopyrazinones 18 2.7 Conclusions 25 References 25 3 PDE4: New Structural Insights into the Regulatory Mechanism and Implications for the Design of Selective Inhibitors 29Jayvardhan Pandit 3.1 Introduction 29 3.2 Isoforms, Domain Organization, and Splice Variants 30 3.3 Structural Features of the Catalytic Site 31 3.4 Regulation of PDE4 Activity 32 3.5 Crystal Structure of Regulatory Domains of PDE4 33 3.6 UCR2 Interaction and Selectivity 38 3.7 Conclusions 39 References 40 4 PDE4: Recent Medicinal Chemistry Strategies to Mitigate Adverse Effects 45Etzer Darout, Elnaz Menhaji-Klotz, and Thomas A. Chappie 4.1 Introduction 45 4.2 Brief Summary of pan-PDE4 Inhibitors 46 4.2.1 Rolipram 47 4.2.2 Roflumilast 48 4.2.3 Cilomilast 48 4.2.4 Apremilast 49 4.3 PDE4 Strategies to Avoid Gastrointestinal Events 49 4.3.1 Allosteric Modulation 49 4.3.2 PDE4D Selectivity 53 4.3.3 Pfizer 53 4.3.4 Novartis 54 4.3.5 Merck-Frosst 54 4.3.6 GEBR-7b 55 4.3.7 PDE4B Selectivity 55 4.3.8 Asahi Kasei 56 4.3.9 GlaxoSmithKline 56 4.3.10 Pfizer 57 4.3.11 Tissue Targeting 57 4.3.12 Polypharmacology 58 4.3.13 Olanzapine Derivatives 58 4.4 Conclusions 59 References 60 5 The Function, Enzyme Kinetics, Structural Biology, and Medicinal Chemistry of PDE10A 65Thomas A. Chappie and Patrick Verhoest 5.1 Enzymology and Protein Structure 66 5.2 Papaverine-Related PDE10A Inhibitors 69 5.3 MP-10/PF-2545920 Class of Inhibitors 72 5.4 PF-2545920/MP-Inspired Inhibitors 74 5.5 PF-2545920/Papaverine/Quinazoline Hybrid Series of Inhibitors 75 5.6 PET Ligand Development 77 5.7 Summary and Future 79 References 79 6 The State of the Art in Selective PDE2A Inhibitor Design 83Christopher W. am Ende, Bethany L. Kormos, and John M. Humphrey 6.1 Introduction 83 6.2 Selective PDE2A Inhibitors 84 6.2.1 Bayer 84 6.2.2 Altana AG 85 6.2.3 Biotie Therapies 87 6.2.4 Boehringer Ingelheim 88 6.2.5 Janssen 89 6.2.6 Lundbeck 92 6.2.7 Merck 93 6.2.8 Neuro3d 95 6.2.9 Pfizer 95 6.3 Methods 100 6.4 Conclusions 100 References 101 7 Crystal Structures of Phosphodiesterase 9A and Insight into Inhibitor Discovery 105Hengming Ke, Yousheng Wang, Yiqian Wan, and Hai-Bin Luo 7.1 Introduction 105 7.2 Subtle Asymmetry of the PDE9 Dimer in the Crystals 105 7.3 The Structure of the PDE9 Catalytic Domain 107 7.4 Interaction of Inhibitors with PDE9 108 7.5 Implication on Inhibitor Selectivity 110 References 114 8 PDEs as CNS Targets: PDE9 Inhibitors for Cognitive Deficit Diseases 117Michelle M. Claffey, Christopher J. Helal, and Xinjun Hou 8.1 PDE9A Enzymology and Pharmacology 117 8.2 Crystal Structures of PDE9A Inhibitors 119 8.3 Medicinal Chemistry Efforts toward Identifying PDE9A Inhibitors for Treating Cognitive Disorders 120 8.3.1 Bayer 120 8.3.2 Pfizer 125 8.3.3 Boehringer Ingelheim 129 8.3.4 Sun Yat-Sen University, China 132 8.3.5 Envivo Pharmaceuticals 133 8.4 Analysis of CNS Desirability of PDE9A Inhibitors 135 8.5 Conclusions 135 References 137 9 Phosphodiesterase 8B 141Stephen W. Wright 9.1 Introduction 141 9.2 Identification 141 9.3 Properties 142 9.4 Expression and Tissue Distribution 143 9.5 Functions of PDE8B 143 9.5.1 Thyroid 144 9.5.2 Adrenal Gland 144 9.5.3 Pancreatic Islets 144 9.6 Inhibitors and Potential Therapeutic Uses 145 References 150 10 Selective New Small-Molecule Inhibitors of Phosphodiesterase 1 155John M. Humphrey 10.1 Introduction 155 10.2 PDE1 Enzymology 155 10.3 PDE1 Inhibitors 156 10.3.1 Non-Selective PDE1 Inhibitors 156 10.3.2 Selective PDE1 inhibitors 158 10.4 Conclusion 161 References 163 11 Recent Advances in the Development of PDE7 Inhibitors 165Nigel A. Swain and Rainer Gewald 11.1 Introduction 165 11.1.1 PDE7: Subtypes and Distribution 165 11.1.2 Rationale for PDE7 as a Therapeutic Target 166 11.2 Historical Development of PDE7 Inhibitors 166 11.2.1 Early Examples of Nonselective and Selective Lead Matter 166 11.2.2 Developing Selective Lead Matter from Nonselective Hits 167 11.2.3 Targeting PDE4/7 Dual Inhibitors 168 11.3 Recent Advances in the Discovery of PDE7 Inhibitors for Peripheral Therapeutic Benefit 169 11.3.1 PDE7 Inhibitors for the Treatment of T Cell-Related Disorders 169 11.3.1.1 Developments in PDE7 Inhibitors for the Treatment of Airway-Related Disorders 170 11.3.1.2 Developments in PDE7 Inhibitors for the Treatment of Nonairway-Related Disorders 171 11.3.1.3 Summary of T-Cell-Related Research 171 11.3.2 PDE7 Inhibitors for the Treatment of Neuropathic Pain 172 11.4 Recent Advances in the Discovery of PDE7 Inhibitors for CNS-Related Disorders 173 11.4.1 Creating PDE7 Inhibitors by Ligand-Based Virtual Screening Methods 173 11.4.2 Repositioning PDE7 Inhibitors Designed for the Treatment of Peripheral Diseases 176 11.5 Recent Advances in the Discovery of Dual PDE7 Inhibitors 178 11.5.1 Dual PDE4/7 Inhibitors 178 11.5.2 Dual PDE7/8 Inhibitors 180 11.6 Identifying Next-Generation PDE7 Inhibitors 181 11.6.1 Emerging Chemotypes as Novel PDE7 Inhibitors 181 11.6.2 Novel Methods to Identify PDE7 Inhibitors 182 11.6.2.1 Computational Methods to Identify New PDE7 Inhibitors 182 11.6.2.2 Fission Yeast-Based HTS to Identify New PDE7 Inhibitors 183 11.7 Summary 184 References 185 12 Inhibitors of Protozoan Phosphodiesterases as Potential Therapeutic Approaches for Tropical Diseases 191Jennifer L. Woodring and Michael P. Pollastri 12.1 Introduction 191 12.2 Malaria 192 12.2.1 PfPDE Inhibition Studies 193 12.3 Chagas Disease 195 12.4 Leishmaniasis 197 12.5 Human African Trypanosomiasis 200 12.6 Conclusion 205 References 206 Index 211

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Book SynopsisCovering the whole value chain - from product requirements and properties via process technologies and equipment to real-world applications - this reference represents a comprehensive overview of the topic. The editors and majority of the authors are members of the European Federation of Chemical Engineering, with backgrounds from academia as well as industry. Therefore, this multifaceted area is highlighted from different angles: essential physico-chemical background, latest measurement and prediction techniques, and numerous applications from cosmetic up to food industry. Recommended reading for process, pharma and chemical engineers, chemists in industry, and those working in the pharmaceutical, food, cosmetics, dyes and pigments industries.Table of ContentsINTRODUCTION RHEOLOGY OF DISPERSE SYSTEMS Introduction Basics of Rheology Experimental Methods of Rheology Rheology of Colloidal Suspensions Rheology of Emulsions RHEOLOGY OF COSMETIC EMULSIONS Introduction Chemistry of Cosmetic Emulsions Rheological Measurements Dynamic Mechanical Tests (Oscillation) RHEOLOGY MODIFIERS, THICKENERS, AND GELS Introduction Classification of Thickeners and Gels Definition of a ``Gel?? Rheological Behavior of a ``Gel?? Classification of Gels Particulate Gels Rheology Modifiers Based on Surfactant Systems USE OF RHEOLOGICAL MEASUREMENTS FOR ASSESSMENT AND PREDICTION OF THE LONG-TERM ASSESSMENT OF CREAMING AND SEDIMENTATION Introduction Accelerated Tests and Their Limitations Application of High Gravity (g) Force Rheological Techniques for Prediction of Sedimentation or Creaming Separation of Formulation (``Syneresis??) Examples of Correlation of Sedimentation or Creaming with Residual (Zero Shear) Viscosity Assessment and Prediction of Flocculation Using Rheological Techniques Examples of Application of Rheology for Assessment and Prediction of Flocculation Assessment and Prediction of Emulsion Coalescence Using Rheological Techniques PREDICTION OF THERMOPHYSICAL PROPERTIES OF LIQUID FORMULATED PRODUCTS Introduction Classification of Products, Properties and Models Pure Compound Property Modeling Functional Bulk Property Modeling ? Mixture Properties Functional Compound Properties in Mixtures ? Modeling Performance Related Property Modeling Software Tools Conclusions SOURCES OF THERMOPHYSICAL PROPERTIES FOR EFFICIENT USE IN PRODUCT DESIGN Introduction Overview of the Important Thermophysical Properties for Phase Equilibria Calculations Reliable Sources of Thermophysical Data Examples of Databases for Thermophysical Properties Special Case and Challenge: Data of Complex Solutions Examples of Databases with Properties of Electrolyte Solutions Properties of New Component Classes: Ionic Liquids and Hyperbranched Polymers CURRENT TRENDS IN IONIC LIQUID RESEARCH Introduction Ionic Liquids as Acido-basic Media Binary Mixtures of Ionic Liquids: Properties and Applications Nanoporous Materials from Ionothermal Synthesis Catalytic Hydrogenation Reactions in Ionic Liquids Concluding Remarks GELLING OF PLANT BASED PROTEINS Introduction ? Overview of Plant Proteins in Industry Structure and Formation of Protein Gels Factors Determining Physical Properties of Protein Gels Evaluating Gelation of Proteins Gelation of Proteins Derived from Plants Protein Gels in Product Application Future Prospects and Challenges ENZYMATICALLY TEXTURIZED PLANT PROTEINS FOR THE FOOD INDUSTRY Introduction Reactions Catalyzed by MTG Current Sources of MTG Need for Novel Sources of MTG Vegetable Proteins Suitable for Crosslinking with MTG Strategies to Modify and Improve Protein Sources for MTG Crosslinking Applications of MTG in Processing Food Products Containing Vegetable Protein Applications of MTG Crosslinked Leguminous Proteins in Food Models and Realistic Food Products Safety of MTG and Isopeptide Bonds in Crosslinked Plant Proteins Conclusions DESIGN OF SKIN CARE PRODUCTS Product Design Skin Care Emulsions Structure of a Skin Care Cream Essential Active Substances from a Medical Point of View Penetration into the Skin Targeted Product Design in the Course of Development Production of Skin Care Products Bottles for Cosmetic Creams Design of all Elements EMULSION GELS IN FOODS Introduction Food Emulsions Creating a Food Emulsion Applications of Gel-Like Type Emulsions Final Considerations INDEX

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Book SynopsisChemical Product Formulation Design and Optimization Explore the cutting-edge in chemical product formulation and design In Chemical Product Formulation Design and Optimization: Methods, Techniques, and Case Studies, a team of renowned technologists and engineers delivers a practice guide to chemical product design. Offering real-world case studies for disinfectant formulation, the optimization of defined media, and the formulation of biocomposites, the book contains introduction to the current product design process. In addition to the background of related statistical techniques, readers will find: Clear illustrations, figures, and tables that improve understanding and retention of critical topics Thorough introductions to the mathematical principles of chemical product design A complete examination of intellectual property considerations in the chemical product design process Ideal for process and chemical engineers, Chemical Product Formulation Design and Optimization: Methods, Techniques, and Case Studies is a must-read resource for professionals in the pharmaceutical and cosmetics industry as well as chemical engineers working in the food, paint, and dye industries who seek a one-stop resource that includes the latest advances in chemical product formulation.Table of ContentsBACKGROUND CHEMICAL PRODUCT DESIGN OVERVIEW Specialty Chemicals Overview Traditional Chemical Product Design BACKGROUND TO STATISTICAL METHODS FOR PRODUCT DESIGN Introduction to Design of Experiments Factorial Design Mixture Design Optimal Design Linear Regression Analysis Nonlinear Regression Analysis Artificial Neural Networks PATENTS AND EXCLUSIVITY Patents Overview US/PCT Patent Application Filing Avoiding Infringements GREEN CHEMISTRY Green Chemistry Overview Background to Chemical Products Toxicity Mammalian Toxicity Aquatic Toxicity Green Chemistry Requirements Green Chemistry Regulations CASE STUDIES CASE STUDY#1, DISINFECTANT FORMULATION DESIGN Background to Disinfectant Products Antimicrobial Tests Stability Tests Corrosion Tests Formulation Optimization CASE STUDY#2, DEFINED MEDIA OPTIMIZATION Background on Medium Development Microorganism Analytical Methods Medium Design and Optimization Verification of the optimized Medium DESIGN OF WHEAT STRAW POLYPROPYLENE COMPOSITES Background on Biocomposites and their Applications. Modeling Fiber Properties before and after Compounding Modeling Composite Properties as a Function of Fiber Properties Materials and Response Measurement Methods Results and Discussions Flexural Modulus Flexural Strength Yield Strength Density Optimum Ratio of MAPP/Wheat Straw Summary and Conclusions Concluding Remarks REFERENCES

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Book SynopsisDieses praxisorientierte Lehrbuch für Ingenieurstudenten der höheren Semester gibt einen Überblick über die ganzheitliche und vertiefte Betrachtungsweise des Apparate Entwurfes. Wärmeübertragung/Wärmeübertrager sind elementare Bestandteile in den Studienrichtungen Verfahrenstechnik und Maschinenbau, aber auch angrenzenden Studienrichtungen. Für diese Studienfächer steht eine ausreichende Anzahl guter Fachliteratur zur Verfügung, die die Lehre bei der wärmetechnischen Auslegung, der Druckverlustberechnung und dem konstruktiven Entwurf unterstützt. Für darüber hinausgehende Themen steht wenig Zeit zur Verfügung oder sie sind nicht Inhalt des Lehrstoffes. Diese Begrenzung der Stoffvermittlung soll mit vorliegendem Fachbuch etwas gelockert werden und im Sinne einer ganzheitlichen Betrachtung den Studierenden einen kleinen Einblick in Themenkreise gewähren, die den Lebenslauf eines Wärmeübertragers charakterisieren. Anhand eines praktischen Beispiels werden nach der üblichen Auslegung des Apparates Grundlagen für den konstruktiven Entwurf diskutiert, die festigkeitsmäßige Bemessung der Bauteile behandelt und die Konstruktion vorgestellt. Anschließend erfolgt ein Überblick über die Fertigung und Montage des Wärmeübertragers und endet mit der Instandhaltung/Instandsetzung und ihren Problemen und Anforderungen. Neben der Anwendung von Wissen aus den Grundlagenfächern soll aber vor allem die Themenhandlung den Studierenden als Ergänzung zum Vorlesungsstoff dienen und ihren Gesichtskreis erweitern. Dadurch wird dieses Buch ein unverzichtbares Lehrbuch für alle Dozenten und Studenten höheren Semesters der Verfahrenstechnik, Maschinenbau, sowie für Ingenieure der Chemie, Maschinenbau und Verfahrenstechnik.Trade Review"eine ganzheitliche und exemplarisch vertiefte Betrachtungsweise des Apparate-Entwurfs" PROCESS (9/2013, 01.09.2013), process.vogel.de (19.07.2013)Table of ContentsVorwort XI 1 Aufgabenstellung „Auslegung und Konstruktion eines Rohrbündel-Wärmeübertragers (RWÜ)“ 1 1.1 Allgemeine Voraussetzungen für die Auslegung eines RWÜ 1 1.2 Hinweise zur Aufgabenstellung 1 1.3 Aufgabenstellung mit Detailangaben: 2 1.4 Hinweise zur Lösungsmethodik 4 2 Wärmetechnische Auslegung des RWÜ 7 2.1 Allgemeines 7 2.2 Verwendete Formelzeichen und Kenngrößen 11 2.3 Ausgangsdiskussion 14 2.3.1 Gegebene Größen 15 2.3.2 Stoffwerte aus der erweiterten Aufgabenstellung 17 2.4 Überschlägige Berechnung der erforderlichen Wärmeübertragungsfläche 17 2.4.1 Ermittlung des abzuleitenden Wärmestromes Q_ 17 2.4.2 Berechnung der erforderlichen Kühlwassermenge m_ 2 18 2.4.3 Wahl des Wärmedurchgangskoeffizientenk 19 2.4.4 Ermittlung der mittleren logarithmischen Temperaturdifferenz Ddm 20 2.4.5 Berechnung der erforderlichen Wärmeübertragungsfläche Aerf 24 2.4.6 Begründung der Medienführung 24 2.4.7 Aussagen zur Verschmutzung von Wärmeübertragungsflächen 25 2.5 Grundlagen für die konstruktive Ausführung 29 2.5.1 Anordnung und Abmessung der Innenrohre 30 2.5.2 Anzahl der Rohre und Länge des Rohrbündels 34 2.6 Nachweise für den Rohrraum und den Mantelraum 38 2.6.1 Wärmeübertragung im Rohrraum 39 2.6.1.1 Ermittlung der Reynoldszahl Re 40 2.6.1.2 Ermittlung der Nusselt-Zahl Nui 40 2.6.1.3 Ermittlung der Wärmeübergangszahl ai 43 2.6.2 Wärmeübertragung im Mantelraum ohne Einbauten 43 2.6.3 Wärmeübertragung im Mantelraum mit Einbauten 45 2.6.3.1 Auswahl der Einbauelemente 45 2.6.3.2 Notwendige Ergebniskorrekturen 47 2.6.3.3 Auslegung der Umlenksegmente 49 2.6.3.4 Ermittlung der Reynoldszahl Rea 52 2.6.3.5 Ermittlung der Nusselt-Zahl Nua 54 2.6.3.6 Ermittlung der Wärmeübergangszahl aa im Außenraum 62 2.6.3.7 Ermittlung der Wärmedurchgangszahlk 63 2.7 Nachweis der Wandtemperatur 65 2.8 Korrektur der Wärmeübertragungsfläche 67 2.9 Kompensatorkriterium 69 2.9.1 Festlegungen in WN 75-0094 Höchst AG [37] 70 2.9.1.1 Kaltes Medium um die Rohre 70 2.9.1.2 Warmes Medium um die Rohre 71 2.9.2 Vorgehensweise in der Fachliteratur 72 2.9.3 Berechnung nach AD 2000-Merkblatt S 3/7 [45] 75 2.10 Zusammenfassung der wärmetechnischen Auslegung 78 3 Druckverlustberechnung im Mantel- und im Rohrraum des RWÜ 83 3.1 Druckverlust im Rohrraum DpRR 84 3.1.1 Druckverlust beim Einströmen in die Eintrittskammer DpE 85 3.1.2 Druckverlust beim Einströmen in die Rohre DpER 88 3.1.3 Druckverlust beim Durchströmen der Rohre DpR 90 3.1.4 Druckverlust beim Ausströmen aus den Rohren DpAR 93 3.1.5 Druckverlust infolge Umlenkung in den Kammern DpU 94 3.1.6 Druckverlust beim Ausströmen aus der Austrittskammer DpA 94 3.1.7 Gesamtdruckverlust im Rohrraum DpRR 95 3.2 Druckverlust im Mantelraum des RWÜ mit Einbauten 97 3.2.1 Druckverlust in den Mantelstutzen DpS 104 3.2.2 Druckverlust in einer Endzone DpQE 105 3.2.3 Druckverlust in der Querströmungszone DpQ 112 3.2.4 Druckverlust in einer Fensterzone DpF 117 3.2.5 Gesamtdruckverlust im Mantelraum 120 3.3 Ergebnis der strömungstechnischen Berechnungen 120 4 Überlegungen zum konstruktiven Entwurf 125 4.1 Allgemeine Vorgehensweise 125 4.2 Berücksichtigung von Gestaltungsanforderungen 127 4.2.1 Funktionsgerechte Gestaltung des RWÜ 127 4.2.2 Werkstoffgerechte Gestaltung des RWÜ 128 4.2.3 Beanspruchungsgerechte Gestaltung des RWÜ 130 4.2.4 Fertigungsgerechte Gestaltung des RWÜ 131 4.2.5 Prüfgerechte Gestaltung und Prüfungen im Lebenslauf des RWÜ 134 4.2.6 Transport- und montagegerechte Gestaltung des RWÜ 135 4.2.7 Wartungs- und instandhaltungsgerechte Gestaltung des RWÜ 139 5 Konstruktive Aufgabenstellung 141 6 Rechnerische Nachweise für die Apparateelemente 145 6.1 Grundlagen 145 6.2 Formelzeichen und Einheiten 147 6.3 Ermittlung von Berechnungswerten [6] 148 6.3.1 Berechnungsdruck p 148 6.3.2 Berechnungstemperatur #, T 149 6.3.3 Festigkeitskennwert K 149 6.3.4 Sicherheitsbeiwert S 149 6.3.5 Ausnutzung der zulässigen Berechnungsspannung in Fügeverbindungen, Faktor zur Berücksichtigung von Verschwächungen n 150 6.3.6 Zuschläge 150 6.3.6.1 Zuschlag zur Berücksichtigung der Wanddickenunterschreitung c1 150 6.3.6.2 Abnutzungszuschlag c2 151 6.4 Werkstoffauswahl 151 6.5 Berechnungsparameter 151 6.6 Berechnung der Apparateelemente 153 6.6.1 Zylindrische Wandung (Mantel) unter innerem Überdruck 153 6.6.2 Gewölbte Böden unter innerem Überdruck 156 6.6.3 Rohrbündelrohre 158 6.6.3.1 Bemessung auf inneren Überdruck 158 6.6.3.2 Bemessung auf äußeren Überdruck 159 6.6.4 Berechnung der Rohrböden 161 6.6.5 Bemessung der Flanschverbindungen 165 6.7 Stabilitätsberechnung 167 6.7.1 Lokale Lasteinleitung durch die Sattellager 168 6.7.1.1 Tragfähigkeitsnachweis für den Zylinder 170 6.7.1.2 Nachweis des Sattellagers 172 6.7.2 Tragfähigkeitsnachweis für die Tragösen und ihren Anschluss 172 6.7.3 Zusatzbelastungen durch Einzelkräfte 177 7 Konstruktion des RWÜ 181 7.1 Konstruktionszeichnung 181 7.2 Entwurfsprüfung 181 8 Fertigung des Rohrbündel-Wärmeübertragers 185 8.1 Wesentliche Einzelteile zur RWÜ-Fertigung 186 8.1.1 Gewölbte Böden 186 8.1.2 Ebene Böden 190 8.1.3 Flanschverbindungen 197 8.1.4 Rohre 202 8.2 Wesentliche allgemeine Fertigungsschritte 203 8.2.1 Fertigung des Mantels 203 8.2.2 Verbindung Rohre/Rohrboden 205 8.2.2.1 Einschweißen der Rohre 206 8.2.2.2 Einwalzen der Rohre 212 8.2.2.3 Hydraulisches Aufweiten der Rohre 216 8.2.2.4 Verbindung Rohr/Rohrboden durch Kombination verschiedener Befestigungsarten 217 8.3 Schlussprüfung und Druckprüfung 219 8.3.1 Schlussprüfung 219 8.3.2 Druckprüfung 220 8.4 Oberflächensauberkeit und Oberflächenschutz 220 8.5 Korrosionsschutzanstrich 224 8.6 Fertigungstechnologie des RWÜ DN 400 225 8.6.1 Fertigung der Ein- und Austrittshauben 225 8.6.2 Fertigung des Mantels 226 8.6.3 Fertigung des Rohrbündels 226 8.6.4 Zusammenbau 227 8.6.5 Abschlussarbeiten 227 9 Transport und Montage des RWÜ 229 9.1 Transport 229 9.2 Montage 231 10 Wärmedämmung 233 10.1 Allgemeine Aussagen 233 10.2 Dämmung als Berührungsschutz für den RWÜ DN 400 238 11 Instandsetzung von Rohrbündel-Wärmeübertragern – Schadensbehebung durch Reinigung 241 11.1 Allgemeines 241 11.2 Logistische Vorleistungen für die mechanische Reinigung von RWÜ 243 11.3 Mechanische Reinigung von RWÜ 248 11.3.1 Hochdruckwasserstrahlreinigung 249 11.3.2 Hochdruckreinigung unter Einsatz entsprechender Reinigungskörper 254 11.3.3 Reinigungsverfahren mit rotierenden Werkzeugen 262 11.4 Chemische Reinigung von RWÜ 262 11.4.1 Allgemeines 262 11.4.2 Anwendung auf den RWÜ DN 400 263 11.5 Thermische Reinigung 266 11.6 Trockeneisreinigung 267 11.7 In-situ-Reinigung von RWÜ 270 12 Instandsetzung von Rohrbündel-Wärmeübertragern – Schadensbehebung durch Verstopfen, Rohraustausch oder Neuberohrung 273 12.1 Allgemeines 273 12.2 Schäden an Rohrbündel-Wärmeübertragern und Schadensbehebung 273 12.2.1 Einsetzen von Stopfen 276 12.2.2 Ersatz einzelner Rohre 281 12.2.3 Neuberohrung 284 12.2.4 Sanierung von Rohrböden 288 Anhang 1 Bezeichnungen und Begriffe für Werkstoffe Kurzzeichen in Werkstoffbezeichnungen 293 Anhang 2 Zusammenstellung der Prüfbescheinigungen nach EN 1024:2004 (D) 295 Anhang 3 Kennwerte für die Bemessung der Rohre nach DIN EN 10 216-1, und DIN EN 10 217-1 (AD 2000-Merkblatt W 4 Tafel A 2) 297 Anhang 4 Kennwerte für Flacherzeugnisse nach DIN EN 10 028-2, Mindestwerte der Dehngrenze Rp0,2 bei erhöhten Temperaturen 299 Anhang 5 Verschwächungsbeiwert vA bei sA=Di ¼ 0,01 AD 2000-Merkblatt B 9 301 Anhang 6 Verschwächungsbeiwert vA bei sA=Di ¼ 0,05 AD 2000-Merkblatt B 9 303 Anhang 7 Verschwächungsbeiwert vA für sA= Di 2 ¼ 0,10 AD 2000-Merkblatt B 9 305 Anhang 8 Berechnungsbeiwerte b für gewölbte Böden in Klöpperform nachAD 2000-Merkblatt B 3 307 Anhang 9 Einsatzgrenzen für Stahlflansche nach DIN EN 1092-1 309 Anhang 10 Diagramme zur Ermittlung der Beiwerte K für Tragösen nach TGL 32903/17 [47] und RKF BR – A 62 [48] 311 Schlussbetrachtung 313 Index 315

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Book SynopsisA guide to industrially relevant products and processes for transportation fuels The Handbook of Fuels offers a comprehensive review of the wide variety of fuels used to power vehicles, aircraft and ships and examines the processes to produce these fuels. The updated second edition reflects the growing importance of fuels and fuel additives from renewable sources. New chapters include information on current production technology and use of bioethanol, biomethanol and biomass-to-liquid fuels. The book also reviews novel additives and performanace enhancers for conventional engines and fuels for novel bybrid engines. This comprehensive resource contains critical information on the legal, safety, and environmental issues associated with the production and use of fuels as well as reviewing important secondary aspects of the use and production of fuels. This authoritative guide includes contributions from authors who are long-standing contributors to the Ullmann's Encyclopedia, the world's most trusted reference for industrial chemistry. This important guide: Contains an updated edition of the authoritative resource to the production and use of fuels used for transportation Includes information that has been selected to reflect only commercially relevant products and processes Presents contributions from a team of noted experts in the field Offers the most recent developments in fuels and additives from renewable sources Written for professionals in the fields of fossil and renewable fuels, engine design, and transportation, Handbook of Fuels is the comprehensive resource that has been revised to reflect the recent developments in fuels used for transportation.Table of ContentsPreface to the Second Edition xvii Preface to the First Edition xix 1 Introduction 1Klaus Reders and Andrea Schütze 1.1 History of the Spark Ignited “Otto” Engine and of Gasoline 3 1.2 History of the Diesel Engine and of Diesel Fuel 14 1.3 History of Alternative Fuels 19 1.3.1 Ethanol 19 1.3.2 Methanol 24 1.3.3 Vegetable Oils and Hydrotreated Vegetable Oils (HVOs) 24 1.3.4 Biodiesel/FAME 25 1.3.5 Liquefied Petroleum Gas (LPG) 28 1.3.6 Natural Gas 30 1.4 Emission RegulationsWorldwide 33 1.4.1 Europe 35 1.4.2 United States 41 1.4.3 Japan 48 1.4.4 China 51 1.5 Well-to-Wheel Analysis of Alternative Fuels 53 1.5.1 Life-cycle Assessment 54 1.5.2 Well-to-Wheel 55 1.5.3 Boundary Conditions of the JRC Study 56 1.5.4 Summary of Results of the JRC Study 57 1.5.4.1 Alternative Liquid Fuels 60 1.5.4.2 Alternative Gaseous Fuels 61 1.5.4.3 Electricity and Hydrogen 61 1.5.4.4 2020+ Horizon 62 References 64 Part I Automotive Fuels 69 2 Engine Technology 71Werner Dabelstein, Arno Reglitzky, Andrea Schütze, and Klaus Reders 2.1 Otto Engines 71 2.2 Diesel Engines 73 References 75 3 Fuel Composition and Engine Efficiency 77Werner Dabelstein, Arno Reglitzky, Andrea Schütze, Klaus Reders, and Andreas Brunner 3.1 Fuel Composition and Engine Efficiency 77 3.1.1 Quality Aspects of Gasoline 77 3.1.1.1 Octane Quality 77 3.1.1.2 Volatility 79 3.1.1.3 Fuel Composition to Reduce Toxicity and Exhaust Emissions 80 3.1.1.4 Stability, Cleanliness, etc. 83 3.1.1.5 Performance Additives 84 3.1.2 Quality Aspects of Diesel Fuels 84 3.1.2.1 Ignition Quality 84 3.1.2.2 Density 85 3.1.2.3 Sulfur Content 85 3.1.2.4 Cold Flow Properties 85 3.1.2.5 Lubricity 85 3.1.2.6 Viscosity 86 3.1.2.7 Volatility 86 3.1.2.8 Diesel Fuel Stability, Cleanliness, and Safety 86 3.1.2.9 Diesel Fuel Effects on Exhaust Emissions 86 3.1.2.10 Performance Additives 88 References 88 4 Fuel Components: Petroleum-derived Fuels 91Werner Dabelstein, Arno Reglitzky, Andrea Schütze, and Klaus Reders 4.1 Petroleum-derived Fuels 91 4.1.1 Gasoline Components 91 4.1.1.1 Straight-run Gasoline 91 4.1.1.2 Thermally Cracked Gasoline 93 4.1.1.3 Catalytically Cracked Gasoline 93 4.1.1.4 Catalytic Reformate (Platformate) 94 4.1.1.5 Isomerate 94 4.1.1.6 Alkylate 94 4.1.1.7 Polymer Gasoline 94 4.1.1.8 Oxygenates 95 4.1.2 Diesel Fuel Components 95 4.1.2.1 Straight-run Middle Distillate 95 4.1.2.2 Thermally Cracked Gas Oil 96 4.1.2.3 Catalytically Cracked Gas Oil 96 4.1.2.4 Hydrocracked Gas Oil 97 4.1.2.5 Kerosene 97 4.1.2.6 Biofuel Components 97 4.1.2.7 Synthetic Diesel Fuel 98 4.1.3 Storage and Transportation 98 References 99 5 Liquefied Petroleum Gas 101Stephen M. Thompson, Gary Robertson, RobertMyers, and Andrea Schütze 5.1 Introduction 101 5.2 Properties 102 5.3 Production and Processing 103 5.3.1 Recovery from Natural Gas 103 5.3.1.1 Recovery and Manufacture in the Refinery 103 5.4 Purification 108 5.4.1 Adsorptive Purification 109 5.4.2 Absorptive Purification 109 5.5 Storage and Transportation 110 5.5.1 Aboveground Storage 110 5.5.2 Underground Storage 110 5.5.3 Transportation 111 5.6 Uses 111 5.6.1 LPG Standards and Regulations 112 5.6.1.1 Refueling Infrastructure 112 5.6.1.2 Vehicle Conversions to LPG 113 5.6.2 Environmental Benefits 113 5.6.2.1 Outlook 115 5.7 Safety Aspects 115 5.7.1 Occupational Health 116 References 116 6 Natural Gas 119Klaus Reders, Margret Schmidt, and Andrea Schütze 6.1 Occurrence 119 6.2 Composition 121 6.3 Processing 123 6.3.1 Oil and Condensate Removal 124 6.3.2 Water Removal 124 6.3.3 Separation of Natural Gas Liquids 125 6.3.3.1 Cryogenic Expansion Process 126 6.3.4 Sulfur and Carbon Dioxide Removal 126 6.4 Transport/Distribution/Local Blending 126 6.5 Properties and Specifications 127 6.6 Natural Gas as Automotive Fuel 129 6.6.1 Vehicle Refueling Systems 133 6.6.1.1 Slow-Fill Refueling 133 6.6.1.2 Fast-Fill Refueling 134 6.6.2 Vehicle and Engine Concepts 134 6.6.2.1 Vehicle Technology 135 6.6.3 CNG Vehicles in the Market 137 6.6.4 Vehicle Fuel Supply System 137 6.6.5 Combustion and Emissions 139 6.7 Safety Aspects 141 6.8 Biomethane 141 6.8.1 Production 142 6.8.1.1 Anaerobic Fermentation 145 6.8.1.2 Biogas from Solids 146 6.8.2 Upgrading of Biogas to Natural Gas Quality 147 6.8.2.1 Water Scrubbing and Physical Scrubbing 147 6.8.2.2 Chemical Absorption 148 6.8.2.3 Membrane Separation 148 6.8.2.4 Pressure Swing Adsorption (PSA) 149 6.8.2.5 Cryogenic Separation 149 6.8.3 Storage and Transportation 149 6.8.3.1 Storage 149 6.8.3.2 Distribution 150 6.8.4 Biomethane Regulations 150 6.8.4.1 Regulations and Standards 151 6.8.5 Well-to-wheel Analysis for LPG, CNG, and Biomethane 152 6.8.5.1 Well-to-Tank Analysis 152 6.8.5.2 Compressed Biomethane (CBM) 155 6.8.5.3 Well-to-Wheels Analysis 156 References 158 7 Synthetic Diesel Fuels 161H.P. Calis, Wolfgang Lüke, Ingo Drescher, and Andrea Schütze 7.1 XTL Fuels 162 7.1.1 History 162 7.1.2 XTL Production Process 162 7.1.2.1 Fischer–Tropsch Process 162 7.1.2.2 IH2 Technology 166 7.1.2.3 BTL Fuels 168 7.1.3 GTL and BTL Fuel Characteristics 170 7.1.3.1 Cold Flow Performance 171 7.1.3.2 Lubricity Performance 174 7.1.3.3 Impact on Injector Cleanliness and Spray Characteristics 174 7.1.3.4 Advantages of Synthetic Fuels for Emission Control 175 7.1.4 Outlook 178 7.2 DME (Dimethyl Ether) and OME Fuels 180 7.2.1 Introduction 180 7.2.2 Fuel Standards 181 7.2.3 Fuel Properties 183 7.2.4 Infrastructure and Safety 186 7.2.4.1 Use as Fuel 187 7.3 Well-to-Wheel (WTW) Analysis for XTL and DME Fuels 190 7.3.1 Well-to-Wheels Analysis for XTL 190 7.3.2 Well-to-Tank Analysis for DME 193 7.4 Well-to-Wheel Analysis for XTL and DME 195 References 196 8 Synthetic Gasoline Fuels 201Andrea Schütze 8.1 GTL Naphtha 201 8.2 Methanol to Gasoline Process (MTG) 202 8.3 Production Process 202 8.4 Fuel Properties 203 References 204 9 Ethanol 207Andrea Schütze 9.1 Production 210 9.1.1 Milling 211 9.1.2 Processing of Starch/Maize Mash 212 9.1.3 Fermentation of Glucose 213 9.1.4 Distillation and Increase of Ethanol Concentration 213 9.2 Feedstock 214 9.3 Land Use 215 9.3.1 Direct Land Use Change Emissions (DLUC) 217 9.3.2 Indirect Land Use Change (ILUC) 217 9.4 Nitrogen Oxide Emissions 217 9.5 Water Foot Print and Impact onWater Table 219 9.6 Other Environmental Effects 219 9.6.1 Soil Quality/Erosion 219 9.6.2 Eutrophication and Acidification 219 9.6.3 Biodiversity 219 9.7 Bioethanol Made from Lignocellulose 220 9.8 Fuel Standards 221 9.9 Fuel Properties 224 9.9.1 Octane Number 224 9.9.1.1 Volatility and Distillation 226 9.9.1.2 Heat of Vaporization 228 9.9.1.3 Energy Content 228 9.9.1.4 Water Content 228 9.9.1.5 Corrosion Protection 228 9.9.1.6 Denaturant and Denaturant Content 229 9.9.1.7 Material Compatibility 229 9.9.1.8 Lubricity 229 9.9.1.9 Emissions 229 9.10 Well-to-Wheels Analysis for Fuel Ethanol and Ethanol Gasoline Blends 230 9.10.1 Pathways 230 9.10.1.1 Sugar Beet to Ethanol 230 9.10.1.2 Wheat to Ethanol 231 9.10.1.3 Straw to Ethanol 231 9.11 WTT Analysis for Bioethanol 236 9.12 WTWAnalysis 237 References 240 10 Methanol 245Martin Bertau,Michael Kraft, Ludolf Plass, and Hans-JürgenWernicke 10.1 Introduction 248 10.2 Physical and Chemical Properties 249 10.3 Production of Methanol 249 10.3.1 Methanol Production Capacities and Markets 250 10.3.2 ConventionalMethanol Production Processes 252 10.3.2.1 Synthesis Gas Generation 252 10.3.2.2 Methanol Synthesis 255 10.3.2.3 Liquid Phase Methanol Synthesis (LPMEOH®) 258 10.3.2.4 Methanol Distillation 258 10.3.3 Renewable Methanol Production Processes 259 10.3.3.1 CO2 – Hydrogenation 260 10.4 Methanol as Fuel 261 10.4.1 History 263 10.4.2 Uses 264 10.4.2.1 Methanol as a Fuel for Otto Engines 264 10.4.2.2 Vehicle Developments 265 10.4.2.3 Conclusions 268 10.4.2.4 Methanol as Marine Fuel 269 10.4.3 Safety Aspects 270 10.4.3.1 Explosion and Fire Control 270 10.4.3.2 Fire Prevention 271 10.4.3.3 Fire Fighting 271 10.4.3.4 Small-scale Storage 271 10.4.3.5 Large-scale Storage 271 10.4.3.6 Large-scale Transportation 272 10.4.3.7 Safety Regulations Governing Transportation 272 10.4.3.8 Methanol as a Hazard 272 10.5 Methanol-based Derivatives as Fuels and Fuel Additives 273 10.5.1 Methanol-to-Gasoline (MTG) 274 10.5.2 Methyl tert-Butyl Ether (MTBE) 276 10.5.3 tert-Amyl Methyl Ether (TAME) 278 10.5.4 Dimethyl Ether (DME) 279 10.5.5 Oxymethylene Ether (OME) 281 10.5.6 Dimethyl Carbonate (DMC) and Methyl Formate (MF) 285 10.6 Economic Aspects 289 10.6.1 Gas-based Methanol 289 10.6.2 Coal-based Methanol 289 10.6.3 Biomass-based Methanol 291 10.6.4 Renewable Methanol Based on the Recycle of Carbon Dioxide 292 10.7 Outlook 297 References 297 11 2,5-Dimethylfuran (DMF) and 2-Methylfuran (MF) 307Andrea Schütze 11.1 Synthesis of Dimethylfuran 307 11.2 Properties of 2,5-Dimethylfuran and Methylfuran 309 11.3 Combustion and Emissions 311 References 312 12 Alternative Biofuel Options – Diesel 315Andrea Schütze 12.1 Biomass-to-Liquids (BTL) 315 12.2 Biodiesel (FAME) 316 12.2.1 Production 318 12.2.1.1 Introduction 318 12.2.1.2 Industrial Process 321 12.2.1.3 Feedstock 322 12.2.1.4 Microalgae 324 12.2.2 AnalyticalMethods 326 12.2.2.1 Ester Content and Fatty Acid Composition 326 12.2.2.2 Polyunsaturated Methyl Esters Content 327 12.2.2.3 Glycerol and Glyceride Content 328 12.2.3 Fuel Standards 332 12.2.3.1 United States 332 12.2.3.2 Europe 336 12.2.4 Fuel Properties 337 12.2.4.1 Cetane Number 338 12.2.4.2 Density and Energy Content 339 12.2.4.3 Kinematic Viscosity 339 12.2.4.4 Cold Temperature Properties 339 12.2.4.5 Filterability 341 12.2.4.6 Distillation 341 12.2.4.7 Fuel Stability 341 12.2.4.8 Water Content and Sediment 343 12.2.4.9 Lubricity 343 12.2.4.10 Material Compatibility 343 12.2.4.11 Engine Deposits 344 12.2.4.12 Emissions 345 12.3 Vegetable Oils (VO) 345 12.3.1 Production 346 12.3.2 Fuel Properties 346 12.3.2.1 Kinematic Viscosity 347 12.3.2.2 Cetane Number 348 12.3.2.3 Flash Point 348 12.3.2.4 Carbon Residue 348 12.3.2.5 Heating Value 348 12.3.2.6 Density 348 12.3.2.7 Iodine Number 349 12.3.2.8 Fuel Stability 349 12.3.2.9 Calcium, Magnesium, and Phosphorus 350 12.3.2.10 Total Contamination andWater Content 350 12.3.2.11 Acid Value 350 12.3.3 Fuel Standards 350 12.4 Hydrotreated Vegetable Oils 351 12.4.1 Production 352 12.4.1.1 Process 352 12.4.1.2 Production Plants 354 12.4.2 Fuel Standard and Properties 354 12.4.2.1 Density and Energy Content 355 12.4.2.2 Distillation Characteristics 355 12.4.2.3 Cold Temperature Properties 356 12.4.2.4 Cetane Number 356 12.4.2.5 Fuel Stability 356 12.4.2.6 Lubricity 357 12.4.2.7 Material Compatibility 357 12.4.2.8 Emissions and Combustion 357 12.5 Well-to-Wheel Analysis of FAME and HVO Fuels 357 12.5.1 FAME Fuels 359 12.5.1.1 WTT Analysis 359 12.5.1.2 WTWAnalysis 361 12.5.2 HVO Fuels 363 12.5.2.1 WTT Analysis 363 12.5.2.2 WTWAnalysis 364 References 366 13 Hydrogen 373Lalit M. Das 13.1 Introduction 373 13.2 Life Cycle Analysis 373 13.3 Hydrogen Production 374 13.4 Historical Overview of Hydrogen Engine: Research and Development 375 13.5 Properties of Hydrogen which Influence Engine Combustion 377 13.6 Undesirable Combustion Phenomena 381 13.7 Design Criteria for Hydrogen Engines 382 13.8 Hydrogen-fueledWankel Engine 384 13.9 Performance Characteristic of a Hydrogen-fueled SI Engine 385 13.10 Exhaust Emissions 386 13.11 Combustion Characteristics 387 13.12 Hydrogen Use in CI Engines 389 13.13 Hydrogen-CNG Blend 391 13.14 Safety Criteria for Hydrogen Engines 392 13.15 Hydrogen Detection 393 13.16 Storage of Hydrogen 393 13.17 Hydrogen Transportation and Distribution 394 13.18 Hydrogen Vehicles based on Internal Combustion Engine 395 13.19 Conclusion 398 References 398 14 Octane Enhancers 403Marco Di Girolamo, Maura Brianti, and MarioMarchionna 14.1 Introduction 403 14.2 Technical Information 405 14.2.1 Combustion in Otto Engines 405 14.2.2 Knock Phenomena 406 14.2.3 Octane Number 406 14.3 Types of Octane Enhancers 409 14.4 Metal-containing Additives 409 14.4.1 Alkyl Lead Compounds 412 14.4.2 Methylcyclopentadienyl Manganese Tricarbonyl 414 14.5 Ashless Octane Enhancers 415 14.5.1 Heteroatom-based Components 415 14.5.1.1 History of Fuel Oxygenates 417 14.5.1.2 Properties of Oxygenates 420 14.5.1.3 Production 424 14.5.1.4 Toxicology 426 14.5.2 Pure Hydrocarbon Components 427 References 428 Further Reading 430 15 Hybrid and Electrified Powertrains 431Jakob Andert, MaximilianWick, Rene Savelsberg, andMichael Stapelbroek 15.1 Introduction 431 15.2 Classification 432 15.2.1 Topologies 432 15.2.1.1 Serial Hybrids 433 15.2.1.2 Parallel Hybrids 434 15.2.1.3 Power-split Hybrids 435 15.2.2 Degree of Hybridization 436 15.3 Functionalities 437 15.3.1 Regenerative Braking 437 15.3.2 Load Point Shift/Boosting 438 15.3.3 E-drive and Sailing 439 15.4 Battery 440 15.4.1 NiMH Batteries 441 15.4.2 Li-ion Batteries 442 15.5 Energy Management 443 15.6 Market Situation and Outlook 444 References 444 16 Fuel Cells 447Sören Tinz, Steffen Dirkes,MariusWalters, and Jakob Andert 16.1 Transportation Applications 447 16.2 Fundamentals 449 16.2.1 Auxiliaries 452 16.2.1.1 Air Supply System 452 16.2.1.2 Hydrogen Supply System 454 16.2.1.3 Cooling Circuit 454 16.2.1.4 HV Architecture 455 16.2.1.5 Controls 455 16.2.1.6 Integrated System Design 455 16.2.2 Onboard Hydrogen Storage 456 16.3 Costs, Durability, and Reliability 457 16.4 Cold and Freeze Start 459 16.5 Efficiency 459 16.6 Summary 460 References 460 Part II Automobile Exhaust Control 465 17 Introduction 467Martin Votsmeier, Thomas Kreuzer, Jürgen Gieshoff, Gerhard Lepperhoff, and Barbara Elvers Reference 469 18 Pollutant Formation and Limitation 471Martin Votsmeier, Thomas Kreuzer, Jürgen Gieshoff, Gerhard Lepperhoff, and Barbara Elvers 18.1 Carbon Monoxide 471 18.2 Hydrocarbons 471 18.3 Oxides of Nitrogen (NOx) 472 18.4 Particulate Emissions 472 18.5 Carbon Dioxide (CO2) 473 18.6 Sulfur Compounds 473 Reference 474 19 Catalytic Exhaust Aftertreatment, General Concepts 475Martin Votsmeier, Thomas Kreuzer, Jürgen Gieshoff, Gerhard Lepperhoff, and Barbara Elvers 19.1 The Physical Design of the Catalytic Converter 475 19.1.1 Ceramic Monoliths 477 19.1.2 MetallicMonoliths 477 19.1.3 Particulate Filters 478 19.1.4 Extruded Catalysts 478 19.2 TheWashcoat 478 19.3 The Catalytic Material 480 19.4 Production of Catalysts 480 References 481 20 Catalytic Aftertreatment of Stoichiometric Exhaust Gas 483Martin Votsmeier, Thomas Kreuzer, Jürgen Gieshoff, Gerhard Lepperhoff, and Barbara Elvers 20.1 Three-way Catalysts 484 20.2 Oxygen Storage in Three-way Catalysts 485 20.3 Precious Metals inThree-way Catalysis 487 References 487 21 Exhaust Aftertreatment for Diesel Vehicles 489Martin Votsmeier, Thomas Kreuzer, Jürgen Gieshoff, Gerhard Lepperhoff, and Barbara Elvers 21.1 The Diesel Oxidation Catalyst 489 21.1.1 Oxidation of Particulate Emissions 490 21.1.2 Oxidation of SO2 490 21.1.3 Oxidation of NO 490 21.1.4 Particulate Filter Regeneration 490 21.1.5 Pt/Pd Dispersion 491 21.2 The Particulate Filter 491 21.2.1 Soot Oxidation by Oxygen 492 21.2.2 Soot Oxidation by NO2 492 21.2.3 Ash Load 493 21.2.4 Open Filter Systems 493 21.3 NOx Treatment of Oxygen-rich Exhaust 494 21.3.1 HC–DeNOx 494 21.3.2 The NOx Adsorber Catalyst 495 21.3.3 Selective Catalytic Reduction (SCR) with Ammonia 496 21.3.4 NH3 Generation Onboard 496 21.3.5 Vanadium SCR Catalysts 497 21.3.6 Zeolite-based SCR Catalysts 498 21.3.7 Oxidation Catalyst Upstream of the SCR Catalyst 498 22 Exhaust Aftertreatment for Lean-burn Gasoline Engines 499Martin Votsmeier, Thomas Kreuzer, Jürgen Gieshoff, Gerhard Lepperhoff, and Barbara Elvers 23 Conclusion and Outlook 501Martin Votsmeier, Thomas Kreuzer, Jürgen Gieshoff, Gerhard Lepperhoff, and Barbara Elvers Part III Aviation Fuels 503 24 Aviation Turbine Fuels 505Geoff J. Bishop and Barbara Elvers 24.1 History 505 24.1.1 Fuel Types and Specifications 505 24.1.1.1 Specification Requirements 507 24.1.1.2 Fuel Properties 507 24.1.1.3 Nonspecification Properties 516 24.1.2 Production 518 24.1.2.1 Fuel 518 24.1.2.2 Additives 520 24.1.3 Handling, Storage, and Transportation 522 24.1.3.1 System Descriptions 522 24.1.3.2 Contamination-removal Equipment 522 24.1.4 Legal Aspects 523 24.1.5 Environmental Aspects 523 24.1.6 Economic Aspects 523 24.1.7 Future Trends 524 24.1.7.1 Petroleum-Derived Fuels 524 24.1.7.2 Alternative Fuels 524 References 525 Further Reading 527 25 Aviation Gasoline (Avgas) 529Geoff J. Bishop and Barbara Elvers 25.1 History 530 25.2 Avgas Grades 530 25.2.1 Avgas 100 530 25.2.2 Avgas 100LL 530 25.2.3 Avgas 100VLL 531 25.2.4 Avgas UL82 531 25.2.5 Avgas UL87 531 25.2.6 Avgas UL91 531 Reference 531 Further Reading 531 Part IV Marine Fuels 533 26 Marine Fuels 535Christopher FriedrichWirz, Torsten Mundt, and Klaus Reders 26.1 History 535 26.2 Specifications 536 26.3 Composition 536 26.4 Properties 537 26.4.1 Distillate Fuels 537 26.4.2 Residual Fuels 537 Reference 540 Index 541

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Book SynopsisEngineering with polymers is a growing technical field which requires special knowledge. Filling a need, this ready reference brings together the hard-to-get and recently acquired knowledge usually only found scattered in the original literature. At the beginning, the reference introduces plastics as a class of technical materials, gives an overview of their properties, presents plastics processing and its possible influence on the achievable quality of plastic parts. Afterwards, plastics testing is presented as a separate, practical-scientific field of work. The possibilities and fields of application of plastics testing will be discussed. This is followed by a comprehensive treatment of the individual, relevant test areas for the characterization and qualification of plastics and plastic molded parts made from them, with descriptions of the corresponding, practical test methods. A comprehensive index provides easy access to relevant information for successful engineering with plastics and suitable methods for material characterization and for quality assurance and damage analysis of parts. Written by experienced academics and industrial researchers and developers who know the problems of plastics engineers in their daily work - and the solutions - inside out, this book offers first-hand practical knowledge and intensive discussion. The book is aimed at industry, scientists and students involved in plastics and plastic engineering and aims to help them gain the necessary understanding of polymer materials and knowledge of practical testing and evaluation of plastics.Table of Contents1 Introduction to Plastics 1 1.1 Plastics 1 1.2 Structure and Behaviour of Plastics 5 1.3 Melting Polymers 12 1.4 Mechanical Behaviour of Polymers 15 1.5 Uniaxial Stress-Strain Behaviour 28 1.6 Resins 37 1.7 Material Selection 39 1.8 Processing of Polymers 40 2 Polymer Testing 45 2.1 Introduction 45 2.2 Objective of Polymer Testing 45 2.3 Sample Preparation and Test Procedure 48 2.4 Sample Extraction/Sampling 49 2.5 Types of Samples 50 2.6 Test Implementation/Operation/Accomplishment 51 2.7 Description of Test Results/Test Report 51 3 Identifcation of Polymers 53 3.1 Introduction 53 3.2 Density Measurement 53 3.3 Infrared Spectroscopy 58 4 Rheological Testing 65 4.1 Introduction 65 4.2 Rheometry 70 4.3 Viscometry 77 5 Mechanical Testing 87 5.1 Introduction 87 5.2 Quasi-Static Loading 88 5.3 Impact Loading 113 5.4 Long-Term Static Loading 120 5.5 Long-Term Dynamic Loading - Fatigue 126 6 Tribological Testing 133 6.1 Introduction 133 6.2 Sliding Behaviour 134 6.3 Friction Coefficient 135 6.4 Wear 136 7 Thermal Testing 139 7.1 Introduction 139 7.2 Tests Under Thermal Loading 141 7.3 Thermal Ageing Behaviour 144 7.4 Di¿erential Scanning Calorimetry (DSC) 144 7.5 Dynamic Mechanical Analysis (DMA) 152 7.6 Thermogravimetric Analysis (TGA) 158 7.7 Thermomechanical Analysis (TMA) - Dilatometry 161 7.8 Calcination Test 164 7.9 Thermal Dimensional Stability 166 7.10 Heat Detection Temperature 169 8 Chemical Testing 173 8.1 Introduction 173 8.2 Chemical Resistance Investigation 173 8.3 Environmental Stress Cracking Resistance (ESCR) Investigation 174 9 Physical Testing 181 9.1 Introduction 181 9.2 Determination of Mass 181 9.3 Determination of Water Absorption 182 10 Geometrical Inspection 187 10.1 Introduction 187 10.2 Sizes and Tolerances 187 10.3 Processing and Post-processing Shrinkage 195 10.4 Warpage 197 11 Optical Testing Methods 199 11.1 Introduction 199 11.2 Visual Inspection 199 11.3 Light Microscope (LM) 201 11.4 Digital Microscope (DM) 207 11.5 Scanning Electron Beam Microscope (SEM) 208 11.6 Polarized Light Inspection 212

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Book SynopsisWith its focus on emerging concerns of kinase and GPCR-mediated antitarget effects, this vital reference for drug developers addresses one of the hot topics in drug safety now and in future. Divided into three major parts, the first section deals with novel technologies and includes the utility of adverse event reports to drug discovery, the translational aspects of preclinical safety findings, broader computational prediction of drug side-effects, and a description of the serotonergic system. The main part of the book looks at some of the most common antitarget-mediated side effects, focusing on hepatotoxicity in drug safety, cardiovascular toxicity and signaling effects via kinase and GPCR anti-targets. In the final section, several case studies of recently developed drugs illustrate how to prevent anti-target effects and how big pharma deals with them if they occur. The more recent field of systems pharmacology has gained prominence and this is reflected in chapters dedicated to the utility in deciphering and modeling anti-targets. The final chapter is concerned with those compounds that inadvertently elicit CNS mediated adverse events, including a pragmatic description of ways to mitigate these types of safety risks. Written as a companion to the successful book on antitargets by Vaz and Klabunde, this new volume focuses on recent progress and new classes, methods and case studies that were not previously covered.Trade Review“Overall, there is plenty of information in this book making it a valuable indepth reading matter for experts working in the complex and quickly evolving scientific field of translational safety. Academic students and new industrial recruits will also profit from selected chapters of this reference book.” (ChemMedChem, 1 October 2015) Table of ContentsList of Contributors XV Preface XXI A Personal Foreword XXIII Section 1 General Concept for Target-based Safety Assessment 1 1 Side Effects of Marketed Drugs: The Utility and Pitfalls of Pharmacovigilance 3Steven Whitebread, Mateusz Maciejewski, Alexander Fekete, Eugen Lounkine, and László Urbán 1.1 Introduction 3 1.2 Postmarketing Pharmacovigilance 6 1.3 Polypharmacy and Pharmacological Promiscuity of Marketed Drugs 9 References 15 2 In Silico Prediction of Drug Side Effects 19Michael J. Keiser 2.1 Large-Scale Prediction of Drug Activity 20 2.1.1 Networks of Known and New Target Activity 21 2.1.2 Resources for Multiscale Inquiry 25 2.2 Multiscale Models of Adverse Drug Reactions 30 2.2.1 Inferring Adverse Reactions 31 2.2.2 Forward Perturbation and Prediction of Mechanisms 33 References 36 3 Translational Value of Preclinical Safety Assessment: System Organ Class (SOC) Representation of Off-Targets 45Mateusz Maciejewski, Eugen Lounkine, Andreas Hartmann, Steven Whitebread, and László Urbán 3.1 Introduction 45 3.2 Terminology: Medicinal Dictionary for Regulatory Activities (MedDRA) 46 3.2.1 Correct Use of MedDRA Terminology at Different Phases of Drug Discovery 48 3.2.2 Determination of Symptoms Associated with a Target 50 3.3 Data Interpretation: Modifying Factors 52 3.3.1 Access to Organs 52 3.3.2 Off-Target Promiscuity: Target Interactions (Synergies and Antagonism) 53 3.4 Conclusions 53 References 54 4 Pathological Conditions Associated with the Disturbance of the 5-HT System 57Daniel Hoyer 4.1 Introduction 57 4.2 From “St. Anthony’s Fire” to Ergot Alkaloids, the Serotonin Syndrome, and Modern 5-HT Pharmacology 59 4.3 Appetite-Reducing Agents, Fenfluramine, and Other 5-HT Releasers 61 4.4 Gastrointestinal and Antiemetic Indications, the 5-HT3/5-HT4 Receptor Links 63 4.5 Antipsychotics and the 5-HT2/Dopamine D2 Link (and Many Other 5-HT Receptors) 65 4.6 Antimigraine Medications of Old and New and the 5-HT1B/1D Receptors 67 4.7 Antidepressants/Anxiolytics Acting at 5-HT and Other Transporters 69 4.8 Conclusions 71 References 72 Section 2 Hepatic Side Effects 81 5 Drug-Induced Liver Injury: Clinical and Diagnostic Aspects 83John R. Senior 5.1 Introduction 83 5.1.1 Postmarketing Hepatotoxicity versus Hepatotoxicity in Development 84 5.1.2 Isoniazid – If It Were Newly Discovered, Would It Be Approved Today? 85 5.2 Special Problems of Postmarketing Hepatotoxicity 89 5.2.1 Voluntary Monitoring after Approval for Marketing 90 5.2.2 Prediction of Serious, Dysfunctional Liver Injury 90 5.2.3 Severity of Liver Injury Is Not Measured by Aminotransferase Elevations 91 5.2.4 Attempts to Standardize Terminology 91 5.2.5 What Is the “Normal” Range, or the “Upper Limit of Normal”? 92 5.2.6 Diagnostic Test Evaluation 93 5.2.7 Determination of the Likely Cause of Liver Abnormalities 94 5.2.8 Treatment and Management of DILI in Practice 95 5.3 Special Problems for New Drug Development 95 5.3.1 How Many? 95 5.3.2 How Much? 96 5.3.3 How Soon? 97 5.3.4 How Likely? 97 5.3.5 Compared with What? 97 5.3.6 ROC Curves 98 5.3.7 eDISH: Especially for Controlled Trials 99 5.3.8 Test Validation and Qualification 100 5.4 Closing Considerations 101 5.4.1 A Handful of “Do Nots” 101 5.4.2 Need to Standardize ALT Measurement and Interpretation of Normal Ranges 102 5.4.3 Research Opportunities 102 References 103 6 Mechanistic Safety Biomarkers for Drug-Induced Liver Injury 107Daniel J. Antoine 6.1 Introduction 107 6.2 Drug-Induced Toxicity and the Liver 110 6.3 Current Status of Biomarkers for the Assessment of DILI 111 6.4 Novel Investigational Biomarkers for DILI 113 6.4.1 Glutamate Dehydrogenase (GLDH) 114 6.4.2 Acylcarnitines 115 6.4.3 High-Mobility Group Box-1 (HMGB1) 116 6.4.4 Keratin 18 (K18) 116 6.4.5 MicroRNA-122 (miR-122) 117 6.5 Conclusions and Future Perspectives 118 References 120 7 In Vitro Models for the Prediction of Drug-Induced Liver Injury in Lead Discovery 125Frederic Moulin and Oliver Flint 7.1 Introduction 125 7.2 Simple Systems for the Detection and Investigation of Hepatic Toxicants 130 7.2.1 Primary Hepatocytes 130 7.2.2 Liver-Derived Cell Lines 135 7.2.3 Differentiated Pluripotent Stem Cells 137 7.3 Models to Mitigate Hepatocyte Dedifferentiation 140 7.3.1 Liver Slices 140 7.3.2 Selective Engineering of Metabolism 141 7.4 Understanding Immune-Mediated Hepatotoxicity 144 7.4.1 Use of Inflammatory Cofactors 145 7.4.2 Innate Immune System and Inflammasome 147 7.5 Conclusions 148 References 149 8 Transporters in the Liver 159Bruno Stieger and Gerd A. Kullak-Ublick 8.1 Introduction 159 8.2 Role of Organic Anion Transporters for Drug Uptake 159 8.3 Drug Interaction with the Bile Salt Export Pump 160 8.4 Susceptibility Factors for Drug–BSEP Interactions 161 8.5 Role of BSEP in Drug Development 162 References 163 9 Mechanistic Modeling of Drug-Induced Liver Injury (DILI) 173Kyunghee Yang, Jeffrey L. Woodhead, Lisl K. Shoda, Yuching Yang, Paul B. Watkins, Kim L.R. Brouwer, Brett A. Howell, and Scott Q. Siler 9.1 Introduction 173 9.2 Mechanistic Modules in DILIsymðD version 3A 175 9.2.1 Oxidative Stress-Mediated Toxicity 175 9.2.2 Innate Immune Responses 178 9.2.3 Mitochondrial Toxicity 179 9.2.4 Bile Acid-Mediated Toxicity 181 9.3 Examples of Bile Acid-Mediated Toxicity Module 184 9.3.1 Troglitazone and Pioglitazone 184 9.3.2 Bosentan and Telmisartan 187 9.4 Conclusions and Future Directions 190 References 191 Section 3 Cardiovascular Side Effects 199 10 Functional Cardiac Safety Evaluation of Novel Therapeutics 201Jean-Pierre Valentin, Brian Guth, Robert L. Hamlin, Pierre Lainée, Dusty Sarazan, and Matt Skinner 10.1 Introduction: What Is the Issue? 201 10.2 Cardiac Function: Definitions and General Principles 203 10.2.1 Definition and Importance of Inotropy and Difference from Ventricular Function 203 10.2.2 Definition and Importance of Lusitropy 207 10.2.3 Components and Importance of the Systemic Arterial Pressure 211 10.3 Methods Available to Assess Cardiac Function 213 10.4 What Do We Know About the Translation of the Nonclinical Findings to Humans? 217 10.5 Risk Assessment 219 10.5.1 Hazard Identification 219 10.5.2 Risk Assessment 221 10.5.3 Risk Management 224 10.5.4 Risk Mitigation 225 10.6 Summary, Recommendations, and Conclusions 227 References 228 11 Safety Aspects of the Cav1.2 Channel 235Berengere Dumotier and Martin Traebert 11.1 Introduction 235 11.2 Structure of Cav1.2 Channels 235 11.2.1 α-Subunit of Cav1.2 Channel 236 11.2.2 β-Subunit of Cav1.2 Channel 236 11.3 Function of Cav1.2 Channels in Cardiac Tissue 237 11.3.1 Role in Conduction and Contractility 239 11.3.2 Modulation of Cav1.2 Channels 240 11.3.3 Cav1.2 and Cardiac Diseases 244 11.4 Pharmacology of Cav1.2 Channels: Translation to the Clinic 245 11.4.1 Cav1.2 Antagonists: Impact on Electromechanical Functions 245 11.5 Prediction of Cav1.2 Off-Target Liability 246 11.5.1 Cav1.2 in Cardiomyocytes Derived from iPS Cells 246 References 247 12 Cardiac Sodium Current (Nav1.5) 253Gary Gintant 12.1 Background and Scope 253 12.2 Structure and Function 255 12.2.1 Molecular Biology 255 12.2.2 SCN5A Mutations Related to Congenital Long QT Syndromes 256 12.2.3 Evidence for Multiple Functional Types of Cardiac Sodium Channels and Heterogeneous Distribution 257 12.3 Physiological Role and Drug Actions 258 12.3.1 Fast Sodium Current (INaF): Conduction and Refractoriness 258 12.3.2 Late (or Residual or Slow) Sodium Current (INaL) 259 12.3.3 Drug Effects on INaF 261 12.3.4 Indirect Modulation of INaF 264 12.4 Methodology 265 12.4.1 Use of Human Stem Cell-Derived Cardiomyocytes 266 12.5 Translation of Effects on INaF: Relation to Conduction Velocity and Proarrhythmia 268 12.6 Conclusions 269 References 270 13 Circulating Biomarkers for Drug-Induced Cardiotoxicity: Reverse Translation from Patients to Nonclinical Species 279Gül Erdemli, Haisong Ju, and Sarita Pereira 13.1 Introduction 279 13.2 Cardiac Troponins 280 13.3 Natriuretic Peptides 282 13.4 Novel/Exploratory Biomarkers: H-FABP, miRNA, and Genomic Biomarkers 285 13.5 Regulatory Perspective 286 13.6 Conclusions and Future Perspectives 288 References 289 14 The Mechanistic Basis of hERG Blockade and the Proarrhythmic Effects Thereof 295Robert A. Pearlstein, K. Andrew MacCannell, Qi-Ying Hu, Ramy Farid, and José S. Duca 14.1 Introduction 295 14.1.1 The Role of hERG Dysfunction/Blockade in Promoting Early After Depolarizations 296 14.1.2 The Dynamics of hERG Blockade 301 14.1.3 Simulations of the Human Cardiac AP in the Presence of hERG Blockade 303 14.1.4 Estimation of Proarrhythmic hERG Occupancy Levels Based on AP Simulations 304 14.1.5 Novel Insights about the Causes of Inadvertent hERG Binding Function 305 14.1.6 Implications of Our Findings for hERG Safety Assessment 313 14.1.7 Conclusion and Future Directions 324 References 324 Section 4 Kinase Antitargets 329 15 Introduction to Kinase Antitargets 331Mark C. Munson References 360 16 Clinical and Nonclinical Adverse Effects of Kinase Inhibitors 365Douglas A. Keller, Richard J. Brennan, and Karen L. Leach 16.1 Introduction 365 16.2 Perspectives on the Clinical Safety of Kinase Inhibitor Therapy 371 16.3 Adverse Effects of Kinase Inhibitor Drugs 372 16.3.1 Hepatic Toxicity 372 16.3.2 Thyroid Toxicity 377 16.3.3 Bone and Tooth Toxicity 379 16.3.4 Cardiovascular Toxicity 380 16.3.5 Cutaneous Toxicity 380 16.3.6 Developmental and Reproductive Toxicity 383 16.3.7 Gastrointestinal Toxicity 385 16.3.8 Hematopoietic Toxicity 385 16.3.9 Ocular Toxicity 387 16.3.10 Pulmonary Toxicity 388 16.3.11 Renal Toxicity 389 16.4 Derisking Strategies for Kinase Inhibitor Toxicity 389 16.5 Concluding Remarks 391 References 391 17 Cardiac Side Effects Associated with Kinase Proteins and Their Signaling Pathways 401Roy J. Vaz and Vinod F. Patel 17.1 A Case Study 401 17.2 Introduction 402 17.3 Cardiac-Specific Kinase Antitargets 404 17.3.1 Preclinical Findings in Genetically Modified or KI-Treated Mice 404 17.3.2 Clinical Findings of Kinase Inhibitors on the Heart and Their Mechanistic Understandings 404 17.4 Current and Future Directions 409 17.4.1 Preclinical Safety and Clinical Outcome Predictions 409 17.5 Conclusions 410 References 411 18 Case Studies: Selective Inhibitors of Protein Kinases – Exploiting Demure Features 413Ellen R. Laird 18.1 Introduction 413 18.2 Case I: Indane Oximes as Selective B-Raf Inhibitors 414 18.3 Case II: ARRY-380 (ONT-380) – an ErbB2 Agent that Spares EGFR 420 18.4 Case III: Discovery of GDC-0068 (Ipatasertib), a Potent and Selective ATP-Competitive Inhibitor of AKT 424 18.5 Concluding Remarks 428 References 429 Section 5 Examples of Clinical Translation 435 19 Torcetrapib and Dalcetrapib Safety: Relevance of Preclinical In Vitro and In Vivo Models 437Eric J. Niesor, Andrea Greiter-Wilke, and Lutz Müller 19.1 Introduction 437 19.2 Effect of Torcetrapib on Blood Pressure 437 19.3 In Vitro Studies 438 19.3.1 Direct Effect of Torcetrapib on Aldosterone Production In Vitro in Cultured H295R Adrenal Corticocarcinoma Cells 439 19.3.2 Molecular Mechanism of Torcetrapib Induction of Aldosterone Secretion 439 19.3.3 Development of Reproducible In Vitro Screening Models for Increase in Aldosterone and Cyp11B2 mRNA in a Human Adrenal Corticocarcinoma Cell Line 440 19.3.4 Application of In Vitro Models for the Successful Derisking of Dalcetrapib, Anacetrapib, and Evacetrapib 440 19.4 In Vivo Studies 441 19.4.1 Effect of Torcetrapib on Aldosterone and BP 441 19.4.2 Molecular Mechanisms of Torcetrapib-Induced BP Increase 444 19.5 General Safety Risk with Increased Aldosterone and BP 447 19.5.1 Inappropriate Increase in Aldosterone Secretion May Increase CV Risks 447 19.6 Relevance of BP and Aldosterone Preclinical Models to Clinical Observation with Dalcetrapib and Anacetrapib 448 19.7 Similarities between Potent CETPi and Halogenated Hydrocarbons 449 19.7.1 The Macrophage Scavenger Receptor MARCO, a Possible Antitarget for Dalcetrapib, and Its Relevance to Humans 450 19.8 Conclusions 451 References 451 20 Targets Associated with Drug-Related Suicidal Ideation and Behavior 457Andreas Hartmann, Steven Whitebread, Jacques Hamon, Alexander Fekete, Christian Trendelenburg, Patrick Y. Müller, and László Urbán 20.1 Introduction 457 20.2 Targets Associated with Increased Suicidal Intent and Behavior 458 20.2.1 G-Protein-Coupled Receptors 458 20.2.2 Transporters 466 20.2.3 Ion Channels 469 20.3 Conclusions 472 References 473 Index 479

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Book SynopsisExtraction processes are essential steps in numerous industrial applications from perfume over pharmaceutical to fine chemical industry. Nowadays, there are three key aspects in industrial extraction processes: economy and quality, as well as environmental considerations. This book presents a complete picture of current knowledge on green extraction in terms of innovative processes, original methods, alternative solvents and safe products, and provides the necessary theoretical background as well as industrial application examples and environmental impacts. Each chapter is written by experts in the field and the strong focus on green chemistry throughout the book makes this book a unique reference source. This book is intended to be a first step towards a future cooperation in a new extraction of natural products, built to improve both fundamental and green parameters of the techniques and to increase the amount of extracts obtained from renewable resources with a minimum consumption of energy and solvents, and the maximum safety for operators and the environment.Table of ContentsPreface XIII List of Contributors XV 1 Green Extraction: From Concepts to Research, Education, and Economical Opportunities 1Farid Chemat, Natacha Rombaut, Anne-Sylvie Fabiano-Tixier, Jean T. Pierson, and Antoine Bily 1.1 Introduction 1 1.2 Orange Fruit is not Limited to Produce Only Juice? 5 1.3 Chemistry of Natural Products 9 1.3.1 Primary Metabolites 9 1.3.1.1 Glucides 9 1.3.1.2 Lipids 10 1.3.1.3 Amino Acids and Proteins 10 1.3.2 Secondary Metabolites 12 1.3.2.1 Terpenoids 12 1.3.2.2 Alkaloids 14 1.3.2.3 Polyphenols 14 1.4 From Metabolites to Ingredients 17 1.5 Green Extraction from Research to Teaching 22 1.5.1 Principle: Innovation by Selection of Varieties and Use of Renewable Plant Resources 28 1.5.2 Principle: Use of Alternative Solvents and Agro Solvent 28 1.5.3 Principle: Production of Coproducts Instead ofWaste to Include Biorefinery 29 1.5.4 Principle: Prioritizing a Non-denatured and Biodegradable Extract without Contaminant 29 1.6 Conclusions and Perspective 29 References 30 2 Process Engineering and Product Design for Green Extraction 37Simon Both, Reinhard Ditz, Martin Tegtmeier, Urban Jenelten, and Jochen Strube 2.1 Market and Market Development 37 2.2 Regulatory Framework 38 2.3 Systematic Apparatus and Process Design 39 2.3.1 Design of Experiments 40 2.3.2 Graphical Calculation Methods 40 2.3.3 Physicochemical Modeling 41 2.3.4 Approaches for Description of Diffusion 45 2.3.4.1 Maxwell-Stefan Approach 46 2.3.4.2 Calculation of Diffusion Coefficients 48 2.3.4.3 Thermodynamic Factor 49 2.3.4.4 Determination of Activity Coefficients 49 2.3.4.5 Proof of Principle 49 2.4 Model-Based Realization: Apparatus and Process Design 50 2.4.1 Quantification of Determining Factors 52 2.4.2 Proof of Principle – Process Optimization 53 2.4.3 Proof of Principle – Cost-Driven Decision 53 2.5 Extract Purification 54 2.5.1 Modeling Approaches 56 2.5.2 Scale-Up and Mini-plant 56 2.6 Total Process Development and Design 62 2.7 Conclusions and Summary 65 Acknowledgments 66 References 66 3 Tailor-Made Production of Plants for Green Extraction 71Hansjoerg Hagels 3.1 Introduction 71 3.2 Sustainable Processes 72 3.2.1 Social Sustainability 73 3.2.2 Environmental Sustainability 74 3.2.3 Economic Sustainability 75 3.3 Production Technology 75 3.3.1 Choice of Cultivation Location 75 3.3.2 Crop Rotation 78 3.3.3 Fertilization 79 3.3.4 Organic Farming 82 3.4 Seed and Seed Stock 84 3.4.1 Breeding 84 3.4.2 Seed 88 3.4.3 Vegetative Propagation 88 3.4.4 Stock Maintenance 89 3.4.4.1 Diseases 89 3.4.5 Pests 90 3.4.5.1 Weed Control 90 3.4.6 Harvesting Technology 91 3.4.7 Purification of Harvest 91 3.4.8 Mechanical Treatment 91 3.4.9 Thermal Treatment 91 3.4.9.1 Natural Drying 92 3.4.9.2 Artificial Drying 92 3.5 Quality Criteria 92 3.5.1 Quality Management 92 3.5.2 Quality Control 95 Glossary and Abbreviations 96 References 96 Further Reading 99 4 Mass Transfer Enhancement for Solid–Liquid Extractions 101Simon Both, Jochen Strube, and Giancarlo Cravatto 4.1 Introduction 101 4.2 State of the Art Solid-Liquid Extraction 102 4.2.1 Batch Processes 105 4.2.2 Continuous Processes 106 4.2.3 Hydro- and Steam Distillation 109 4.2.4 Alembic Distillation 111 4.2.5 Mechanical Expression (Extrusion) 112 4.3 Enhancement of Solid–Liquid Extraction Processes 115 4.3.1 Microwave-Assisted Extraction (MAE) 115 4.3.2 Ultrasound-Assisted Extraction (UAE) 118 4.3.3 Turbo Extraction 119 4.4 Example Processes for Solid–Liquid Extraction Enhancement 122 4.4.1 Extraction of Polyphenols from Black Tea – Conventional and Ultrasound-Assisted Extraction 122 4.4.1.1 Material and Methods 123 4.4.1.2 Equipment Concepts 126 4.4.1.3 Equilibrium Line by Multistage Maceration and Total Extraction 127 4.4.1.4 Mass Transport Kinetics 130 4.4.1.5 Particle Size Distribution 131 4.4.1.6 SEM Measurements – Cell Disruption 132 4.4.1.7 Conclusions 132 4.4.2 Pilot Scale UAE of Clove Buds in Batch and Flow Reactors 134 4.4.2.1 Experimental Methods and Reactors 135 4.4.2.2 Results and Discussion 137 4.4.2.3 Conclusions 139 4.4.3 UAE and MAE of Lipids from Microalgae 139 4.4.3.1 Experimental Methods and Equipments 139 4.4.3.2 Conclusions 141 4.5 Conclusion 141 Symbols 142 References 142 5 Fundamentals of Process-Intensification Strategy for Green Extraction Operations 145Tamara Allaf and Karim Allaf 5.1 Process-Intensification Strategy PI-S from High Capacity to High Controlled Quality Industrial Manufacturing 145 5.2 What Does “Intensified Industrial Manufacturing” Mean? 145 5.2.1 Unit Operation Performance 146 5.2.2 Final Product Quality 146 5.2.3 Equipment Reliability 147 5.3 Intensification Strategy as a Pluridimensional Approach 148 5.3.1 Objectives of Intensification Strategy 148 5.3.2 Specific Case of Food Industry 148 5.3.3 PI-S as a Continual Progressing-Development Strategy 148 5.4 Fundamentals for Starting Basis Analyses 149 5.4.1 Intensification Procedure 149 5.4.1.1 Intensification Cycle 149 5.4.1.2 Multi-cycle Intensification Procedure 150 5.4.1.3 Intensification Charter 150 5.4.2 Specificities of Instant Controlled Pressure DIC Drop in Process Intensification Strategy PI-S 151 5.4.2.1 Introduction 151 5.4.2.2 Transfer Phenomena in Instantaneous Controlled Pressure Drop DIC Treatment 152 5.4.2.3 DIC – Texturing 155 5.4.3 Mass Transfer by Permeability 156 5.5 Processes of Extraction 158 5.5.1 Extraction of Volatile Compounds 158 5.5.1.1 Kinetics 159 5.5.1.2 Intensification of Essential Oil Extraction 161 5.5.2 Case of Solvent extraction 162 5.5.2.1 Introduction 162 5.5.2.2 Extraction Process Issues 162 5.5.2.3 Kinetic Modeling 166 5.5.3 Conclusion: Process Intensification Strategy: How to Use PI-S Solvent Extraction Processes? 168 5.6 Conclusion 170 References 170 6 Panorama of Sustainable Solvents for Green Extraction Processes 173Iraj Koudous,Werner Kunz, and Jochen Strube 6.1 Introduction 173 6.2 Thermodynamic Models of Mixing and Dissolving 176 6.2.1 UNIFAC and Modified UNIFAC 176 6.2.2 The Hansen Solubility Parameters 178 6.2.3 COSMO and COSMO-RS 180 6.2.3.1 Example 1: Mutual Solubility of Acetone with Benzene, Chloroform, and Carbon disulfide 183 6.2.3.2 Example 2: Solubility Screening for Indigo 184 6.3 Solvent Selection for Green Solid–Liquid Extraction 187 6.3.1 General Green Solvent Ranking with COSMO-RS 188 6.3.2 Concrete Example: Solid–Liquid Extraction of Carnesol and Carnosic Acid from Sage 188 6.3.3 Experimental Validation of COSMO-RS Solvent Ranking 192 6.3.4 Conclusion 192 6.4 Alternative Solvents for Green Extraction 194 6.4.1 Ionic Liquids 194 6.4.2 Low-Transition-Temperature Mixtures and Deep Eutectic Solvents 196 6.4.3 Ionic Liquids Screening with COSMO-RS 197 6.5 Purification Strategies of Natural Products 199 6.5.1 Databased and Calculated Physicochemical Properties 204 6.5.2 Feed Characterization 213 6.5.2.1 Conceptual Process Design 216 6.5.2.2 Modeling Depths and Feed Characterization Approach 219 6.5.2.3 System 1: Vanillin 223 6.5.2.4 Potential Unit Operations for Product Purification 223 6.5.2.5 Data Evaluation 225 6.5.2.6 Model-Based Process Design and Calculation of Separation Costs 225 6.5.2.7 Separation Cost Estimation 228 6.5.2.8 System 2: Tea Aroma 228 6.5.2.9 Data for Potential Unit Operation 228 6.5.2.10 Process Design and Cost Estimation 229 6.5.2.11 Discussion and Conclusions 230 Symbols 231 Greek Letters 232 Indices 232 References 232 7 Water as Green Solvent for Extraction of Natural Products 237Loïc Petigny, Mustafa Zafer Özel, Sandrine Périno, Joël Wajsman, and Farid Chemat 7.1 Introduction 237 7.2 Maceration 239 7.2.1 Principle and Process 239 7.2.2 Applications 240 7.3 Subcritical Water Extraction 243 7.3.1 Principle and Process 243 7.3.2 Applications 245 7.4 Enzymatic Assistance 248 7.4.1 Principles and Process 248 7.4.2 Applications 249 7.5 Micellar Extraction 251 7.5.1 Principle and Process 251 7.5.2 Applications 252 7.6 Hydrotropes 255 7.6.1 Principles and Process 255 7.6.2 Applications 256 7.7 Conclusion 259 References 260 8 Coverage Exploitation of By-Products from the Agrofood Industry 265Carlos A. Ledesma-Escobar and María D. Luque de Castro 8.1 Introduction 265 8.2 Treatments for Safe Disposal/Exploitation of Agrofood Wastes or Residues 265 8.2.1 Physical Processes 266 8.2.2 Physicochemical Processes 267 8.2.3 Advanced Oxidation Processes 267 8.2.4 Thermal Processes 268 8.2.5 Biological Treatments 270 8.3 Exploitation of By-products from Olive Trees and Olive Oil Production 271 8.3.1 Generalities 271 8.3.2 Exploitation of Alpechín 277 8.3.3 Overall Use of Either Alperujo or Orujo 278 8.3.4 Partial Use of Either Alpechín or Alperujo 279 8.3.5 Olive Leaf Exploitation 280 8.3.6 Foreseeable/Desirable Future Uses of Olive Tree–Olive Oil Wastes 280 8.4 Exploitation of By-products from Vineyards and Wine Production 283 8.4.1 Generalities 283 8.4.2 Types and Characteristics of Vineyard Residues 286 8.4.3 Present and Potential Exploitation of Vineyard Residues 286 8.4.4 Types and Characteristics ofWine Residues 288 8.4.5 Present and Potential Exploitation ofWine Residues: Overall and Partial Exploitation 288 8.5 Exploitation of By-products from the Citrus Juice Industry 291 8.5.1 Generalities 291 8.5.2 Uses and Potential Applications of Bioactive Compounds from Citrus Residues 293 8.5.3 Potential Exploitation of Citrus Residues for Energy Production 296 8.5.4 Other Overall and Partial Uses of Citrus Residues 297 Acknowledgments 297 List of Abbreviations 298 References 298 9 Selective Extraction from Food Plants and Residues by Pulsed Electric Field 307Eugene Vorobiev and Nikolai Lebovka 9.1 Introduction 307 9.2 Basics of PEF-Assisted Extraction 308 9.3 Application of PEF for Different Food Plants and Residues 310 9.3.1 Sugar Beets 310 9.3.2 Red Beets 313 9.3.3 Chicory Roots 316 9.3.4 Apples 317 9.3.5 Grapes 318 9.3.6 Other Fruits and Vegetables 319 9.3.7 Egg Yolk 320 9.3.8 Bio-suspensions and Yeasts 320 9.3.9 Microalgae 321 9.3.10 Rhizomes 323 9.3.11 Bones 323 9.3.12 Eggshell 324 9.3.13 Leaves 324 9.3.14 Herbs 324 9.3.15 Ginseng 325 9.3.16 Peels 325 9.3.17 Mushrooms 325 9.3.18 Juices and Juice-Based Beverages 326 9.4 Conclusions 327 Acknowledgments 327 References 327 10 Green Extraction of Artemisinin fromArtemisia annua L 333Alexei A. Lapkin 10.1 Introduction 333 10.2 Extraction Technologies for Isolation of Artemisinin from A. annua 333 10.2.1 Industrial Extraction Processes 336 10.2.2 Cleaner and Intensified Processes for Extraction of Artemisinin 339 10.2.2.1 Innovative Process Conditions for Extraction 339 10.2.2.2 Alternative Solvents for Extraction of Artemisinin 340 10.3 Innovation in Artemisinin Purification 346 10.3.1 Hybrid Adsorption–Crystallization Separation 346 10.3.2 Column and HPLC Chromatography 347 10.3.3 Countercurrent Chromatography 348 10.4 Analysis of Artemisinin and Co-metabolites 348 10.5 Conclusions and Outlook 350 References 351 Index 357

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Book SynopsisThis book presents comprehensively the science and technology behind the formulation of disperse systems like emulsions, suspensions, foams and others. Starting with a general introduction, the book covers a broad range of topics like the role of different classes of surfactants, stability of disperse systems, formulation of different dispersions, evaluation of formulations and many more. Many examples are included, too. Written by the experienced author and editor Tharwart Tadros, this book is indispensable for every scientist working in the field.Table of ContentsPreface GENERAL INTRODUCTION Suspensions Latexes Emulsions Suspoemulsions Multiple Emulsions Nanosuspensions Nanoemulsions Microemulsions Pigment and Ink Dispersions Foams SURFACTANTS USED IN FORMULATION OF DISPERSIONS General Classification of Surface-Active Agents PHYSICAL CHEMISTRY OF SURFACTANT SOLUTIONS AND THE PROCESS OF MICELLISATION Thermodynamics of Micellisation Enthalpy and Entropy of Micellisation DISPERSANTS AND POLYMERIC SURFACTANTS Solution Properties of Polymeric Surfactants General Classification of Polymeric Surfactants Polyelectrolytes ADSORPTION OF SURFACTANTS AT THE AIR/LIQUID, LIQUID/LIQUID, AND SOLID/LIQUID INTERFACES Introduction Adsorption of Surfactants at the Air/Liquid (A/L) and Liquid/Liquid (L/L) Interfaces The Gibbs Adsorption Isotherm Equation of State Approach The Langmuir, Szyszkowski, and Frumkin Equations Interfacial Tension Measurements Adsorption of Surfactants at the Solid/Liquid (S/L) Interface ADSORPTION OF POLYMERIC SURFACTANTS AT THE SOLID/LIQUID INTERFACE Theories of Polymer Adsorption Experimental Techniques for Studying Polymeric Surfactant Adsorption Determination of Segment Density Distribution p(z) and Adsorbed Layer Thickness Examples of the Adsorption Isotherms of Nonionic Polymeric Surfactants COLLOID STABILITY OF DISPERSE SYSTEMS CONTAINING ELECTRICAL DOUBLE LAYERS Origin of Charge on Surfaces Structure of the Electrical Double Layer Stern-Grahame Model of the Double Layer Distinction between Specific and Nonspecific Adsorbed Ions Electrical Double Layer Repulsion van der Waals Attraction Total Energy of Interaction Flocculation of Suspensions Criteria for Stabilisation of Dispersions with Double Layer Interaction STABILITY OF DISPERSE SYSTEMS CONTAINING ADSORBED NONIONIC SURFACTANTS OR POLYMERS: STERIC STABILISATION Introduction Interaction between Particles Containing Adsorbed Nonionic and Polymeric Surfactant Layers (Steric Stabilisation) Mixing Interaction Gmix Elastic Interaction Gel Total Energy of Interaction Criteria for Effective Steric Stabilisation Flocculation of Sterically Stabilised Dispersions FORMULATION OF SOLID/LIQUID DISPERSIONS (SUSPENSIONS) Introduction Preparation of Suspensions Condensation Methods: Nucleation and Growth Dispersion Methods Bulk Properties of Suspensions FORMULATION OF LIQUID/LIQUID DISPERSIONS (EMULSIONS) Introduction Industrial Applications of Emulsions Physical Chemistry of Emulsion Systems Adsorption of Surfactants at the Liquid/Liquid Interface Selection of Emulsifiers Creaming or Sedimentation of Emulsions Flocculation of Emulsions General Rules for Reducing (Eliminating) Flocculation Ostwald Ripening Emulsion Coalescence Phase Inversion FORMULATION OF SUSPOEMULSIONS (MIXTURES OF SUSPENSIONS AND EMULSIONS) Introduction Suspoemulsions in Paints Suspoemulsions in Agrochemicals FORMULATION OF MULTIPLE EMULSIONS Introduction Preparation of Multiple Emulsions Types of Multiple Emulsions Breakdown Processes of Multiple Emulsions Factors Affecting Stability of Multiple Emulsions, and Criteria for Their Stabilisation General Description of Polymeric Surfactants Interaction between Oil or Water Droplets Containing an Adsorbed Polymeric Surfactant: Steric Stabilisation Examples of Multiple Emulsions Using Polymeric Surfactants Characterisation of Multiple Emulsions Rheological Measurements PREPARATION OF NANOSUSPENSIONS Introduction Nucleation and Growth, and Control of Particle Size Distribution Preparation of Nanosuspensions by Bottom-Up Processes Preparation of Nanosuspensions Using the Bottom-Down Process FORMULATION OF NANOEMULSIONS Introduction Mechanism of Emulsification Methods of Emulsification and the Role of Surfactants Preparation of Nanoemulsions Steric Stabilisation and the Role of the Adsorbed Layer Thickness FORMULATION OF MICROEMULSIONS Introduction Thermodynamic Definition of Microemulsions Mixed-Film and Solubilisation Theories of Microemulsions Thermodynamic Theory of Microemulsion Formation Characterisation of Microemulsions Using Scattering Techniques Characterisation of Microemulsions Using Conductivity NMR Measurements Formulation of Microemulsions FORMULATION OF FOAMS Introduction Foam Preparation Foam Structure Classification of Foam Stability Drainage and Thinning of Foam Films Theories of Foam Stability Foam Inhibitors Physical Properties of Foams Experimental Techniques for Studying Foams FORMULATION OF LATEXES Introduction Emulsion Polymerisation Polymeric Surfactants for Stabilisatoin of Preformed Latex Dispersions Dispersion Polymerisation FORMULATION OF PIGMENT AND INK DISPERSIONS Introduction Powder Wetting Breaking of Aggregates and Agglomerates (Deagglomeration) Classification of Dispersants METHODS OF EVALUATING FORMULATIONS AFTER DILUTION Introduction Assessment of the Structure of the Solid/Liquid Interface Assessment of Sedimentation of Suspensions Assessment of Flocculation and Ostwald Ripening (Crystal Growth) Scattering Techniques Measurement of Rate of Flocculation Measurement of Incipient Flocculation Measurement of Crystal Growth (Ostwald Ripening) Bulk Properties of Suspensions: Equilibrium Sediment Volume (or Height) and Redispersion EVALUATING FORMULATIONS WITHOUT DILUTION: RHEOLOGICAL TECHNIQUES Introduction Steady-State Measurements Constant Stress (Creep) Measurements Dynamic (Oscillatory) Measurements ASSESSMENT AND PREDICTION OF CREAMING, SEDIMENTATION, FLOCCULATIO, AND COALESCENCE OF FORMULATIONS Assessment and Prediction of Creaming and Sedimentation Assessment and Prediction of Flocculation Using Rheological Techniques Assessment and Prediction of Emulsion Coalescence Using Rheological Techniques Index

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Book SynopsisThis is the first book to provide an integrated introduction to the nature, formation and occurrence, stability, propagation, and uses of the most common types of colloidal dispersion in the process-related industries. The primary focus is on the applications of the principles, paying attention to practical processes and problems. This is done both as part of the treatment of the fundamentals, where appropriate, and also in the separate sections devoted to specifi c kinds of industries. Throughout, the treatment is integrated, with the principles of colloid and interface science common to each dispersion type presented for each major physical property class, followed by separate treatments of features unique to emulsions, foams, or suspensions. The first half of the book introduces the fundamental principles, introducing readers to suspension formation and stability, characterization, and fl ow properties, emphasizing practical aspects throughout. The following chapters discuss a wide range of industrial applications and examples, serving to emphasize the diff erent methodologies that have been successfully applied. The author assumes no prior knowledge of colloid chemistry and, with its glossary of key terms, complete cross-referencing and indexing, this is a must-have for graduate and professional scientists and engineers who may encounter or use emulsions, foams, or suspensions, or combinations thereof, whether in process design, industrial production, or in related R&D fields.Table of ContentsINTRODUCTION From the Colloidal State to Nanotechnology Classification of Emulsions, Foams, Suspensions and Aerosols Characterization and Stability DISPERSION AND DISPERSED SPECIES CHARACTERIZATION Introduction Surface Area, Surfaces, Porosity and Permeability Size and Size Distribution Conductivity Sedimentation, Creaming and Centrifugation Characterization of Emulsions Characterization of Foams Characterization of Suspensions Characterization of Aerosols INTERFACIAL ENERGETICS Surface Area Surface and Interfacial Tensions Pressure and Curved Surfaces Contact Angle and Wettability Surfactants and Micelles Applications of Surface Activity Other Lyophilic Colloids: Microemulsions ELECTROKINETICS Charged Interfaces Electric Double Layer Electrokinetic Phenomena Electrostatic Properties in Non-aqueous Media COLLOID STABILITY Introduction Electrostatic and Dispersion Forces DLVO Theory and Practice Hydration and Steric Effects Additional Stabilizing Influences Kinetics Destabilization of Colloids COLLOID RHEOLOGY Introduction Principles Measurement Non-Newtonian Flow Properties Other Viscosity Nomenclature and Parameters Dispersion Rheology Surface Rheology Flow in Pipelines and Constraining Media PREPARATION, INHIBITION AND DESTRUCTION OF DISPERSIONS Introduction Preparation Destruction and/or Inhibition INTRODUCTION TO PRACTICAL AND INDUSTRIAL APPLICATIONS General Uses Emulsions Foams Suspensions Aerosols Hazards APPLICATIONS IN THE ENVIRONMENT Introduction Rocks, Sediments and Soils Environmental Soil Remediation Water and Wastewater Treatment Spills and Other Hazards Environmental Foam Blankets Environmental Aerosols MINING AND MINERAL PROCESSING APPLICATIONS Introduction Hydraulic Mining and Hydrotransport Mineral Flotation Tailings and Tailings Ponds Dust-Suppressing Foam Blankets PETROLEUM INDUSTRY APPLICATIONS Oilwells, Gas Wells and Near Wells Reservoirs Surface Operations MANUFACTURING AND MATERIALS SCIENCE APPLICATIONS Introduction Wood Processing and Papermaking Inks and Printing Emulsions for Road Paving Metalworking Cleaning Processes Surface Coatings Including Paints Polymer Synthesis Ceramics Manufacture Firefighting Foams Other Applications FOOD PRODUCT AND AGRICULTURAL APPLICATIONS Introduction to Food Colloids Stabilizing Agents Preparation Stability Protein-Stabilized Emulsions Non-Protein-Stabilized Emulsions Foam Food Products Other Food Colloids Introduction to Agricultural Colloids BIOLOGICAL AND MEDICAL APPLICATIONS Introduction Vesicle Carriers Polymer Coatings Emulsion Carriers Colloids in Diagnostics Smart Materials in Medicine PERSONAL CARE PRODUCT APPLICATIONS Introduction Detergents, Shampoos and Conditioners Cosmetic Skin Care Products Other Personal Care Products EMERGING AREAS IN EMULSION, FOAMS, SUSPENSIONS AND AEROSOLS Introduction Microscopy, Supermicroscopy and Nanoscopy Combatting Terror Agents Smart Colloids and Smart Materials Nanomaterials and Nanodispersions Nanoscience Phenomenology and Biomimetics Index

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Book SynopsisFrom its origins as a niche technique more than 15 years ago, fragment-based approaches have become a major tool for drug and ligand discovery, often yielding results where other methods have failed. Written by the pioneers in the field, this book provides a comprehensive overview of current methods and applications of fragment-based discovery, as well as an outlook on where the field is headed. The first part discusses basic considerations of when to use fragment-based methods, how to select targets, and how to build libraries in the chemical fragment space. The second part describes established, novel and emerging methods for fragment screening, including empirical as well as computational approaches. Special cases of fragment-based screening, e. g. for complex target systems and for covalent inhibitors are also discussed. The third part presents several case studies from recent and on-going drug discovery projects for a variety of target classes, from kinases and phosphatases to targeting protein-protein interaction and epigenetic targets.Table of ContentsContributors XV Preface XXI A Personal Foreword XXIII Part I The Concept of Fragment-based Drug Discovery 1 1 The Role of Fragment-based Discovery in Lead Finding 3Roderick E. Hubbard 1.1 Introduction 3 1.2 What is FBLD? 4 1.3 FBLD: Current Practice 5 1.3.1 Using Fragments: Conventional Targets 5 1.3.2 Using Fragments: Unconventional Targets 13 1.4 What do Fragments Bring to Lead Discovery? 14 1.5 How did We Get Here? 16 1.5.1 Evolution of the Early Ideas and History 16 1.5.2 What has Changed Since the First Book was Published in 2006? 16 1.6 Evolution of the Methods and Their Application Since 2005 19 1.6.1 Developments in Fragment Libraries 21 1.6.2 Fragment Hit Rate and Druggability 22 1.6.3 Developments in Fragment Screening 23 1.6.4 Ways of Evolving Fragments 23 1.6.5 Integrating Fragments Alongside Other Lead-Finding Strategies 23 1.6.6 Fragments Can be Selective 24 1.6.7 Fragment Binding Modes 25 1.6.8 Fragments, Chemical Space, and Novelty 27 1.7 Current Application and Impact 27 1.8 Future Opportunities 28 References 29 2 Selecting the Right Targets for Fragment-Based Drug Discovery 37Thomas G. Davies, Harren Jhoti, Puja Pathuri, and Glyn Williams 2.1 Introduction 37 2.2 Properties of Targets and Binding Sites 39 2.3 Assessing Druggability 41 2.4 Properties of Ligands and Drugs 42 2.5 Case Studies 43 2.5.1 Case Study 1: Inhibitors of Apoptosis Proteins (IAPs) 44 2.5.2 Case Study 2: HCV-NS3 46 2.5.3 Case Study 3: PKM2 47 2.5.4 Case Study 4: Soluble Adenylate Cyclase 49 2.6 Conclusions 50 References 51 3 Enumeration of Chemical Fragment Space 57Jean-Louis Reymond, Ricardo Visini, and Mahendra Awale 3.1 Introduction 57 3.2 The Enumeration of Chemical Space 58 3.2.1 Counting and Sampling Approaches 58 3.2.2 Enumeration of the Chemical Universe Database GDB 58 3.2.3 GDB Contents 59 3.3 Using and Understanding GDB 61 3.3.1 Drug Discovery 61 3.3.2 The MQN System 62 3.3.3 Other Fingerprints 63 3.4 Fragments from GDB 65 3.4.1 Fragment Replacement 65 3.4.2 Shape Diversity of GDB Fragments 66 3.4.3 Aromatic Fragments from GDB 68 3.5 Conclusions and Outlook 68 Acknowledgment 69 References 69 4 Ligand Efficiency Metrics and their Use in Fragment Optimizations 75György G. Ferenczy and György M. Keserû 4.1 Introduction 75 4.2 Ligand Efficiency 75 4.3 Binding Thermodynamics and Efficiency Indices 78 4.4 Enthalpic Efficiency Indices 81 4.5 Lipophilic Efficiency Indices 83 4.6 Application of Efficiency Indices in Fragment-Based Drug Discovery Programs 88 4.7 Conclusions 94 References 95 Part II Methods and Approaches for Fragment-based Drug Discovery 99 5 Strategies for Fragment Library Design 101Justin Bower, Angelo Pugliese, and Martin Drysdale 5.1 Introduction 101 5.2 Aims 102 5.3 Progress 102 5.3.1 BDDP Fragment Library Design: Maximizing Diversity 103 5.3.2 Assessing Three-Dimensionality 103 5.3.3 3DFrag Consortium 104 5.3.4 Commercial Fragment Space Analysis 105 5.3.5 BDDP Fragment Library Design 108 5.3.6 Fragment Complexity 111 5.3.6.1 Diversity-Oriented Synthesis-Derived Fragment-Like Molecules 113 5.4 Future Plans 114 5.5 Summary 116 5.6 Key Achievements 116 References 116 6 The Synthesis of Biophysical Methods In Support of Robust Fragment-Based Lead Discovery 119Ben J. Davis and Anthony M. Giannetti 6.1 Introduction 119 6.2 Fragment-Based Lead Discovery on a Difficult Kinase 121 6.3 Application of Orthogonal Biophysical Methods to Identify and Overcome an Unusual Ligand: Protein Interaction 127 6.4 Direct Comparison of Orthogonal Screening Methods Against a Well-Characterized Protein System 131 6.5 Conclusions 135 References 136 7 Differential Scanning Fluorimetry as Part of a Biophysical Screening Cascade 139Duncan E. Scott, Christina Spry, and Chris Abell 7.1 Introduction 139 7.2 Theory 140 7.2.1 Equilbria are Temperature Dependent 140 7.2.2 Thermodynamics of Protein Unfolding 142 7.2.3 Exact Mathematical Solutions to Ligand-Induced Thermal Shifts 143 7.2.4 Ligand Binding and Protein Unfolding Thermodynamics Contribute to the Magnitude of Thermal Shifts 145 7.2.5 Ligand Concentration and the Magnitude of Thermal Shifts 147 7.2.6 Models of Protein Unfolding Equilibria and Ligand Binding 148 7.2.7 Negative Thermal Shifts and General Confusions 150 7.2.8 Lessons Learnt from Theoretical Analysis of DSF 151 7.3 Practical Considerations for Applying DSF in Fragment-Based Approaches 152 7.4 Application of DSF to Fragment-Based Drug Discovery 154 7.4.1 DSF as a Primary Enrichment Technique 154 7.4.2 DSF Compared with Other Hit Identification Techniques 159 7.4.3 Pursuing Destabilizing Fragment Hits 166 7.4.4 Lessons Learnt from Literature Examples of DSF in Fragment-Based Drug Discovery 168 7.5 Concluding Remarks 169 Acknowledgments 169 References 170 8 Emerging Technologies for Fragment Screening 173Sten Ohlson and Minh-Dao Duong-Thi 8.1 Introduction 173 8.2 Emerging Technologies 175 8.2.1 Weak Affinity Chromatography 175 8.2.1.1 Introduction 175 8.2.1.2 Theory 177 8.2.1.3 Fragment Screening 179 8.2.2 Mass Spectrometry 185 8.2.2.1 Introduction 185 8.2.2.2 Theory 186 8.2.2.3 Applications 186 8.2.3 Microscale Thermophoresis 187 8.2.3.1 Introduction 187 8.2.3.2 Theory 189 8.2.3.3 Applications 189 8.3 Conclusions 189 Acknowledgments 191 References 191 9 Computational Methods to Support Fragment-based Drug Discovery 197Laurie E. Grove, Sandor Vajda, and Dima Kozakov 9.1 Computational Aspects of FBDD 197 9.2 Detection of Ligand Binding Sites and Binding Hot Spots 198 9.2.1 Geometry-based Methods 199 9.2.2 Energy-based Methods 201 9.2.3 Evolutionary and Structure-based Methods 202 9.2.4 Combination Methods 202 9.3 Assessment of Druggability 203 9.4 Generation of Fragment Libraries 205 9.4.1 Known Drugs 206 9.4.2 Natural Compounds 207 9.4.3 Novel Scaffolds 208 9.5 Docking Fragments and Scoring 209 9.5.1 Challenges of Fragment Docking 209 9.5.2 Examples of Fragment Docking 210 9.6 Expansion of Fragments 212 9.7 Outlook 214 References 214 10 Making FBDD Work in Academia 223Stacie L. Bulfer, Frantz Jean-Francois, and Michelle R. Arkin 10.1 Introduction 223 10.2 How Academic and Industry Drug Discovery Efforts Differ 225 10.3 The Making of a Good Academic FBDD Project 226 10.4 FBDD Techniques Currently Used in Academia 228 10.4.1 Nuclear Magnetic Resonance 229 10.4.2 X-Ray Crystallography 230 10.4.3 Surface Plasmon Resonance/Biolayer Interferometry 231 10.4.4 Differential Scanning Fluorimetry 232 10.4.5 Isothermal Titration Calorimetry 232 10.4.6 Virtual Screening 232 10.4.7 Mass Spectrometry 233 10.4.7.1 Native MS 233 10.4.7.2 Site-Directed Disulfide Trapping (Tethering) 234 10.4.8 High-Concentration Bioassays 234 10.5 Project Structures for Doing FBDD in Academia 235 10.5.1 Targeting p97: A Chemical Biology Consortium Project 235 10.5.2 Targeting Caspase-6: An Academic–Industry Partnership 236 10.6 Conclusions and Perspectives 239 References 240 11 Site-Directed Fragment Discovery for Allostery 247T. Justin Rettenmaier, Sean A. Hudson, and James A. Wells 11.1 Introduction 247 11.2 Caspases 249 11.2.1 Tethered Allosteric Inhibitors of Executioner Caspases-3 and -7 249 11.2.2 Tethering Inflammatory Caspase-1 250 11.2.3 Tethered Allosteric Inhibitors of Caspase-5 251 11.2.4 General Allosteric Regulation at the Caspase Dimer Interface 252 11.2.5 Using Disulfide Fragments as “Chemi-Locks” to Generate Conformation-Specific Antibodies 253 11.3 Tethering K-Ras(G12C) 254 11.4 The Master Transcriptional Coactivator CREB Binding Protein 256 11.4.1 Tethering to Find Stabilizers of the KIX Domain of CBP 256 11.4.2 Dissecting the Allosteric Coupling between Binding Sites on KIX 257 11.4.3 Rapid Identification of pKID-Competitive Fragments for KIX 258 11.5 Tethering Against the PIF Pocket of Phosphoinositide-Dependent Kinase 1 (PDK1) 259 11.6 Tethering Against GPCRs: Complement 5A Receptor 261 11.7 Conclusions and Future Directions 263 References 264 12 Fragment Screening in Complex Systems 267Miles Congreve and John A. Christopher 12.1 Introduction 267 12.2 Fragment Screening and Detection of Fragment Hits 268 12.2.1 Fragment Screening Using NMR Techniques 270 12.2.2 Fragment Screening Using Surface Plasmon Resonance 271 12.2.3 Fragment Screening Using Capillary Electrophoresis 272 12.2.4 Fragment Screening Using Radioligand and Fluorescence-Based Binding Assays 273 12.2.5 Ion Channel Fragment Screening 275 12.3 Validating Fragment Hits 276 12.4 Fragment to Hit 279 12.4.1 Fragment Evolution 280 12.4.2 Fragment Linking 281 12.5 Fragment to Lead Approaches 281 12.5.1 Fragment Evolution 282 12.5.2 Fragment Linking 284 12.6 Perspective and Conclusions 285 Acknowledgments 287 References 287 13 Protein-Templated Fragment Ligation Methods: Emerging Technologies in Fragment-Based Drug Discovery 293Mike Jaegle, Eric Nawrotzky, Ee Lin Wong, Christoph Arkona, and Jörg Rademann 13.1 Introduction: Challenges and Visions in Fragment-Based Drug Discovery 293 13.2 Target-Guided Fragment Ligation: Concepts and Definitions 294 13.3 Reversible Fragment Ligation 295 13.3.1 Dynamic Reversible Fragment Ligation Strategies 295 13.3.2 Chemical Reactions Used in Dynamic Fragment Ligations 296 13.3.3 Detection Strategies in Dynamic Fragment Ligations 299 13.3.4 Applications of Dynamic Fragment Ligations in FBDD 301 13.4 Irreversible Fragment Ligation 311 13.4.1 Irreversible Fragment Ligation Strategies: Pros and Cons 311 13.4.2 Detection in Irreversible Fragment Ligation 311 13.4.3 Applications of Irreversible Fragment Ligations in FBDD 313 13.5 Fragment Ligations Involving Covalent Reactions with Proteins 316 13.6 Conclusions and Future Outlook: How Far did We Get and What will be Possible? 319 References 320 Part III Successes from Fragment-based Drug Discovery 327 14 BACE Inhibitors 329Daniel F. Wyss, Jared N. Cumming, Corey O. Strickland, and Andrew W. Stamford 14.1 Introduction 329 14.2 FBDD Efforts on BACE1 333 14.2.1 Fragment Hit Identification, Validation, and Expansion 333 14.2.2 Fragment Optimization 333 14.2.3 From a Key Pharmacophore to Clinical Candidates 340 14.3 Conclusions 346 References 346 15 Epigenetics and Fragment-Based Drug Discovery 355Aman Iqbal and Peter J. Brown 15.1 Introduction 355 15.2 Epigenetic Families and Drug Targets 357 15.3 Epigenetics Drug Discovery Approaches and Challenges 358 15.4 FBDD Case Studies 359 15.4.1 BRD4 (Bromodomain) 360 15.4.2 EP300 (Bromodomain) 363 15.4.3 ATAD2 (Bromodomain) 364 15.4.4 BAZ2B (Bromodomain) 364 15.4.5 SIRT2 (Histone Deacetylase) 365 15.4.6 Next-Generation Epigenetic Targets: The “Royal Family” and Histone Demethylases 366 15.5 Conclusions 367 Abbreviations 368 References 368 16 Discovery of Inhibitors of Protein–Protein Interactions Using Fragment-Based Methods 371Feng Wang and Stephen W. Fesik 16.1 Introduction 371 16.2 Fragment-Based Strategies for Targeting PPIs 372 16.2.1 Fragment Library Construction 372 16.2.2 NMR-Based Fragment Screening Methods 373 16.2.3 Structure Determination of Complexes 374 16.2.4 Structure-Guided Hit-to-Lead Optimization 375 16.3 Recent Examples from Our Laboratory 376 16.3.1 Discovery of RPA Inhibitors 377 16.3.2 Discovery of Potent Mcl-1 Inhibitors 378 16.3.3 Discovery of Small Molecules that Bind to K-Ras 379 16.4 Summary and Conclusions 382 Acknowledgments 383 References 384 17 Fragment-Based Discovery of Inhibitors of Lactate Dehydrogenase A 391Alexander L. Breeze, Richard A. Ward, and Jon Winter 17.1 Aerobic Glycolysis, Lactate Metabolism, and Cancer 391 17.2 Lactate Dehydrogenase as a Cancer Target 392 17.3 “Ligandability” Characteristics of the Cofactor and Substrate Binding Sites in LDHA 394 17.4 Previously Reported LDH Inhibitors 395 17.5 Fragment-Based Approach to LDHA Inhibition at AstraZeneca 398 17.5.1 High-Throughput Screening Against LDHA 398 17.5.2 Rationale and Strategy for Exploration of Fragment-Based Approaches 399 17.5.3 Development of Our Biophysical and Structural Biology Platform 400 17.5.4 Elaboration of Adenine Pocket Fragments 404 17.5.5 Screening for Fragments Binding in the Substrate and Nicotinamide Pockets 405 17.5.6 Reaching out Across the Void 407 17.5.7 Fragment Linking and Optimization 408 17.6 Fragment-Based LDHA Inhibitors from Other Groups 410 17.6.1 Nottingham 410 17.6.2 Ariad 413 17.7 Conclusions and Future Perspectives 417 References 419 18 FBDD Applications to Kinase Drug Hunting 425Gordon Saxty 18.1 Introduction 425 18.2 Virtual Screening and X-ray for PI3K 426 18.3 High-Concentration Screening and X-ray for Rock1/2 427 18.4 Surface Plasmon Resonance for MAP4K4 428 18.5 Weak Affinity Chromatography for GAK 429 18.6 X-ray for CDK 4/6 430 18.7 High-Concentration Screening, Thermal Shift, and X-ray for CHK2 432 18.8 Virtual Screening and Computational Modeling for AMPK 433 18.9 High-Concentration Screening, NMR, and X-ray FBDD for PDK1 434 18.10 Tethering Mass Spectometry and X-ray for PDK1 435 18.11 NMR and X-ray Case Study for Abl (Allosteric) 436 18.12 Review of Current Kinase IND’s and Conclusions 437 References 442 19 An Integrated Approach for Fragment-Based Lead Discovery: Virtual, NMR, and High-Throughput Screening Combined with Structure-Guided Design. Application to the Aspartyl Protease Renin 447 Simon Rüdisser, Eric Vangrevelinghe, and Jürgen Maibaum 19.1 Introduction 447 19.2 Renin as a Drug Target 449 19.3 The Catalytic Mechanism of Renin 451 19.4 Virtual Screening 452 19.5 Fragment-Based Lead Finding Applied to Renin and Other Aspartyl Proteases 455 19.6 Renin Fragment Library Design 464 19.7 Fragment Screening by NMR T1ρ Ligand Observation 469 19.8 X-Ray Crystallography 473 19.9 Renin Fragment Hit-to-Lead Evolution 475 19.10 Integration of Fragment Hits and HTS Hits 476 19.11 Conclusions 479 References 480 Index 487

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Book SynopsisDiscover this timely, comprehensive, and up-to-date exploration of crucial aspects of the use of nanomaterials in analytical chemistry Sample Preparation with Nanomaterials: Next Generation Techniques for Sample Preparation delivers insightful and complete overview of recent progress in the use of nanomaterials in sample preparation. The book begins with an overview of special features of nanomaterials and their applications in analytical sciences. Important types of nanomaterials, like carbon nanotubes and magnetic particles, are reviewed and biological sample preparation and lab-on-a-chip systems are presented. The distinguished author places special emphasis on approaches that tend to green and reduce the cost of sample treatment processes. He also discusses the legal, economical, and toxicity aspects of nanomaterial samples. This book includes extensive reference material, like a complete list of manufacturers, that makes it invaluable for professionals in analytical chemistry. Sample Preparation with Nanomaterials offers considerations of the economic aspects of nanomaterials, as well as the assessment of their toxicity and risk. Readers will also benefit from the inclusion of: A thorough introduction to nanomaterials in the analytical sciences and special properties of nanomaterials for sample preparation An exploration of the mechanism of adsorption and desorption on nanomaterials, including carbon nanomaterials used as adsorbents Discussions of membrane applications of nanomaterials, surface enhanced raman spectroscopy, and the use of nanomaterials for biological sample preparation A treatment of magnetic nanomaterials, lab-on-a-chip nanomaterials, and toxicity and risk assessment of nanomaterials Perfect for analytical chemists, materials scientists, and process engineers, Sample Preparation with Nanomaterials: Next Generation Techniques for Sample Preparation will also earn a place in the libraries of analytical laboratories, universities, and companies who conduct research into nanomaterials and seek a one-stop resource for sample preparation. Trade Review"... an excellent contribution in the field of sample preparation, showing the interesting possibilities offered by nanomaterials as analytical tools. It combines basic scientific principles of NMs with practical aspects, and provides examples of analytical applications. Overall, it presents a good resource on sample preparation alternatives for analytical purposes involving NMs." —Ángel Ríos, Analytical and Bioanalytical Chemistry, https://doi.org/10.1007/s00216-021-03759-wTable of Contents1 Nanomaterials (NMs) in Analytical Sciences 1 1.1 Introduction 1 1.2 Types of NMs 2 1.2.1 Graphene 2 1.2.2 Carbon Nanotubes (CNTs) 3 1.2.3 Fullerenes (FULs) 4 1.2.4 Inorganic Nanoparticles 6 1.2.4.1 Gold and Silver Nanoparticles 6 1.2.4.2 Titanium Nanoparticles 7 1.2.4.3 Silica Nanoparticles 7 1.2.5 Magnetic Nanoparticles 7 1.3 Applications of NMs 8 1.3.1 NMs in Separation Processes 8 1.3.2 NMs in Biomedical Applications 8 1.3.3 NMs in Sensor Platforms 12 1.4 Conclusions 16 References 19 2 Special Properties of Nanomaterials (NMs) for Sample Preparation 27 2.1 Introduction 27 2.2 Mechanical Properties of NMs 28 2.2.1 Hardness and Strength 28 2.2.2 Ductility 30 2.2.3 Applications of Mechanical Properties 32 2.3 Thermal Properties of NMs 33 2.4 Electrical Properties of NMs 35 2.5 Optical Properties of NMs 36 2.6 Magnetic Properties of NMs 37 2.7 Adsorption Properties of NMs 38 2.8 Conclusions 39 References 40 3 Adsorption Mechanism on Nanomaterials (NMs) 47 3.1 Introduction 47 3.2 Adsorption Process 48 3.2.1 Adsorption Isotherms 48 3.2.1.1 Langmuir Isotherm 50 3.2.1.2 Freundlich Isotherm 50 3.2.1.3 Temkin Isotherm 50 3.2.1.4 Dubinin–Radushkevich Model 51 3.2.1.5 Harkins–Jura and Halsey Isotherms 51 3.2.1.6 Redlich–Peterson Isotherm 51 3.2.1.7 BET (Brunauer, Emmett, and Teller) Isotherm 52 3.2.2 Adsorption Kinetics and Thermodynamics 52 3.2.2.1 Pseudo-first-order Kinetics 52 3.2.2.2 Pseudo-second-order Kinetics 53 3.2.2.3 Intraparticle Diffusion Model 53 3.2.2.4 Thermodynamic Study 53 3.2.3 Adsorption Process on Nanoparticles 54 3.2.3.1 Silver Nanoparticles 54 3.2.3.2 Gold Nanoparticles 55 3.2.3.3 Zinc Oxide Nanoparticles 56 3.2.3.4 Magnetic Fe3O4 Nanoparticles 56 3.2.4 Adsorption Process on Carbon Nanomaterials 58 3.2.4.1 Activated Carbon 58 3.2.4.2 Carbon Nanotubes (CNTs) 59 3.2.4.3 Graphene Oxide (GO) 60 3.3 Conclusions and Future Perspective 63 References 63 4 Carbon Nanomaterials (CNMs) as Adsorbents for Sample Preparation 71 4.1 Introduction 71 4.2 Carbon Nanomaterials (CNMs) 72 4.2.1 Carbon Nanotubes (CNTs) 72 4.2.2 Graphene 73 4.2.3 Fullerenes (FULs) 75 4.3 Adsorption on CNMs 76 4.4 Applications of CNMs 77 4.4.1 Extraction and Separation Applications 77 4.4.2 Chromatographic Applications 80 4.4.2.1 Chromatographic Stationary Phases Having CNTs 81 4.4.2.2 Chromatographic Stationary Phases Having FULs 83 4.5 Conclusions 84 References 84 5 Membrane Applications of Nanomaterials (NMs) 93 5.1 Introduction 93 5.2 Traditional Membranes 93 5.3 Carbon Nanomaterial-based Membranes 94 5.3.1 Graphene-based Membranes 94 5.3.2 Carbon Nanotube-based Membranes 97 5.3.3 Fullerene-based Membranes 100 5.4 Nanoparticle-based Membranes 101 5.5 Molecularly Imprinted Polymer (MIP)-based Membranes 102 5.6 Conclusions 105 References 108 6 Surface-Enhanced Raman Spectroscopy (SERS) with Nanomaterials (NMs) 117 6.1 Introduction 117 6.2 Theory of SERS 118 6.3 SERS Mechanisms 118 6.3.1 Electromagnetic Enhancement 119 6.3.2 Chemical Enhancement 120 6.4 Determination of SERS Enhancement Factor 121 6.5 Selection Rules 121 6.5.1 Image Field Model 121 6.5.2 Electromagnetic Field Model 122 6.6 Fabrications of SERS Substrates 123 6.6.1 Template-assisted Fabrication 124 6.6.2 Hybrid Fabrication 124 6.6.3 Fabrication by Using Colloids 124 6.6.4 Direct Deposition 125 6.7 Applications of SERS 125 6.7.1 SERS-Based Separation Applications 125 6.7.2 SERS-Based Sensor Applications 126 6.7.2.1 Environmental Analysis 126 6.7.2.2 Forensic Analysis 129 6.7.2.3 Biological Applications 131 6.8 Conclusions 133 References 133 7 Nanomaterials (NMs) for Biological Sample Preparations 147 7.1 Introduction 147 7.2 The Use of NMs in Diagnostic Platforms 148 7.2.1 The Optimization of NMs in Diagnostic Platforms 148 7.2.2 Biofunctionalization of NMs in Diagnostic Platforms 149 7.3 NMs-based Lab-on-a-chip (LOC) Platforms 150 7.3.1 Paper-based LOC Platforms 152 7.3.2 Centrifugal LOC Platforms 152 7.3.3 Droplet-based LOC Platforms 152 7.3.4 Digital LOC Platforms 152 7.3.5 Surface AcousticWave-based LOC Platforms 152 7.3.6 LOC Platforms for Biological Applications 153 7.4 Biomedical Applications of NMs 155 7.5 Sensor Applications of NMs 157 7.6 Conclusions 162 References 162 8 Magnetic Nanomaterials for Sample Preparation 173 8.1 Introduction 173 8.2 Synthesis of Magnetic Nanoparticles 174 8.2.1 Thermal Decomposition Technique 174 8.2.2 Coprecipitation Technique 175 8.2.3 Sol–Gel Synthesis 175 8.2.4 Hydrothermal Synthesis 176 8.2.5 Microemulsion-Based Synthesis 176 8.2.6 Flow Injection Synthesis 176 8.2.7 Aerosol/Vapor-Phase-Based Synthesis 176 8.3 Solid-Phase Extraction (SPE) 177 8.4 Magnetic Solid-Phase Extraction (MSPE) 177 8.4.1 MSPE for Environmental Samples 178 8.4.2 MSPE for Food and Beverage Samples 183 8.4.3 MSPE for Biological Samples 185 8.5 Conclusions and Future Trends 186 References 187 9 Lab-on-a-Chip with Nanomaterials (NMs) 195 9.1 Introduction 195 9.2 Lab-on-a-Chip (LOC) Concept 196 9.2.1 Paper-based LOC Systems 198 9.2.2 Centrifugal LOC Systems 198 9.2.3 Droplet-Based LOC Systems 198 9.2.4 Digital LOC Systems 199 9.2.5 Surface AcousticWave-Based LOC Systems 199 9.3 NM-Based LOC Platforms 199 9.3.1 NM-Based Transducers 199 9.3.1.1 Electrochemical Detection Systems 199 9.3.1.2 Optical Detection Systems 202 9.3.1.3 Other Detection Techniques 205 9.3.2 Nanoparticles as Labels in Microfluidics 206 9.3.3 NMs for Process Improvement 208 9.4 Conclusions and Future Perspectives 209 References 210 10 Toxicity and Risk Assessment of Nanomaterials 219 10.1 Introduction 219 10.2 Hazard Assessment of Nanomaterials 220 10.2.1 Dermal Toxicity of Nanomaterials 220 10.2.2 Inhalational Toxicity of Nanomater𝚤als 221 10.2.3 Carcinogenicity and Genotoxicity of Nanomaterials 223 10.2.4 Neurotoxicity of Nanomaterials 226 10.3 Toxicity Mechanism of Nanomaterials 227 10.4 The Traditional Risk Assessment Paradigm 229 10.5 Strategies for Improving Specific Risk Assessment 230 10.5.1 Combining Life Cycle Methodology with the Risk Assessment Approach 230 10.5.2 The Support of Risk-Based Classification Systems 231 10.6 Conclusions 232 References 232 11 Economic Aspects of Nanomaterials (NMs) for Sample Preparation 241 11.1 Introduction 241 11.2 Toxicity Concerns of NMs 242 11.3 Global Market for NM-Based Products 243 11.4 Conclusions 245 References 246 12 Legal Aspects of Nanomaterials (NMs) for Sample Preparation 251 12.1 Introduction 251 12.2 Safety Issues of NMs 251 12.3 Regulatory Aspects of NMs 252 12.3.1 Ethical Concerns in the Environmental Effects of NMs 253 12.3.2 Ethical Concerns in Occupational Health and Safety ofWorkers 254 12.3.3 Ethical Concerns of NMs in Food 255 12.3.4 Ethical Concerns of NMs in Drugs, Cosmetics, and Human Health 255 12.4 Conclusions 256 References 257 13 Monitoring of Nanomaterials (NMs) in the Environment 261 13.1 Introduction 261 13.2 Toxicity and Safety Concerns of NMs 262 13.3 Main Sources and Transport Routes of Nanopollutants 264 13.4 Requirements of Analytical Approaches 266 13.5 Sampling of NMs in Environmental Samples 266 13.6 Separation of NMs in Environmental Samples 267 13.7 Detection Techniques for the Characterization of NMs 268 13.8 Conclusions 270 References 270 14 Future Prospect of Sampling 275 14.1 Introduction 275 14.2 Sampling 276 14.3 Sample Preparation 276 14.4 Green Chemistry 278 14.5 Miniaturization of Analytical Systems 280 14.5.1 Miniaturization of Separation Techniques 281 14.5.2 Lab-on-a-Valve (LOV) as a Powerful Tool to Meet Green Chemical Principles 283 14.6 Conclusions 283 References 284 Index 289

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Book SynopsisA comprehensive overview and summary of recent achievements and the latest trends in bioinspired thermal materials. Following an introduction to different thermal materials and their effective heat transfer to other materials, the text discusses heat detection materials that are inspired by biological systems, such as fire beetles and butterflies. There then follow descriptions of materials with thermal management functionality, including those for evaporation and condensation, heat transfer and thermal insulation materials, as modeled on snake skins, polar bears and fire-resistant trees. A discussion of thermoresponsive materials with thermally switchable surfaces and controllable nanochannels as well as those with high thermal conductivity and piezoelectric sensors is rounded off by a look toward future trends in the bioinspired engineering of thermal materials. Straightforward and well structured, this is an essential reference for newcomers as well as experienced researchers in this exciting field.Table of Contents1 Introduction to Thermal Properties of Materials 1 Rui Feng and Chengyi Song 1.1 Conventional Macroscale Heat Transfer 1 1.1.1 Normalization 2 1.1.2 Thermal Equilibrium and Nonequilibrium 2 1.1.3 Integral Structural Heat Transfer 3 1.1.4 Control Volume and Interface 4 1.1.5 Conduction in Single and Multiphase Medium 6 1.1.5.1 Single-phase Medium 6 1.1.5.2 Multiphase Composite Medium 6 1.1.6 Heat Capacity 8 1.1.7 Phase Change 9 1.2 Micro/Nanoscale Heat Transfer 10 1.2.1 Micro/Nanoscale Heat Carriers 10 1.2.2 Nanoscale Thermal Dynamic Theory via Boltzmann Equation 13 1.2.3 Molecular Dynamics Calculation 15 1.2.4 Photothermal Effect via SPR Heating 16 1.3 Bioinspired Thermal Materials 17 1.3.1 Bioinspired Thermal Materials for Heat Conduction 17 1.3.2 Bioinspired Materials for Thermal Storage 18 1.3.3 Bioinspired Thermal Detection 19 1.3.4 Bioinpsired Materials for Energy Conversion 19 1.4 Perspective and Outlook 20 Acknowledgments 21 References 21 2 The Engineering History of Thermal Materials 25 Mohammed T. Ababneh 2.1 Introduction 25 2.2 Engineering History of Thermal Materials 25 2.2.1 Thermal Conductivity 25 2.2.2 Development of Materials with High Thermal Conductivity 27 2.3 Engineering Applications with Bioinspired Thermal Materials 33 2.3.1 Hydrophilic and Hydrophobic Surfaces 33 2.3.2 Dropwise Condensation 34 2.3.3 Heat Pipes 37 2.4 Bioinspired Multiscale Wicks 38 2.5 Hybrid Superhydrophilic/Superhydrophobic Wicks 40 2.6 Flexible Heat Pipes with Integrated Bioinspired Design 42 References 44 3 Bioinspired Surfaces for Enhanced Boiling 47 Yangying Zhu, Dion S. Antao, and Evelyn N. Wang 3.1 Introduction 47 3.2 Bioinspired Surfaces for Boiling 49 3.3 Surface-Structure-Enhanced Pool Boiling 52 3.4 Biphilic and Biconductive Surface-Enhanced Boiling 55 3.5 Surfactant-Enhanced Pool Boiling 59 3.6 Flow Boiling 62 3.7 Conclusions and Outlook 66 Acknowledgments 67 References 67 4 Bioinspired Materials in Evaporation 73 Yanming Liu and Chengyi Song 4.1 Introduction 73 4.2 What Is Evaporation? 74 4.2.1 Theoretical Models of Evaporation via Bulk Heating or Interfacial Heating 74 4.2.2 Examples of Bulk Heating and Interfacial Heating 76 4.3 Bioinspired Materials in Evaporation 80 4.3.1 Bioinspired Enhancing of Evaporation Rate via Interfacial Localized Heating 81 4.3.2 Skin-Mimic Evaporative Cooling System 86 4.3.3 Application of Bioinspired Materials in Evaporation 88 4.3.3.1 Distillation 88 4.3.3.2 Sterilization 89 4.3.3.3 Desalination 91 4.3.3.4 Wastewater Treatment 92 4.3.3.5 Electronics Cooling System 94 4.4 Summary and Perspectives 95 Acknowledgments 96 References 96 5 Bioinspired Engineering of Photothermal Materials 99 Wang Zhang and Junlong Tian 5.1 Antireflection and Photothermal Biomaterials 99 5.1.1 Nipple Arrays Antireflection Biomaterials 100 5.1.2 Protuberances Arrays Antireflection Biomaterials 101 5.1.3 Triangular Roof-Type Antireflection and Photothermal Materials 103 5.2 Bioinspired Photothermal Materials 105 5.2.1 Bioinspired Photothermal Materials Synthesis Approach 106 5.2.2 Bioinspired Metal–Semiconductor Photothermal Materials 106 5.2.3 Bioinspired Carbon-Matrix Metal Functional Materials 116 References 122 6 Bioinspired Microfluidic Cooling 129 Charlie Wasyl Katrycz and Benjamin D. Hatton 6.1 Introduction 129 6.2 Biological Heat Exchange 131 6.3 Wearable Fluidics 132 6.3.1 Liquid Cooling Garments 132 6.3.2 Head Cooling 134 6.3.3 Wearable Microfluidics 136 6.4 Fluidic-Based Windows and Facades for Buildings 136 6.4.1 Thermal Storage in Fluidic Layers 139 6.4.2 Forced Convection for Thermal Control 140 6.4.3 One-Dimensional Steady-State Heat Transfer Model 142 6.4.4 Fluidic Networks for Adaptive Windows 143 6.5 Fabrication Methods for Large-Area Fluidic Networks 145 6.5.1 3D Printing 145 6.5.2 Radio Frequency Welding 147 6.5.3 CNC Milling 148 6.5.4 Micro Molding 148 6.5.5 Viscous Fingering 150 6.6 Summary 153 References 153 7 Thermal Emissivity: Basics, Measurement, and Biological Examples 159 Lars Olof Björn and Annica M. Nilsson 7.1 Terminology 159 7.2 Basic Radiation Laws 160 7.3 Direct Emissivity Measurements 160 7.4 Kirchhoff’s Law 161 7.5 Measurements Using Kirchhoff’s Law 162 7.6 Attenuated Total Reflectance 164 7.7 Ways to Determine Hemispherical Emissivity 165 7.8 Specular and Diffuse Reflectance 166 7.9 Problems with Sample Shape 168 7.10 Remote Sensing from Aircraft or Satellites 168 7.11 Examples of Emissivity Determinations of Biological Samples 168 References 171 8 Bioinspired Thermal Detection 175 Zhen Luo and Wen Shang 8.1 Introduction 175 8.2 Thermal Detection 176 8.2.1 Invasive Thermal Detection 177 8.2.1.1 Thermometers 177 8.2.1.2 Thermocouple 178 8.2.1.3 Thermistors 179 8.2.2 Noninvasive Thermal Detection 179 8.2.2.1 Electron or Molecule Excitation-Based Noninvasive Thermal Detection 179 8.2.2.2 Noninvasive Thermal Detection Based on the Change of Other Physical Properties 180 8.3 Bioinspired Thermal Detection 181 8.3.1 Thermal Detection by Direct Use of Biological Materials 181 8.3.1.1 Bimaterials Combining Biological Materials and Thermal Materials 181 8.3.1.2 Temperature-Dependent Photoluminescence (PL) Sensor 182 8.3.1.3 Biomolecule Thermosensors 183 8.3.2 Thermal Detection Inspired by Biological Structures that Might Not Be Related to Thermal Function of Biological Systems 187 8.3.3 Thermal Detection Inspired by the Thermal Function of Biological Systems 189 8.3.3.1 Thermosensitive Biological Polymers 189 8.3.3.2 Thermal Detection Inspired by Skin 189 8.3.4 Application of Bioinspired Thermal Detection 193 8.4 Perspectives 195 References 197 9 Bioinspired Thermal Insulation and Storage Materials 201 Peng Tao and Dominic J. McCafferty 9.1 Introduction to Thermal Insulation Materials 201 9.1.1 Introduction 201 9.1.2 Fundamentals of Thermal Insulation 202 9.2 Engineering of Thermal Insulation Materials 204 9.2.1 Conventional Thermal Insulation Materials 204 9.2.2 Advanced Thermal Insulation Materials 206 9.2.3 Application of Thermal Insulation Materials 208 9.2.3.1 Thermal Insulation for Buildings 208 9.2.3.2 Thermal Insulation for Spacecraft 208 9.2.3.3 Thermal Insulation for Mechanical Systems 210 9.2.3.4 Thermal Insulation for Textile Industries 210 9.3 Bioinspired Thermal Insulation and Storage Materials 211 9.3.1 Biological Thermal Insulation 211 9.3.1.1 Fat and Blubber 211 9.3.1.2 Feathers and Plumage 212 9.3.1.3 Hair, Fur and Wool 212 9.3.1.4 Heat Transfer Processes in Animal Coats 212 9.3.2 Advanced Thermal Insulation Materials Inspired by Animals 214 9.3.3 Thermal Storage Inspired by Black Butterflies 216 9.4 Summary and Outlook 219 Acknowledgments 219 References 219 10 Bioinspired Icephobicity 225 Ri li 10.1 Icing Nucleation of Sessile Drops 226 10.2 Literature Review – Icing of Water Drops on Surfaces 230 10.3 Icing of Stationary Water Drops 231 10.4 Icing of Water Drops Impacting Surfaces 235 References 238 Index 241

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Book SynopsisSurface-Functionalized Ceramics Focused coverage of making and using functional ceramic materials for a wide variety of scientific and technical applications Surface-Functionalized Ceramics provides a comprehensive overview of surface functionalization approaches for ceramic materials, including alumina, zirconia, titania, and silica, and their uses as sensors, chemical, and biological probes, chromatographic supports for (bio)molecule purification and analysis, and adsorbents for toxic substances and pollutants. Overall, the text provides a broad picture of the enormous possibilities offered by surface functionalization and addresses the current challenges regarding surface analysis, characterization, and stability. As a well-rounded resource, the text points out opportunities of surface-functionalized ceramics, their issues such as achieving surface stability and complex analysis, and how to counter them. Edited by two experts in the field of advanced materials surfaces, Surface-Functionalized Ceramics covers topics such as: Processing methods for advanced ceramics, surface modification of ceramic materials, and methods for electrokinetic surface characteristics Surface imaging and chemical surface analysis using atomic force microscopy Surface chemical analysis and ceramic-enhanced analytics Biological and living matter-surface interactions including protein adsorption mechanisms as well as bacteria behavior in terms of biofilm formation and prevention for antibacterial applications Mesoporous silica and organosilica biosensors for water quality and environmental monitoring, plus ceramic-based adsorbents in bioproduct recovery and purification For professionals, researchers, and academics in the fields of materials science, biotechnology, biotechnological industry, environmental sciences, and ceramics industry, Surface-Functionalized Ceramics is a one-stop reference on the subject that provides different approaches to obtain surfaces of ceramic materials that perform desired functions.Table of ContentsIntroduction to Ceramic Materials Processing Methods for Advanced Ceramics Surface Modification of Ceramic Materials Surface Imaging and Structure Methods for Chemical Surface Analysis: Atomic Force Microscopy Surface Chemical Analysis of Ceramics and Ceramic-Enhanced Analytics Methods for Electrokinetic Surface Characteristics Functionalized Surfaces and Interactions with Biomolecules Bacteria-Surface Interactions: Biofilm Formation and Prevention Carbon Nanomaterials for Antibacterial Applications Mesoporous Silica and Organosilica Biosensors for Water Quality and Environmental Monitoring Ceramic-Based Adsorbents in Bioproduct Recovery and Purification

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Book SynopsisWith its content taken from only the very latest results, this is an extensive summary of the various polymeric materials used for biomedical applications. Following an introduction listing various functional polymers, including conductive, biocompatible and conjugated polymers, the book goes on to discuss different synthetic polymers that can be used, for example, as hydrogels, biochemical sensors, functional surfaces, and natural degradable materials. Throughout, the focus is on applications, with worked examples for training purposes as well as case studies included. The whole is rounded off with a look at future trends.Trade Review"[R]esearchers with a chemical background who are entering the biomedical field are the ones who will get the most out of this book. Others, coming from a more mechanical background will still find the book very useful owing to the number of concise comparisons of the materials within the various classes which will facilitate material selection and design of biomedical technologies. Indeed, it is an excellent picture of the current state and direction of research in this area, well supported by a wealth of references in each chapter (there are between 40 – 300 references per chapter) with pertinent and well-presented figures throughout." (Applied Rheology June 2017)Table of ContentsList of Contributors XV Preface XIX 1 Biomaterials for Biomedical Applications 1Brahatheeswaran Dhandayuthapani and Dasappan Sakthi kumar 1.1 Introduction 1 1.2 Polymers as Hydrogels in Cell Encapsulation and Soft Tissue Replacement 2 1.3 Biomaterials for Drug Delivery Systems 4 1.4 Biomaterials for Heart Valves and Arteries 7 1.5 Biomaterials for Bone Repair 9 1.6 Conclusion 11 Abbreviations 12 References 13 2 Conducting Polymers: An Introduction 21Nidhin Joy, Joby Eldho, and Raju Francis 2.1 Introduction 21 2.2 Types of Conducting Polymers 24 2.3 Synthesis of Conducting Polymers 28 2.4 Surface Functionalization of Conducting Polymers 28 Abbreviations 30 References 31 3 Conducting Polymers: Biomedical Applications 37Nidhin Joy, Geethy P. Gopalan, Joby Eldho, and Raju Francis 3.1 Applications 37 3.2 Conclusions 72 Abbreviations 72 References 73 4 Plasma-Assisted Fabrication and Processing of Biomaterials 91Kateryna Bazaka, Daniel S. Grant, Surjith Alancherry, and Mohan V. Jacob 4.1 Introduction 91 4.2 Conclusion 113 References 114 5 Smart Electroactive Polymers and Composite Materials 125T.P.D. Rajan and J. Mary Gladis 5.1 Introduction 125 5.2 Types of Electroactive Polymers 126 5.3 Polymer Gels 126 5.4 Conducting Polymers 129 5.5 Ionic Polymer–Metal Composites (IPMC) 131 5.6 Conjugated Polymer 132 5.7 Piezoelectric and Electrostrictive Polymers 133 5.8 Dielectric Elastomers 135 5.9 Summary 137 References 137 6 Synthetic Polymer Hydrogels 141Anitha C. Kumar and Harikrishna Erothu 6.1 Introduction 141 6.2 Polymer Hydrogels 141 6.3 Synthetic Polymer Hydrogels 142 6.4 Applications of Synthetic Polymer Hydrogels 155 6.5 Conclusion 156 Abbreviations 156 References 157 7 Hydrophilic Polymers 163Harikrishna Erothu and Anitha C. Kumar 7.1 Introduction 163 7.2 Classification 163 7.3 Applications of Hydrophilic Polymers 175 7.4 Conclusions 177 Abbreviations 177 References 178 8 Properties of Stimuli-Responsive Polymers 187Raju Francis, Geethy P. Gopalan, Anjaly Sivadas, and Nidhin Joy 8.1 Introduction 187 8.2 Physically Dependent Stimuli 188 8.3 Chemically Dependent Stimuli 203 8.4 Biologically Dependant Stimuli 207 8.5 Dual Stimuli 209 8.6 MultiStimuli-Responsive Materials 213 8.7 Conclusion 217 Abbreviations 218 References 220 9 Stimuli-Responsive Polymers: Biomedical Applications 233Raju Francis, Nidhin Joy, Anjaly Sivadas, Geethy P. Gopalan, and Deepa K. Baby 9.1 Introduction 233 9.2 Imaging 235 9.3 Sensing 238 9.4 Delivery ofTherapeutic Molecules 241 9.5 Other Applications 249 9.6 Conclusion 252 Abbreviations 252 References 253 10 Functionally Engineered Sol–Gel Derived Inorganic Gels and Hybrid Nanoarchitectures for Biomedical Applications 261Vazhayal Linsha, Kallyadan Veettil Mahesh, and Solaiappan Ananthakumar 10.1 Introduction 261 10.2 Some of the Useful Definitions of Various Gel Forms 263 10.3 Inorganic Metal-Oxide Gels and Hybrid Nanoarchitectures 267 10.4 Sol–Gel Synthesis of Inorganic Metal-Oxide Gels 267 10.5 Physically Cross-Linked Inorganic and Hybrid Gel 271 10.6 Sol–Gel Derived Hybrid Metal-Oxides Nanostructures 273 10.7 Biomedical Applications of Sol–Gel Derived Inorganic and Hybrid Nanoarchitectures for Both Therapeutic and Diagnostic (Theranostics) Functions 275 10.8 Sol–Gel Matrices for Controlled Drug Delivery 276 10.9 Stimuli-Responsive Drug Delivery Systems 282 10.10 Sol–Gel Matrix Targeted CancerTherapy 286 10.11 Sol–Gel Matrices for Imaging and Radiotherapy (Radiolabeling) 288 10.12 Concluding Remarks and Future Perspectives 294 Acknowledgment 296 Abbreviations 296 References 297 11 Relevance of Natural Degradable Polymers in the Biomedical Field 303Raju Francis, Nidhin Joy, and Anjaly Sivadas 11.1 Introduction 303 11.2 Natural Biopolymers and its Application 304 11.3 Conclusion 342 Abbreviations 343 References 344 12 Synthetic Biodegradable Polymers for Medical and Clinical Applications 361Raju Francis, Nidhin Joy, and Anjaly Sivadas 12.1 Introduction 361 12.2 Polyesters/Poly(α-hydroxy acids) 363 12.3 Poly(glycolide) 364 12.4 Polylactide 364 12.5 Poly(lactic-co-glycolic) Acid 365 12.6 Poly(ε-caprolactone) 366 12.7 Polyurethanes 366 12.8 Polyanhydrides 367 12.9 Polyphosphazenes 367 12.10 Polyhydroxyalkanoates 368 12.11 Polyorthoesters 368 12.12 Poly(propylene fumarate) 369 12.13 Polyacetals 369 12.14 Polycarbonates 369 12.15 Polyphosphoesters 370 12.16 Synthesis and Application of Different Modified Synthetic Biopolymer 371 12.17 Conclusion 376 Abbreviations 377 References 377 Index 383

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Book SynopsisHighlighting sustainable catalytic processes in synthetic organic chemistry and industry, this useful guide places special emphasis on catalytic reactions carried out at room temperature. It describes the fundamentals, summarizes key advances, and covers applications in industrial processes in the field of energy generation from renewables, food science, and pollution control. Throughout, the latest research from various disciplines is combined, such as homogeneous and heterogeneous catalysis, biocatalysis, and photocatalysis. The book concludes with a chapter on future trends and energy challenges for the latter half of the 21st century. With its multidisciplinary approach this is an essential reference for academic and industrial researchers in catalysis science aiming to design more sustainable and energy-efficient processes.Table of Contents1 Introduction to Room-Temperature Catalysis 1Eduardo J. Garcia-Suarez and Anders Riisager 1.1 Introduction 1 1.2 Room-Temperature Homogeneous Catalysts 2 1.2.1 Ionic-Liquid-Based Catalytic Systems at Room Temperature 2 1.2.2 Transition Metal Homogeneous Catalysts 6 1.2.2.1 Group 9-Based Homogeneous Catalysts (Co, Rh, Ir) 6 1.2.2.2 Group 10-Based Homogeneous Catalysts (Ni, Pd, Pt) 7 1.2.2.3 Group 11-Based Homogeneous Catalysts (Ag, Au) 10 1.3 Room-Temperature Heterogeneous Catalysts 10 1.3.1 Group 9-Based Heterogeneous Catalysts (Co, Rh, Ir) 11 1.3.2 Group 10-Based Heterogeneous Catalysts (Ni, Pd, Pt) 13 1.3.3 Group 11-Based Heterogeneous Catalysts (Cu, Pt, Au) 23 1.4 Conclusions and Perspectives 29 References 31 2 Functionalized Ionic Liquid-based Catalytic Systems with Diversified Performance Enhancements 35Shiguo Zhang and Yanlong Gu 2.1 Introduction 35 2.2 Functionalized ILs for Enhancing Catalytic Activity 36 2.3 Functionalized ILs for Improving Reaction Selectivity 38 2.4 Functionalized ILs for Facilitating Catalyst Recycling and Product Isolation 40 2.5 Functionalized ILs for Making Relay Catalysis 43 2.6 Cation and Anion Synergistic Catalysis in Ionic Liquids 45 2.7 Functionalized ILs for Aqueous Catalysis 46 2.8 Catalysis by Porous Poly-ILs 47 2.9 Functionalized IL-Based Carbon Material for Catalysis 49 2.10 Summary and Conclusions 54 References 54 3 Heterogeneous Room Temperature Catalysis – Nanomaterials 59Liyu Chen and Yingwei Li 3.1 Introduction 59 3.2 Solid-Acid-Based Nanomaterials 60 3.3 Grafted-Metal-Ions-Based Nanomaterial 65 3.4 Metal NPs-Based Nanomaterial 67 3.4.1 Metal NPs Stabilized by Ligands 67 3.4.2 Metal NPs@Polymers 68 3.4.3 Metal NPs@Metal Oxides 70 3.4.4 Metal NPs@Carbonaceous Support 72 3.4.5 Metal NPs@Siliceous Base Support 74 3.4.6 Metal NPs@MOF Nanocomposites 77 3.5 Metal Oxide NPs-Based Nanomaterial 82 3.6 Summary and Conclusions 83 References 84 4 Biocatalysis at Room Temperature 89Ivaldo Itabaiana Jr and Rodrigo O. M. A. De Souza 4.1 Introduction 89 4.2 Transaminases 90 4.2.1 General Features 90 4.2.2 Transaminase Applications at Room Temperature 90 4.3 Hydrolases 98 4.3.1 General Features 98 4.3.2 Application of Hydrolases at Room Temperature 100 4.3.2.1 Lipases 100 4.3.2.2 Aldol Additions 101 4.3.2.3 Michael Addition 102 4.3.2.4 Mannich Reaction 102 4.3.2.5 C-Heteroatom and Heteroatom–Heteroatom Bond Formations 103 4.3.2.6 Epoxidation 103 4.3.2.7 Synthesis of Heterocycles 104 4.3.2.8 Kinetic Resolutions 105 4.3.3 Cutinases 107 4.4 Laccases 108 4.4.1 General Features 108 4.4.2 Applications of Laccases 110 4.5 Enzymes in Ionic Liquids 115 4.5.1 General Features 115 References 125 5 Room Temperature Catalysis Enabled by Light 135Timothy Noël 5.1 Introduction 135 5.2 UV Photochemistry 136 5.3 Visible Light Photoredox Catalysis 139 5.4 Room Temperature Cross-Coupling Enabled by Light 141 5.5 Photochemistry and Microreactor Technology –A Perfect Match? 144 5.6 The Use of Photochemistry in Material Science 146 5.7 Solar Fuels 149 5.8 Conclusion 151 References 151 6 Mechanochemically Enhanced Organic Transformations 155Davin Tan and Tomislav Frišcic 6.1 Introduction 155 6.2 Mechanochemical Techniques and Mechanisms: Neat versus Liquid-Assisted Grinding (LAG) 156 6.3 Oxidation and Reduction Using Mechanochemistry 160 6.3.1 Direct Oxidation of Organic Substrates Using Oxone 160 6.3.2 Mechanochemical Halogenations Aided by Oxone 162 6.3.3 Reduction Reactions by Mechanochemistry 163 6.4 Electrocyclic Reactions: Equilibrium and Templating in Mechanochemistry 165 6.4.1 The Diels–Alder Reaction: Mechanochemical Equilibrium in Reversible C—C Bond Formation 165 6.4.2 Photochemical [2+2] Cycloaddition during Grinding: Supramolecular Catalysis and Structure Templating 167 6.5 Recent Advances in Metal-CatalyzedMechanochemical Reactions 168 6.5.1 Copper-Catalyzed [2+3] Cycloaddition (Huisgen Coupling) 168 6.5.2 Olefin Metathesis by Ball Milling 169 6.5.3 Mechanochemical C—H Bond Activation 170 6.5.4 Cyclopropanation of Alkenes Using Silver Foil as a Catalyst Source 171 6.6 New Frontiers in Organic Synthesis Enabled by Mechanochemistry 171 6.6.1 Synthesis of Active Pharmaceutical Ingredients (APIs) 172 6.6.2 Reactivity Enabled or Facilitated by Mechanochemistry 173 6.6.3 Trapping Unstable Reaction Intermediates 175 6.7 Conclusion and Outlook 176 Acknowledgments 176 References 176 7 Palladium-Catalyzed Cross-Coupling in Continuous Flow at Room andMild Temperature 183Christophe Len 7.1 Introduction 183 7.2 Suzuki Cross-Coupling in Continuous Flow 184 7.3 Heck Cross-Coupling in Continuous Flow 192 7.4 Murahashi Cross-Coupling in Continuous Flow 199 7.5 Concluding Remarks 202 References 202 8 Catalysis for Environmental Applications 207Changseok Han, Endalkachew Sahle-Demessie, Afzal Shah, Saima Nawaz, Latif-ur-Rahman, Niall B.McGuinness, Suresh C. Pillai, Hyeok Choi, Dionysios, D. Dionysiou, andMallikarjuna N. Nadagouda 8.1 Introduction 207 8.2 Ferrate (FeO42−) forWater Treatment 208 8.3 Magnetically Separable Ferrite forWater Treatment 209 8.3.1 Magnetic Nanoparticles 209 8.3.2 Magnetic Recovery of Materials Used forWater Treatment 211 8.3.3 Ferrite Photocatalyst forWater Treatment 212 8.4 UV, Solar, and Visible Light-Activated TiO2 Photocatalysts for Environmental Application 212 8.5 Catalysis for Remediation of Contaminated Groundwater and Soils 215 8.5.1 Catalytic Oxidative Pathways 215 8.5.2 Catalytic Reductive Pathways 217 8.5.3 Prospects and Limitations 218 8.6 Novel Catalysis for Environmental Applications 218 8.6.1 Graphene and Graphene Composites 219 8.6.2 Perovskites and Perovskites Composites 221 8.6.3 Graphitic Carbon Nitride (g-C3N4) and g-C3N4 Composites 222 8.7 Summary and Conclusions 223 Acknowledgments 224 Disclaimer 224 References 224 9 Future Development in Room-Temperature Catalysis and Challenges in the Twenty-first Century 231Fannie P. Y. Lau, R. Luque, and Frank L. Y. Lam Case Study 1: Magnetic Pd Catalysts for Benzyl Alcohol Oxidation to Benzaldehyde 237Yingying Li, Frank L.-Y. Lam, and Xijun Hu 1.1 Introduction 237 1.2 Pd/MagSBA Magnetic Catalyst for Selective Benzyl Alcohol Oxidation to Benzaldehyde 239 1.2.1 Results and Discussion 239 1.2.1.1 Characterization 239 1.2.1.2 Effect of Reaction Temperature 240 1.2.1.3 Effect of Pd Loading 241 1.2.1.4 Recycling Test 246 1.3 Summary and Conclusions 246 References 247 Case Study 2: Development of Hydrothermally Stable Functional Materials for Sustainable Conversion of Biomass to Furan Compounds 251Amrita Chatterjee, Xijun Hu, and Frank L.-Y. Lam 2.1 Introduction 251 2.2 Metal–Organic-Framework as a Potential Catalyst for Biomass Valorization 254 2.3 Xylose Dehydration to Furfural Using Metal–Organic-Framework, MIL-101(Cr) 255 2.3.1 Xylose Dehydration Catalyzed by Organosilane Coated MIL-101(Cr) 255 2.3.2 Xylose to Furfural Transformation Catalyzed by Fly-Ash and MIL-101(Cr) Composite 258 2.3.3 Xylose to Furfural Transformation Catalyzed by Tin Phosphate and MIL-101(Cr) Composite 262 2.3.4 Role of Acid Sites, Textural Properties and Hydrothermal Stability of Catalyst in Xylose Dehydration Reaction 264 2.4 Conclusion 267 References 268 Index 273

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Book SynopsisDie Biotechnologie liefert die Grundlagen für eine nachhaltige Herstellung von Produkten zur Versorgung der Weltbevölkerung mit Nahrungsmitteln, Medikamenten und anderen notwendigen Gütern. Um den weltweit steigenden Bedarf an biotechnologischen Prozessen zu realisieren, sind Ingenieurinnen und Ingenieure mit biotechnologischen Kenntnissen erforderlich. In diesem praxisnahen Buch werden Aufgaben aus den Bereichen Bioreaktoren, Bioreaktionstechnik, Steriltechnik, Scale-Up, Anlagenplanung- und betrieb, Investitions- und Kostenanalyse und Wirtschaftlichkeit exemplarisch gelöst und erlauben dem Leser eine einfache Nachvollziehbarkeit. Zahlreiche Referenzen geben dem Leser außerdem die Möglichkeit zur Vertiefung des erworbenen Wissens und diese Aufgabensammlung stellt damit die perfekte Ergänzung zum Standardwerk "Bioverfahrensentwicklung" von Professor Storhas dar. Neben einer integrierten Formelsammlung und einer kurzen, praxisorientierten Einführung umfasst das didaktische Konzept eine Einteilung der Aufgaben in unterschiedliche Typen, die exemplarisch und mit Hilfe von Kommentaren und Faustformeln aus der Praxis gelöst werden. Diese anwendungsbezogene Vertiefung in der Bioverfahrensentwicklung eignet sich besonders für Interessierte im Bereich der Bioverfahrenstechnik und verwandter Disziplinen, Studenten der Ingenieurs- und Naturwissenschaften sowie Verfahrenstechniker.Trade Review"Gestellte Aufgaben werden mithilfe von bewährten Faustformeln gelöst und verbinden Hochschullehre und industrielle Praxis." PROCESS (06/2018) "Mit den Themenbereichen Bioreaktoren, Bioreaktionstechnik, Steriltechnik, Scale-Up, Anlagenplanung- und betrieb, Wirtschaftlichkeit, Investitions- und Kostenanalyse deckt das Buch alle relevanten industriellen Fragestellungen ab." LVT ? Lebensmittel Industrie (06/2018) "Die Aufgaben werden exemplarisch mit Hilfe von bewährten Faustformeln gelöst und verbinden Hochschullehre und industrielle Praxis miteinander." LABO (05/2018) "Das Buch deckt alle relevanten industriellen Fragestellungen ab." Allgemeines Ministerialblatt der Staatsregierung Bayern (31.07.2018) Table of ContentsVorwort XI Formelzeichenerklärung XV Indizes XIX 1 Ergänzende Theorien 1 1.1 Bedeutung des Leistungseintrags – Methoden zur Bestimmung 1 1.1.1 Standard und klassische Methoden 1 1.1.2 Wärmebilanz und Schnittpunktmethode aus Temperaturmessungen 2 1.2 Kritische Toträume aus Sicht der Sterilisation 5 1.2.1 Sterilkonstruktionen aus Sicht des Sterilisierens 5 1.2.2 Praktische Bedeutung realer Konstruktionsdetails 7 1.3 Auslegungsroutine eines Sterilisationsprozesses 9 1.3.1 Einleitung 9 1.3.2 Ermittlung des Sterilisationskriteriums 11 1.3.3 Ermittlung eines Mediumskriteriums 14 1.3.4 Sterilisationsarbeitsdiagramm 17 1.3.5 Umsetzung in kontinuierlich betriebene Sterilisationsanlagen 21 1.4 Spezielle Betrachtungen zum Sauerstoffsignal 23 1.4.1 Sauerstoffsignal (Partialdruck, Gelöstkonzentration) 23 1.4.2 Methode zur Bestimmung des Henry-Koeffizienten 30 1.5 Erweiterung der Zweifilmtheorie 35 1.5.1 Basis 1. Fick’sches Gesetz 35 1.5.2 Erweiterte Gedanken zur kL ⋅ a-Bestimmung 43 1.5.3 Dynamische Methode 45 1.6 Auswahl eines Bioreaktors – Update 48 1.6.1 Kurzfassung der Auswahlroutine 48 1.6.2 Reaktorvolumen 50 1.7 Besonderheiten zur Gasbilanzierung 50 1.7.1 Einleitung 50 1.7.2 Angabe der Begasungsrate 50 1.7.3 Gasbilanzierung 52 1.8 Modellierung und Simulation von Betriebsweisen 57 1.8.1 Allgemeine Betrachtungen 57 1.8.2 Modellaufbau 58 1.8.3 Modellierungsgrundlagen 59 1.9 Modellierung der synchronisierten Parallelfermentation für den Scale-up 63 1.9.1 Einleitung 63 1.9.2 Parameterblockbildung (Systematik, Probleme, Grenzen, Gegenläufigkeit, Bewertung, Zusammenstellung) 64 1.9.3 Synchronisierte Parallelfermentationen 65 1.9.4 Symbiose von Simulation und synchronisierter Parallelfermentation 68 1.9.5 Simulationsmodell in Berkeley-MADONNA® 70 1.10 Konzeption einer Anlagenplanung 74 1.10.1 Allgemeine Betrachtungen 74 1.10.2 SuperPro Designer® 74 2 Rechenaufgabenmanagement und Aufgabentypen 77 2.1 Beschreibung der Aufgabentypen 77 2.1.1 Bioreaktoren 77 2.1.2 Bioreaktions- und Bioverfahrenstechnik 85 2.2 Problemmanagement 117 2.2.1 Lösungsstrategien 117 2.2.2 Vorgehen bei der Formulierung einer Aufgabenstellung 119 2.2.3 Vorgehen bei der Lösung einer Aufgabenstellung 119 2.3 Vorgehensweise bei der Aufgabenbearbeitung 120 2.3.1 Isolation der gegebenen Größen 120 2.3.2 Herausarbeitung der gesuchten Größen 121 2.3.3 Lösungen und Interpretation der Ergebnisse 121 3 Aufgabenthemen 123 3.1 Bioreaktorauswahl und Konstruktionsdetails 123 3.1.1 Auswahl eines geeigneten Bioreaktors 123 3.1.2 Kritische Stellen im Sterilbereich 124 3.1.3 Dichtigkeit unter dem Aspekt der Steriltechnik 126 3.1.4 Beurteilung von Sterilkonstruktionen 128 3.1.5 Lösungsebene 1 zu Abschn. 3.1.1 bis 3.1.4 131 3.1.6 Lösungsebene 2 zu Abschn. 3.1.1 bis 3.1.4 137 3.2 Wärmetechnische Betrachtungen 143 3.2.1 Abgaskühlung (Wärmeaustausch allgemein) 143 3.2.2 Wärmeaustausch unter dem Aspekt des Scale-ups 145 3.2.3 Wärmetausch und Scale-up – Lösungsansätze 146 3.2.4 Lösungsebene 1 zu Abschn. 3.2.1 bis 3.2.3 147 3.2.5 Lösungsebene 2 zu Abschn. 3.2.1 bis 3.2.3 152 3.3 Wirbelschicht 156 3.3.1 Auslegung einer Wirbelschicht mit Carrier 156 3.3.2 Auslegung einer Wirbelschicht mit Fibra-Cel®-Disc 157 3.3.3 Auslegung einer Wirbelschicht mit dem Reh-Diagramm 159 3.3.4 Lösungsebene 1 zu Abschn. 3.3.1 bis 3.3.3 162 3.3.5 Lösungsebene 2 zu Abschn. 3.3.1 bis 3.3.3 168 3.4 Sterilisation 174 3.4.1 Beweisführung der Steigung 174 3.4.2 Sterilisation: Vergleich chemisch – Hitze 176 3.4.3 Sterilisation: Vergleich Batch und KONTI 179 3.4.4 KONTISTER: Rohr oder Wendel 180 3.4.5 Mediumssterilisation – Durchflusssterilisation ideal und real 182 3.4.6 Titerreduktion von Viren 183 3.4.7 Sterilisation bei realem Temperaturverlauf 184 3.4.8 Lösungsebene 1 zu Abschn. 3.4.1 bis 3.4.7 187 3.4.9 Lösungsebene 2 zu Abschn. 3.4.1 bis 3.4.7 201 3.5 Messtechnische Effekte 218 3.5.1 Bewertung des Sauerstoffsignals und Bestimmung des Henry-Koeffizienten 218 3.5.2 Onlinebestimmung von Milchsäure 220 3.5.3 Bestimmung eines Limitierungszustandes für Sauerstoff 223 3.5.4 Leistungsberechnung 225 3.5.5 Lösungsebene 1 zu Abschn. 3.5.1 bis 3.5.4 227 3.5.6 Lösungsebene 2 zu Abschn. 3.5.1 bis 3.5.4 234 3.6 Fermentation 246 3.6.1 Auslegung einer Fermentation 246 3.6.2 Auslegung und Entsorgung 248 3.6.3 Stofftransport mit Begasungsrate 250 3.6.4 Fermentation und Biomassegewinnung 251 3.6.5 Stofftransport – OTR = OUR, Diffusionskoeffizient bestimmen 252 3.6.6 Wirkstoffherstellung mit einem Pilz in Blasensäule – Scherung 254 3.6.7 Fermentation im Spiegel des Scale-ups 256 3.6.8 Vom Schüttelkolben in die Produktion – Hilferuf aus dem Labor 257 3.6.9 Mischgüte und Scherung bei pH-Wert-Kontrolle 259 3.6.10 Lösungsebene 1 zu Abschn. 3.6.1 bis 3.6.9 261 3.6.11 Lösungsebene 2 zu Abschn. 3.6.1 bis 3.6.9 276 3.7 Aufarbeitung – Down-Stream-Processing 289 3.7.1 Reinigung durch Auswaschen 289 3.7.2 Abtrennung von Ethanol aus wässrigem Medium (Wasser) 291 3.7.3 Lösungsebene 1 zu Abschn. 3.7.1 und 3.7.2 294 3.7.4 Lösungsebene 2 zu Abschn. 3.7.1 und 3.7.2 297 3.8 Modellierung 303 3.8.1 Simulation von Batch – Fedbatch – KONTI 303 3.8.2 Symbiose von Simulation, SPF und Scale-up einer Fermentation 314 3.8.3 Lösungsebene 1 zu Abschn. 3.8.1 und 3.8.2 316 3.8.4 Lösungsebene 2 zu Abschn. 3.8.1 und 3.8.2 332 3.9 Anlagenplanung 343 3.9.1 Wirtschaftlichkeitsbetrachtung der β-Galactosidaseherstellung 343 3.9.2 Wirtschaftlichkeitsbetrachtung eines Vakuumprozesses zur Ethanolherstellung 346 3.9.3 Lösungsebene 1 zu Abschn. 3.9.1 und 3.9.2 347 3.9.4 Lösungsebene 2 zu Abschn. 3.9.1 und 3.9.2 368 3.9.5 „Tierische“ Bioverfahrenstechnik – Der BioVT-Zoo 380 Anhang A Formelsammlung 385 A.1 Leistungsberechnung, Mischzeitcharakteristik und Kräfte (→ Einheiten siehe Formelzeichenerklärung am Anfang des Buches) 385 A.2 Volumen- und Flächenberechnungen (Längen – Flächen – Volumen) 386 A.3 Stofftransportvorgänge, -geschwindigkeit – Wärmetransport 389 A.4 Reaktion, Kinetiken, Umsatz 391 A.4.1 Volumen und Reaktionskinetiken 391 A.4.2 Sterilisationskriterien, Mediumskriterium 393 A.4.3 Monod-Kinetiken 393 A.5 Bilanzgleichungen: Umsatz, Ausbeute, Selektivität 393 A.6 Feuchte Luft und andere Stoffdaten 394 A.7 Verweilzeitverteilung 395 A.8 Wirbelschicht 396 A.9 Enzymkinetik – Hemmtypen 398 A.10 Dichtigkeit 398 A.11 Übertragungsregeln – Scale-up-Regeln 399 A.12 Allgemeine mathematische Regeln 399 A.13 Kennzahlen und Sonstiges 399 A.14 Kostenschätzung – Wirtschaftlichkeit 400 A.15 Konstanten 401 Anhang B Hilfsmittel 403 B.1 Nomogramm zur Ermittlung des Kontaminationsfaktors 403 B.2 Unterteilung von Bioreaktoren 404 B.2.1 Bioreaktorgruppe 1 – pneumatisch und hydraulisch betrieben 404 B.2.2 Bioreaktoren 2 – hydraulisch und mechanisch betrieben 405 B.3 Tabelle der Einsatzbereichsmöglichkeiten der zwölf Bioreaktoren 406 B.4 Kritische Stellen 407 B.5 Widerstandsbeiwert an einer umströmten Kugel 408 B.6 Dampfdruckkurve 409 B.7 Reh-Diagramm zur Auslegung einer Wirbelschicht 410 B.8 Mollier-Diagramme 411 B.9 Schüttelkolben – Becherglas 413 Anhang C Ergänzende Hinweise 415 C.1 Theorie (zu Kapitel 1) 415 C.2 Sterilisation 418 C.3 Modellierung und Simulation 420 C.3.1 Simulation Batch 420 C.3.2 Fed-Batch 421 C.3.3 KONTI (A) 426 C.3.4 KONTI (B) (CSTR Steady-State) 427 C.4 Löslichkeit von Gasen in Wasser u. ä. 429 C.5 Dampftabelle 430 C.6 Faustwerte – Standardwerte – Erfahrungswerte 430 Literatur 433 Stichwortverzeichnis 437

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Book SynopsisEdited and written by renowned experts in the field, this is the first book to reflect the state of the art of nanocatalysis in ionic liquids. Divided into two core areas, the first part of the book describes the different classes of metal nanoparticles as well as their synthesis in ionic liquids, while the second focuses on such emerging issues as the application of such systems to energy and biomass conversion.Table of ContentsList of Contributors XI Preface XV Foreword XIX Symbols and Abbreviations XXI Part I Synthesis, Characterization, and Evaluation of Nanocatalysts in Ionic Liquids 1 1 Fe, Ru, and Os Nanoparticles 3Madhu Kaushik, Yuting Feng, Nathaniel Boyce, and Audrey Moores 1.1 Introduction 3 1.2 Synthesis of Fe, Ru, and Os NPs in ILs 4 1.2.1 Synthesis via Reduction of Metal Precursors or Ligands 6 1.3 Ionic Liquid Stabilization of Metal Nanoparticles 9 1.4 Applications of Ru, Fe, and Os Nanoparticles to Catalysis 11 1.5 Conclusion 21 Acknowledgments 21 References 21 2 Co, Rh, and Ir Nanoparticles 25Jackson D. Scholten andMuhammad I. Qadir 2.1 Introduction 25 2.2 Chemical Routes for the Synthesis of Metal NPs in ILs 26 2.3 Catalytic Application of Metal NPs in ILs 31 2.4 Conclusions 37 References 37 3 Ni and Pt Nanoparticles 41Carla Weber Scheeren 3.1 Introduction 41 3.2 Synthesis and Characterization of Pt NPs in ILs 42 3.3 Catalytic Applications of Pt NPs in ILs 47 3.4 Synthesis and Characterization of Ni NPs in ILs 48 3.5 Catalytic Applications of Ni NPs in ILs 53 3.6 Summary and Conclusions 58 Symbols and Abbreviations 59 Characterization Methods 59 Ionic Liquids 59 References 59 4 Pd Nanoparticles for Coupling Reactions and Domino/Tandem Reactions 63Anna M. Trzeciak 4.1 Introduction 63 4.2 Formation of Pd NPs in ILs 65 4.3 The Heck Coupling 68 4.4 The Suzuki Reaction 74 4.5 The Stille Coupling 75 4.6 The Sonogashira Coupling 76 4.7 Summary and Conclusions 78 Acknowledgments 79 References 79 5 Soluble Pd Nanoparticles for Catalytic Hydrogenation 83Ran Zhang and Zhenshan Hou 5.1 Introduction 83 5.2 Synthesis of Pd Nanoparticles in ILs 85 5.3 Pd Nanoparticles for Hydrogenation 88 5.4 Summary and Conclusions 93 Ionic Liquid Abbreviations 93 References 94 6 Au, Ag, and Cu Nanostructures 97Abhinandan Banerjee and RobertW. J. Scott 6.1 Introduction 97 6.2 Au NPs in the Presence of ILs 98 6.3 Catalytic Applications of AuNP/IL Composites 106 6.4 Ag NPs in the Presence of ILs 108 6.5 Cu NPs in the Presence of ILs 113 6.6 Summary and Conclusions 118 Acronyms 119 References 119 7 Bimetallic Nanoparticles in Ionic Liquids: Synthesis and Catalytic Applications 125Isabelle Favier, Emmanuelle Teuma, and Montserrat Gómez 7.1 Introduction 125 7.2 Synthesis of Bimetallic Nanoparticles in Ionic Liquids 127 7.3 Applications in Catalysis 137 7.4 Summary and Outlook 143 Acknowledgments 144 References 144 8 Synthesis and Application of Metal Nanoparticle Catalysts in Ionic Liquid Media using Metal Carbonyl Complexes as Precursors 147Raquel Marcos Esteban and Christoph Janiak 8.1 Introduction 147 8.2 Metal Carbonyls – Synthesis, Structure, and Bonding 150 8.3 Metal Carbonyls for the Synthesis of Metal Nanoparticles (M-NPs) 152 8.4 Catalytic Applications of Metal Nanoparticles from Metal Carbonyls in ILs 160 8.5 Conclusions 163 Acknowledgment 164 References 164 9 Top-Down Synthesis Methods for Nanoscale Catalysts 171Tsukasa Torimoto, Tatsuya Kameyama, and Susumu Kuwabata 9.1 Introduction 171 9.2 Sputter Deposition of Metals in RTILs 172 9.3 Thermal Vapor Deposition on RTILs for Preparation of Metal Nanoparticles 196 9.4 Laser-Induced Downsizing and Ablation of Materials 197 9.5 Preparation of Single Crystals by Vapor Deposition onto RTILs 199 9.6 Conclusion 202 References 203 10 Electrochemical Preparation of Metal Nanoparticles in Ionic Liquids 207Yasushi Katayama 10.1 Introduction 207 10.2 Basics of Electrodeposition 208 10.3 Electrodeposition of Silver and Formation of Silver Nanoparticles in Ionic Liquids 210 10.4 Electrochemical Formation of the Nanoparticles of Various Metals 215 10.5 Summary and Conclusions 225 References 227 Part II Perspectives for Application of Nanocatalysts in Ionic Liquids 231 11 Tailoring Biomass Conversions using Ionic Liquid Immobilized Metal Nanoparticles 233Srinidhi Narayanan, Jiaguang Zhang, and Ning Yan 11.1 Introduction 233 11.2 Cellulose 234 11.3 Lignin 238 11.4 Fatty Acid and Its Derivatives 241 11.5 Other Biomass Substrates 243 11.6 Conclusion 245 References 245 12 Nanoparticles on Supported Ionic Liquid Phases – Opportunities for Application in Catalysis 249Pedro Migowski, Kylie L. Luska, and Walter Leitner 12.1 Introduction 249 12.2 Synthesis of Supported Ionic Liquid Phases (SILPs) 250 12.3 Nanoparticles Immobilized onto Supported Ionic Liquid Phases (NPs@SILPs) 252 12.4 Catalytic Applications of NPs@SILPs 256 12.5 Summary and Conclusions 268 Acknowledgments 269 References 269 13 Photovoltaic, Photocatalytic Application, andWater Splitting 275Adriano F. Feil, Heberton Wender, and Renato V. Gonçalves 13.1 Introduction 275 13.2 Photovoltaic Cells 276 13.3 Photocatalytic Processes 281 13.4 Water Splitting 285 13.5 Summary and Conclusions 291 References 292 Index 295

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Book SynopsisA valuable learning tool as well as a reference, this book provides students and researchers in surface science and nanoscience with the theoretical crystallographic foundations, which are necessary to understand local structure and symmetry of bulk crystals, including ideal and real single crystal surfaces. The author deals with the subject at an introductory level, providing numerous graphic examples to illustrate the mathematical formalism. The book brings together and logically connects many seemingly disparate structural issues and notations used frequently by surface scientists and nanoscientists. Numerous exercises of varying difficulty, ranging from simple questions to small research projects, are included to stimulate discussions about the different subjects. From the contents: Bulk Crystals, Three-Dimensional Lattices - Crystal Layers, Two-Dimensional Lattices, Symmetry - Ideal Single Crystal Surfaces - Real Crystal Surfaces - Adsorbate layers - Interference Lattices - Chiral Surfaces - Experimental Analysis of Real Crystal Surfaces - Nanoparticles and Crystallites - Quasicrystals - NanotubesTable of ContentsPreface to the Second Edition IX Preface to the First Edition XI 1 Introduction 1 2 Bulk Crystals: Three-Dimensional Lattices 7 2.1 Basic Definition 7 2.2 Representation of Bulk Crystals 11 2.2.1 Alternative Descriptions Conserving the Lattice Representation 12 2.2.2 Alternative Descriptions Affecting the Lattice Representation 14 2.2.2.1 Cubic, Hexagonal, and Trigonal Lattices 16 2.2.2.2 Superlattices and Repeated Slabs 25 2.2.2.3 Linear Transformations of Lattice Vectors 29 2.2.3 Centered Lattices 31 2.3 Periodicity Cells of Lattices 35 2.4 Lattice Symmetry 38 2.5 Reciprocal Lattice 49 2.6 Neighbor Shells 52 2.7 Nanoparticles and Crystallites 63 2.8 Incommensurate Crystals and Quasicrystals 71 2.8.1 Modulated Structures 71 2.8.2 Incommensurate Composite Crystals 73 2.8.3 Quasicrystals 76 2.9 Exercises 82 3 Crystal Layers: Two-Dimensional Lattices 91 3.1 Basic Definition, Miller Indices 91 3.2 Netplane-Adapted Lattice Vectors 96 3.3 Symmetrically Appropriate Lattice Vectors: Minkowski Reduction 98 3.4 Miller Indices for Cubic and Trigonal Lattices 100 3.5 Alternative Definition of Miller Indices and Miller–Bravais Indices 106 3.6 Symmetry Properties of Netplanes 109 3.6.1 Centered Netplanes 110 3.6.2 Inversion 111 3.6.3 Rotation 114 3.6.4 Mirror Operation 119 3.6.5 Glide Reflection 131 3.6.6 Symmetry Groups 139 3.7 Crystal Systems and Bravais Lattices in Two Dimensions 144 3.8 Crystallographic Classification of Netplanes and Monolayers 149 3.8.1 Oblique Netplanes 151 3.8.2 Primitive Rectangular Netplanes 151 3.8.3 Centered Rectangular Netplanes 155 3.8.4 Square Netplanes 157 3.8.5 Hexagonal Netplanes 158 3.8.6 Classification Overview 163 3.9 Exercises 164 4 Ideal Single Crystal Surfaces 169 4.1 Basic Definition, Termination 169 4.2 Morphology of Surfaces, Stepped and Kinked Surfaces 175 4.3 Miller Index Decomposition 178 4.4 Chiral and Achiral Surfaces 192 4.5 Exercises 204 5 Real Crystal Surfaces 209 5.1 Surface Relaxation 209 5.2 Surface Reconstruction 210 5.3 Growth Processes 222 5.4 Faceting 226 5.5 Exercises 231 6 Adsorbate Layers 235 6.1 Definition and Classification 235 6.2 Adsorbate Sites 241 6.3 Wood Notation of Surface Structure 251 6.4 High-Order Commensurate (HOC) Overlayers 258 6.5 Interference Lattices 263 6.5.1 Basic Formalism 264 6.5.2 Interference and Wood Notation 272 6.5.3 Anisotropic Scaling, Stretching, and Shifting 279 6.6 Symmetry and Domain Formation 283 6.7 Adsorption at Surfaces and Chirality 293 6.8 Exercises 299 7 Experimental Analysis of Real Crystal Surfaces 305 7.1 Experimental Methods 305 7.2 Surface Structure Compilations 306 7.3 Database Formats for Surface and Nanostructures 311 7.4 Exercises 313 8 Nanotubes 315 8.1 Basic Definition 315 8.2 Nanotubes and Symmetry 319 8.3 Complex Nanotubes 323 8.4 Exercises 326 Appendix A: Sketches of High-Symmetry Adsorbate Sites 329 A.1 Face-Centered Cubic (fcc) Surface Sites 330 A.2 Body-Centered Cubic (bcc) Surface Sites 338 A.3 Hexagonal Close-Packed (hcp) Surface Sites 342 A.4 Diamond Surface Sites 346 A.5 Zincblende Surface Sites 349 Appendix B: Parameter Tables of Crystals 351 Appendix C: Mathematics of the Wood Notation 355 C.1 Basic Formalism and Examples 355 C.2 Wood-Representability 361 Appendix D: Mathematics of the Minkowski Reduction 367 Appendix E: Details of Number Theory 371 E.1 Basic Definitions and Functions 371 E.2 Euclid’s Algorithm 376 E.3 Linear Diophantine Equations 377 E.4 Quadratic Diophantine Equations 380 E.5 Number Theory and 2 × 2 Matrices 386 Appendix F: Details of Vector Calculus and Linear Algebra 391 Appendix G: Details of Fourier Theory 395 Appendix H: List of Surface Web Sites 399 Appendix I: List of Surface Structures 401 Glossary and Abbreviations 403 References 417 Index 425

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Book Synopsis"Polymorphism in the Pharmaceutical Industry - Solid Form and Drug Development" highlights the relevance of polymorphism in modern pharmaceutical chemistry, with a focus on quality by design (QbD) concepts. It covers all important issues by way of case studies, ranging from properties and crystallization, via thermodynamics, analytics and theoretical modelling right up to patent issues. As such, the book underscores the importance of solid-state chemistry within chemical and pharmaceutical development. It emphasizes why solid-state issues are important, the approaches needed to avoid problems and the opportunities offered by solid-state properties. The authors include true polymorphs as well as solvates and hydrates, while providing information on physicochemical properties, crystallization thermodynamics, quantum-mechanical modelling, and up-scaling. Important analytical tools to characterize solid-state forms and to quantify mixtures are summarized, and case studies on solid-state development processes in industry are also provided. Written by acknowledged experts in the field, this is a high-quality reference for researchers, project managers and quality assurance managers in pharmaceutical, agrochemical and fine chemical companies as well as for academics and newcomers to organic solid-state chemistry.Table of ContentsPreface to the Second Edition xv 1 Solid State and Polymorphism of the Drug Substance in the Context of Quality by Design and ICH Guidelines Q8–Q12 1Markus von Raumer and Rolf Hilfiker 1.1 Introduction 1 1.2 A Short Introduction to Polymorphism and Solid-State Development 1 1.3 A Short Introduction to Quality by Design (QbD) 3 1.4 The Solid State in the Context of Pharmaceutical Development 7 1.4.1 Typical Drug Discovery and Development 7 1.4.2 The Solid State at the Interface of Drug Substance and Drug Product 10 1.4.3 Biopharmaceutics and Bioavailability of Solids 11 1.4.4 Pharmaceutical Quality Assessment 14 1.5 Solid-State Development at Various Stages of the Pharmaceutical Development Process 15 1.5.1 The Solid State in the Discovery Phase 16 1.5.2 Salt and Co-crystal Screening and Selection 16 1.5.3 Polymorph Screening, Polymorph Landscape, and Polymorph Transformations 17 1.5.4 Crystallization and Downstream Processes 20 1.5.5 Formulation 21 1.5.6 AnalyticalMethods for Characterization and Physical Purity Determination 22 1.6 Conclusions 23 References 23 2 Alternative Solid Forms: Salts 31P.H. Stahl, Bertrand Sutter, Arnaud Grandeury and Michael Mutz 2.1 Introduction 31 2.2 Salt Formation and Polymorphism in Pharmaceutical Development 31 2.3 Target Properties of Active Substances for Drug Products 33 2.3.1 Injectables 34 2.3.2 Solid Dosage Forms 35 2.3.3 Dosage Forms for Other Routes of Application 36 2.3.3.1 Inhalation 36 2.3.3.2 Topical Products and Transdermal Route 36 2.4 The Basics of Salt Formation 37 2.4.1 Dissociation Constant 37 2.4.2 Ionization and pH 39 2.4.3 Solubility 40 2.4.4 Disproportionation 43 2.5 Approaches to Salt Preparation and Characterization 45 2.5.1 Initial Data 45 2.5.2 Selection of Salt Formers 45 2.5.3 Salt Preparation Procedures 46 2.6 Selection Strategies 49 2.6.1 Points to be Considered 49 2.6.2 Final Decision 51 2.6.3 Salt Form and Life Cycle Management of Drug Products 52 2.7 Case Reports 53 2.7.1 Overview of Salt Forms Selected 53 2.7.2 The Salt Selection Process 53 2.7.3 Case 1: NVP-BS001 53 2.7.4 Case 2: NVP-BS002 54 2.8 Discussion and Decision 56 References 56 3 Alternative Solid Forms: Co-crystals 61JohanWouters, Dario Braga, Fabrizia Grepioni, Luc Aerts and Luc Quéré 3.1 Introduction 61 3.2 Types of Pharmaceutical Co-crystals 62 3.2.1 Salts vs Co-crystals 62 3.2.2 Ionic Co-crystals of API 63 3.2.3 Polymorphism and Co-crystals 65 3.3 Relevant Pharmaceutical Co-crystal Properties 65 3.3.1 Solubility 66 3.3.2 Dissolution Rate 67 3.3.3 Bioavailability 69 3.3.4 Melting Point 69 3.3.5 Stability 70 3.3.6 Challenges and Undesired Effect of Co-crystallization 71 3.4 Analytical Tools to Characterize Co-crystals 73 3.4.1 Microscopy 74 3.4.2 X-Ray Diffraction 75 3.4.3 Thermal Analysis 77 3.4.4 Vibrational Spectroscopy 77 3.4.5 Solid-State NMR 78 3.5 Patent Literature Review 79 3.6 Current View on Regulatory Aspects of PCCs 83 3.6.1 Rules Governing Manufacturing (API GMP) 84 3.6.2 ICH Tripartite Guidelines on Specifications for New Drug Substances and New Drug Products 85 3.7 Conclusions 85 Acknowledgment 85 References 86 4 Thermodynamics of Polymorphs and Solvates 91Gerard Coquerel 4.1 Basic Notions 91 4.1.1 Chemical Purity 92 4.1.2 Isotopic Purity 92 4.1.3 Structural Purity 92 4.1.4 Stability of the Component 93 4.1.5 Polymorphism, Desmotropy, Allotropism, and Chirality 93 4.1.6 Gibbs Phase Rule 93 4.1.7 Unary System or Unary SectionWithout Polymorphism 94 4.2 Unary System or Unary Section with Polymorphism 95 4.2.1 Access to Polymorphs 97 4.2.2 Mechanisms of Polymorphic Transition 98 4.3 Polymorphism in Binary Systems 98 4.3.1 No Mixed Crystals 98 4.3.1.1 Polymorphism of One Component Only 98 4.3.1.2 Three Enantiotropic Polymorphs 100 4.3.1.3 Two Enantiotropic Polymorphs and One Form with Monotropic Character 100 4.3.1.4 One Stable Polymorph and Two Forms with a Monotropic Character 100 4.3.1.5 Polymorphism of a Stoichiometric Compound 100 4.3.2 Polymorphism and Mixed Crystals 102 4.3.2.1 Polymorphism of One Component Only 102 4.3.2.2 Two Stable Polymorphic Forms for One Component with Full Miscibility in the Solid State (at a Certain Temperature) 105 4.3.2.3 Two Stable Polymorphic Forms for One Component with Limited Miscibility in the Solid State 108 4.3.2.4 One Stable Form and One Metastable Form (Monotropic Character) with Full Miscibility for the Metastable Form 109 4.3.2.5 One Stable Form and One Metastable Form (Monotropic Character) with Full Miscibility for the Metastable Form 111 4.3.2.6 Two Isostructural Monotropic Forms When Mixed Could Lead to an Enantiotropy 112 4.3.2.7 Limitations of the Concept of Polymorphism and Other Solid(s) to Solid(s) Transitions 112 4.3.3 Solvates 114 4.3.3.1 Differentiation between Stoichiometric and Nonstoichiometric Solvates 116 4.3.3.2 Hygroscopicity, Deliquescence, and Efflorescence 117 4.4 Ternary Systems 119 4.4.1 Chiral Discrimination via the Formation of Solvates 121 4.5 Temperature of Desolvation – Tg and New Polymorphs Only AccessibleThrough a Smooth Solvation – Desolvation Process 123 4.6 Concluding Remarks 126 Acknowledgments 127 References 127 5 Toward Computational Polymorph Prediction 133Sarah L. Price and Louise S. Price 5.1 Could a Computer Predict Polymorphs for the Pharmaceutical Industry? 133 5.1.1 Predicting theThermodynamically Most Stable Structure from the Chemical Diagram 134 5.1.2 Using Crystal Structure Prediction Studies as a Complement to Solid-form Screening 134 5.2 Methods of Calculating the Relative Energies of Crystals 136 5.2.1 Lattice Energy 136 5.2.2 Free Energy 139 5.3 Searching for Possible Crystal Structures 140 5.4 Comparing Crystal Structures 141 5.5 Calculation of Properties from Crystal Structures 142 5.5.1 Spectroscopic – PXRD, IR, ss-NMR 142 5.5.2 Other Properties: Solubilities, Morphologies, and Mechanical Properties 143 5.6 Crystal Energy Landscapes 145 5.6.1 Interpretation of Crystal Energy Landscapes 145 5.6.2 Example of Tazofelone 146 5.7 Potential Uses of Crystal Energy Landscapes in the Pharmaceutical Industry 148 5.7.1 Confirming the Most Stable Structure is Known 148 5.7.2 Suggesting Experiments to Find New Polymorphs 148 5.7.3 Aiding Structural Characterization from Limited Experimental Data 149 5.7.4 Anticipating Disorder 149 5.7.5 Understanding Crystallization Behaviors 149 5.8 Outlook 150 References 151 6 Hygroscopicity and Hydrates in Pharmaceutical Solids 159SusanM. Reutzel-Edens, Doris E. Braun, and AnnW. Newman 6.1 Introduction 159 6.2 Thermodynamics ofWater–Solid Interactions 160 6.3 Hygroscopicity 161 6.3.1 Moisture Sorption Analysis 162 6.3.2 Hygroscopic Behaviors in Pharmaceutical Solids 166 6.4 Hydrates 168 6.4.1 Statistics of Hydrate Appearance 168 6.4.2 Hydrate Crystallization 170 6.4.3 Structures and Properties 174 6.5 Significance and Strategies for Developing Hydrate-Forming Systems 180 6.6 Conclusions 184 References 184 7 The Amorphous State 189Marc Descamps, Emeline Dudognon, and Jean-FrançoisWillart 7.1 Introduction 189 7.2 Amorphous/Crystalline Solids: Terminology and Brief Confrontation 190 7.2.1 Structural Aspects 190 7.2.2 The Concept(s) of Solid State: Rheological Aspect 191 7.2.3 Crystal Melting vs Glass Softening 192 7.3 Order and Disorder: Structural Identification of Amorphous and Crystal States 193 7.3.1 How Disordered can a Crystal Be? 193 7.3.1.1 Crystallinity: Definition, Experimental Identification 193 7.3.1.2 Small or Disordered “Perfect” Crystals 193 7.3.2 Structure of Glassy and Amorphous Compounds. How Ordered can they be? 194 7.4 Amorphous Stability, Crystallization Avoidance, and Glass Formation 198 7.4.1 Metastability, Driving Force for Crystallization 198 7.4.2 Kinetics of Crystallization via Nucleation and Growth 198 7.4.3 Conventional Glass Formation 201 7.4.4 Notes on the Assessment and Prediction of Amorphous Stability 202 7.4.4.1 Role of Molecular Mobility 202 7.4.4.2 Role of the Liquid/Crystal Interface Energy and Structural Similarity 202 7.4.4.3 Role of Polymorphism 203 7.4.4.4 Heterogeneous Nucleation 204 7.4.4.5 Confinement and Size Effect 204 7.4.4.6 To Summarize 205 7.5 The Glass Transition 205 7.5.1 Calorimetric Signature at Tg 205 7.5.2 Calorimetric Glass Transition: Signification 206 7.5.3 The Cp Jump at Tg: Fragile and Strong Glass Formers 207 7.5.4 Glass Transition and Entropy Crisis:The Kauzmann Paradox 207 7.5.5 Glassy Amorphous State: Instability and Energy Landscape 208 7.6 Molecular Mobility for T >Tg 210 7.6.1 Mobility of Fragile and Strong Glass Formers 210 7.6.2 Link between Mobility and Entropy 212 7.6.3 Cooperative Rearrangement Regions (CRR) 213 7.6.4 Dynamic Heterogeneity: Non-exponentiality of the Relaxation 213 7.7 Molecular Mobility and Instability for T 7.7.1 The Aging Phenomenon 214 7.7.2 Approximate Assessment of Stability 215 7.7.2.1 Fictive Temperature 216 7.7.3 Nonlinearity 217 7.7.4 Secondary Relaxations 218 7.8 Multicomponent Amorphous Systems: Solubility and Stability Issues 220 7.8.1 Solubility: Comparison of Crystalline and Amorphous States 220 7.8.2 Tg of Amorphous Multicomponent System 223 7.8.3 Improved Dissolution Properties 2 24 7.8.4 Mixing and Stabilization 224 7.9 Methods of Amorphization 226 7.10 Influence of Processing on Properties 230 7.11 Concluding Remarks 231 References 232 8 Approaches to Solid-Form Screening 241Rolf Hilfiker, Fritz Blatter, Martin Szelagiewicz, and Markus von Raumer 8.1 Screening for Salts and Co-crystals 242 8.1.1 Example of a Co-crystal Screen 243 8.2 Polymorphs, Hydrates, and Solvates 245 8.3 Screening for Polymorphs, Hydrates, and Solvates 245 8.3.1 CrystallizationMethods 248 8.3.2 Choice of Solvent 250 8.3.3 Types of Polymorph Screens 251 8.3.4 Characterization and Selection 253 8.4 Conclusion 255 References 256 9 Nucleation 261MarcoMazzotti, Thomas Vetter, David R. Ochsenbein, Giovanni M. Maggioni, and Christian Lindenberg 9.1 Introduction 261 9.2 Homogeneous Nucleation 262 9.2.1 Classical Nucleation Theory 264 9.2.2 Two-Step Nucleation Theory 266 9.3 Heterogeneous and Secondary Nucleation 268 9.3.1 Heterogeneous Nucleation 268 9.3.2 Secondary Nucleation 268 9.4 Characterization of Nucleation 270 9.4.1 Deterministic Nucleation Rates 270 9.4.2 Stochastic Nucleation Rates 272 9.5 Order of Polymorph Appearance – Ostwald’s Rule of Stages 275 9.6 To Seed or Not to Seed? 277 9.6.1 Process Control 277 9.6.2 Polymorphism Control 279 9.6.3 Impurity Control 279 References 280 10 Crystallization Process Modeling 285MarcoMazzotti, Thomas Vetter, and David R. Ochsenbein 10.1 Introduction 285 10.1.1 Population Balance Equations 286 10.1.2 Notes Regarding Population Balance Models 288 10.1.2.1 Energy Balances and Fluid Dynamics 288 10.1.2.2 Solution of Population Balance Equations 288 10.1.2.3 Applications 289 10.2 System Characterization and Optimization 289 10.2.1 Crystal Growth 290 10.2.2 Polymorph Transformation 291 10.2.3 Agglomeration 292 10.2.4 Optimization 295 10.3 Multidimensional Population Balance Modeling 297 10.4 Conclusion 300 References 301 11 Crystallization Process Scale-Up, a Quality by Design (QbD) Perspective 305Andrei A. Zlota 11.1 Introduction 305 11.2 API Critical Quality Attributes (CQAs) 306 11.3 Statistical Design of Experiments (DoE) for Crystallization Process Development 306 11.3.1 Example: DoE Methodology to Develop a Robust Crystallization Process, a Case of an API Developed as a Polymorphic Mixture 307 11.4 Process Analytical Technology (PAT) for Polymorph Control 314 11.5 Mixing and Scale-Up Investigations 316 11.5.1 Scale-Up Factors, Mass Transfer 316 11.5.2 Scale-Up Factors in Crystallization Processes 318 11.5.3 Mixing Impact on the Metastable ZoneWidth (MSZW) 324 11.5.4 Disappearing Polymorphs during Scale-Up 324 11.5.5 Polymorph Control Methods Based on Mixing 324 11.5.6 Heat Transfer 325 11.6 Conclusions and Outlook 326 References 326 12 Processing-Induced Phase Transformations and Their Implications on Pharmaceutical Product Quality 329Seema Thakral, Ramprakash Govindarajan, and Raj Suryanarayanan 12.1 Introduction 329 12.2 Pharmaceutical Processes Causing Unintended Phase Transformations 333 12.2.1 Milling 333 12.2.2 Granulation and Drying – Hydration and Dehydration 336 12.2.2.1 Hydrate Formation 337 12.2.2.2 Dehydration 338 12.2.3 Compression 342 12.2.4 Freezing Aqueous Solutions 345 12.3 Pharmaceutical Processes Causing Intended Phase Transformations – Obtaining the Desired Physical Form 346 12.3.1 Spray-drying 346 12.3.2 Freeze-drying 347 12.3.3 Hot Melt Extrusion 349 12.3.4 Co-milling/Co-grinding 350 12.4 Phase Transformations during Pharmaceutical Processing – Implications 351 12.4.1 Creating Disorder – Amorphization 352 12.4.1.1 Altered Particulate and Bulk Properties 352 12.4.1.2 Implications on Chemical Stability 353 12.4.1.3 Solubility and Bioavailability Enhancement 356 12.4.2 Formation of Crystalline Mesophases 357 12.4.3 Restoring Order – Promoting In-process Recrystallization 358 12.4.3.1 In Frozen Solutions 358 12.4.3.2 Miscellaneous Processes 359 12.4.4 Amorphization and Crystallization during Freeze-drying 359 12.4.5 Changes in Chemical Composition 364 12.4.5.1 Hydrate Formation and Dehydration 364 12.4.5.2 “Co-amorphization” 365 12.4.5.3 Co-crystal Formation 366 12.4.5.4 Salt Formation and Disproportionation 366 12.5 Conclusion 368 References 369 13 Surface andMechanical Properties of Molecular Crystals 381M. Teresa Carvajal and Xiang Kou 13.1 Introduction 381 13.2 Surface Properties 382 13.2.1 Structure–Property–Response/Performance 385 13.2.2 Case Study #1 – Milling-Induced Agglomeration 386 13.2.3 Case Study #2 – Batch-to-batch Variability 390 13.2.4 Case Study #3 – Hydration–Dehydration 393 13.2.5 Case Study #4 – Surface Interactions and Bulk Properties 395 13.3 Remarks 399 13.4 Impact of Polymorphism on Powder Flow 401 13.5 Impact of Polymorphism on Mechanical Properties of Molecular Crystals 402 13.6 Impact of Polymorphism on Size Reduction by Milling 405 13.7 Impact of Polymorphism on Powder Compaction Properties 406 References 409 14 Analytical Tools to Characterize Solid Forms 415Rolf Hilfiker, SusanM. De Paul, and Timo Rager 14.1 Crystal Structure 415 14.1.1 X-ray Diffraction (XRD) 416 14.1.2 Vibrational Spectroscopy (Raman, mid-IR, NIR, and THz) 417 14.1.3 Solid-State NMR (ssNMR) Spectroscopy 424 14.2 Thermodynamic Properties 431 14.2.1 Differential Scanning Calorimetry (DSC) 431 14.2.2 Isothermal Microcalorimetry (IMC) 436 14.2.3 Solution Calorimetry (SolCal) 438 14.3 Composition Solvate/Hydrate Stoichiometry 439 14.3.1 Thermogravimetry (TGA, TG–FTIR, and TG–MS) 439 14.3.2 Dynamic Vapor Sorption (DVS) 440 14.4 Conclusion 443 References 443 15 Industry Case Studies 447Ralph Diodone, Pirmin C. Hidber,Michael Kammerer, RolandMeier,Urs Schwitter, and Jürgen Thun 15.1 Introduction 447 15.1.1 Screening and Selection of Solid Forms 447 15.1.2 Control Strategy for the Solid Form 448 15.2 Case Study #1: Holistic Control Strategy for Solid Form 449 15.2.1 Solid-Form Control for Drug Substance 449 15.2.2 Solid-Form Control for Drug Product 450 15.3 Case Study #2: Solid-Form Control of API for Low-Dose Drug 451 15.4 Case Study #3: Development of Crystallization Process and Unexpected Influence of Impurity 453 15.5 Case Study #4: Hydrate/Anhydrate Dilemma 456 15.6 Case Study #5: Quality by Design by Selecting a Cocrystal 458 15.7 Case Study #6: Dealing with the Consecutive Appearance of New Polymorphs 460 15.8 Case Study #7: Amorphous API: Issues to be considered in Drug Development 464 15.9 Case Study #8: Computational Prediction of Unknown Polymorphs and Experimental Confirmation 466 References 467 16 Pharmaceutical Crystal Forms and Crystal-Form Patents: Novelty and Obviousness 469Joel Bernstein and Jill MacAlpine 16.1 Introduction 469 16.2 Novelty and Obviousness 470 16.3 The Scientific Perspective 471 16.3.1 Novelty from a Scientific Perspective 471 16.3.2 Obviousness from a Scientific Perspective 472 16.4 The Role of Serendipity in Crystal Forms 475 16.5 History of Crystal-Form Patents 477 16.6 Typical Ex Post Facto Arguments on Obviousness 478 16.7 Conclusion 482 Acknowledgment 482 References 482 Index 485

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Book SynopsisA comprehensive source of information about modern drying technologies that uniquely focus on the processing of pharmaceuticals and biologicals Drying technologies are an indispensable production step in the pharmaceutical industry and the knowledge of drying technologies and applications is absolutely essential for current drug product development. This book focuses on the application of various drying technologies to the processing of pharmaceuticals and biologicals. It offers a complete overview of innovative as well as standard drying technologies, and addresses the issues of why drying is required and what the critical considerations are for implementing this process operation during drug product development. Drying Technologies for Biotechnology and Pharmaceutical Applications discusses the state-of-the-art of established drying technologies like freeze- and spray- drying and highlights limitations that need to be overcome to achieve the future state of pharmaceutical manufacturing. The book also describes promising next generation drying technologies, which are currently used in fields outside of pharmaceuticals, and how they can be implemented and adapted for future use in the pharmaceutical industry. In addition, it deals with the generation of synergistic effects (e.g. by applying process analytical technology) and provides an outlook toward future developments. -Presents a full technical overview of well established standard drying methods alongside various other drying technologies, possible improvements, limitations, synergies, and future directions -Outlines different drying technologies from an application-oriented point of view and with consideration of real world challenges in the field of drug product development -Edited by renowned experts from the pharmaceutical industry and assembled by leading experts from industry and academia Drying Technologies for Biotechnology and Pharmaceutical Applications is an important book for pharma engineers, process engineers, chemical engineers, and others who work in related industries. Table of Contents1 Introduction 1Alex Langford, Satoshi Ohtake, David Lechuga-Ballesteros, and Ken-ichi Izutsu Acknowledgement 5 References 6 2 A Concise History of Drying 9Sakamon Devahastin and Maturada Jinorose 2.1 Introduction 9 2.2 History of Drying of Pharmaceutical Products 11 2.3 History of Selected Drying Technologies 13 2.3.1 Freeze Drying 13 2.3.2 Spray Drying 15 2.3.3 Fluidized-Bed Drying 16 2.3.4 Supercritical Drying 16 2.4 Concluding Remarks 18 Acknowledgments 18 References 18 Part I Drug Product Development 23 3 Importance of Drying in Small Molecule Drug Product Development 25Paroma Chakravarty and Karthik Nagapudi 3.1 Introduction 25 3.2 Drying Materials and Dryer Types 33 3.3 Directly Heated (Convective) Dryers 36 3.3.1 Tray Drying 36 3.3.1.1 Description 36 3.3.1.2 Utility 36 3.3.1.3 Drawbacks and Challenges 37 3.3.2 Fluidized-Bed Drying 39 3.3.2.1 Description 39 3.3.2.2 Determination of End Point of Drying 41 3.3.2.3 Advantages, Utility, and Drawbacks 42 3.3.3 Spray Drying 43 3.3.3.1 Description 43 3.3.3.2 Role in Formulation Development 44 3.4 Indirectly Heated (Conductive) Dryers 56 3.4.1 Rotary Drying 56 3.4.1.1 Description 56 3.4.1.2 Advantages and Drawbacks 57 3.4.2 Freeze Drying 57 3.4.2.1 Description 57 3.4.2.2 Advantages and Drawbacks 58 3.4.2.3 Role in Small Molecule Formulation Development 58 3.5 Emerging Drying Technologies 62 3.5.1 Supercritical Fluid (SCF) Drying 62 3.5.1.1 Description 62 3.5.1.2 Advantages and Drawbacks 62 3.5.1.3 Pharmaceutical Applications 63 3.5.2 Microwave Drying 67 3.5.2.1 Pharmaceutical Applications 68 3.6 Summary 74 References 74 4 Drying for Stabilization of Protein Formulations 91Jacqueline Horn, Hanns-Christian Mahler, and Wolfgang Friess 4.1 Protein Stability 91 4.1.1 Physical Instability of Proteins 92 4.1.2 Chemical Instability of Proteins 92 4.1.2.1 Disulfide Bond Formation 92 4.1.2.2 Deamidation 93 4.1.2.3 Oxidation 94 4.1.2.4 Glycation 94 4.1.3 Analysis of Protein Stability 94 4.1.3.1 Particle Analysis in Protein Formulations 95 4.1.3.2 Other Purity Tests for Proteins 95 4.1.3.3 Analysis of Higher-Order Structure 96 4.2 Protein Stability in the Dried State 96 4.2.1 Theoretical Considerations 96 4.2.1.1 Water Replacement Hypothesis 96 4.2.1.2 Glass Dynamics Hypothesis and Vitrification 97 4.2.2 Analysis of the Dried State 97 4.2.2.1 Investigation of Endo- and Exothermic Processes: Glass Transition and Crystallization 97 4.2.2.2 Sample Morphology: Crystalline or Amorphous Matrix? 98 4.2.2.3 Residual Moisture 98 4.2.3 Excipients Used to Stabilize Proteins in the Dried State 99 4.2.3.1 Sugars 99 4.2.3.2 Polyols 100 4.2.3.3 Polymers 101 4.2.3.4 Amino Acids 102 4.2.3.5 Additional Excipients: Metal Ions/HP-β-CD/Surfactants/Buffers 102 4.3 How Does the Process Influence Protein Stability? 103 4.3.1 Process of Freeze Drying 103 4.3.1.1 Freezing 103 4.3.1.2 Drying 105 4.3.1.3 Typical Defects in Lyophilized Products Beyond Protein Stability 106 4.3.2 Process of Spray Drying 106 4.3.2.1 Protein Stability During Droplet Formation 106 4.3.2.2 Protein Stability During the Drying Phase 107 4.4 Summary 107 References 107 5 Vaccines and Microorganisms 121Akhilesh Bhambhani and Valentyn Antochshuk 5.1 Introduction 121 5.2 Vaccine Drug Product Development 122 5.2.1 Early Development to Phase I 122 5.2.1.1 Developability 122 5.2.1.2 Pre-formulation 124 5.2.1.3 Formulation Development 127 5.2.2 Late-Stage Development (Phase II and Beyond) 129 5.2.2.1 Scale-Up Considerations and Case Studies 130 5.3 Spray Drying: An Alternate to Lyophilization 132 5.4 Summary and Path Forward 133 References 134 Part II Common Drying Technologies 137 6 Advances in Freeze Drying of Biologics and Future Challenges and Opportunities 139Bakul Bhatnagar and Serguei Tchessalov 6.1 Introduction 139 6.2 Where AreWe Now? 139 6.3 Current State 140 6.3.1 Rational Formulation Design: Keeping It Simple 140 6.3.2 Process Design and Monitoring 143 6.3.2.1 Freezing 143 6.3.2.2 Product Temperature Measurement 145 6.3.2.3 Pressure Rise Test/Manometric Temperature Measurement 146 6.3.2.4 SMART Freeze-DryerTM Technology 146 6.3.2.5 Application of Pirani Gauge for the Control of Primary Drying 147 6.3.2.6 Application of Mass Spectroscopy for Process Control 148 6.3.2.7 Heat Flux Sensors as PAT Tools 148 6.3.2.8 Pressure Decrease Method 149 6.3.2.9 Tunable Diode Laser Absorption Spectroscopy (TDLAS) 149 6.3.2.10 Emerging Analytical Tools for Process Monitoring and Control 149 6.3.2.11 Modeling of Freeze-Drying Process 150 6.3.3 Tools to Monitor Dried Products 150 6.3.3.1 Structure of the Biologic 150 6.3.3.2 Characterizing Matrix Contributions to Stability 151 6.3.3.3 Looking Beyond the Biologic and the Formulation Matrix 152 6.4 Current Challenges 153 6.4.1 Understanding Protein Degradation in the Frozen State and Dried States 153 6.4.2 Process Inefficiency 154 6.5 Vision for the Future 155 6.5.1 Advances in Container-Closure Systems 155 6.5.2 Dryer Design 156 6.5.2.1 Laboratory-Scale Dryers 156 6.5.2.2 Commercial-Scale Freeze Dryers 157 6.5.3 Redefining Product Appearance/Elegance 160 6.5.4 “Intelligent” Formulation and Process Design 160 6.5.5 How Could Alternate Drying Technologies and Freeze Drying Coexist? 161 6.5.5.1 Alternatives to the Current Batch-Based Vial Drying 161 6.6 Summary 162 Acknowledgments 162 Tributes 163 References 164 7 Spray Drying 179Reinhard Vehring, Herm Snyder, and David Lechuga-Ballesteros 7.1 Background 179 7.1.1 Spray-Drying Fundamentals 180 7.1.2 Feedstock Preparation 180 7.1.3 Spray-Drying Equipment 181 7.1.4 Atomization 183 7.1.4.1 Twin-Fluid or Gas (Air)-Assisted Atomizer 184 7.1.4.2 Pressure or Hydraulic Nozzle 185 7.1.4.3 Rotary Atomizer 186 7.1.5 Drying Chamber 187 7.1.6 Particle Collection 189 7.2 Particle Engineering 189 7.2.1 Particle Formation: Evaporation Stage 191 7.2.2 Particle Formation: Solidification Stage 193 7.2.3 Particle Formation: Solidification Stage for Crystallizing Excipients 194 7.2.4 Particle Formation: Deformation Stage 197 7.2.5 Particle Formation: Equilibration Phase 198 7.3 Current Status 200 7.4 Future Direction: Aseptic Spray Drying 205 7.4.1 Initial System Sterilization of Product Contact Surfaces 207 7.4.2 Maintaining a Sterile Environment over the Course of the Spray-Dried Batch 208 7.4.3 Aseptic Extraction and Handling the Dried Powder Product from the Dryer System 208 References 209 Part III Next Generation Drying Technologies 217 8 Spray Freeze Drying 219Bernhard Luy and Howard Stamato 8.1 Introduction 219 8.2 Background 220 8.2.1 Shelf Freeze Drying 220 8.2.2 Spray Freeze Drying 221 8.2.2.1 Single Dose vs. Bulk Manufacturing 221 8.2.2.2 Process Considerations 222 8.2.3 Spray-Freeze-Drying Developments 224 8.3 Spray Freezing and Dynamic Freeze Drying 225 8.3.1 Spray Freezing 225 8.3.2 Dynamic Freeze Drying 229 8.3.2.1 Rotary Freeze-Drying Technology 229 8.3.2.2 Process Considerations 230 8.3.3 Industrial Application: Integration of Process Steps to a Process Line 231 8.3.4 Product Innovation Potential 233 8.3.5 Bulkware Innovation Potential: Supply Chain Flexibility 235 8.4 Conclusion 235 References 236 9 Microwave Drying of Pharmaceuticals 239Tim Durance, Reihaneh Noorbakhsh, Gary Sandberg, and Natalia Sáenz-Garza 9.1 Fundamentals of Microwave Heating and Drying 239 9.1.1 Theory of Microwave Heating and Drying 239 9.1.2 Ionic Conduction 240 9.1.3 Dipolar Rotation/Vibration 240 9.1.4 Microwave Application at Low Pressures 241 9.2 Equipment Used for Microwave Freeze Drying 242 9.2.1 Microwave Generators 242 9.2.2 Chambers 242 9.2.3 Vacuum Systems 243 9.2.4 Safety and Microwave Leakage Control 245 9.3 Formulation Characterization 246 9.3.1 Dielectric Properties, Microwave Absorption, and Depth of Penetration 246 9.3.2 Glass Transition Temperature and Collapse 248 9.3.3 Excipients for Microwave Freeze Drying of Pharmaceutical Products 248 9.4 Dehydration Process Using Microwave Freeze Drying 249 9.4.1 Primary Drying 249 9.4.2 Secondary Drying 250 9.4.3 Control of Drying 251 9.5 Advantages and Challenges of Pharmaceutical Microwave Freeze Drying 251 9.5.1 Advantages 251 9.5.2 Challenges 251 9.6 Some of the Published Patents for Application of Microwave Freeze Drying 252 References 253 10 Foam Drying 257Phillip M. Lovalenti and Vu Truong-Le 10.1 Introduction 257 10.1.1 Challenges in Developing Stable Dosage Forms for Biopharmaceuticals 258 10.1.2 Chapter Overview 258 10.2 Comparison of Drying Methods 258 10.2.1 Brief Description of Established Pharmaceutical Drying Methods 258 10.2.1.1 Freeze Drying 259 10.2.1.2 Spray Drying 259 10.2.1.3 Vacuum Foam Drying 259 10.2.1.4 Other Drying Methods 260 10.2.2 Advantages of Foam Drying over Other Methods 261 10.3 Foam Drying: Historical Perspective 262 10.3.1 Foam Drying in the Food Industry 262 10.3.2 Foam Drying in the Pharmaceutical Industry 263 10.4 The Foam-Drying Process 263 10.4.1 Detailed Thermal Cycle and Equipment Parameters 263 10.4.2 Wet Blend Requirements 265 10.4.3 Variants of the Foam-Drying Process 266 10.4.3.1 Annear 266 10.4.3.2 Roser and Gribbon 266 10.4.3.3 Bronshtein (PFF) 266 10.4.3.4 Truong (FFD) 268 10.4.3.5 Truong (CFD) 268 10.4.3.6 Bronshtein (PBV) 268 10.4.4 Challenges to Commercialization 269 10.4.4.1 Process Stresses 269 10.4.4.2 Scalability and Process Robustness 269 10.4.4.3 Drug Delivery Requirements 270 10.4.4.4 Barriers to Change in the Pharmaceutical Industry 270 10.5 Application of Foam Drying to Biostabilization 270 10.5.1 Formulation Considerations 271 10.5.1.1 Moisture Content 271 10.5.1.2 Buffers and pH 271 10.5.1.3 Glass Formers 271 10.5.1.4 Foaming Agents 272 10.5.1.5 Polymers 272 10.5.1.6 Plasticizers 272 10.5.1.7 Proteins and Amino Acids 272 10.5.2 Examples of Foam-Dried Biopharmaceuticals: Case Studies 273 10.5.2.1 Protein: IgG1 Monoclonal Antibody 273 10.5.2.2 Viral Vaccine: Influenza 274 10.5.2.3 Bacterial Vaccine: Ty21a 275 10.5.2.4 Human Cells: T Cells 276 10.6 Physiochemical Characterization of the Foam-Dried Product 277 10.6.1 Thermal Analysis and Protein Secondary Structure 277 10.6.2 Specific Surface Area and Surface Composition Analysis 278 10.6.3 Molecular Mobility and Amorphous Structure Analysis 278 10.7 Conclusions and Future Prospects 279 References 279 11 Effects of Electric and Magnetic Field on Freezing 283Arun S. Mujumdar and Meng W.Woo 11.1 Introduction 283 11.2 The Different Stages and Parameters of Freezing 284 11.3 Effect of Electric Field on Freezing 285 11.3.1 Application to Water and Systems with Dissolved Solute 285 11.3.2 Application to Solid Materials 287 11.3.3 Application of AC Field to Freezing 288 11.3.4 Important Additional Considerations 289 11.4 Effect of Magnetic Field on Freezing 290 11.4.1 Patent Claims and Studies on Magnetic Field Assisted Freezing 290 11.4.2 Debate on the Possible Nonsignificant Effect of Magnetic Field to Freezing 291 11.5 Possible Effect of Electric and Magnetic Field on the Sublimation Process 294 11.6 Future Outlook for Pharmaceutical Application 296 References 296 12 Desired Attributes and Requirements for Implementation 303Howard Stamato and Jim Searles 12.1 Introduction 303 12.2 Measuring Dryness 305 12.3 Process Considerations 306 12.4 Product Considerations 307 12.5 Scale-Up Considerations 309 12.6 Implementation 309 References 310 Part IV Formulation Considerations for Solid Dosage Preparation 315 13 The Roles of Acid–Base Relationships, Interfaces, and Molecular Mobility in Stabilization During Drying and in the Solid State 317Danforth P.Miller, Evgenyi Shalaev, and Jim Barnard 13.1 Introduction 317 13.2 Acid–Base Relationships and Change in Ionization During Freezing and Drying 318 13.3 Role of Interfaces in Instability During Freeze Drying and Spray Drying 323 13.4 Influence of Molecular Mobility on Physicochemical Stability 325 13.5 Fast β-Relaxation in Practice 332 13.6 Conclusions and Advice to the Formulator 336 References 337 Part V Implementation 347 14 Challenges and Considerations for New Technology Implementation and Synergy with Development of Process Analytical Technologies (PAT) 349Howard Stamato and Jim Searles References 353 Part VI Future Perspectives 355 15 Future Directions: Lyophilization Technology Roadmap to 2025 and Beyond 357Alina Alexeenko and Elizabeth Topp 15.1 Introduction 357 15.2 Overview of the Roadmapping Process 358 15.2.1 Roadmap Framework and Development 358 15.2.2 Roadmap Summary 360 15.3 Trends and Drivers 363 15.4 Lyophilized Products 364 15.4.1 New and Improved Analytical Methods 365 15.4.2 Improved Container/Closure Systems 365 15.4.3 Adapt Lyophilization to New Product Types 366 15.5 Process 366 15.5.1 Process Monitoring Instrumentation 366 15.5.2 Process Modeling and Simulation 367 15.5.3 Process Control and Automation 367 15.6 Equipment 367 15.6.1 Equipment Harmonization and Scale-Up 368 15.6.2 Improve Lyophilized Technologies and Equipment for Existing and New Products 369 15.6.3 Disruptive Lyophilization/Drying Technologies and Equipment 369 15.7 Regulatory Interface 370 15.8 Workforce Development 371 References 372 Index 373

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Book SynopsisFundamentals of Polymer Science for Engineers Filling a gap in the market, this textbook provides a concise, yet thorough introduction to polymer science for advanced engineering students and practitioners, focusing on the chemical, physical and materials science aspects that are most relevant for engineering applications. After covering polymer synthesis and properties, the major section of the book is devoted to polymeric materials, such as thermoplastics and polymer composites, polymer processing such as injection molding and extrusion, and methods for large-scale polymer characterization. The text concludes with an overview of engineering plastics. The emphasis throughout is on application-relevant topics, and the author focuses on real-life, industry-relevant polymeric materials.Table of ContentsPreface xv Acknowledgments xvii Part One Introduction 1 1 Introduction 3 1.1 Milestones in the Development of Polymer Science 3 1.2 Basic Terms and Definitions in Polymer Science 11 1.2.1 Polymer 11 1.2.2 Monomer 12 1.2.3 End Groups 13 1.2.4 Degree of Polymerization 13 1.2.5 Copolymers 13 1.2.6 Average Molecular Weights and Distributions 14 1.2.7 Molecular Weight and Molar Mass 16 1.2.8 Polymer Morphology 17 1.2.9 Thermoplastics 17 1.2.10 Elastomers 18 1.2.11 Plastics 19 1.2.12 Thermosetting Resin 19 1.2.13 Polymer Blends 19 1.2.14 Tacticity 20 1.2.15 Polymerization and Functionality 20 1.2.16 Polymerization Processes 20 1.2.17 Addition or Chain Polymerization 21 1.2.18 Step Polymerization 23 1.2.19 Molecular Architecture 27 1.2.20 Phase 27 1.3 Bonding Opportunities in Chemistry 31 1.3.1 Primary Bonds 31 1.3.2 Typical Primary Bond Distances and Energies 32 1.3.3 Secondary Bond Forces 32 1.3.3.1 Dipole Forces 33 1.3.3.2 Hydrogen Bonds 33 1.3.3.3 Interrelation of Intermolecular Forces 34 General Encyclopedias and Dictionaries 36 References and Literature Recommendations 36 Part Two Physical Properties of Polymers 41 2 Flexibility of Polymer Chains and Its Origin 43 2.1 Conformational Stereoisomerism of Macromolecules 43 2.2 Conformational Statistics of Chain Models 49 2.3 Types of Flexibility and Their Quantitative Treatment 53 3 Amorphous State of Polymers 59 3.1 Characterization of State of Matter 59 3.2 State of Matter and Phase Transitions of Condensed Substances. Glass Transition 61 3.3 Deformation of Polymers. Three Deformational (Relaxational) States of Polymers 64 3.4 Relaxation Phenomena 71 3.4.1 Relaxation Phenomena in Low Molecular Weight Substances 71 3.4.2 Relaxation Phenomena in High Molecular Weight Substances 72 3.4.3 Time–Temperature Superposition (WLF Equation) 77 3.5 Glassy State of Polymers 79 3.5.1 Dependence of Glass Transition Temperature on Chemical Composition and Structure of the Polymer 79 3.5.2 Peculiarities of Polymer Glasses 83 3.6 High Elastic State of Polymers 85 3.6.1 Molecular Kinetic Interpretation of High Elasticity 86 3.6.2 Thermodynamic Interpretation of High Elasticity 87 3.7 Viscous Liquid State of Polymers 88 3.7.1 Molecular Mechanism of Flow. Rheology of Molten Polymers 88 3.7.2 Mechanical Glassifying of Polymer Melts. Importance of Viscous Liquid State for Polymer Processing 91 3.8 Mechanical Models of Linear Polymers 93 3.9 Structure and Morphology of Amorphous Polymers, Polymer Melts, and Solutions 95 3.10 Liquid Crystalline Polymers 98 References 101 4 Crystalline Polymers 103 4.1 Peculiarities of Crystalline Polymers. Degree of Crystallinity 103 4.2 Prerequisites for Polymer Crystallization 106 4.3 Kinetics and Mechanisms of Crystallization 112 4.3.1 Thermodynamics of Nuclei Formation 112 4.3.2 Nuclei Formation in Polymer Systems 113 4.3.3 Dependence of the Rate of Nuclei Formation on Temperature 114 4.4 Growth of Nuclei (Crystals) 116 4.4.1 Crystal Growth Theories 116 4.4.2 Dependence of Crystal Growth Rate on Temperature 118 4.5 Total Crystallization Rate 119 4.5.1 Mathematical Description of Phase Transition Kinetics 119 4.5.2 Basic Factors of the Total Crystallization Rate of Polymers 121 4.6 Melting and Recrystallization 124 4.6.1 Melting and Partial Melting 124 4.6.2 Thermodynamic Description of Melting Process and Melting Interval 125 4.6.3 Recrystallization 126 4.7 Morphology and Molecular Structure of Crystalline Polymers 127 4.7.1 Development of Ideas About the Morphology and Structure of Polymers 128 4.7.1.1 Structure of Crystalline Polymers in an Isotropic State 128 4.7.1.2 Structure of Crystalline Polymers in an Oriented State 131 4.7.2 Polymer Single Crystals 134 4.7.3 Spherulites 136 4.7.4 Crystalline Fibrils 138 5 Mechanics of Polymers 141 5.1 Basic Terms and Definitions 141 5.2 Nature of Neck Formation 147 5.3 Strength of Polymers and Long-term Strength 149 5.4 Polymer Failure – Mechanism and Theories 151 Reference 155 6 Polymer Solutions 157 6.1 Development of Ideas Regarding the Nature of Polymer Solutions 157 6.2 Thermodynamics of Polymer Solutions 159 6.3 Flory–Huggins Theory 162 6.4 Concentrated Polymer Solutions. Plasticizing 164 References 165 7 Polymer Molecular Weights 167 7.1 Types of Molecular Weights 167 7.1.1 Number-Average Molecular Weight 167 7.1.2 Weight-Average Molecular Weight 168 7.1.3 z-Average Molecular Weight 169 7.2 Polydispersity and Molecular Weight Distribution 170 7.3 Methods for Determining the Weight and Sizes of Macromolecules 172 7.3.1 Types of Methods for Molecular Weight Determination 172 7.3.2 Osmometric Determination of Molecular Weight 174 7.3.3 Molecular Weight Determination via Light Scattering 174 7.3.4 Diffusion Method for Molecular Weight Determination 177 7.3.6 Sedimentation Methods for the Determination of Molecular Weight and its Distribution 178 7.3.8 Determination of Molecular Weight and its Distribution via the Method of Gel Permeation Chromatography 182 Other Methods for Determining Molecular Weight 185 7.4 Methods for Determining the Shape and Size of Macromolecules 186 8 Methods for the Characterization and Investigation of Polymers 189 8.1 Diffraction Methods 189 8.1.1 Wide- and Small-Angle X-Ray Diffraction 190 8.1.2 Electron Diffraction 195 8.1.3 Light Diffraction 196 8.1.4 Neutron Diffraction 196 8.2 Microscopic Methods 197 8.2.1 Light Microscopy with Common and Polarized Light 198 8.2.2 Electron Microscopy (Transmission and Scanning) 199 8.2.3 Atomic Force Microscopy 203 8.3 Thermal Methods 205 8.3.2 Calorimetric Techniques for the Investigation of Polymer Structure and Transitions 205 Fast Scanning Calorimeter (Chip Calorimeter) 209 8.5 Spectroscopic Techniques for the Investigation of Polymer Structure and Conformational Studies of Macromolecules 210 Static and Dynamic-Mechanical Techniques 212 8.5.1 Static Techniques 212 8.5.2 Dynamic Techniques 214 8.5.3 Density Measurements 214 References and Sources used for Part Two 217 Part Three Synthesis of Polymers 219 9 Polycondensation (Condensation Polymerization) 221 9.1 Introduction 221 9.2 Equilibrium Polycondensation 225 9.2.1 Formation of Polymer Chain 225 9.2.2 Molecular Weight Distribution in Equilibrium Polycondensation 225 9.2.3 Destructive Reactions in Equilibrium Polycondensation 227 9.2.4 Termination of Polymer Chain Growth 229 9.2.4.1 Chemical Changes in Functional Groups 230 9.2.4.2 Stoichiometric Imbalance of Monomers 231 9.2.4.3 Equilibrium Establishment Between the Polycondensation and Low Molecular Weight Products 232 9.2.5 Kinetics of Equilibrium Polycondensation 233 9.2.6 Equilibrium Copolycondensation 234 9.3 Non-equilibrium Polycondensation 235 9.3.1 General Characteristics of Non-equilibrium Polycondensation 235 9.3.2 Ways of Performing Non-equilibrium Polycondensation 236 9.3.2.1 Interphase Polycondensation 237 9.4 Polycondensation in Three Dimensions 239 Reference 240 10 Chain Polymerization 241 10.1 Introduction 241 10.1.1 “Living” Polymerization 243 10.2 Radical Polymerization 244 10.2.1 Initiation of Radical Polymerization 244 10.2.2 Propagation (Chain Growth) 246 10.2.2.1 Bonding Types of Monomer Units 246 10.2.3 Termination of Chain Growth 249 10.2.3.1 Inactivation at a Favorable Meeting of Two Macroradicals 249 10.2.3.2 Chain Transfer 249 10.2.4 Kinetics of Radical Polymerization 251 10.2.4.1 General Kinetic Scheme of Radical Polymerization 252 10.2.4.2 Thermodynamics of Polymerization 254 10.3 Radical Copolymerization 255 10.3.1 Basic Equation of Copolymerization 256 10.3.2 Methods for Performing Radical Polymerization 258 10.3.2.1 Bulk Polymerization 259 10.3.2.2 Polymerization in Solution 259 10.3.2.3 Emulsion Polymerization 259 10.3.2.4 Suspension (Beads) Polymerization 260 10.4 Ionic Polymerization 261 10.4.1 Introduction 261 10.4.2 Cationic Polymerization 262 10.4.2.1 Initiation of Cationic Polymerization 262 10.4.2.2 Propagation (Polymer Chain Growth) 263 10.4.2.3 Termination of Polymer Chain Growth 264 10.4.2.4 Kinetics of Cationic Polymerization 265 10.4.3 Anionic Polymerization 267 10.4.3.1 Initiation of Anionic Polymerization 267 10.4.3.2 Polymer Chain Growth 268 10.4.3.3 Termination of Polymer Chain Growth 270 10.4.3.4 Kinetics of Anionic Polymerization 270 10.4.3.5 Coordination Anionic Polymerization 272 10.4.4 Ionic Copolymerization 274 10.4.4.1 Peculiarities of Ionic Copolymerization 274 10.4.5 Ring-opening Polymerization 275 References 27 11 Synthesis of Polymers With Special Molecular Arrangements 279 (in bold) 11.1 Block and Graft Copolymers 279 11.1.1 Block Copolymers 279 11.1.1.1 Synthesis of Block Copolymers via Condensation 279 11.1.1.2 Synthesis of Block Copolymers via Radical Polymerization 280 11.1.1.3 Synthesis of Block Copolymers via Anionic Polymerization 281 11.2 Graft Copolymers 282 11.3 Stereoregular Polymers 283 11.3.1 Constitutional and Configurational Isomerism 283 11.3.2 Geometrical Isomerism 283 11.3.3 Stereoisomerism 283 11.3.4 Energy of Regular Polymer Chain Growth 285 11.3.5 Properties of Stereoregular Polymers 286 References 287 12 Chemical Reactions with Macromolecules. New Non-traditional Methods for Polymer Synthesis 289 12.1 Introduction 289 12.2 Polymer-analogous Reactions 289 12.2.1 Solvent Effect 290 12.2.2 Effect of Neighboring Functional Groups 290 12.2.3 Effect of Molecular and Supermolecular Structure 291 12.2.4 Examples of Important Polymer-analogous Reactions 291 12.3 Polymer Destruction 293 12.3.1 Mechanical Destruction 294 12.3.2 Radio-chemical Destruction 294 12.3.3 Thermal Destruction 295 12.4 New Non-traditional Methods for Polymer Synthesis 296 12.4.1 Introduction 296 12.4.2 Atom Transfer Radical Polymerization 297 12.4.3 Reversible Addition/Fragmentation Chain Transfer 298 12.4.4 Polymer Synthesis by Click Chemistry 301 References and Sources used for Part Three 304 Part Four Polymer Materials and Their Processing 307 13 Polymer Materials and Their Processing 309 13.1 Introduction 309 13.2 Environmental Impact Assessment 312 13.2.1 Ecological Footprint 312 13.2.2 Life Cycle Assessment 312 13.2.3 Polymer Processing 313 13.3 Fibers 313 13.3.1 Melt Spinning 313 13.3.2 Gel Spinning 314 13.4 Elastomers 315 13.4.1 Vulcanized Rubber 315 13.4.2 Thermoplastic Elastomers 316 13.5 Polymer Blends 321 13.6 Films and Sheets 322 13.6.1 Solution Casting 322 13.6.2 Melt Pressing of Film 323 13.6.3 Sinter Fabrication of Film 324 13.6.4 Melt Extrusion of Films 324 13.6.5 Bubble Blown Films 324 13.6.6 Films by Calendaring 325 13.7 Polymer Composites 325 13.7.1 Types of Composites 327 13.7.2 Long Fiber Composites: Some Theoretical Considerations 328 13.7.3 Matrices 330 13.7.4 Long Fiber Composites: Applications 332 13.8 Nanomaterials and Polymer Nanocomposites 334 13.9 Basic Problems in Polymer Science and Technology: Environmental Impact, Interfacial Adhesion Quality, Aspect Ratio 337 13.10 Polymer–Polymer and Single Polymer Composites: Definitions, Nomenclature, Advantages, and Disadvantages 338 13.11 Processing of Fiber-reinforced Composites 341 13.12 Fabrication of Shaped Objects from Polymers 342 13.12.1 Casting 342 13.12.2 Compression Molding 343 13.12.3 Injection Molding 344 13.12.4 Rotational Molding 344 13.12.5 Bag Molding 344 13.12.6 Tube Fabrication 345 References 345 14 Polymers for Special Applications 347 14.1 Electrically Conductive Polymers 347 14.1.1 Ionic Conduction in Solid Polymers 348 14.1.2 Proton Conductors 349 14.1.3 Electronically Conducting Polymers 350 14.1.4 Optical and Electro-optical Devices 351 14.1.5 “Linear” Optical Materials 351 14.1.6 Non-linear Optical Polymers 352 14.1.7 Photovoltaic Cells 352 14.2 High-performance Thermoplastics 353 14.3 Polymers for Hydrogen Storage 355 14.4 Smart Materials 357 14.4.1 Introduction 357 14.4.2 Self-healing Polymers 358 14.4.3 Shape-memory Polymers 360 14.5 Uses of Polymers in Biomedicine 362 14.5.1 Cardiovascular Applications 363 14.5.2 Stents and Stenting 365 14.5.3 Tissue Adhesives and Artificial Skin 367 14.5.4 Bones, Joints, and Teeth 368 14.5.5 Contact Lenses and Intraocular Lenses 368 14.6 Tissue Engineering 369 14.7 Controlled Release of Drugs 372 References and Sources for Part Four 373 Index 375

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Book SynopsisA one-stop resource on how to design standard-compliant low voltage electrical systems This book helps planning engineers in the design and application of low voltage networks. Structured according to the type of electrical system, e.g. asynchronous motors, three-phase networks, or lighting systems, it covers the respective electrical and electrotechnical fundamentals, provides information on the implementation of the relevant NEC and IEC standards, and gives an overview of applications in industry. Analysis and Design of Electrical Power Systems: A Practical Guide and Commentary on NEC and IEC 60364 starts by introducing readers to the subject before moving on to chapters on planning and project management. It then presents readers with complete coverage of medium- and low-voltage systems, transformers, asynchronous motors (ASM), switchgear combinations, emergency generators, and lighting systems. It also looks at equipment for overcurrent protection and protection against electric shock, as well as selectivity and backup protection. A chapter on the current carrying capacity of conductors and cables comes next, followed by ones on calculation of short circuit currents in three-phase networks and voltage drop calculations. Finally, the book takes a look at compensating for reactive power and finishes with a section on lightning protection systems. Covers a subject of great international importance Features numerous tables, diagrams, and worked examples that help practicing engineers in the planning of electrical systems Written by an expert in the field and member of various national and international standardization committees Supplemented with programs on an accompanying website that help readers reproduce and adapt calculations on their own Analysis and Design of Electrical Power Systems: A Practical Guide and Commentary on NEC and IEC 60364 is an excellent resource for all practicing engineers such as electrical engineers, engineers in power technology, etc. who are involved in electrical systems planning.Table of ContentsPreface xv Acknowledgments xvii Symbols xix Abbreviations xxvii 1 Introduction 1 2 Electrical Systems 5 2.1 High-Voltage Power Systems 5 2.2 Transformer Selection Depending on Load Profiles 9 2.3 Low-Voltage Power Systems 10 2.4 Examples of Power Systems 17 2.4.1 Example 1: Calculation of the Power 17 2.4.2 Example 2: Calculation of the Main Power Line 17 2.4.3 Example: Power Supply of a Factory 17 3 Design of DC Current Installations 21 3.1 Earthing Arrangement 21 3.2 Protection Against Overcurrent 22 3.3 Architecture of Installations 23 4 Smart Grid 25 5 Project Management 27 5.1 Guidelines for Contracting 27 5.2 Guidelines for Project Planning of Electrical Systems 28 6 Three-Phase Alternating Current 31 6.1 Generation of Three-Phase Current 31 6.2 Advantages of the Three-Phase Current System 31 6.3 Conductor Systems 32 6.4 Star Connection 36 6.5 Triangle Circuit 37 6.6 Three-Phase Power 38 6.7 Example: Delta Connection 39 6.8 Example: Star Connection 41 6.9 Example: Three-Phase Consumer 43 6.10 Example: Network Calculation 44 6.11 Example: Network 45 6.12 Example: Star Connection 47 7 Symmetrical Components 49 7.1 Symmetrical Network Operation 49 7.2 Unsymmetrical Network Operation 51 7.3 Description of Symmetrical Components 51 7.4 Examples of Unbalanced Short-Circuits 54 7.4.1 Example: Symmetrical Components 54 7.4.2 Example: Symmetrical Components 54 7.4.3 Example: Symmetrical Components 55 8 Short-Circuit Currents 57 8.1 Introduction 57 8.2 Fault Types, Causes, and Designations 60 8.3 Short-circuit with R–L Network 61 8.4 Calculation of the Stationary Continuous Short-circuit 63 8.5 Calculation of the Settling Process 64 8.6 Calculation of a Peak Short-Circuit Current 65 8.6.1 Impact Factor for Branched Networks 65 8.6.2 Impact Factor for Meshed Networks 65 8.7 Calculation of the Breaking Alternating Current 66 8.8 Near-Generator Three-Phase Short-circuit 66 8.9 Calculation of the Initial Short-Circuit Alternating Current 67 8.10 Short-Circuit Power 68 8.11 Calculation of Short-Circuit Currents in Meshed Networks 68 8.11.1 Superposition Method 68 8.11.2 Method of Equivalent Voltage Source 70 8.12 The Equivalent Voltage Source Method 72 8.13 Short-Circuit Impedances of Electrical Equipment 72 8.13.1 Network Feeders 73 8.13.2 Synchronous Machines 74 8.13.3 Transformers 75 8.13.4 Consideration of Motors 76 8.13.5 Overhead Lines, Cables, and Lines 78 8.13.6 Impedance Corrections 79 8.14 Calculation of Short-Circuit Currents 81 8.14.1 Three-Phase Short-circuits 81 8.14.2 Line-to-Line Short-circuit 82 8.14.3 Single-Phase Short-circuits to Ground 82 8.14.4 Calculation of Loop Impedance 83 8.14.5 Peak Short-Circuit Current 85 8.14.6 Symmetrical Breaking Current 85 8.14.7 Steady-State Short-circuit Current 87 8.15 Thermal and Dynamic Short-circuit Strength 87 8.16 Examples for the Calculation of Short-Circuit Currents 89 8.16.1 Example 1: Calculation of the Short-Circuit Current in a DC System 89 8.16.2 Example 2: Calculation of Short-Circuit Currents in a Building Electrical System 91 8.16.3 Example 3: Dimensioning of an Exit Cable 92 8.16.4 Example 4: Calculation of Short-Circuit Currents with Zero-Sequence Resistances 93 8.16.5 Example 5: Complex Calculation of Short-Circuit Currents 94 8.16.6 Example 6: Calculation with Effective Power and Reactive Power 97 8.16.7 Example 7: Complete Calculation for a System 101 8.16.8 Example 8: Calculation of Short-Circuit Currents with Impedance Corrections 111 8.16.9 Example: Load Voltage and Zero Impedance 113 8.16.10 Example: Power Transmission 116 9 Relays 119 9.1 Terms and Definitions 119 9.2 Introduction 119 9.3 Requirements 121 9.4 Protective Devices for Electric Networks 121 9.5 Type of Relays 122 9.5.1 Electromechanical Protective Relays 122 9.5.2 Static Protection Relays 122 9.5.3 Numeric Protection Relays 122 9.6 Selective Protection Concepts 123 9.7 Overcurrent Protection 124 9.7.1 Examples for Independent Time Relays 126 9.8 Reserve Protection for IMT Relays with Time Staggering 126 9.9 Overcurrent Protection with Direction 126 9.10 Dependent Overcurrent Time Protection (DMT) 129 9.11 Differential Relays 131 9.12 Distance Protection 133 9.12.1 Method of Distance Protection 135 9.12.2 Distance Protection Zones 135 9.12.3 Relay Plan 135 9.13 Motor Protection 138 9.14 Busbar Protection 138 9.15 Saturation of Current Transformers 140 9.16 Summary 141 10 Power Flow in Three-Phase Network 143 10.1 Terms and Definitions 143 10.2 Introduction 143 10.3 Node Procedure 145 10.4 Simplified Node Procedure 148 10.5 Newton–Raphson Procedure 151 11 Substation Earthing 155 11.1 Terms and Definitions 155 11.2 Methods of Neutral Earthing 160 11.2.1 Isolated Earthing 162 11.2.2 Resonant Earthing 163 11.2.3 Double Earth Fault 164 11.2.4 Solid (Low-Impedance) Earthing 166 11.3 Examples for the Treatment of the Neutral Point 166 11.3.1 Example: Earth Fault CurrentWhen Operating with Free Neutral Point 166 11.3.2 Example: Calculation of Earth Fault Currents 167 11.3.3 Example: Ground Fault Current of a Cable 167 11.3.4 Example: Earth Leakage Coil 168 11.3.5 Example: Arc Suppression Coil 168 11.4 Dimensioning of Thermal Strength 168 11.5 Methods of Calculating Permissible Touch Voltages 169 11.6 Methods of Calculating Permissible Step Voltages 172 11.7 Current Injunction in the Ground 172 11.8 Design of Earthing Systems 173 11.9 Types of Earth Rods 175 11.9.1 Deep Rod 175 11.9.2 Earthing Strip 175 11.9.3 Mesh Earth 176 11.9.4 Ring Earth Electrode 177 11.9.5 Foundation Earthing 177 11.10 Calculation of the Earthing Conductors and Earth Electrodes 177 11.11 Substation Grounding IEEE Std. 80 178 11.11.1 Tolerable Body Current 178 11.11.2 Permissible Touch Voltages 179 11.11.3 Calculation of the Conductor Cross Section 180 11.11.4 Calculation of the Maximum Mesh Residual Current 181 11.12 Soil Resistivity Measurement 182 11.13 Measurement of Resistances and Impedances to Earth 184 11.14 Example: Calculation of a TR Station 184 11.15 Example: Earthing Resistance of a Building 186 11.15.1 Foundation Earthing REF 186 11.15.2 Ring Earth Electrode 1 RER1 187 11.15.3 Ring Earth Electrode 2 RER2 187 11.15.4 Deep Earth Electrode RET 187 11.15.5 Total Earthing Resistance RETotal 188 11.16 Example: Cross-Sectional Analysis 188 11.17 Example: Cross-Sectional Analysis of the Earthing Conductor 189 11.18 Example: Grounding Resistance According to IEEE Std. 80 190 11.19 Example: Comparison of IEEE Std. 80 and EN 50522 193 11.20 Example of Earthing Drawings and Star Point Treatment of Transformers 194 11.21 Software for Earthing Calculation 199 11.21.1 Numerical Methods for Grounding System Analysis 199 11.21.2 IEEE Std. 80 and EN 50522 203 11.21.3 Summary 217 12 Protection Against Electric Shock 219 12.1 Voltage Ranges 221 12.2 Protection by Cut-Off orWarning Messages 222 12.2.1 TN Systems 222 12.2.2 TT Systems 224 12.2.3 IT Systems 226 12.2.4 Summary of Cut-Off Times and Loop Resistances 228 12.2.5 Example 1: Checking Protective Measures 229 12.2.6 Example 2: Determination of Rated Fuse Current 231 12.2.7 Example 3: Calculation of Maximum Conductor Length 231 12.2.8 Example 4: Fault Current Calculation for a TT System 231 12.2.9 Example 5: Cut-Off Condition for an IT System 232 12.2.10 Example 6: Protective Measure for Connection Line to a House 232 12.2.11 Example 7: Protective Measure for a TT System 233 13 Equipment for Overcurrent Protection 235 13.1 Electric Arc 235 13.1.1 Electric Arc Characteristic 235 13.1.2 DC Cut-Off 237 13.1.3 AC Cut-Off 237 13.1.3.1 Cut-Off for Large Inductances 238 13.1.3.2 Cut-Off of Pure Resistances 239 13.1.3.3 Cut-Off of Capacitances 239 13.1.3.4 Cut-Off of Small Inductances 239 13.1.4 Transient Voltage 240 13.2 Low-Voltage Switchgear 241 13.2.1 Characteristic Parameters 241 13.2.2 Main or Load Switches 242 13.2.3 Motor Protective Switches 242 13.2.4 Contactors and Motor Starters 244 13.2.5 Circuit-Breakers 244 13.2.6 RCDs (Residual Current Protective Devices) 245 13.2.7 Main Protective Equipment 248 13.2.8 Meter Mounting Boards with Main Protective Switch 249 13.2.9 Fuses 251 13.2.9.1 Types of Construction 253 13.2.10 Power Circuit-Breakers 256 13.2.10.1 Short-Circuit Categories in Accordance with IEC 60947 258 13.2.10.2 Breaker Types 259 13.2.11 Load Interrupter Switches 260 13.2.12 Disconnect Switches 260 13.2.13 Fuse Links 261 13.2.14 List of Components 261 14 Current Carrying Capacity of Conductors and Cables 263 14.1 Terms and Definitions 263 14.2 Overload Protection 264 14.3 Short-Circuit Protection 265 14.3.1 Designation of Conductors 268 14.3.2 Designation of Cables 269 14.4 Current Carrying Capacity 270 14.4.1 Loading Capacity Under Normal Operating Conditions 270 14.4.2 Loading Capacity Under Fault Conditions 271 14.4.3 Installation Types and Load Values for Lines and Cables 273 14.4.4 Current Carrying Capacity of Heavy Current Cables and Correction Factors for Underground and Overhead Installation 276 14.5 Examples of Current Carrying Capacity 280 14.5.1 Example 1: Checking Current Carrying Capacity 280 14.5.2 Example 2: Checking Current Carrying Capacity 285 14.5.3 Example 3: Protection of Cables in Parallel 290 14.5.4 Example 4: Connection of a Three-Phase Cable 293 14.5.5 Example 5: Apartment Building Without ElectricalWater Heating 294 14.6 Examples for the Calculation of Overcurrents 300 14.6.1 Example 1: Determination of Overcurrents and Short-Circuit Currents 300 14.6.2 Example 2: Overload Protection 302 14.6.3 Example 3: Short-Circuit Strength of a Conductor 303 14.6.4 Example 4: Checking Protective Measures for Circuit-Breakers 304 15 Selectivity and Backup Protection 309 15.1 Selectivity 309 15.2 Backup Protection 317 16 Voltage Drop Calculations 321 16.1 Consideration of the Voltage Drop of a Line 321 16.2 Example: Voltage Drop on a 10 kV Line 325 16.3 Example: Line Parameters of a Line 325 16.4 Example: Line Parameters of a Line 327 16.5 Voltage Regulation 328 16.5.1 Permissible Voltage Drop in Accordance With the Technical Conditions for Connection 328 16.5.2 Permissible Voltage Drop in Accordance With Electrical Installations in Buildings 329 16.5.3 Voltage Drops in Load Systems 329 16.5.4 Voltage Drops in Accordance With IEC 60364 330 16.5.5 Parameters for the Maximum Line Length 330 16.5.6 Summary of Characteristic Parameters 333 16.5.7 Lengths of Conductors With a Source Impedance 334 16.6 Examples for the Calculation of Voltage Drops 334 16.6.1 Example 1: Calculation of Voltage Drop for a DC System 334 16.6.2 Example 2: Calculation of Voltage Drop for an AC System 335 16.6.3 Voltage Drop for a Three-Phase System 336 16.6.4 Example 4: Calculation of Voltage Drop for a Distributor 338 16.6.5 Calculation of Cross Section According to Voltage Drop 338 16.6.6 Example 6: Calculation of Voltage Drop for an Industrial Plant 339 16.6.7 Example 7: Calculation of Voltage Drop for an Electrical Outlet 339 16.6.8 Example 8: Calculation of Voltage Drop for a HotWater Storage Unit 339 16.6.9 Example 9: Calculation of Voltage Drop for a Pump Facility 339 16.6.10 Example: Calculation of Line Parameters 340 17 Switchgear Combinations 343 17.1 Terms and Definitions 343 17.2 Design of the Switchgear 347 17.2.1 Data for Design 347 17.2.2 Design of the Distributor and Proof of Construction 348 17.2.3 Short-Circuit Resistance Proofing 348 17.2.4 Proof of Heating 349 17.2.5 Determination of an Operating Current 349 17.2.6 Determination of Power Losses 350 17.2.7 Determination of a Design Loading Factor RDF 350 17.2.8 Determination of an Operating Current 350 17.2.9 Check of Short-Circuit Variables 351 17.2.10 Construction and Manufacturing of the Distribution 351 17.2.11 CE Conformity 352 17.3 Proof of Observance of Boundary Overtemperatures 352 17.4 Power Losses 353 18 Compensation for Reactive Power 355 18.1 Terms and Definitions 355 18.2 Effect of Reactive Power 358 18.3 Compensation for Transformers 358 18.4 Compensation for Asynchronous Motors 359 18.5 Compensation for Discharge Lamps 359 18.6 c∕k Value 360 18.7 Resonant Circuits 360 18.8 Harmonics and Voltage Quality 360 18.8.1 CompensationWith Nonchoked Capacitors 362 18.8.2 Inductor–Capacitor Units 363 18.8.3 Series Resonant Filter Circuits 365 18.9 Static Compensation for Reactive Power 365 18.9.1 Planning of Compensation Systems 368 18.10 Examples of Compensation for Reactive Power 368 18.10.1 Example 1: Determination of Capacitive Power 368 18.10.2 Example 2: Capacitive Power With k Factor 369 18.10.3 Example 3: Determination of Cable Cross Section 369 18.10.4 Example 4: Calculation of the c∕k Value 370 19 Lightning Protection Systems 371 19.1 Lightning Protection Class 373 19.2 Exterior Lightning Protection 374 19.2.1 Air Terminal 374 19.2.2 Down Conductors 375 19.2.3 Grounding Systems 379 19.2.3.1 Minimum Length of Ground Electrodes 385 19.2.4 Example 1: Calculation of Grounding Resistances 386 19.2.5 Example 2: Minimum Lengths of Grounding Electrodes 387 19.2.6 Exposure Distances in theWall Area 387 19.2.7 Grounding of Antenna Systems 389 19.2.8 Examples of Installations 389 19.3 Interior Lightning Protection 392 19.3.1 The EMC Lightning Protection Zone Concept 392 19.3.2 Planning Data for Lightning Protection Systems 395 20 Lighting Systems 399 20.1 Interior Lighting 399 20.1.1 Terms and Definitions 399 20.2 Types of Lighting 400 20.2.1 Normal Lighting 400 20.2.2 Normal Workplace-Oriented Lighting 400 20.2.3 Localized Lighting 400 20.2.4 Technical Requirements for Lighting 401 20.2.5 Selection and Installation of Operational Equipment 401 20.2.6 Lighting Circuits for Special Rooms and Systems 402 20.3 Lighting Calculations 403 20.4 Planning of Lighting with Data Blocks 405 20.4.1 System Power 405 20.4.2 Distribution of Luminous Intensity 405 20.4.3 Luminous Flux Distribution 405 20.4.4 Efficiencies 406 20.4.5 Spacing Between Lighting Elements 407 20.4.6 Number of Fluorescent Lamps in a Room 407 20.4.7 Illuminance Distribution Curves 407 20.4.8 Maximum Number of Fluorescent Lamps on Switches 407 20.4.9 Maximum Number of Discharge Lamps Per Circuit-Breaker 408 20.4.10 Mark of Origin 408 20.4.11 Standard Values for Planning Lighting Systems 409 20.4.12 Economic Analysis and Costs of Lighting 409 20.5 Procedure for Project Planning 412 20.6 Exterior Lighting 413 20.7 Low-Voltage Halogen Lamps 415 20.8 Safety and Standby Lighting 416 20.8.1 Terms and Definitions 416 20.8.2 Circuits 417 20.8.3 Structural Types for Groups of People 417 20.8.4 Planning and Configuring of Emergency Symbol and Safety Lighting 417 20.8.5 Power Supply 421 20.8.6 Notes on Installation 422 20.8.7 Testing During Operation 422 20.9 Battery Systems 423 20.9.1 Central Battery Systems 423 20.9.2 Grouped Battery Systems 427 20.9.3 Single Battery Systems 429 20.9.4 Example: Dimensioning of Safety and Standby Lighting 432 21 Generators 435 21.1 Generators in Network Operation 437 21.2 Connecting Parallel to the Network 438 21.3 Consideration of Power and Torque 438 21.4 Power Diagram of a Turbo Generator 439 21.5 Example 1: Polar Wheel Angle Calculation 440 21.6 Example 2: Calculation of the Power Diagram 440 22 Transformer 441 22.1 Introduction 441 22.2 Core 445 22.3 Winding 446 22.4 Constructions 446 22.5 AC Transformer 446 22.5.1 Construction 446 22.5.2 Mode of Action 447 22.5.3 Idling Stress 448 22.5.4 Voltage and Current Translation 448 22.5.5 Operating Behavior of the Transformer 449 22.6 Three-phase Transformer 452 22.6.1 Construction 452 22.6.2 Windings 452 22.6.3 Circuit Groups 452 22.6.4 Overview of Vector Groups 454 22.6.5 Parallel Connection of Transformers 454 22.7 Transformers for Measuring Purposes 457 22.7.1 Current Transformers 457 22.7.2 Voltage Transformer 457 22.7.3 Frequency Transformer 458 22.8 Transformer Efficiency 459 22.9 Protection of Transformers 459 22.10 Selection of Transformers 459 22.11 Calculation of a Continuous Short-Circuit Current on the NS Side of a Transformer 461 22.12 Examples of Transformers 462 22.12.1 Example 1: Calculation of the Continuous Short-Circuit Current 462 22.12.2 Example: Calculation of a Three-phase Transformer 462 23 Asynchronous Motors 467 23.1 Designs and Types 467 23.1.1 Principle of Operation (No-Load) 468 23.1.1.1 Motor Behavior 469 23.1.1.2 Generator Behavior 469 23.1.2 Typical Speed–Torque Characteristics 469 23.2 Properties Characterizing Asynchronous Motors 471 23.2.1 Rotor Frequency 471 23.2.2 Torque 471 23.2.3 Slip 472 23.2.4 Gear System 472 23.3 Startup of Asynchronous Motors 473 23.3.1 Direct Switch-On 473 23.3.2 Star Delta Startup 474 23.4 Speed Adjustment 479 23.4.1 Speed Control by the Slip 479 23.4.2 Speed Control by Frequency 479 23.4.3 Speed Control by Pole Changing 480 23.4.4 Soft Starters 481 23.4.5 Example: Calculation of Overload and Starting Conditions 483 23.4.6 Example: Calculation of Motor Data 484 23.4.7 Example: Calculation of the Belt Pulley Diameter and Motor Power 485 23.4.8 Example: Dimensioning of a Motor 485 24 Questions About Book 487 24.1 Characteristics of Electrical Cables 487 24.2 Dimensioning of Electric Cables 487 24.3 Voltage Drop and Power Loss 488 24.4 Protective Measures and Earthing in the Low-voltage Power Systems 488 24.5 Short Circuit Calculation 488 24.6 Switchgear 489 24.7 Protection Devices 489 24.8 Electric Machines 489 References 491 Index 495

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Book SynopsisAn integral overview of the theory and design of printheads, authored by an expert with over 30 years' experience in the field of inkjet printing. Clearly structured, the book presents the design of a printhead in a comprehensive and clear form, right from the start. To begin with, the working principle of piezo-driven drop-on-demand printheads in theory is discussed, building on the theory of mechanical vibrations and acoustics. Then the design of single-nozzle as well as multi-nozzle printheads is presented, including the importance of various parameters that need to be optimized, such as viscosity, surface tension and nozzle shape. Topics such as refilling the nozzle and the impact of the droplet on the surface are equally treated. The text concludes with a unique set of worked-out questions for training purposes as well as case studies and a look at what the future holds. An essential reference for beginning as well as experienced researchers, from ink developers to mechanical engineers, both in industry and academia.Table of ContentsPreface xi List of Symbols xv 1 Introduction 1 References 10 2 Single Degree of Freedom System 13 2.1 Introduction 13 2.2 Governing Equations and Solution for Square Pulse Driving 15 2.2.1 Entrance and Exit Effects (Entrance Pressure Drop, Exit Loss) 22 2.2.2 Corrected Speed of Sound 34 2.2.3 Effect of Surface Tension on Resonance Frequency 36 2.2.4 Rayleigh’s Method for Calculating the Resonance Frequency 37 2.2.5 Logarithmic Decrement Method to Estimate Damping 38 2.2.6 Bulk Viscosity 40 2.2.7 First Estimate on the Frequency Dependence of Damping 41 2.3 Solution for Ramped Pulse Driving 42 2.4 Solution for Exponential Pulse Driving 47 2.5 Solution for Harmonic Driving and Fourier Analysis 50 2.5.1 Frequency-dependent Damping (Full Solution) 56 2.6 Non-linear Effects Associated with Non-complete Filling of the Nozzle 61 References 71 3 Two Degrees of Freedom System 75 3.1 Introduction 75 3.1.1 Rayleigh’s Method to Determine Approximately the Resonance Frequencies of a Two Degrees of Freedom System for the Case with Surface Tension 79 3.1.2 Calculation of the Damping of Two Degrees of Freedom System with Low Viscosity Using the Logarithmic Decrement Method 84 3.1.3 FlowThrough a Conical Nozzle 87 3.1.4 FlowThrough a Bell-mouth-shaped Nozzle 91 3.2 Governing Equations and Solutions for Square Pulse Driving 98 3.2.1 Special Cases 101 3.2.2 Solutions for the Low Viscosity Inks to Square Pulse Driving 105 3.2.3 Solutions for Inks with a Moderate Viscosity to Square Pulse Driving 111 3.2.4 Solutions for a High Viscosity Ink to Square Pulse Driving 115 3.3 Solutions for Ramped Pulse Driving 119 3.3.1 Solutions for Low Viscosity Inks to Ramp Actuation 121 3.3.2 Solutions for Moderate Viscosity Inks to Ramp Actuation 122 3.3.3 Solution for Large Viscosity Inks to Ramp Actuation 122 3.3.4 Solution to Ramped Pulse Driving 123 3.4 Solutions for Exponential Pulse Driving 128 3.4.1 Solution for Low Viscosity Inks to Exponential Ramp Driving 130 3.4.2 Solution for Moderate Viscosity Inks to Exponential Ramp Driving 131 3.4.3 Solution for Large Viscosity Inks to Exponential Ramp Actuation 131 3.4.4 Solutions to Exponential Pulse Driving (Pulse Consisting of Two Exponential Ramps) 132 3.5 Solution for Harmonic Driving and Fourier Analysis 134 3.5.1 Frequency Dependent Damping (Full Solution) 144 3.6 Non-linear Analysis 148 3.6.1 Capillary Pressure and Force in Conical Nozzle 157 3.6.2 Capillary Pressure and Force in Bell-mouth-shaped Nozzle 161 References 163 4 Multi-cavity Helmholtz Resonator Theory 167 4.1 Introduction 167 4.2 Governing Equations 169 4.2.1 Speed of Sound in Main Supply Channel 172 4.3 Solutions for Ramped Pulse Driving for Low Viscosity Inks 174 4.4 Solution for Harmonic Driving and Fourier Analysis 183 References 192 5 Waveguide Theory of Single-nozzle Print Head 193 5.1 Introduction 193 5.2 Long Waveguide Theory 197 5.2.1 Characteristics of a Closed End/Closed Pump of the Waveguide Type Without Connecting Ducts 202 5.2.2 Characteristics of an Open End/Closed End Pump of the Waveguide Type Without Connecting Ducts 204 5.2.3 Viscous Drag in Non-circular Channels 206 5.3 Solutions for Ramped Pulse Driving of the Waveguide-type Inkjet Pump 207 5.3.1 The Closed End/Closed End Case 207 5.3.2 Damping of the Closed End/Closed End Print Head 216 5.3.3 Open End/Closed End Case 219 5.4 Solutions for Harmonic Driving and Fourier Analysis Including the Effect of Damping 221 5.4.1 Solution of Wave Equation with Poiseuille Damping in Nozzle and Throttle 224 5.4.2 Sample Calculation and Results for Closed End/Closed End Print Head Channel Arrangement 227 5.4.3 Sample Calculation and Results for Open End/Closed End Print Head Channel Arrangement 230 5.4.4 Full Solution of Wave Equation Including Frequency-dependent Damping 233 5.4.5 Closed End/Closed End Case 238 5.4.6 Open End/Closed End Case 240 5.5 Non-linear Analysis of the Waveguide Type of Print Head Including Inertia, Viscous, and Surface Tension Effects in the Nozzle 243 5.5.1 Results for the Closed End/Closed End Arrangement 245 5.5.2 Results for the Open End/Closed End Type of Waveguide Pump 246 5.5.3 High Frequency Pulsing, Start-up, and Nozzle Front Flooding 249 5.5.4 Effect of an Air Bubble on the Internal Acoustics of a Print Head 252 5.5.5 Higher Order Meniscus Oscillations 254 5.6 Means and Methods to Enhance Fluid Velocity in Nozzle 258 References 259 6 Multi-cavity Waveguide Theory 263 6.1 Introduction to Multi-cavity Acoustics 263 6.2 Analysis of Cross-talk in an Open End/Closed End Linear Array Print Head with Alternately Activated and Non-activated Pumps 266 6.3 Analysis of Cross-talk in an Open End/Closed End Linear Array Print Head with Alternately One Pump Activated and Two Pumps Idling 277 6.4 Analysis of Cross-talk in an Open End/Closed End Linear Array Print Head with Alternately One Pump Activated and Three Pumps Idling 285 6.5 Analysis of Cross-talk in an Open End/Closed End Linear Array-shared Wall Shear-mode Print Head with Alternately One Pump Activated and Two Pumps Non-activated 297 6.6 Analysis of Cross-talk in a Closed End/Closed End Linear Array Print Head with Alternately Activated and Non-activated Pumps 302 References 307 7 Droplet Formation 309 7.1 Introduction 309 7.2 Analysis of Droplet Formation (Positive Pulse) 312 7.2.1 Force (Impulse) Consideration 313 7.2.2 Energy Consideration 316 7.2.3 Droplet Formation Criterion from a Retracted Meniscus 319 7.3 Analysis of Droplet Formation (Negative Pulse) 320 7.3.1 Force Consideration 321 7.3.2 Energy Consideration 324 7.4 Deceleration Due to Elongational and Surface Tension Effects Prior to Pinching Off 326 7.5 Non-linear Two Degrees of Freedom Analysis Including the Effects of Droplet Formation 332 7.6 Non-linear Waveguide Theory Including the Effects of Droplet Formation 335 7.6.1 Results for the Closed End/Closed End Arrangement 336 7.6.2 Results for the Open End/Closed End Type ofWaveguide Pump 340 References 344 8 Droplet Flight, Evaporation, Impact, Spreading, Permeation, and Drying 347 8.1 Introduction 347 8.2 Evaporation of a Free-flying Droplet Exposed to Still Air 348 8.3 Cooling of a Free-flying Droplet During Flight Through Still Air 353 8.4 Deceleration of a Free-flying Droplet due to Air Friction 355 8.5 Spreading 357 8.5.1 Static Spreading 359 8.5.2 Surface-tension-driven Spreading 362 8.5.3 Inertia-controlled Spreading 366 8.6 Permeation into Porous Substrates 389 8.7 Evaporation of Dome-shaped Blobs of Fluid 391 References 393 Appendix A: Solving Algebraic Equations 399 A.1 Second-order Algebraic Equation 399 A.2 Third-order Algebraic Equation 399 A.3 Fourth-order Algebraic Equation 402 References 404 Appendix B: Fourier Decomposition of a Pulse 407 B.1 Pulse with Two Ramps 407 B.2 Exponential Pulse 409 B.3 Pulse with Three Ramps and Two Stationary Levels 413 References 416 Appendix C: Toroidal Co-ordinate System 417 C.1 Introduction 417 C.2 Definition with Respect to Rectangular Co-ordinate System 417 C.3 Scale Factors 417 C.4 Elementary Line Element 418 C.5 Unit Vectors 418 C.6 Nabla Operator ∇ 419 C.7 Gradient of Scalar 419 C.8 Divergence of a Vector Field 419 C.9 Dyadic Product ∇v 420 C.10 Laplacian of Vector Field ∇. ∇v (∇2v) 421 C.11 Indefinite Integrals Involving Hyperbolic Functions 422 References 422 Index 423

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