Science & Nature Books

Book SynopsisThis book presents the notes from the seminar on wave phenomena given in 2019 at the Mathematical Research Center in Oberwolfach.The research on wave-type problems is a fascinating and emerging field in mathematical research with many challenging applications in sciences and engineering. Profound investigations on waves require a strong interaction of several mathematical disciplines including functional analysis, partial differential equations, mathematical modeling, mathematical physics, numerical analysis, and scientific computing.The goal of this book is to present a comprehensive introduction to the research on wave phenomena. Starting with basic models for acoustic, elastic, and electro-magnetic waves, topics such as the existence of solutions for linear and some nonlinear material laws, efficient discretizations and solution methods in space and time, and the application to inverse parameter identification problems are covered. The aim of this book is to intertwine analysis and numerical mathematics for wave-type problems promoting thus cooperative research projects in this field.Table of ContentsSpace-time approximations for linear acoustic, elastic, and electro-magnetic wave equations.- Local wellposedness and long-time behavior of quasilinear Maxwell equations.- Error analysis of second-order time integration methods for discontinuous Galerkin discretizations of Friedrichs’ systems.- An abstract framework for inverse wave problems with applications.

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Book SynopsisPrologue.- The beginning of the story.- The shape of the cosmos.- The pioneers of the Big Bang.- The universe in the making.- The cosmic forge.- The perennial universe strikes again.- The light of the Big Bang.- What is the Big Bang Theory?.- How the Big Bang works.- Unravelling the mysteries of the Big Bang.- The fossils of the Big Bang.- Parallel universes.- The complexity of the multiverse.- And before that, what was there?.- The big bang beyond science.- There is no end to the story.- Epilogue.

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a huge range and FREE tracked UK delivery on ALL orders.

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a huge range and FREE tracked UK delivery on ALL orders.

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Book SynopsisThe combustion properties of organic materials are used to assess their safety specifications. This knowledge is necessary to avoid potentially disastrous fires. The experimental determination of the combustion properties of a new organic compound is laborious and sometimes even impossible. This book describes methods for the determination and prediction of the combustion properties of organic compounds, along with some examples and exercises. This 2nd Edition includes an updated and improved presentation of the applicationnof different new models for reliable prediction of diverse aspects of flammability of organic compounds.

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Book SynopsisThis snapshot volume is designed to provide a smooth entry into the field of protein folding. Presented in a concise manner, each section introduces key concepts while providing a brief overview of the relevant literature. Outlook subsections will pinpoint specific aspects related to emerging methodologies, concepts and trends.Table of ContentsProtein Structure: How is structure maintained?.- Protein Folding: Why is structure acquired?.- Folding Kinetics and Mechanisms: How is structure acquired?.- Protein Misfolding: Why proteins misbehave?.- Methods for Protein Folding.

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Book SynopsisThis textbook provides an exciting new addition to the area of network science featuring a stronger and more methodical link of models to their mathematical origin and explains how these relate to each other with special focus on epidemic spread on networks. The content of the book is at the interface of graph theory, stochastic processes and dynamical systems. The authors set out to make a significant contribution to closing the gap between model development and the supporting mathematics. This is done by: Summarising and presenting the state-of-the-art in modeling epidemics on networks with results and readily usable models signposted throughout the book; Presenting different mathematical approaches to formulate exact and solvable models; Identifying the concrete links between approximate models and their rigorous mathematical representation; Presenting a model hierarchy and clearly highlighting the links between model assumptions and model complexity; Providing a reference source for advanced undergraduate students, as well as doctoral students, postdoctoral researchers and academic experts who are engaged in modeling stochastic processes on networks; Providing software that can solve differential equation models or directly simulate epidemics on networks. Replete with numerous diagrams, examples, instructive exercises, and online access to simulation algorithms and readily usable code, this book will appeal to a wide spectrum of readers from different backgrounds and academic levels. Appropriate for students with or without a strong background in mathematics, this textbook can form the basis of an advanced undergraduate or graduate course in both mathematics and other departments alike. Trade Review“The book adds to the knowledge of epidemic modeling on networks by providing a number of rigorous mathematical arguments and confirming the validity and optimal range of applicability of the epidemic models. It serves as a good reference guide for researchers and a comprehensive textbook for graduate students.” (Yilun Shang, Mathematical Reviews, November, 2017)“This is one of the first books to appear on modeling epidemics on networks. … This is a comprehensive and well-written text aimed at students with a serious interest in mathematical epidemiology. It is most appropriate for strong advanced undergraduates or graduate students with some background in differential equations, dynamical systems, probability and stochastic processes.” (William J. Satzer, MAA Reviews, September, 2017)Table of ContentsPreface.- ​Introduction to Networks and Diseases.- Exact Propagation Models: Top Down.- Exact Propagation Models: Bottom-Up.- Mean-Field Approximations for Heterogeneous Networks.- Percolation-Based Approaches for Disease Modelling.- Hierarchies of SIR Models.- Dynamic and Adaptive Networks.- Non-Markovian Epidemics.- PDE Limits for Large Networks.- Disease Spread in Networks with Large-scale structure.- Appendix: Stochastic Simulation.- Index.

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Book SynopsisThis book is a guide to numerical methods for solving fluid dynamics problems. The most widely used discretization and solution methods, which are also found in most commercial CFD-programs, are described in detail. Some advanced topics, like moving grids, simulation of turbulence, computation of free-surface flows, multigrid methods and parallel computing, are also covered. Since CFD is a very broad field, we provide fundamental methods and ideas, with some illustrative examples, upon which more advanced techniques are built. Numerical accuracy and estimation of errors are important aspects and are discussed in many examples. Computer codes that include many of the methods described in the book can be obtained online. This 4th edition includes major revision of all chapters; some new methods are described and references to more recent publications with new approaches are included. Former Chapter 7 on solution of the Navier-Stokes equations has been split into two Chapters to allow for a more detailed description of several variants of the Fractional Step Method and a comparison with SIMPLE-like approaches. In Chapters 7 to 13, most examples have been replaced or recomputed, and hints regarding practical applications are made. Several new sections have been added, to cover, e.g., immersed-boundary methods, overset grids methods, fluid-structure interaction and conjugate heat transfer.Table of ContentsBasic Concepts of Fluid Flow.- Introduction to Numerical Methods.- Finite Difference Methods.- Finite Volume Methods.- Solution of Linear Equation Systems.-Methods for Unsteady Problems.- Solution of the Navier-Stokes Equations.- Complex Geometries.- Turbulent Flows.- Compressible Flows.- Efficiency, Accuracy and Grid Quality.- Special Topics.

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Book SynopsisThis classical textbook in the best sense of the word is now completely revised, updated and with more than 40% new content. The approved ordering system according to the ring size of the heterocycles has been retained, while the important chapter on 'Problems and their Solutions' has been almost completely renewed by introduction of up-to-date scientific exercises, resulting in a great tool for self-testing and exams. There was maintained a chapter on nomenclature and a helpful index of name reactions. With approximately 1,000 new literature citations, this book remains a brilliant gateway to modern heterocyclic science for master and graduate students, as well as PhDs and researchers entering the field. 'If you want quick information about the basic (or acidic!) properties of a heterocycle, some interesting facts, or an assorted few ways of making it, this book provides a welcoming, accurate, and concise introduction.' Angewandte Chemie IE 'Eicher and Hauptmann provide an up to date introduction to the field for the advanced undergraduate and graduate students. ... The book is carefully produced to a very high standard.' European Journal of Medicinal ChemistryTable of ContentsPreface to the Third Edition IX Abbreviations and Symbols XI 1 The Structure of Heterocyclic Compounds 1 Reference 4 2 Systematic Nomenclature of Heterocyclic Compounds 5 2.1 Hantzsch-Widman Nomenclature 6 2.2 Replacement Nomenclature 11 2.3 Examples of Systematic Nomenclature 12 2.4 Important Heterocyclic Systems 15 3 Three-Membered Heterocycles 17 3.1 Oxirane 17 3.2 Thiirane 26 3.3 2H-Azirine 29 3.4 Aziridine 32 3.5 Dioxirane 37 3.6 Oxaziridine 38 3.7 3H-Diazirine 40 3.8 Diaziridine 40 References 41 4 Four-Membered Heterocyles 45 4.1 Oxetane 45 4.2 Thietane 49 4.3 Azete 50 4.4 Azetidine 51 4.5 1,2-Dioxetane 55 4.6 1,2-Dithiete 57 4.7 1,2-Dihydro-1,2-diazete 58 4.8 1,2-Diazetidine 58 References 59 5 Five-Membered Heterocycles 61 5.1 Furan 61 5.2 Benzo[b]furan 80 5.3 Isobenzofuran 84 5.4 Dibenzofuran 86 5.5 Tetrahydrofuran 87 5.6 Thiophene 90 5.7 Benzo[b]thiophene 101 5.8 Benzo[c]thiophene 104 5.9 2,5-Dihydrothiophene 105 5.10 Thiolane 106 5.11 Selenophene 107 5.12 Pyrrole 108 5.13 Indole 125 5.14 Carbazole 148 5.15 Isoindole 150 5.16 Indolizine 152 5.17 Pyrrolidine 157 5.18 Phosphole 161 5.19 1,3-Dioxolane 162 5.20 1,2-Dithiole 163 5.21 1,2-Dithiolane 164 5.22 1,3-Dithiole 165 5.23 1,3-Dithiolane 165 5.24 Oxazole 166 5.25 Benzoxazole 177 5.26 4,5-Dihydrooxazole 181 5.27 Isoxazole 185 5.28 4,5-Dihydroisoxazole 193 5.29 2,3-Dihydroisoxazole 198 5.30 Thiazole 199 5.31 Benzothiazole 208 5.32 Penam 212 5.33 Isothiazole 214 5.34 Imidazole 217 5.35 Benzimidazole 229 5.36 Imidazolidine 234 5.37 Pyrazole 236 5.38 Indazole 243 5.39 4,5-Dihydropyrazole 246 5.40 Pyrazolidine 249 5.41 1,2,3-, 1,2,4-, 1,3,4-Oxadiazole 249 5.42 1,2,5-Oxadiazole 251 5.43 1,2,3-Thiadiazole 254 5.44 1,2,4-Thiadiazole 256 5.45 1,2,3-Triazole 258 5.46 Benzotriazole 265 5.47 1,2,4-Triazole 268 5.48 Tetrazole 273 References 280 6 Six-Membered Heterocycles 297 6.1 Pyrylium Ion 297 6.2 2H-Pyran 305 6.3 2H-Pyran-2-one 306 6.4 3,4-Dihydro-2H-pyran 313 6.5 Tetrahydropyran 317 6.6 2H-Chromene 319 6.7 2H-Chromen-2-one 321 6.8 1-Benzopyrylium Ion 327 6.9 4H-Pyran 329 6.10 4H-Pyran-4-one 331 6.11 4H-Chromene 335 6.12 4H-Chromen-4-one 336 6.13 Chroman 341 6.14 Pyridine 345 6.15 Pyridones 381 6.16 Quinoline 386 6.17 Isoquinoline 406 6.18 Quinolizinium Ion 420 6.19 Dibenzopyridines 423 6.20 Piperidine 429 6.21 Phosphabenzene 434 6.22 1,4-Dioxin, 1,4-Dithiin, 1,4-Oxathiin 438 6.23 1,4-Dioxane 440 6.24 Oxazines 442 6.25 Morpholine 447 6.26 1,3-Dioxane 449 6.27 1,3-Dithiane 453 6.28 Cepham 455 6.29 Pyridazine 458 6.30 Pyrimidine 463 6.31 Purine 474 6.32 Pyrazine 481 6.33 Piperazine 486 6.34 Pteridine 487 6.35 Benzodiazines 491 6.36 1,2,3-Triazine 501 6.37 1,2,4-Triazine 504 6.38 1,3,5-Triazine 508 6.39 1,2,4,5-Tetrazine 512 References 517 7 Seven-Membered Heterocycles 529 7.1 Oxepin 529 7.2 Thiepin 532 7.3 Azepine 533 7.4 Diazepines 540 References 545 8 Larger Ring Heterocycles 547 8.1 Azocine 547 8.2 Heteronines and Larger-Membered Heterocycles 549 8.3 Tetrapyrroles 551 References 558 9 Problems and Their Solutions 561 References 614 Indices 621

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Book SynopsisThis second edition of the well-established bestseller is completely updated and revised with approximately 30 % additional material, including two new chapters on applications, which has seen the most significant developments. The comprehensive overview written at an introductory level covers fundamental aspects, principles of instrumentation and practical applications, while providing many valuable tips. For photochemists and photophysicists, physical chemists, molecular physicists, biophysicists, biochemists and biologists, lecturers and students of chemistry, physics, and biology.Trade Review"The strength of the book lies in its clear and understandable presentation, and in the thoroughness of the descriptions of fluorescence applications, enabling one to quickly appreciate the many questions and problems in the field of fluorescence. Molecular Fluorescence is more a textbook than a monograph, and therefore it is of special interest for students and beginners in the field, and be recommended." - Angewandte Chemie (international edition), 2002; Vol. 41 No. 16Table of ContentsINTRODUCTION What Is Luminescence? A Brief History of Fluorescence and Phosphorescence Photoluminescence of Organic and Inorganic Species: Fluorescence or Phosphorescence? Various De-Excitation Processes of Excited Molecules Fluorescent Probes, Indicators, Labels, and Tracers Ultimate Temporal and Spatial Resolution: Femtoseconds, Femtoliters, Femtomoles, and Single-Molecule Detection PART I: PRINCIPLES ABSORPTION OF ULTRAVIOLET, VISIBLE, AND NEAR-INFRARED RADIATION Electronic Transitions Transition Probabilities: The Beer - Lambert Law, Oscillator Strength Selection Rules The Franck - Condon Principle Multiphoton Absorption and Harmonic Generation CHARACTERISTICS OF FLUORESCENCE EMISSION Radiative and Nonradiative Transitions between Electronic States Lifetimes and Quantum Yields Emission and Excitation Spectra STRUCTURAL EFFECTS ON FLUORESCENCE EMISSION Effects of the Molecular Structure of Organic Molecules on Their Fluorescence Fluorescence of Conjugated Polymers (CPs) Luminescence of Carbon Nanostructures: Fullerenes, Nanotubes, and Carbon Dots Luminescence of Metal Compounds, Metal Complexes, and Metal Clusters Luminescence of Semiconductor Nanocrystals (Quantum Dots and Quantum Rods) ENVIRONMENTAL EFFECTS ON FLUORESCENCE EMISSION Homogeneous and Inhomogeneous Band Broadening - Red-Edge Effects General Considerations on Solvent Effects Solvent Relaxation Subsequent to Photoinduced Charge Transfer (PCT) Theory of Solvatochromic Shifts Effects of Specific Interactions Empirical Scales of Solvent Polarity Viscosity Effects Fluorescence in Gas Phase: Supersonic Jets EFFECTS OF INTERMOLECULAR PHOTOPHYSICAL PROCESSES ON FLUORESCENCE EMISSION Introduction Overview of the Intermolecular De-Excitation Processes of Excited Molecules Leading to Fluorescence Quenching Photoinduced Electron Transfer Formation of Excimers and Exciplexes Photoinduced Proton Transfer FLUORESCENCE POLARIZATION: EMISSION ANISOTROPY Polarized Light and Photoselection of Absorbing Molecules Characterization of the Polarization State of Fluorescence (Polarization Ratio and Emission Anisotropy) Instantaneous and Steady-State Anisotropy Additivity Law of Anisotropy Relation between Emission Anisotropy and Angular Distribution of the Emission Transition Moments Case of Motionless Molecules with Random Orientation Effect of Rotational Motion Applications EXCITATION ENERGY TRANSFER Introduction Distinction between Radiative and Nonradiative Transfer Radiative Energy Transfer Nonradiative Energy Transfer Determination of Distances at a Supramolecular Level Using FRET FRET in Ensembles of Donors and Acceptors FRET between Like Molecules: Excitation Energy Migration in Assemblies of Chromophores Overview of Qualitative and Quantitative Applications of FRET PART II: TECHNIQUES STEADY-STATE SPECTROFL UOROMETRY Operating Principles of a Spectrofl uorometer Correction of Excitation Spectra Correction of Emission Spectra Measurement of Fluorescence Quantum Yields Possible Artifacts in Spectrofl uorometry Measurement of Steady-State Emission Anisotropy: Polarization Spectra TIME-RESOLVED FLUORESCENCE TECHNIQUES Basic Equations of Pulse and Phase-Modulation Fluorimetries Pulse Fluorimetry Phase-Modulation Fluorimetry Artifacts in Time-Resolved Fluorimetry Data Analysis Lifetime Standards Time-Resolved Polarization Measurements Time-Resolved Fluorescence Spectra Lifetime-Based Decomposition of Spectra Comparison between Single-Photon Timing Fluorimetry and Phase-Modulation Fluorimetry FLUORESCENCE MICROSCOPY Wide-Field (Conventional), Confocal, and Two-Photon Fluorescence Microscopies Super-Resolution (Subdiffraction) Techniques Fluorescence Lifetime Imaging Microscopy (FLIM) Applications FLUORESCENCE CORRELATION SPECTROSCOPY AND SINGLE-MOLECULE FLUORESCENCE SPECTROSCOPY Fluorescence Correlation Spectroscopy (FCS) Single-Molecule Fluorescence Spectroscopy PART III: APPLICATIONS EVALUATION OF LOCAL PHYSICAL PARAMETERS BY MEANS OF FLUORESCENT PROBES Fluorescent Probes for Polarity Estimation of 'Microviscosity', Fluidity, and Molecular Mobility Temperature Pressure CHEMICAL SENSING VIA FLUORESCENCE Introduction Various Approaches of Fluorescence Sensing Fluorescent pH Indicators 412 Transfer (PET) Design Principles of Fluorescent Molecular Sensors Based on Ion or Molecule Recognition Fluorescent Molecular Sensors of Metal Ions Fluorescent Molecular Sensors of Anions Fluorescent Molecular Sensors of Neutral Molecules Fluorescence Sensing of Gases Sensing Devices Remote Sensing by Fluorescence LIDAR AUTOFL UORESCENCE AND FLUORESCENCE LABELING IN BIOLOGY AND MEDICINE Introduction Natural (Intrinsic) Chromophores and Fluorophores Fluorescent Proteins (FPs) Fluorescent Small Molecules Quantum Dots and Other Luminescent Nanoparticles Conclusion MISCELLANEOUS APPLICATIONS Fluorescent Whitening Agents Fluorescent Nondestructive Testing Food Science Forensics Counterfeit Detection Fluorescence in Art APPENDIX: CHARACTERISTICS OF FLUORESCENT ORGANIC COMPOUNDS INDEX

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Book SynopsisThe first and ultimate guide for anyone working in transition organometallic chemistry and related fields, providing the background and practical guidance on how to efficiently work with routine research problems in NMR. The book adopts a problem-solving approach with many examples taken from recent literature to show readers how to interpret the data. Perfect for PhD students, postdocs and other newcomers in organometallic and inorganic chemistry, as well as for organic chemists involved in transition metal catalysis.Trade Review“However, it certainly conveys its author’s undoubted enthusiasm, and most organometallic and coordination chemists will find it well worth their while to dip into it.” (Applied Organometal.Chemistry, 1 June 2013)"Ein super-Buch für die experimentell arbeitenden Studierenden, beginnend mit dem Bachelorstudium bis hin zur Promotionsphase." Prof. Dr. Rüdiger Beckhaus, Universität OldenburgTable of ContentsPreface XI Abbreviations XIII 1 Introduction 1 2 Routine Measuring and Relaxation 7 3 COSY and HMQC 2-D Sequences 19 4 Overhauser Effects and 2-D NOESY 39 5 Diffusion Constants via NMR Measurements 55 6 Chemical Shifts 63 7 Coupling Constants 207 8 Dynamics 279 9 Preface to the Problems 311 10 Organometallic Introduction 313 11 NMR Problems 319 12 Solutions to the Problems and Comments 361 Index 389

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Book SynopsisThis essential guide to the knowledge and tools in the field includes everything from the basic concepts to modern methods, while also forming a bridge to bioinformatics.The textbook offers a very clear and didactical structure, starting from the basics and the theory, before going on to provide an overview of the methods. Learning is now even easier thanks to exercises at the end of each section or chapter. Software tools are explained in detail, so that the students not only learn the necessary theoretical background, but also how to use the different software packages available. The wide range of applications is presented in the corresponding book Applied Chemoinformatics - Achievements and Future Opportunities (ISBN 9783527342013). For Master and PhD students in chemistry, biochemistry and computer science, as well as providing an excellent introduction for other newcomers to the field.Table of ContentsForeword xxi List of Contributors xxv 1 Introduction 1Thomas Engel and Johann Gasteiger 1.1 The Rationale for the Books 1 1.2 The Objectives of Chemoinformatics 2 1.3 Learning in Chemoinformatics 4 1.4 Outline of the Book 5 1.5 The Scope of the Book 7 1.6 Teaching Chemoinformatics 8 References 8 2 Principles of Molecular Representations 9Thomas Engel 2.1 Introduction 9 2.2 Chemical Nomenclature 11 2.2.1 Non-systematic Nomenclature (Trivial Names) 11 2.2.2 Systematic Nomenclature of Chemical Compounds 12 2.2.3 Drawbacks of Chemical Nomenclature for Data Processing 12 2.3 Chemical Notations 12 2.3.1 Empirical Formulas of Inorganic and Organic Compounds 12 2.3.2 Line Notations 14 2.4 Mathematical Notations 14 2.4.1 Introduction into Graph Theory 15 2.4.2 Matrix Representations 18 2.4.2.1 Adjacency Matrix 18 2.4.2.2 Incidence Matrix 19 2.4.2.3 Distance Matrix 20 2.4.2.4 Bond Matrix 21 2.4.2.5 Bond–Electron Matrix 21 2.4.2.6 Summary on Matrix Representations 23 2.4.3 Connection Table 23 2.5 Specific Types of Chemical Structures 25 2.5.1 General Concepts of Isomerism 25 2.5.2 Tautomerism 26 2.5.3 Markush Structures 27 2.5.4 Beyond a Connection Table Representation 28 2.5.4.1 Representation of Molecular Structures by Electron Systems 28 2.6 Spatial Representation of Structures 31 2.6.1 Representation of Configurational Isomers 32 2.6.2 Chirality 33 2.6.3 3D Coordinate Systems 36 2.7 Molecular Surfaces 37 Selected Reading 38 References 393 3 Computer Processing of Chemical Structure Information 43Thomas Engel 3.1 Introduction 43 3.2 Standard File Formats for Chemical Structure Information 44 3.2.1 SMILES 44 3.2.1.1 Stereochemistry in SMILES 47 3.2.1.2 Summary on SMILES 47 3.2.2 SMARTS 47 3.2.3 SYBYL Line Notation 48 3.2.4 The International Chemical Identifier (InChI) and InChIKey 48 3.2.5 XYZ Format 50 3.2.6 Z-Matrix 51 3.2.7 The Molfile Format Family 52 3.2.7.1 Structure of a Molfile 53 3.2.7.2 Stereochemistry in the Molfile 57 3.2.7.3 Structure of an SDfile 57 3.2.8 The PDB File Format 58 3.2.8.1 Introduction/History 58 3.2.8.2 General Description 58 3.2.8.3 Analysis of a Sample PDB File 60 3.2.9 Metadata Formats 65 3.2.9.1 STAR-Based File Formats and Dictionaries 65 3.2.9.2 CIF File Format 66 3.2.9.3 mmCIF File Format 67 3.2.9.4 CML 68 3.2.9.5 CSRML 68 3.2.10 Libraries for Handling Information in Structure File Formats 69 3.3 Input and Output of Chemical Structures 70 3.3.1 Molecule Editors 72 3.3.2 Molecule Viewers 73 3.4 Processing Constitutional Information 73 3.4.1 Structure Isomers and Isomorphism 73 3.4.2 Tautomerism 74 3.4.3 Unambiguous and Biunique Representation by Canonicalization 76 3.4.3.1 The Morgan Algorithm 77 3.4.4 Ring Perception 79 3.4.4.1 Introduction 79 3.4.4.2 Graph Terminology 80 3.4.4.3 Ring Perception Strategies 81 3.5 Processing 3D Structure Information 86 3.5.1 Detection and Specification of Chirality 86 3.5.1.1 Detection of Chirality 87 3.5.1.2 Specification of Chirality 87 3.5.2 Automatic Generation of 3D Structures 90 3.5.3 Automatic Generation of Ensemble of Conformations 94 3.6 Visualization of Molecular Models 100 3.6.1 Introduction 100 3.6.2 Models of the 3D Structure 101 3.6.2.1 Wire Frame and Capped Sticks Model 101 3.6.2.2 Ball-and-Stick Model 101 3.6.2.3 Space-Filling Model 102 3.6.2.4 Crystallographic Models 102 3.6.3 Models of Biological Macromolecules 102 3.6.4 Virtual Reality 103 3.6.5 3D Printing 103 3.7 Calculation of Molecular Surfaces 103 3.7.1 Van der Waals Surface 104 3.7.2 Connolly Surface 104 3.7.3 Solvent-Accessible Surface 105 3.7.4 Enzyme Cavity Surface (Union Surface) 106 3.7.5 Isovalue-Based Electron Density Surface 106 3.7.6 Experimentally Determined Surfaces 106 3.7.7 Visualization of Molecular Surface Properties 107 3.7.8 Property-based Isosurfaces 107 3.7.8.1 Electrostatic Potentials 108 3.7.8.2 Hydrogen Bonding Potential 108 3.7.8.3 Polarizability and Hydrophobicity Potential 108 3.7.8.4 Spin Density 108 3.7.8.5 Vector Fields 108 3.7.8.6 Volumetric Properties 108 3.8 Chemoinformatic Toolkits and Workflow Environments 109 Selected Reading 111 References 111 4 Representation of Chemical Reactions 121Oliver Sacher and Johann Gasteiger 4.1 Introduction 121 4.2 Reaction Equation 122 4.3 Reaction Types 123 4.4 Reaction Center and Reaction Mechanisms 125 4.5 Chemical Reactivity 126 4.5.1 Physicochemical Effects 126 4.5.1.1 Charge Distribution 126 4.5.1.2 Inductive Effect 127 4.5.1.3 Resonance Effect 127 4.5.1.4 Polarizability Effect 128 4.5.1.5 Steric Effect 128 4.5.1.6 Stereoelectronic Effects 128 4.5.2 Simple Methods for Quantifying Chemical Reactivity 128 4.5.2.1 Frontier Molecular Orbital Theory 128 4.5.2.2 Linear Free Energy Relationships 130 4.6 Learning from Reaction Information 132 4.7 Building of Reaction Databases 133 4.7.1 Contents 133 4.7.2 Reaction Data Exchange Formats 134 4.7.2.1 RXN/RDF format by MDL/Symyx 134 4.7.2.2 Reaction SMILES/SMIRKS by Daylight Chemical Information Systems 134 4.7.2.3 Chemical Markup Language 135 4.7.2.4 International Chemical Identifier for Reactions (RinChI) 135 4.7.3 Input and Output of Reactions 135 4.8 Reaction Center Perception 138 4.9 Reaction Classification 139 4.9.1 Model-Driven Approaches 139 4.9.1.1 Ugi’s Scheme and Some Follow-Ups 140 4.9.1.2 InfoChem’s Reaction Classification 143 4.9.2 Data-Driven Approaches 145 4.9.2.1 HORACE 145 4.9.2.2 Reaction Landscapes 146 4.10 Stereochemistry of Reactions 148 4.11 Reaction Networks 149 Selected Reading 151 References 152 5 The Data 155 5.1 Introduction 155 5.2 Data Types 156 5.2.1 Numerical Data 157 5.2.2 Molecular Structures 159 5.2.3 Bit Vectors 160 5.2.3.1 Hash Codes 160 5.2.3.2 Structural Keys 162 5.2.3.3 Fingerprints 163 5.2.4 Chemical Reactions 164 5.2.5 Molecular Spectra 165 5.3 Storage and Manipulation of Data 169 5.3.1 Experimental Data 169 5.3.1.1 Types of Data on Properties 170 5.3.1.2 Accuracy of the Data 170 5.3.2 Data Storage and Exchange 171 5.3.2.1 DAT File 171 5.3.2.2 JCAMP-DX 171 5.3.2.3 Predictive Model Markup Language (PMML) 172 5.3.3 Real-World Data 173 5.3.3.1 Data Complexity 173 5.3.3.2 Outliers and Redundant Objects 174 5.3.4 Data Transformation 175 5.3.4.1 Fast Fourier Transformation 175 5.3.4.2 Wavelet Transformation 175 5.3.5 Preparation of Datasets for Building of Models and Validations of Their Quality 176 5.4 Conclusions 177 Selected Reading 178 References 179 6 Databases and Data Sources in Chemistry 185Engelbert Zass and Thomas Engel 6.1 Introduction 185 6.2 Chemical Literature and Databases 186 6.2.1 Classification of Chemical Literature 186 6.2.2 The Origin of Chemical Databases 187 6.2.3 Evolution of Database Systems and User Interfaces 187 6.3 Major Chemical Database Systems 188 6.3.1 SciFinder 188 6.3.2 Reaxys 189 6.3.3 SciFinder versus Reaxys 190 6.4 Compound Databases 191 6.4.1 2D Structures 191 6.4.1.1 Searching Organic Compounds 192 6.4.1.2 Searching Inorganic and Coordination Compounds 194 6.4.2 Sequences of Biopolymers 195 6.4.3 3D Structures 198 6.4.4 Catalog Databases 200 6.5 Databases with Properties of Compounds 200 6.5.1 Physical Properties 201 6.5.2 Thermodynamic and Thermochemical Data 202 6.5.3 Spectra 204 6.5.3.1 Spectroscopic Databases 205 6.5.3.2 Compound Databases with Spectroscopic Information 205 6.5.4 Biological, Environmental, and Safety Information Sources 206 6.5.4.1 Biological Information 207 6.5.4.2 Pharmaceutical and Medical Information 208 6.5.4.3 Toxicity, Environmental, and Safety Information 209 6.6 Reaction Databases 210 6.6.1 Comprehensive Reaction Databases 210 6.6.2 Synthetic Methodology Databases 212 6.7 Bibliographic and Citation Databases 212 6.7.1 Bibliographic Databases 213 6.7.1.1 Special Bibliographic Databases 213 6.7.1.2 Patent Bibliographic Databases 214 6.7.1.3 Searching Bibliographic Databases 216 6.7.1.4 Linking to Full Text 216 6.7.2 Citation Databases 217 6.7.2.1 General Citation Databases 218 6.7.2.2 Patent Citation Databases 219 6.8 Full-Text Databases 219 6.8.1 Electronic Journals 219 6.8.2 Patents 220 6.8.3 Lexika and Encyclopedias 221 6.9 Architecture of a Structure-Searchable Database 222 Selected Reading 224 References 224 7 Searching Chemical Structures 231Nikolay Kochev, Valentin Monev, and Ivan Bangov 7.1 Introduction 231 7.2 Full Structure Search 232 7.3 Substructure Search 235 7.3.1 Basic Concepts 235 7.3.2 Backtracking Algorithm 236 7.3.3 Optimization of the Backtracking Algorithm 238 7.3.4 Screening 239 7.3.5 Superstructure Searching 241 7.3.6 Automorphism Searching 241 7.3.7 Maximum Common Substructure Searching 242 7.3.8 Specific Line Notations for Substructure Searching 243 7.3.9 Chemotypes for Database Searching 244 7.4 Similarity Search 245 7.4.1 Similarity Basics 245 7.4.2 Similarity Measures 247 7.4.3 Descriptor Selection and Coding 249 7.4.4 Similarity Measures Based on Maximum Common Substructure 250 7.5 Three-Dimensional Structure Search Methods 250 7.5.1 Pharmacophore Searching 251 7.5.2 3D Similarity Searching 252 7.6 Sequence Searching in Protein and Nucleic Acid Databases 254 7.6.1 Sequence Similarity Definition 255 7.6.2 Dynamic Programming Algorithm 256 7.6.3 Fast Sequence Searching in Large Databases 258 7.7 Summary 259 Selected Reading 261 References 262 8 Computational Chemistry 267 8.1 Empirical Approaches to the Calculation of Properties 269Johann Gasteiger 8.1.1 Introduction 269 8.1.2 Additivity of Atomic Contributions 269 8.1.3 Attenuation Models 271 8.1.3.1 Calculation of Charge Distribution 271 8.1.3.2 Polarizability Effect 275 Selected Reading 277 References 277 8.2 Molecular Mechanics 279Harald Lanig 8.2.1 Introduction 279 8.2.2 No Force Field Calculation without Atom Types 280 8.2.3 The Functional Form of Common Force Fields 281 8.2.3.1 Bond Stretching 282 8.2.3.2 Angle Bending 283 8.2.3.3 Torsional Terms 284 8.2.3.4 Out-of-Plane Bending 285 8.2.3.5 Electrostatic Interactions 286 8.2.3.6 Van der Waals Interactions 287 8.2.3.7 Cross Terms 289 8.2.3.8 Advanced Interatomic Potentials and Future Development 290 8.2.4 Available Force Fields 291 8.2.4.1 Force Fields for Small Molecules 292 8.2.4.2 Force Fields for Biomolecules 293 Selected Readings 296 References 296 8.3 Molecular Dynamics 301Harald Lanig 8.3.1 Introduction 301 8.3.2 The Continuous Movement of Molecules 302 8.3.3 Methods 302 8.3.3.1 Algorithms 303 8.3.3.2 Ways for Speeding up the Calculations 304 8.3.3.3 Solvent Effects 305 8.3.3.4 Periodic Boundary Conditions 308 8.3.4 Constant Energy, Temperature, or Pressure? 308 8.3.5 Long-Range Forces 310 8.3.6 Application of Molecular Dynamics Techniques 311 8.3.7 Future Perspectives 315 Selected Readings 317 References 317 8.4 Quantum Mechanics 320Tim Clark 8.4.1 Hückel Molecular Orbital Theory 320 8.4.2 Semiempirical MO Theory 324 8.4.3 Ab Initio Molecular Orbital Theory 327 8.4.4 Density Functional Theory 332 8.4.5 Properties from Quantum Mechanical Calculations 334 8.4.5.1 Net Atomic Charges 334 8.4.5.2 Dipole and Higher Multipole Moments 335 8.4.5.3 Polarizabilities 335 8.4.5.4 Orbital Energies 336 8.4.5.5 Surface Descriptors 336 8.4.5.6 Local Ionization Potential 336 8.4.6 Quantum Mechanical Techniques for Very Largen Molecules 337 8.4.6.1 Linear Scaling Methods 337 8.4.6.2 Hybrid QM/MM Calculations 338 8.4.7 The Future of Quantum Mechanical Methods in Chemoinformatics 338 Selected Reading 340 References 341 9 Modeling and Prediction of Properties (QSPR/QSAR) 345Johann Gasteiger 10 Calculation of Structure Descriptors 349Lothar Terfloth and Johann Gasteiger 10.1 Introduction 349 10.1.1 QSPR/QSAR Modeling 349 10.1.2 Overview 349 10.1.3 Classification of Compounds and Similarity Searching 350 10.1.4 Definition of the Terms “Structure Descriptor” and “Molecular Descriptor” 351 10.1.5 Classification of Structure Descriptors 351 10.1.6 Structure Descriptors with a Fixed Length 351 10.2 Structure Descriptors for Classification and Similarity Searching 352 10.2.1 2D Structure Descriptors (Topological Descriptors) 352 10.2.1.1 Structural Keys 352 10.2.1.2 Fingerprints 353 10.2.1.3 Distance and Similarity Measures 354 10.2.1.4 Chemotypes: Data Mining for Compounds with Structural Features 356 10.2.1.5 Multilevel Neighborhoods of Atoms 358 10.2.1.6 Descriptors from Shannon Entropy Calculations 359 10.2.1.7 Chemically Advanced Template Search (CATS2D) Descriptors 360 10.2.1.8 Descriptors from Chemical Bond Information 360 10.2.2 3D Descriptors 361 10.2.2.1 Geometric Atom Pair Descriptors 361 10.2.2.2 CATS3D and CHARGE3D 361 10.2.2.3 Pharmacophores 362 10.2.3 Field-Based Molecular Similarity 362 10.2.3.1 Electron Density 362 10.2.3.2 General Field-Based Similarity Indices 363 10.3 Structure Descriptors for Quantitative Modeling 363 10.3.1 0-D Molecular Descriptors 363 10.3.2 1D Molecular Descriptors 363 10.3.3 2D Molecular Descriptors (Topological Descriptors) 365 10.3.3.1 Single-Valued Descriptors 365 10.3.3.2 Topological Descriptors as Vectors 366 10.3.4 3D Descriptors 369 10.3.4.1 3D Structure Generation 369 10.3.4.2 3D Autocorrelation Vector 370 10.3.4.3 3D Molecule Representation of Structures Based on Electron Diffraction Code (3D MoRSE Code) 370 10.3.4.4 Radial Distribution Function Code 371 10.3.4.5 Other 3D Descriptors 375 10.3.5 Chirality Descriptors 375 10.3.5.1 Chirality Codes 376 10.3.5.2 Conformation-Independent Chirality Code (CICC) 376 10.3.5.3 Conformation-Dependent Chirality Code (CDCC) 377 10.3.5.4 Descriptors of Molecular Shape and Molecular Surfaces 377 10.3.5.5 Global Shape Descriptors 378 10.3.5.6 Autocorrelation of Molecular Surface Properties 378 10.3.5.7 2D Maps of Molecular Surfaces 379 10.3.5.8 Charged Partial Surface Area 382 10.3.6 Field-Based Methods 383 10.3.6.1 Comparative Molecular Field Analysis (CoMFA) 383 10.3.6.2 Comparative Molecular Similarity Analysis (CoMSIA) 384 10.3.6.3 3D Molecular Interaction Fields 384 10.3.7 Descriptors for an Ensemble of Conformations (4D Descriptors) 384 10.3.7.1 4D-QSAR 384 10.3.8 Quantum Chemical Descriptors 385 10.4 Descriptors That Are Not Calculated from the Chemical Structure 385 10.5 Summary and Outlook 387 Selected Reading 390 References 390 11 Data Analysis and Data Handling (QSPR/QSAR) 397 11.1 Methods for Multivariate Data Analysis 399Kurt Varmuza 11.1.1 Introduction into Multivariate Data Analysis 399 11.1.1.1 Aims 399 11.1.1.2 Notation and Symbols 400 11.1.2 Basics of Statistical Data Evaluation 401 11.1.2.1 Data Distribution, Central Value, and Spread 401 11.1.2.2 Correlation 404 11.1.2.3 Discrimination 405 11.1.3 Multivariate Data 406 11.1.3.1 Overview 406 11.1.3.2 Preprocessing 407 11.1.3.3 Distances and Similarities 408 11.1.3.4 Linear Latent Variables 410 11.1.4 Evaluation of Empirical Models 412 11.1.4.1 Overview 412 11.1.4.2 Optimum Model Complexity 412 11.1.4.3 Performance Criteria for Calibration Models 413 11.1.4.4 Performance Criteria for Classification Models 414 11.1.4.5 Cross-Validation 415 11.1.4.6 Bootstrap 416 11.1.5 Exploration: Analyzing the Independent Variables 417 11.1.5.1 Overview 417 11.1.5.2 Principal Component Analysis (PCA) 417 11.1.5.3 Nonlinear Mapping 419 11.1.5.4 Cluster Analysis 419 11.1.5.5 Example: Exploratory Data Analysis of Mass Spectra from Meteorite Samples 421 11.1.6 Calibration: Building a Quantitative Model 423 11.1.6.1 Overview 423 11.1.6.2 Ordinary Least Squares (OLS) Regression 424 11.1.6.3 Principal Component Regression (PCR) 424 11.1.6.4 Partial Least Squares (PLS) Regression 425 11.1.6.5 Variable Selection 426 11.1.6.6 Example: Prediction of Gas Chromatographic Retention Indices for Polycyclic Aromatic Hydrocarbons 427 11.1.7 Classification: Discriminating Samples 428 11.1.7.1 Overview 428 11.1.7.2 Linear Discriminant Analysis (LDA) 430 11.1.7.3 Discriminant Partial Least Squares (D-PLS) Analysis 430 11.1.7.4 k-Nearest Neighbor (KNN) Classification 430 11.1.7.5 Support Vector Machine (SVM) 431 11.1.7.6 Classification Trees (CART) 432 11.1.7.7 Example: Classification of Meteorite Samples Using Mass Spectral Data 432 Acknowledgements 434 Selected Reading 435 References 435 11.2 Artificial Neural Networks (ANNs) 438Jure Zupan 11.2.1 How to Learn a New Method? 438 11.2.2 Multivariate Representation of Data 439 11.2.3 Overview of Artificial Neural Networks (ANNs) 442 11.2.4 Error Back-Propagation ANNs 443 11.2.5 Kohonen and Counter-Propagation ANN 445 11.2.6 Training of the ANN: Adapting the Weights 448 11.2.7 Controlling Model Complexity and Optimizing Predictivity 450 11.2.8 Few General Remarks about ANNs 450 Selected Reading 451 References 451 11.3 Deep and Shallow Neural Networks 453David A. Winkler 11.3.1 Drug Design in the Era of Big Data and Artificial Intelligence (AI) 453 11.3.2 Deep Learning 454 11.3.3 Controlling Model Complexity and Optimizing Predictivity Using Regularization 455 11.3.4 Universal Approximation Theorem 458 11.3.5 Do QSAR Models Generated by Neural Networks Meet the Requirements of the Universal Approximation Theorem? 458 11.3.6 Comparison of the Performance of Deep and Shallow Regularized Neural Networks on Drug Datasets 459 11.3.7 A Few General Remarks about Neural Networks for Drug Discovery 460 Selected Reading 462 References 462 12 QSAR/QSPR Revisited 465Alexander Golbraikh and Alexander Tropsha 12.1 Best Practices of QSAR Modeling 466 12.1.1 Introduction 466 12.1.2 Key Concepts 467 12.1.3 Predictive QSAR Modeling Workflow 468 12.1.4 Dataset Curation 469 12.1.5 Modelability Studies 470 12.1.6 Development of QSAR Models: Internal and External Validation 471 12.1.7 Prediction Accuracy Criteria for QSAR Models for a Continuous Response Variable 472 12.1.8 Prediction Accuracy Criteria for Category QSAR Models 473 12.1.9 Time-Split Validation 475 12.1.10 Validation by Y-Randomization 475 12.1.11 Applicability Domain of QSAR Models 475 12.1.11.1 Leverage AD for Regression QSAR Models 476 12.1.11.2 Residual Standard Deviation (RSD) as AD 476 12.1.11.3 Other widely Used ADs 476 12.1.12 Ensemble Modeling 478 12.1.13 Model Interpretation: Structural Alerts 478 12.1.14 Virtual Screening 479 12.1.15 Conclusions 480 12.2 The Data Science of QSAR Modeling 480 12.2.1 Introduction 480 12.2.2 Data Curation: Trust but Verify! 482 12.2.3 Models as Decision Support Tools 487 12.2.4 Conclusions 487 Selected Reading 489 References 489 13 Bioinformatics 497Heinrich Sticht 13.1 Introduction 497 13.2 Sequence Databases 499 13.2.1 GenBank 499 13.2.2 UniProt 501 13.3 Searching Sequence Databases 502 13.3.1 Tools for Sequence Database Searches 503 13.3.2 Scoring Matrices 503 13.3.3 Interpretation of the Results of a Database Search 507 13.4 Characterization of Protein Families 509 13.4.1 Multiple Sequence Alignment 509 13.4.2 Sequence Signatures 512 13.5 Homology Modeling 515 Selected Reading 520 References 520 14 Future Directions 525Johann Gasteiger 14.1 Access to Chemical Information 525 14.2 Representation of Chemical Compounds 527 14.3 Representation of Chemical Reactions 527 14.4 Learning from Chemical Information 528 14.5 Training in Chemoinformatics 529 Answers Section 531 Index 555

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Book SynopsisWhile there are many publications on the topic written by experts for experts, this text is specifically designed to allow advanced students and researchers with no background in physics to comprehend novel fluorescence microscopy techniques. This second edition features new chapters and a subsequent focus on super-resolution and single-molecule microscopy as well as an expanded introduction. Each chapter is written by a renowned expert in the field, and has been thoroughly revised to reflect the developments in recent years.Table of ContentsList of Contributors xv Preface xix 1 Introduction to Optics 1Rainer Heintzmann and Ulrich Kubitscheck 1.1 A Short History of Theories about Light 1 1.2 Properties of LightWaves 2 1.3 Four Effects of Interference 7 1.4 Optical Elements 13 1.5 Optical Aberrations 20 2 Principles of LightMicroscopy 23Ulrich Kubitscheck 2.1 Introduction 23 2.2 Construction of Light Microscopes 23 2.3 Wave Optics and Resolution 32 2.4 Apertures, Pupils, and Telecentricity 50 2.5 Microscope Objectives 53 2.6 Contrast 67 2.7 Summary 82 3 Fluorescence Microscopy 85JurekW. Dobrucki and Ulrich Kubitscheck 3.1 Contrast in Optical Microscopy 85 3.2 Physical Foundations of Fluorescence 86 3.3 Features of Fluorescence Microscopy 90 3.4 A Fluorescence Microscope 95 3.5 Types ofNoise in a Digital Microscopy Image 114 3.6 Quantitative Fluorescence Microscopy 119 3.7 Limitations of Fluorescence Microscopy 124 3.8 Summary and Outlook 128 4 Fluorescence Labeling 133Gerd Ulrich Nienhaus and Karin Nienhaus 4.1 Introduction 133 4.2 Key Properties of Fluorescent Labels 133 4.3 Synthetic Fluorophores 138 4.4 Genetically Encoded Labels 149 4.5 Label Selection for Particular Applications 155 5 Confocal Microscopy 165Nikolaus Naredi-Rainer, Jens Prescher, Achim Hartschuh, and Don C. Lamb 5.1 Evolution and Limits of ConventionalWidefield Microscopy 165 5.2 Theory of Confocal Microscopy 166 5.3 Applications of Confocal Microscopy 186 6 Two-Photon Excitation Microscopy for Three-Dimensional Imaging of Living Intact Tissues 203David W. Piston 6.1 Introduction 203 6.2 What is Two-Photon Excitation? 205 6.3 How Does Two-Photon Excitation MicroscopyWork in Practice? 211 6.4 Instrumentation 216 6.5 Limitations of Two-Photon Excitation Microscopy 222 6.6 When is 2PMthe Best Option? 229 6.7 Applications of Two-Photon Microscopy 231 6.8 Other NonlinearMicroscopies 239 6.9 Future Outlook for 2PM 240 7 Light Sheet Microscopy 243Gopi Shah,MichaelWeber, and Jan Huisken 7.1 Principle of Light Sheet Microscopy 244 7.2 Light Sheet Microscopy: Key Advantages 245 7.3 Construction andWorking of a Light Sheet Microscope 246 7.4 Theory of Light Sheet Microscopy 247 7.5 Light Sheet Interaction with Tissue 251 7.6 3D Imaging 253 7.7 Multiview Imaging 255 7.8 Different Lens Configurations 257 7.9 Sample Mounting 258 7.10 Recent Advances in Light Sheet Microscopy 259 7.11 Outlook 260 8 Localization-Based Super-Resolution Microscopy 267Markus Sauer and Mike Heilemann 8.1 Super-Resolution Microscopy: An Introduction 267 8.2 The Principle of Single-Molecule Localization Microscopy 269 8.3 Photoactivatable and Photoconvertible Probes 272 8.4 Intrinsically Photoswitchable Probes 272 8.5 Photoswitching of Organic Fluorophores by Chemical Reactions 273 8.6 Experimental Setup for Localization Microscopy 273 8.7 Optical Resolution and Imaging Artifacts 276 8.8 Fluorescence Labeling for Super-Resolution Microscopy 278 8.9 Measures for Improving Imaging Contrast 283 8.10 SMLM Software 283 8.11 Reference Structures for SMLM 285 8.12 Quantification of SMLM Data 286 9 Super-Resolution Microscopy: Interference and Pattern Techniques 291Udo Birk, Gerrit Best, Roman Amberger, and Christoph Cremer 9.1 Introduction 291 9.2 Structured Illumination Microscopy (SIM) 293 9.3 SpatiallyModulated Illumination (SMI) Microscopy 307 9.4 Application of Patterned Techniques 313 10 STEDMicroscopy 321Travis J. Gould, Lena K. Schroeder, Patrina A. Pellett, and Joerg Bewersdorf 10.1 Introduction 321 10.2 The Concepts behind STED Microscopy 322 10.3 Experimental Setup 330 10.4 Applications 334 11 Fluorescence Photobleaching Techniques 339Reiner Peters 11.1 Introduction 339 11.2 Basic Concepts and Procedures 340 11.3 Fluorescence Recovery after Photobleaching (FRAP) 345 11.4 Continuous Fluorescence Microphotolysis (CFM) 352 11.5 CLSM-Assisted Photobleaching Methods 356 12 Single-Molecule Microscopy in the Life Sciences 365Markus Axmann, JosefMadl, and Gerhard J. Schütz 12.1 Encircling the Problem 365 12.2 What is the Unique Information? 367 12.3 Building a Single-Molecule Microscope 372 12.4 Analyzing Single-Molecule Signals: Position, Orientation, Color, and Brightness 387 12.5 Learning from Single-Molecule Signals 394 13 Förster Resonance Energy Transfer and Fluorescence Lifetime Imaging 405Fred S.Wouters 13.1 General Introduction 405 13.2 Förster Resonance Energy Transfer 406 13.3 Measuring FRET 426 13.4 FLIM 439 13.5 Analysis and Pitfalls 444 A Appendix A:What Exactly is a Digital Image? 453Ulrich Kubitscheck A.1 Introduction 453 A.2 Digital Images as Matrices 453 A.3 Look-up Table 457 A.4 Intensity Histograms 457 A.5 Image Processing 458 A.6 Pitfalls 460 B Appendix B: Practical Guide to Optical Alignment 463Rainer Heintzmann B.1 How to Obtain aWidened Parallel Laser Beam? 463 B.2 Mirror Alignment 465 B.3 Lens Alignment 466 B.4 Autocollimation Telescope 466 B.5 Aligning a Single Lens Using a Laser Beam 466 B.6 How to Find the Focal Plane of a Lens? 469 B.7 How to Focus to the Back Focal Plane of an Objective Lens? 470 Index 473

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Book SynopsisAnalytical methods are the essential enabling tools of the modern biosciences. This book presents a comprehensive introduction into these analytical methods, including their physical and chemical backgrounds, as well as a discussion of the strengths and weakness of each method. It covers all major techniques for the determination and experimental analysis of biological macromolecules, including proteins, carbohydrates, lipids and nucleic acids. The presentation includes frequent cross-references in order to highlight the many connections between different techniques. The book provides a bird's eye view of the entire subject and enables the reader to select the most appropriate method for any given bioanalytical challenge. This makes the book a handy resource for students and researchers in setting up and evaluating experimental research. The depth of the analysis and the comprehensive nature of the coverage mean that there is also a great deal of new material, even for experienced experimentalists. The following techniques are covered in detail: - Purification and determination of proteins - Measuring enzymatic activity - Microcalorimetry - Immunoassays, affinity chromatography and other immunological methods - Cross-linking, cleavage, and chemical modification of proteins - Light microscopy, electron microscopy and atomic force microscopy - Chromatographic and electrophoretic techniques - Protein sequence and composition analysis - Mass spectrometry methods - Measuring protein-protein interactions - Biosensors - NMR and EPR of biomolecules - Electron microscopy and X-ray structure analysis - Carbohydrate and lipid analysis - Analysis of posttranslational modifications - Isolation and determination of nucleic acids - DNA hybridization techniques - Polymerase chain reaction techniques - Protein sequence and composition analysis - DNA sequence and epigenetic modification analysis - Analysis of protein-nucleic acid interactions - Analysis of sequence data - Proteomics, metabolomics, peptidomics and toponomics - Chemical biologyTable of ContentsPreface XV Introduction XIX Part I Protein Analytics 1 1 Protein Purification 3 2 Protein determination 23 3 Enzyme Activity Testing 35 4 Microcalorimetry 47 5 Immunological Techniques 63 6 Chemical Modification of Proteins and Protein Complexes 107 7 Spectroscopy 131 8 Light Microscopy Techniques – Imaging 181 9 Cleavage of Proteins 207 10 Chromatographic Separation Methods 219 11 Electrophoretic Techniques 243 12 Capillary Electrophoresis 275 13 Amino Acid Analysis 301 14 Protein Sequence Analysis 313 15 Mass Spectrometry 329 16 Protein–Protein Interactions 381 17 Biosensors 419 Part II 3D Structure Determination 431 18 Magnetic Resonance Spectroscopy of Biomolecules 433 19 Electron Microscopy 485 20 Atomic Force Microscopy 519 21 X-Ray Structure Analysis 529 Part III Peptides, Carbohydrates, and Lipids 553 22 Analytics of Synthetic Peptides 555 23 Carbohydrate Analysis 571 24 Lipid Analysis 613 25 Analysis of Post-translational Modifications: Phosphorylation and Acetylation of Proteins 645 Part IV Nucleic Acid Analytics 663 26 Isolation and Purification of Nucleic Acids 665 27 Analysis of Nucleic Acids 681 28 Techniques for the Hybridization and Detection of Nucleic Acids 719 29 Polymerase Chain Reaction 755 30 DNA Sequencing 785 31 Analysis of Epigenetic Modifications 817 32 Protein–Nucleic Acid Interactions 831 Part V Functional and Systems Analytics 873 33 Sequence Data Analysis 875 34 Analysis of Promoter Strength and Nascent RNA Synthesis 895 35 Fluorescent In Situ Hybridization in Molecular Cytogenetics 917 36 Physical and Genetic Mapping of Genomes 925 37 DNA-Microarray Technology 945 38 The Use of Oligonucleotides as Tools in Cell Biology 959 39 Proteome Analysis 977 40 Metabolomics and Peptidomics 1023 41 Interactomics – Systematic Protein–Protein Interactions 1033 42 Chemical Biology 1041 43 Toponome Analysis 1057 Appendix 1: Amino Acids and Posttranslational Modifications 1073 Appendix 2: Symbols and Abbreviations 1075 Appendix 3: Standard Amino Acids (three and one letter code) 1081 Appendix 4: Nucleic Acid Bases 1083 Index 1085

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Book SynopsisWritten by an excellent, highly experienced and motivated team of lecturers, this textbook is based on one of the most successful courses in catalysis and as such is tried-and-tested by generations of graduate and PhD students, i.e. the Catalysis-An-Integrated-Approach (CAIA) course organized by NIOK, the Dutch Catalysis research school. It covers all essential aspects of this important topic, including homogeneous, heterogeneous and biocatalysis, but also kinetics, catalyst characterization and preparation, reactor design and engineering. The perfect source of information for graduate and PhD students in chemistry and chemical engineering, as well as for scientists wanting to refresh their knowledgeTable of ContentsPreface xiii 1 Introduction 1Leon Lefferts, Ulf Hanefeld, and Harry Bitter 1.1 A FewWords at the Beginning 1 1.2 Catalysis in a Nutshell 1 1.3 History of Catalysis 3 1.3.1 Industrial Catalysis 4 1.3.2 Environmental Catalysis 5 1.4 Integration Homo–Hetero-Biocatalysis 5 1.5 Research in Catalysis 10 1.5.1 S-Curve, Old Processes Improvement Is Knowledge Intensive 10 1.5.2 Interdependence with Other Fields 11 1.5.3 Recent and Future Issues 12 1.6 Catalysis and Integrated Approach or How to Use this Book 14 References 14 2 Heterogeneous Catalysis 15Leon Lefferts, Emiel Hensen, and Hans Niemantsverdriet 2.1 Introduction 15 2.1.1 Concept of Heterogeneous Catalysis 15 2.1.2 Applications of Heterogeneous Catalysis 16 2.1.3 Catalytic Cycle 23 2.2 Adsorption on Surfaces 23 2.2.1 Physisorption and Chemisorption 24 2.2.2 Adsorption Isotherms 26 2.2.3 Chemisorption and Chemical Bonding 28 2.2.4 Connecting Kinetic andThermodynamic Formulations 33 2.3 Surface Reactions 35 2.3.1 Reaction Mechanism and Kinetics 35 2.4 Types of Heterogeneous Catalysts 41 2.4.1 Supported Metals 41 2.4.2 Oxides and Sulfides 51 2.4.3 Solid Acid Catalysts 62 Question 1 69 Question 2 69 References 70 3 Homogeneous Catalysis 73Elisabeth Bouwman,Martin C. Feiters, and Robertus J. M. Klein Gebbink 3.1 Framework and Outline 73 3.1.1 Outline of this Chapter 73 3.1.2 Definitions and Terminology 74 3.2 Coordination and Organometallic Chemistry 75 3.2.1 Coordination Chemistry: d Orbitals, Geometries, Crystal Field Theory 75 3.2.2 σ and π donors and back-donation: CO, alkene, phosphane, H2 77 3.2.3 Organometallics: Hapticity, Metal–Alkyl/Allyl, Agostic Interaction, Carbenes 80 3.2.4 Electron Counting: Ionogenic or Donor-Pair versus Covalent or Neutral-Ligand 81 3.2.5 Effect of Binding on Ligands andMetal Ions, Stabilization of Oxidation States 83 3.3 Elementary Steps in Homogeneous Catalysis 84 3.3.1 Formation of the Active Catalyst Species 84 3.3.2 Oxidative Addition and Reductive Elimination 85 3.3.3 Migration and Elimination 87 3.3.4 Oxidative Coupling and Reductive Cleavage 90 3.3.5 Alkene or Alkyne Metathesis and σ-Bond Metathesis 90 3.3.6 Nucleophilic and Electrophilic Attack 92 3.4 Homogeneous Hydrogenation 95 3.4.1 Background and Scope 95 3.4.2 H2 DihydrideMechanism:Wilkinson’s Catalyst 96 3.4.3 H2 Monohydride Mechanism and Heterolytic Cleavage 97 3.4.4 Asymmetric Homogeneous Hydrogenation 98 3.4.5 Transfer Hydrogenation with 2-Propanol 100 3.4.6 Other Alkene Addition Reactions 102 3.5 Hydroformylation 104 3.5.1 Scope and Importance of the Reaction and Its Products 104 3.5.2 Cobalt-Catalyzed Hydroformylation 105 3.5.3 Rhodium-Catalyzed Hydroformylation 107 3.5.4 Asymmetric Hydroformylation 110 3.6 Oligomerization and Polymerization of Alkenes 112 3.6.1 Scope and Importance of Oligomerization and Polymerization 112 3.6.2 Oligomerization of Ethene (Ni, Cr) 113 3.6.3 Stereochemistry and Mechanism of Propene Polymerization 115 3.6.4 Metallocene Catalysis 117 3.6.5 Polymerization with Non-Metallocenes (Pd, Ni, Fe, Co) 118 3.7 Miscellaneous Homogeneously Catalyzed Reactions 118 3.7.1 Cross-Coupling Reactions: Pd-Catalyzed C–C Bond Formation 118 3.7.2 Metathesis Reactions 120 Question 1 (total 20 points) 122 Question 2 (total 20 points) 122 References 123 Further Reading 124 4 Biocatalysis 127Guzman Torrelo, Frank Hollmann, and Ulf Hanefeld 4.1 Introduction 127 4.2 Why Are Enzymes So Huge? 129 4.3 Classification of Enzymes 137 4.3.1 Oxidoreductases (EC 1) 139 4.3.2 Transferases (EC 2) 147 4.3.3 Hydrolases (EC 3) 147 4.3.4 Lyases (EC 4) 157 4.4 Concepts and Methods 157 4.4.1 Cofactor Regeneration Systems 158 4.4.2 Methods to Shift Unfavorable Equilibria 159 4.4.3 Two-Liquid-Phase Systems (and Related) 164 4.4.4 (Dynamic) Kinetic Resolutions and Desymmetrization 164 4.4.5 Enantiomeric Ratio E 168 4.5 Applications and Case Studies 169 4.5.1 Oxidoreductases (E.C. 1) 169 4.5.2 Transferases (EC 2) 177 4.5.3 Hydrolases (EC 3) 179 4.5.3.1 Lipases and Esterases (EC 3.1.1) 179 4.5.4 Lyases (EC 4) 181 Question 1 186 Question 2 186 Question 3 187 Question 4 188 Further Reading 188 5 Chemical Kinetics of Catalyzed Reactions 191Freek Kapteijn, Jorge Gascon, and T. Alexander Nijhuis 5.1 Introduction 191 5.2 Rate Expressions – Quasi-Steady-State Approximation and Quasi-Equilibrium Assumption 193 5.3 Adsorption Isotherms 198 5.3.1 One-Component Adsorption 198 5.3.2 Multicomponent Adsorption 199 5.3.3 Dissociative Adsorption 200 5.4 Rate Expressions – Other Models and Generalizations 200 5.5 Limiting Cases – Reactant and Product Concentrations 202 5.6 Temperature and Pressure Dependence 206 5.6.1 Transition-StateTheory 207 5.6.2 Forward Reaction – Temperature and Pressure Dependence 208 5.6.3 Forward Reaction – Limiting Cases 209 5.7 Sabatier Principle – Volcano Plot 213 5.8 Concluding Remarks 214 Notation 216 Greek 217 Subscripts 217 Superscripts 217 Question 1 217 Question 2 218 Question 3 218 References 219 6 Catalytic Reaction Engineering 221Freek Kapteijn, Jorge Gascon, and T. Alexander Nijhuis 6.1 Introduction 221 6.2 Chemical Reactors 222 6.2.1 Balance and Definitions 222 6.2.2 Batch Reactor 224 6.2.2.1 Multiple Reactions 226 6.2.3 Continuous Flow Stirred Tank Reactor (CSTR) 228 6.2.4 Plug-Flow Reactor (PFR) 231 6.2.5 Comparison between Plug-flow and CSTR reactor 233 6.3 Reaction and Mass Transport 236 6.3.1 External Mass Transfer 237 6.3.2 Internal Mass Transport 242 6.3.3 Gas–Liquid Mass Transfer 248 6.3.4 Heat Transfer 254 6.4 Criteria to Check for Transport Limitations 257 6.4.1 Numerical Checks 257 6.4.2 Experimental Checks 260 Notation 264 Greek symbols 265 Subscripts 265 Question 1 265 Question 2 266 Question 3 267 References 269 7 Characterization of Catalysts 271Guido Mul, Frank de Groot, Barbara Mojet-Mol, and Moniek Tromp 7.1 Introduction 271 7.1.1 Importance of Characterization of Catalysts 271 7.1.2 Overview of the Various Techniques 271 7.2 Techniques Based on Probe Molecules 273 7.2.1 Temperature-Programmed Techniques 273 7.2.2 Physisorption and Chemisorption 275 7.3 Electron Microscopy Techniques 280 7.4 Techniques from Ultraviolet up to Infrared Radiation 283 7.4.1 UV/Vis Spectroscopy 283 7.4.2 Infrared Spectroscopy 286 7.4.3 Raman Spectroscopy 289 7.5 Techniques Based on X-Rays 291 7.5.1 Introduction 291 7.5.2 Interaction of X-Rays with Matter 293 7.5.3 X-Ray Photoelectron Spectroscopy (XPS) 294 7.5.4 X-ray Absorption Spectroscopy (XAS) 295 7.5.5 X-Ray Scattering 299 7.5.6 X-Ray Microscopy 302 7.6 Ion Spectroscopies 303 7.7 Magnetic Resonance Spectroscopy Techniques 304 7.7.1 NMR 304 7.7.2 EPR 306 7.8 Summary 310 Question 1 310 Question 2 311 Question 3 312 References 313 8 Synthesis of Solid Supports and Catalysts 315Petra de Jongh and Krijn de Jong 8.1 Introduction 315 8.2 Support Materials 317 8.2.1 Mesoporous Metal Oxides 318 8.2.2 Ordered Microporous Materials 326 8.2.3 Carbon Materials 331 8.2.4 Shaping 333 8.3 Synthesis of Supported Catalysts 333 8.3.1 Colloidal Synthesis Routes 334 8.3.2 Chemical Vapor Deposition 335 8.3.3 Ion Adsorption 338 8.3.4 Deposition Precipitation 341 8.3.5 Co-Precipitation 345 8.3.6 Impregnation and Drying 349 Question 1 357 Question 2 357 Question 3 358 References 358 Index 361

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Book SynopsisFosters a thorough understand of radiation dosimetry concepts: detailed solutions to the exercises in the textbook "Fundamentals of Ionizing Radiation Dosimetry"!Table of ContentsPreface vii 1 Background and Essentials 1 2 Charged Particle Interactions 5 3 Uncharged Particle Interactions with Matter 23 4 Field and Dosimetric Quantities and Radiation Equilibrium: Definitions and Interrelations 35 5 Elementary Aspects of the Attenuation of Uncharged Particles through Matter 47 6 Macroscopic Aspects of the Transport of Radiation through Matter 53 Implementation 54 Normalization of Results 55 7 Characterization of Radiation Quality 57 8 The Monte Carlo Simulation of the Transport of Radiation through Matter 69 9 Cavity Theory 85 10 Overview of Radiation Detectors and Measurements 93 11 Primary Radiation Standards 99 12 Ionization Chambers 109 13 Chemical Dosimeters 117 14 Solid-State Dosimeters 123 15 Reference Dosimetry for External Beam Radiation Therapy 129 16 Dosimetry of Small and Composite Radiotherapy Photon Beams 143 17 Reference Dosimetry for Diagnostic and Interventional Radiology 145 18 Absorbed-Dose Determination for Radionuclides 153 19 Neutron Dosimetry 169

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Book SynopsisA one-stop reference that reviews protein design strategies to applications in industrial and medical biotechnology Protein Engineering: Tools and Applications is a comprehensive resource that offers a systematic and comprehensive review of the most recent advances in the field, and contains detailed information on the methodologies and strategies behind these approaches. The authors—noted experts on the topic—explore the distinctive advantages and disadvantages of the presented methodologies and strategies in a targeted and focused manner that allows for the adaptation and implementation of the strategies for new applications. The book contains information on the directed evolution, rational design, and semi-rational design of proteins and offers a review of the most recent applications in industrial and medical biotechnology. This important book: Covers technologies and methodologies used in protein engineering Includes the strategies behind the approaches, designed to help with the adaptation and implementation of these strategies for new applications Offers a comprehensive and thorough treatment of protein engineering from primary strategies to applications in industrial and medical biotechnology Presents cutting edge advances in the continuously evolving field of protein engineering Written for students and professionals of bioengineering, biotechnology, biochemistry, Protein Engineering: Tools and Applications offers an essential resource to the design strategies in protein engineering and reviews recent applications.Table of ContentsPart I Directed Evolution 1 1 Continuous Evolution of Proteins In Vivo 3Alon Wellner, Arjun Ravikumar, and Chang C. Liu 1.1 Introduction 3 1.2 Challenges in Achieving In Vivo Continuous Evolution 5 1.3 Phage-Assisted Continuous Evolution (PACE) 10 1.4 Systems That Allow In Vivo Continuous Directed Evolution 13 1.4.1 Targeted Mutagenesis in E. coli with Error-Prone DNA Polymerase I 13 1.4.2 Yeast Systems That Do Not Use Engineered DNA Polymerases for Mutagenesis 16 1.4.3 Somatic Hypermutation as a Means for Targeted Mutagenesis of GOIs 18 1.4.4 Orthogonal DNA Replication (OrthoRep) 20 1.5 Conclusion 22 References 22 2 In Vivo Biosensors for Directed Protein Evolution 29Song Buck Tay and Ee Lui Ang 2.1 Introduction 29 2.2 Nucleic Acid-Based In Vivo Biosensors for Directed Protein Evolution 32 2.2.1 RNA-Type Biosensors 32 2.2.2 DNA-Type Biosensors 35 2.3 Protein-Based In Vivo Biosensors for Directed Protein Evolution 37 2.3.1 Transcription Factor-Type Biosensors 37 2.3.2 Enzyme-Type Biosensors 41 2.4 Characteristics of Biosensors for In Vivo Directed Protein Evolution 44 2.5 Conclusions and Future Perspectives 45 Acknowledgments 46 References 46 3 High-Throughput Mass Spectrometry Complements Protein Engineering 57Tong Si, Pu Xue, Kisurb Choe, Huimin Zhao, and Jonathan V. Sweedler 3.1 Introduction 57 3.2 Procedures and Instrumentation for MS-Based Protein Assays 59 3.3 Technology Advances Focusing on Throughput Improvement 62 3.4 Applications of MS-Based Protein Assays: Summary 63 3.4.1 Applications of MS-Based Assays: Protein Analysis 64 3.4.2 Applications of MS-Based Assays: Protein Engineering 66 3.5 Conclusions and Perspectives 68 Acknowledgments 68 References 69 4 Recent Advances in Cell Surface Display Technologies for Directed Protein Evolution 81Maryam Raeeszadeh-Sarmazdeh and Wilfred Chen 4.1 Cell Display Methods 81 4.1.1 Phage Display 81 4.1.2 Bacterial Display Systems 83 4.1.3 Yeast Surface Display 84 4.1.4 Mammalian Display 85 4.2 Selection Methods and Strategies 86 4.2.1 High-Throughput Cell Screening 86 4.2.1.1 Panning 86 4.2.1.2 FACS 86 4.2.1.3 MACS 87 4.2.2 Selection Strategies 88 4.2.2.1 Competitive Selection (Counter Selection) 88 4.2.2.2 Negative/Positive Selection 89 4.3 Modifications of Cell Surface Display Systems 89 4.3.1 Modification of YSD for Enzyme Engineering 89 4.3.2 Yeast Co-display System 91 4.3.3 Surface Display of Multiple Proteins 91 4.4 Recent Advances to Expand Cell-Display Directed Evolution Techniques 93 4.4.1 μSCALE (Microcapillary Single-Cell Analysis and Laser Extraction) 93 4.4.2 Combining Cell Surface Display and Next-Generation Sequencing 94 4.4.3 PACE (Phage-Assisted Continuous Evolution) 94 4.5 Conclusion and Outlook 96 References 97 5 Iterative Saturation Mutagenesis for Semi-rational Enzyme Design 105Ge Qu, Zhoutong Sun, and Manfred T. Reetz 5.1 Introduction 105 5.2 Recent Methodology Developments in ISM-Based Directed Evolution 108 5.2.1 Choosing Reduced Amino Acid Alphabets Properly 109 5.2.1.1 Limonene Epoxide Hydrolase as the Catalyst in Hydrolytic Desymmetrization 109 5.2.1.2 Alcohol Dehydrogenase TbSADH as the Catalyst in Asymmetric Transformation of Difficult-to-Reduce Ketones 110 5.2.1.3 P450-BM3 as the Chemo- and Stereoselective Catalyst in a Whole-Cell Cascade Sequence 112 5.2.1.4 Multi-parameter Evolution Aided by Mutability Landscaping 115 5.2.2 Further Methodology Developments of CAST/ISM 117 5.2.2.1 Advances Based on Novel Molecular Biological Techniques and Computational Methods 117 5.2.2.2 Advances Based on Solid-Phase Chemical Synthesis of SM Libraries 118 5.3 B-FIT as an ISM Method for Enhancing Protein Thermostability 120 5.4 Learning from CAST/ISM-Based Directed Evolution 121 5.5 Conclusions and Perspectives 121 Acknowledgment 124 References 124 Part II Rational and Semi-Rational Design 133 6 Data-driven Protein Engineering 135Jonathan Greenhalgh, Apoorv Saraogee, and Philip A. Romero 6.1 Introduction 135 6.2 The Data Revolution in Biology 136 6.3 Statistical Representations of Protein Sequence, Structure, and Function 138 6.3.1 Representing Protein Sequences 138 6.3.2 Representing Protein Structures 140 6.4 Learning the Sequence-Function Mapping from Data 141 6.4.1 Supervised Learning (Regression/Classification) 141 6.4.2 Unsupervised/Semisupervised Learning 144 6.5 Applying Statistical Models to Engineer Proteins 145 6.6 Conclusions and Future Outlook 147 References 148 7 Protein Engineering by Efficient Sequence Space Exploration Through Combination of Directed Evolution and Computational Design Methodologies 153Subrata Pramanik, Francisca Contreras, Mehdi D. Davari, and Ulrich Schwaneberg 7.1 Introduction 153 7.2 Protein Engineering Strategies 154 7.2.1 Computer-Aided Rational Design 155 7.2.1.1 FRESCO 155 7.2.1.2 FoldX 157 7.2.1.3 CNA 158 7.2.1.4 PROSS 159 7.2.1.5 ProSAR 160 7.2.2 Knowledge Based Directed Evolution 161 7.2.2.1 Iterative Saturation Mutagenesis (ISM) 161 7.2.2.2 Mutagenic Organized Recombination Process by Homologous In Vivo Grouping (MORPHING) 161 7.2.2.3 Knowledge Gaining Directed Evolution (KnowVolution) 162 7.3 Conclusions and Future Perspectives 171 Acknowledgments 171 References 171 8 Engineering Artificial Metalloenzymes 177Kevin A. Harnden, Yajie Wang, Lam Vo, Huimin Zhao, and Yi Lu 8.1 Introduction 177 8.2 Rational Design 177 8.2.1 Rational Design of Metalloenzymes Using De Novo Designed Scaffolds 177 8.2.2 Rational Design of Metalloenzymes Using Native Scaffolds 179 8.2.2.1 Redesign of Native Proteins 179 8.2.2.2 Cofactor Replacement in Native Proteins 181 8.2.2.3 Covalent Anchoring in Native Protein 184 8.2.2.4 Supramolecular Anchoring in Native Protein 187 8.3 Engineering Artificial Metalloenzyme by Directed Evolution in Combination with Rational Design 188 8.3.1 Directed Evolution of Metalloenzymes Using De Novo Designed Scaffolds 188 8.3.2 Directed Evolution of Metalloenzymes Using Native Scaffolds 189 8.3.2.1 Cofactor Replacement in Native Proteins 189 8.3.2.2 Covalent Anchoring in Native Protein 192 8.3.2.3 Non-covalent Anchoring in Native Proteins 194 8.4 Summary and Outlook 200 Acknowledgment 201 References 201 9 Engineered Cytochromes P450 for Biocatalysis 207Hanan Alwaseem and Rudi Fasan 9.1 Cytochrome P450 Monooxygenases 207 9.2 Engineered Bacterial P450s for Biocatalytic Applications 210 9.2.1 Oxyfunctionalization of Small Organic Substrates 211 9.2.2 Late-Stage Functionalization of Natural Products 220 9.2.3 Synthesis of Drug Metabolites 224 9.3 High-throughput Methods for Screening Engineered P450s 227 9.4 Engineering of Hybrid P450 Systems 229 9.5 Engineered P450s with Improved Thermostability and Solubility 230 9.6 Conclusions 231 Acknowledgments 232 References 232 Part III Applications in Industrial Biotechnology 243 10 Protein Engineering Using Unnatural Amino Acids 245Yang Yu, Xiaohong Liu, and Jiangyun Wang 10.1 Introduction 245 10.2 Methods for Unnatural Amino Acid Incorporation 246 10.3 Applications of Unnatural Amino Acids in Protein Engineering 247 10.3.1 Enhancing Stability 248 10.3.2 Mechanistic Study Using Spectroscopic Methods 248 10.3.3 Tuning Catalytic Activity 250 10.3.4 Tuning Selectivity 252 10.3.5 Enzyme Design 252 10.3.6 Protein Engineering Toward a Synthetic Life 255 10.4 Outlook 256 10.5 Conclusions 258 References 258 11 Application of Engineered Biocatalysts for the Synthesis of Active Pharmaceutical Ingredients (APIs) 265Juan Mangas-Sanchez, Sebastian C. Cosgrove, and Nicholas J. Turner 11.1 Introduction 265 11.1.1 Transferases 266 11.1.1.1 Transaminases 266 11.1.2 Oxidoreductases 267 11.1.2.1 Ketoreductases 267 11.1.2.2 Amino Acid Dehydrogenases 271 11.1.2.3 Cytochrome P450 Monoxygenases 272 11.1.2.4 Baeyer–Villiger Monoxygenases 273 11.1.2.5 Amine Oxidases 274 11.1.2.6 Hydroxylases 276 11.1.2.7 Imine Reductases 276 11.1.3 Lyases 278 11.1.3.1 Ammonia Lyases 278 11.1.4 Isomerases 278 11.1.5 Hydrolases 279 11.1.5.1 Esterases 279 11.1.5.2 Haloalkane Dehalogenase 279 11.1.6 Multi-enzyme Cascade 281 11.2 Conclusions 282 References 287 12 Directing Evolution of the Fungal Ligninolytic Secretome 295Javier Viña-Gonzalez and Miguel Alcalde 12.1 The Fungal Ligninolytic Secretome 295 12.2 Functional Expression in Yeast 297 12.2.1 The Evolution of Signal Peptides 297 12.2.2 Secretion Mutations in Mature Protein 300 12.2.3 The Importance of Codon Usage 301 12.3 Yeast as a Tool-Box in the Generation of DNA Diversity 302 12.4 Bringing Together Evolutionary Strategies and Computational Tools 305 12.5 High-Throughput Screening (HTS) Assays for Ligninase Evolution 306 12.6 Conclusions and Outlook 309 Acknowledgments 309 References 310 13 Engineering Antibody-Based Therapeutics: Progress and Opportunities 317Annalee W. Nguyen and Jennifer A. Maynard 13.1 Introduction 317 13.2 Antibody Formats 318 13.2.1 Human IgG1 Structure 318 13.2.2 Antibody-Drug Conjugates 319 13.2.3 Bispecific Antibodies 320 13.2.4 Single Domain Antibodies 321 13.2.5 Chimeric Antigen Receptors 321 13.3 Antibody Discovery 322 13.3.1 Antibody Target Identification 322 13.3.1.1 Cancer and Autoimmune Disease Targets 323 13.3.1.2 Infectious Disease Targets 323 13.3.2 Screening for Target-Binding Antibodies 324 13.3.2.1 Synthetic Library Derived Antibodies 324 13.3.2.2 Host-Derived Antibodies 325 13.3.2.3 Immunization 325 13.3.2.4 Pairing the Light and Heavy Variable Regions 326 13.3.2.5 Humanization 327 13.3.2.6 Hybrid Approaches to Antibody Discovery 328 13.4 Therapeutic Optimization of Antibodies 328 13.4.1 Serum Half-Life 328 13.4.1.1 Antibody Half-Life Extension 329 13.4.1.2 Antibody Half-Life Reduction 331 13.4.1.3 Effect of Half-Life Modification on Effector Functions 331 13.4.2 Effector Functions 331 13.4.2.1 Effector Function Considerations for Cancer Therapeutics 332 13.4.2.2 Effector Function Considerations for Infectious Disease Prophylaxis and Therapy 333 13.4.2.3 Effector Function Considerations for Treating Autoimmune Disease 334 13.4.2.4 Approaches to Engineering the Effector Functions of the IgG1 Fc 334 13.4.3 Tissue Localization 335 13.4.4 Immunogenicity 335 13.4.4.1 Reducing T-Cell Recognition 336 13.4.4.2 Reducing Aggregation 336 13.5 Manufacturability of Antibodies 336 13.5.1 Increasing Antibody Yield 337 13.5.1.1 Codon Usage 337 13.5.1.2 Signal Peptide Optimization 337 13.5.1.3 Expression Optimization 338 13.5.2 Alternative Production Methods 338 13.6 Conclusions 339 Acknowledgments 339 References 339 14 Programming Novel Cancer Therapeutics: Design Principles for Chimeric Antigen Receptors 353Andrew J. Hou and Yvonne Y. Chen 14.1 Introduction 353 14.2 Metrics to Evaluate CAR-T Cell Function 354 14.3 Antigen-Recognition Domain 356 14.3.1 Tuning the Antigen-Recognition Domain to Manage Toxicity 356 14.3.2 Incorporation of Multiple Antigen-Recognition Domains to Engineer “Smarter” CARs 356 14.3.3 Novel Antigen-Recognition Domains to Enhance CAR Modularity 359 14.3.4 Engineering CARs that Target Soluble Factors 360 14.4 Extracellular Spacer 360 14.5 Transmembrane Domain 362 14.6 Signaling Domain 362 14.6.1 First- and Second-Generation CARs 362 14.6.2 Combinatorial Co-stimulation 363 14.6.3 Other Co-stimulatory Domains: ICOS, OX40, TLR2 364 14.6.4 Additional Considerations for CAR Signaling Domains 364 14.7 High-Throughput CAR Engineering 366 14.8 Novel Receptor Modalities 367 References 369 Part IV Applications in Medical Biotechnology 377 15 Development of Novel Cellular Imaging Tools Using Protein Engineering 379Praopim Limsakul, Chi-Wei Man, Qin Peng, Shaoying Lu, and Yingxiao Wang 15.1 Introduction 379 15.2 Cellular Imaging Tools Developed by Protein Engineering 380 15.2.1 Fluorescent Proteins 380 15.2.1.1 The FP Color Palette 380 15.2.1.2 Photocontrollable Fluorescent Proteins 381 15.2.1.3 Other Engineered Fluorescent Proteins 383 15.2.2 Antibodies and Protein Scaffolds 383 15.2.2.1 Antibodies 383 15.2.2.2 Antibody-Like Protein Scaffolds 384 15.2.2.3 Directed Evolution 384 15.2.3 Genetically Encoded Non-fluorescent Protein Tags 385 15.3 Application in Cellular Imaging 386 15.3.1 Cell Biology Applications 386 15.3.1.1 Localization 386 15.3.1.2 Cell Signaling 387 15.3.2 Application in Diagnostics and Medicine 390 15.3.2.1 Detection 390 15.3.2.2 Screening for Drugs 392 15.4 Conclusion and Perspectives 393 References 394 Index 403

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Book SynopsisProvides the background, tools, and models required to understand organic synthesis and plan chemical reactions more efficiently Knowledge of physical chemistry is essential for achieving successful chemical reactions in organic chemistry. Chemists must be competent in a range of areas to understand organic synthesis. Organic Chemistry provides the methods, models, and tools necessary to fully comprehend organic reactions. Written by two internationally recognized experts in the field, this much-needed textbook fills a gap in current literature on physical organic chemistry. Rigorous yet straightforward chapters first examine chemical equilibria, thermodynamics, reaction rates and mechanisms, and molecular orbital theory, providing readers with a strong foundation in physical organic chemistry. Subsequent chapters demonstrate various reactions involving organic, organometallic, and biochemical reactants and catalysts. Throughout the text, numerous questions and exercises, over 800 in total, help readers strengthen their comprehension of the subject and highlight key points of learning. The companion Organic Chemistry Workbook contains complete references and answers to every question in this text. A much-needed resource for students and working chemists alike, this text: -Presents models that establish if a reaction is possible, estimate how long it will take, and determine its properties -Describes reactions with broad practical value in synthesis and biology, such as C-C-coupling reactions, pericyclic reactions, and catalytic reactions -Enables readers to plan chemical reactions more efficiently -Features clear illustrations, figures, and tables -With a Foreword by Nobel Prize Laureate Robert H. Grubbs Organic Chemistry: Theory, Reactivity, and Mechanisms in Modern Synthesis is an ideal textbook for students and instructors of chemistry, and a valuable work of reference for organic chemists, physical chemists, and chemical engineers. Trade Review"Ich bin von diesem Buch begeistert, weil es mir als Dozenten eine unglaubliche Fülle an aktuellem Material zu Mechanismen und zu theoretischen Behandlung von organischen Reaktionen bietet. Als direktes Lehrbuch für einen M.Sc. Kurs ist es aufgrund des hochverdichteten Stoffes und der unglaublichen Datenmenge für Studierende nicht geeignet. Aufgrund der zahllosen Details gerät das große Ganze, das man in einer Lehrveranstaltung vermitteln möchte, etwas aus dem Blick. Ausschnittsweise könnte man es für einen Doktorandenkurs einsetzen. Es ist jedoch ein phantastisches Nachschlagewerk, das wir mit mehreren Exemplaren gerne in der Bibliothek und auch in meiner Abteilung vorhalten." Prof. Dr. Michael Schmittel, Universität Siegen Table of ContentsPreface xv Foreword xxix 1 Equilibria and thermochemistry 1 1.1 Introduction 1 1.2 Equilibrium-free enthalpy: reaction-free energy or Gibbs energy 1 1.3 Heat of reaction and variation of the entropy of reaction (reaction entropy) 2 1.4 Statistical thermodynamics 4 1.4.1 Contributions from translation energy levels 5 1.4.2 Contributions from rotational energy levels 5 1.4.3 Contributions from vibrational energy levels 6 1.4.4 Entropy of reaction depends above all on the change of the number of molecules between products and reactants 7 1.4.5 Additions are favored thermodynamically on cooling, fragmentations on heating 7 1.5 Standard heats of formation 8 1.6 What do standard heats of formation tell us about chemical bonding and ground-state properties of organic compounds? 9 1.6.1 Effect of electronegativity on bond strength 10 1.6.2 Effects of electronegativity and of hyperconjugation 11 1.6.3 π-Conjugation and hyperconjugation in carboxylic functions 12 1.6.4 Degree of chain branching and Markovnikov’s rule 13 1.7 Standard heats of typical organic reactions 14 1.7.1 Standard heats of hydrogenation and hydrocarbation 14 1.7.2 Standard heats of C–H oxidations 15 1.7.3 Relative stabilities of alkyl-substituted ethylenes 17 1.7.4 Effect of fluoro substituents on hydrocarbon stabilities 17 1.7.5 Storage of hydrogen in the form of formic acid 18 1.8 Ionization energies and electron affinities 20 1.9 Homolytic bond dissociations; heats of formation of radicals 22 1.9.1 Measurement of bond dissociation energies 22 1.9.2 Substituent effects on the relative stabilities of radicals 25 1.9.3 π-Conjugation in benzyl, allyl, and propargyl radicals 25 1.10 Heterolytic bond dissociation enthalpies 28 1.10.1 Measurement of gas-phase heterolytic bond dissociation enthalpies 28 1.10.2 Thermochemistry of ions in the gas phase 29 1.10.3 Gas-phase acidities 30 1.11 Electron transfer equilibria 32 1.12 Heats of formation of neutral, transient compounds 32 1.12.1 Measurements of the heats of formation of carbenes 32 1.12.2 Measurements of the heats of formation of diradicals 33 1.12.3 Keto/enol tautomerism 33 1.12.4 Heat of formation of highly reactive cyclobutadiene 36 1.12.5 Estimate of heats of formation of diradicals 36 1.13 Electronegativity and absolute hardness 37 1.14 Chemical conversion and selectivity controlled by thermodynamics 40 1.14.1 Equilibrium shifts (Le Chatelier’s principle in action) 40 1.14.2 Importance of chirality in biology and medicine 41 1.14.3 Resolution of racemates into enantiomers 43 1.14.4 Thermodynamically controlled deracemization 46 1.14.5 Self-disproportionation of enantiomers 48 1.15 Thermodynamic (equilibrium) isotopic effects 49 1.A Appendix, Table 1.A.1 to Table 1.A.24 53 References 92 2 Additivity rules for thermodynamic parameters and deviations 109 2.1 Introduction 109 2.2 Molecular groups 110 2.3 Determination of the standard group equivalents (group equivalents) 111 2.4 Determination of standard entropy increments 113 2.5 Steric effects 114 2.5.1 Gauche interactions: the preferred conformations of alkyl chains 114 2.5.2 (E)- vs. (Z)-alkenes and ortho-substitution in benzene derivatives 117 2.6 Ring strain and conformational flexibility of cyclic compounds 117 2.6.1 Cyclopropane and cyclobutane have nearly the same strain energy 118 2.6.2 Cyclopentane is a flexible cycloalkane 119 2.6.3 Conformational analysis of cyclohexane 119 2.6.4 Conformational analysis of cyclohexanones 121 2.6.5 Conformational analysis of cyclohexene 122 2.6.6 Medium-sized cycloalkanes 122 2.6.7 Conformations and ring strain in polycycloalkanes 124 2.6.8 Ring strain in cycloalkenes 125 2.6.9 Bredt’s rule and “anti-Bredt” alkenes 125 2.6.10 Allylic 1,3- and 1,2-strain: the model of banana bonds 126 2.7 𝜋/π-, n/π-, σ/π-, and n/σ-interactions 127 2.7.1 Conjugated dienes and diynes 127 2.7.2 Atropisomerism in 1,3-dienes and diaryl compounds 129 2.7.3 𝛼,β-Unsaturated carbonyl compounds 130 2.7.4 Stabilization by aromaticity 130 2.7.5 Stabilization by n(Z:)/𝜋 conjugation 132 2.7.6 𝜋/π-Conjugation and 𝜎/π-hyperconjugation in esters, thioesters, and amides 133 2.7.7 Oximes are more stable than imines toward hydrolysis 136 2.7.8 Aromatic stabilization energies of heterocyclic compounds 136 2.7.9 Geminal disubstitution: enthalpic anomeric effects 139 2.7.10 Conformational anomeric effect 141 2.8 Other deviations to additivity rules 144 2.9 Major role of translational entropy on equilibria 146 2.9.1 Aldol and crotonalization reactions 146 2.9.2 Aging of wines 148 2.10 Entropy of cyclization: loss of degrees of free rotation 151 2.11 Entropy as a synthetic tool 151 2.11.1 Pyrolysis of esters 151 2.11.2 Method of Chugaev 152 2.11.3 Eschenmoser–Tanabe fragmentation 152 2.11.4 Eschenmoser fragmentation 153 2.11.5 Thermal 1,4-eliminations 153 2.11.6 Retro-Diels–Alder reactions 156 2.A Appendix, Table 2.A.1 to Table 2.A.2 157 References 161 3 Rates of chemical reactions 177 3.1 Introduction 177 3.2 Differential and integrated rate laws 177 3.2.1 Order of reactions 178 3.2.2 Molecularity and reaction mechanisms 179 3.2.3 Examples of zero order reactions 181 3.2.4 Reversible reactions 182 3.2.5 Parallel reactions 183 3.2.6 Consecutive reactions and steady-state approximation 183 3.2.7 Consecutive reactions: maximum yield of the intermediate product 184 3.2.8 Homogeneous catalysis: Michaelis–Menten kinetics 185 3.2.9 Competitive vs. noncompetitive inhibition 186 3.2.10 Heterogeneous catalysis: reactions at surfaces 187 3.3 Activation parameters 188 3.3.1 Temperature effect on the selectivity of two parallel reactions 190 3.3.2 The Curtin–Hammett principle 190 3.4 Relationship between activation entropy and the reaction mechanism 192 3.4.1 Homolysis and radical combination in the gas phase 192 3.4.2 Isomerizations in the gas phase 193 3.4.3 Example of homolysis assisted by bond formation: the Cope rearrangement 195 3.4.4 Example of homolysis assisted by bond-breaking and bond-forming processes: retro–carbonyl–ene reaction 195 3.4.5 Can a reaction be assisted by neighboring groups? 197 3.5 Competition between cyclization and intermolecular condensation 197 3.5.1 Thorpe–Ingold effect 198 3.6 Effect of pressure: activation volume 201 3.6.1 Relationship between activation volume and the mechanism of reaction 201 3.6.2 Detection of change of mechanism 202 3.6.3 Synthetic applications of high pressure 203 3.6.4 Rate enhancement by compression of reactants along the reaction coordinates 204 3.6.5 Structural effects on the rate of the Bergman rearrangement 205 3.7 Asymmetric organic synthesis 206 3.7.1 Kinetic resolution 206 3.7.2 Parallel kinetic resolution 211 3.7.3 Dynamic kinetic resolution: kinetic deracemization 212 3.7.4 Synthesis starting from enantiomerically pure natural compounds 215 3.7.5 Use of recoverable chiral auxiliaries 217 3.7.6 Catalytic desymmetrization of achiral compounds 220 3.7.7 Nonlinear effects in asymmetric synthesis 226 3.7.8 Asymmetric autocatalysis 228 3.8 Chemo- and site-selective reactions 229 3.9 Kinetic isotope effects and reaction mechanisms 231 3.9.1 Primary kinetic isotope effects: the case of hydrogen transfers 231 3.9.2 Tunneling effects 232 3.9.3 Nucleophilic substitution and elimination reactions 234 3.9.4 Steric effect on kinetic isotope effects 239 3.9.5 Simultaneous determination of multiple small kinetic isotope effects at natural abundance 239 References 240 4 Molecular orbital theories 271 4.1 Introduction 271 4.2 Background of quantum chemistry 271 4.3 Schrödinger equation 272 4.4 Coulson and Longuet-Higgins approach 274 4.4.1 Hydrogen molecule 275 4.4.2 Hydrogenoid molecules: The PMO theory 276 4.5 Hückel method 277 4.5.1 π-Molecular orbitals of ethylene 278 4.5.2 Allyl cation, radical, and anion 279 4.5.3 Shape of allyl π-molecular orbitals 282 4.5.4 Cyclopropenyl systems 282 4.5.5 Butadiene 285 4.5.6 Cyclobutadiene and its electronic destabilization (antiaromaticity) 286 4.5.7 Geometries of cyclobutadienes, singlet and triplet states 288 4.5.8 Pentadienyl and cyclopentadienyl systems 291 4.5.9 Cyclopentadienyl anion and bishomocyclopentadienyl anions 292 4.5.10 Benzene and its aromatic stabilization energy 294 4.5.11 3,4-Dimethylidenecyclobutene is not stabilized by π-conjugation 295 4.5.12 Fulvene 297 4.5.13 [N]Annulenes 298 4.5.14 Cyclooctatetraene 301 4.5.15 π-systems with heteroatoms 302 4.6 Aromatic stabilization energy of heterocyclic compounds 305 4.7 Homoconjugation 308 4.7.1 Homoaromaticity in cyclobutenyl cation 308 4.7.2 Homoaromaticity in homotropylium cation 308 4.7.3 Homoaromaticity in cycloheptatriene 310 4.7.4 Bishomoaromaticity in bishomotropylium ions 311 4.7.5 Bishomoaromaticity in neutral semibullvalene derivatives 312 4.7.6 Barrelene effect 313 4.8 Hyperconjugation 314 4.8.1 Neutral, positive, and negative hyperconjugation 314 4.8.2 Hyperconjugation in cyclopentadienes 315 4.8.3 Nonplanarity of bicyclo[2.2.1]hept-2-ene double bond 315 4.8.4 Conformation of unsaturated and saturated systems 317 4.8.5 Hyperconjugation in radicals 319 4.8.6 Hyperconjugation in carbenium ions 320 4.8.7 Hyperconjugation in carbanions 320 4.8.8 Cyclopropyl vs. cyclobutyl substituent effect 322 4.9 Heilbronner Möbius aromatic [N]annulenes 324 4.10 Conclusion 326 References 326 5 Pericyclic reactions 339 5.1 Introduction 339 5.2 Electrocyclic reactions 340 5.2.1 Stereochemistry of thermal cyclobutene-butadiene isomerization: four-electron electrocyclic reactions 340 5.2.2 Longuet-Higgins correlation of electronic configurations 342 5.2.3 Woodward–Hoffmann simplification 345 5.2.4 Aromaticity of transition states in cyclobutene/butadiene electrocyclizations 346 5.2.5 Torquoselectivity of cyclobutene electrocyclic reactions 347 5.2.6 Nazarov cyclizations 350 5.2.7 Thermal openings of three-membered ring systems 354 5.2.8 Six-electron electrocyclic reactions 357 5.2.9 Eight-electron electrocyclic reactions 360 5.3 Cycloadditions and cycloreversions 361 5.3.1 Stereoselectivity of thermal [𝜋2+𝜋2]-cycloadditions: Longuet-Higgins model 362 5.3.2 Woodward–Hoffmann rules for cycloadditions 364 5.3.3 Aromaticity of cycloaddition transition structures 366 5.3.4 Mechanism of thermal [𝜋2+𝜋2]-cycloadditions and [𝜎2+𝜎2]-cycloreversions: 1,4- diradical/zwitterion intermediates or diradicaloid transition structures 368 5.3.5 Cycloadditions of allenes 372 5.3.6 Cycloadditions of ketenes and keteniminium salts 373 5.3.7 Wittig olefination 380 5.3.8 Olefinations analogous to the Wittig reaction 384 5.3.9 Diels–Alder reaction: concerted and non-concerted mechanisms compete 387 5.3.10 Concerted Diels–Alder reactions with synchronous or asynchronous transition states 391 5.3.11 Diradicaloid model for transition states of concerted Diels–Alder reactions 392 5.3.12 Structural effects on the Diels–Alder reactivity 397 5.3.13 Regioselectivity of Diels–Alder reactions 399 5.3.14 Stereoselectivity of Diels–Alder reactions: the Alder “endo rule” 406 5.3.15 π-Facial selectivity of Diels–Alder reactions 408 5.3.16 Examples of hetero-Diels–Alder reactions 411 5.3.17 1,3-Dipolar cycloadditions 420 5.3.18 Sharpless asymmetric dihydroxylation of alkenes 428 5.3.19 Thermal (2+2+2)-cycloadditions 428 5.3.20 Noncatalyzed (4+3)- and (5+2)-cycloadditions 431 5.3.21 Thermal higher order (m+n)-cycloadditions 434 5.4 Cheletropic reactions 437 5.4.1 Cyclopropanation by (2+1)-cheletropic reaction of carbenes 437 5.4.2 Aziridination by (2+1)-cheletropic addition of nitrenes 440 5.4.3 Decarbonylation of cyclic ketones by cheletropic elimination 442 5.4.4 Cheletropic reactions of sulfur dioxide 444 5.4.5 Cheletropic reactions of heavier congeners of carbenes and nitrenes 447 5.5 Thermal sigmatropic rearrangements 451 5.5.1 (1,2)-Sigmatropic rearrangement of carbenium ions 451 5.5.2 (1,2)-Sigmatropic rearrangements of radicals 456 5.5.3 (1,2)-Sigmatropic rearrangements of organoalkali compounds 459 5.5.4 (1,3)-Sigmatropic rearrangements 462 5.5.5 (1,4)-Sigmatropic rearrangements 465 5.5.6 (1,5)-Sigmatropic rearrangements 467 5.5.7 (1,7)-Sigmatropic rearrangements 469 5.5.8 (2,3)-Sigmatropic rearrangements 470 5.5.9 (3,3)-Sigmatropic rearrangements 476 5.5.9.1 Fischer indole synthesis (3,4-diaza-Cope rearrangement) 476 5.5.9.2 Claisen rearrangement and its variants (3-oxa-Cope rearrangements) 476 5.5.9.3 Aza-Claisen rearrangements (3-aza-Cope rearrangements) 481 5.5.9.4 Overman rearrangement (1-oxa-3-aza-Cope rearrangement) 483 5.5.9.5 Thia-Claisen rearrangement (3-thia-Cope rearrangement) 484 5.5.9.6 Cope rearrangements 484 5.5.9.7 Facile anionic oxy-Cope rearrangements 489 5.5.9.8 Acetylenic Cope rearrangements 491 5.5.9.9 Other hetero-Cope rearrangements 492 5.6 Dyotropic rearrangements and transfers 495 5.6.1 Type I dyotropic rearrangements 496 5.6.2 Alkene and alkyne reductions with diimide 498 5.6.3 Type II dyotropic rearrangements 499 5.7 Ene-reactions and related reactions 500 5.7.1 Thermal Alder ene-reactions 501 5.7.2 Carbonyl ene-reactions 504 5.7.3 Other hetero-ene reactions involving hydrogen transfers 504 5.7.4 Metallo-ene-reactions 508 5.7.5 Carbonyl allylation with allylmetals: carbonyl metallo-ene-reactions 509 5.7.6 Aldol reaction 514 5.7.7 Reactions of metal enolates with carbonyl compounds 518 References 526 6 Organic photochemistry 615 6.1 Introduction 615 6.2 Photophysical processes of organic compounds 615 6.2.1 UV–visible spectroscopy: electronic transitions 616 6.2.2 Fluorescence and phosphorescence: singlet and triplet excited states 620 6.2.3 Bimolecular photophysical processes 623 6.3 Unimolecular photochemical reactions of unsaturated hydrocarbons 626 6.3.1 Photoinduced (E)/(Z)-isomerization of alkenes 626 6.3.2 Photochemistry of cyclopropenes, allenes, and alkynes 630 6.3.3 Electrocyclic ring closures of conjugated dienes and ring opening of cyclobutenes 631 6.3.4 The di-π-methane (Zimmerman) rearrangement of 1,4-dienes 633 6.3.5 Electrocyclic interconversions of cyclohexa-1,3-dienes and hexa-1,3,5-trienes 635 6.4 Unimolecular photochemical reactions of carbonyl compounds 637 6.4.1 Norrish type I reaction (α-cleavage) 637 6.4.2 Norrish type II reaction and other intramolecular hydrogen transfers 639 6.4.3 Unimolecular photochemistry of enones and dienones 642 6.5 Unimolecular photoreactions of benzene and heteroaromatic analogs 644 6.5.1 Photoisomerization of benzene 644 6.5.2 Photoisomerizations of pyridines, pyridinium salts, and diazines 646 6.5.3 Photolysis of five-membered ring heteroaromatic compounds 647 6.6 Photocleavage of carbon–heteroatom bonds 649 6.6.1 Photo-Fries, photo-Claisen, and related rearrangements 649 6.6.2 Photolysis of 1,2-diazenes, 3H-diazirines, and diazo compounds 651 6.6.3 Photolysis of alkyl halides 654 6.6.4 Solution photochemistry of aryl and alkenyl halides 657 6.6.5 Photolysis of phenyliodonium salts: formation of aryl and alkenyl cation intermediates 659 6.6.6 Photolytic decomposition of arenediazonium salts in solution 660 6.7 Photocleavage of nitrogen—nitrogen bonds 661 6.7.1 Photolysis of azides 662 6.7.2 Photo-Curtius rearrangement 664 6.7.3 Photolysis of geminal diazides 665 6.7.4 Photolysis of 1,2,3-triazoles and of tetrazoles 666 6.8 Photochemical cycloadditions of unsaturated compounds 667 6.8.1 Photochemical intramolecular (2+2)-cycloadditions of alkenes 668 6.8.2 Photochemical intermolecular (2+2)-cycloadditions of alkenes 672 6.8.3 Photochemical intermolecular (4+2)-cycloadditions of dienes and alkenes 676 6.8.4 Photochemical cycloadditions of benzene and derivatives to alkenes 677 6.8.5 Photochemical cycloadditions of carbonyl compounds 681 6.8.6 Photochemical cycloadditions of imines and related C=N double-bonded compounds 686 6.9 Photo-oxygenation 688 6.9.1 Reactions of ground-state molecular oxygen with hydrocarbons 688 6.9.2 Singlet molecular oxygen 691 6.9.3 Diels–Alder reactions of singlet oxygen 695 6.9.4 Dioxa-ene reactions of singlet oxygen 700 6.9.5 (2+2)-Cycloadditions of singlet oxygen 704 6.9.6 1,3-Dipolar cycloadditions of singlet oxygen 705 6.9.7 Nonpericyclic reactions of singlet oxygen 707 6.10 Photoinduced electron transfers 710 6.10.1 Marcus model 711 6.10.2 Catalysis through photoreduction 711 6.10.3 Photoinduced net reductions 715 6.10.4 Catalysis through photo-oxidation 717 6.10.5 Photoinduced net oxidations 721 6.10.6 Generation of radical intermediates by PET 724 6.10.7 Dye-sensitized solar cells 726 6.11 Chemiluminescence and bioluminescence 727 6.11.1 Thermal isomerization of Dewar benzene into benzene 728 6.11.2 Oxygenation of electron-rich organic compounds 729 6.11.3 Thermal fragmentation of 1,2-dioxetanes 732 6.11.4 Peroxylate chemiluminescence 734 6.11.5 Firefly bioluminescence 734 References 735 7 Catalytic reactions 795 7.1 Introduction 795 7.2 Acyl group transfers 798 7.2.1 Esterification and ester hydrolysis 798 7.2.2 Acid or base-catalyzed acyl transfers 799 7.2.3 Amphoteric compounds are good catalysts for acyl transfers 802 7.2.4 Catalysis by nucleofugal group substitution 802 7.2.5 N-heterocyclic carbene-catalyzed transesterifications 804 7.2.6 Enzyme-catalyzed acyl transfers 806 7.2.7 Mimics of carboxypeptidase A 807 7.2.8 Direct amide bond formation from amines and carboxylic acids 807 7.3 Catalysis of nucleophilic additions 810 7.3.1 Catalysis of nucleophilic additions to aldehydes, ketones and imines 810 7.3.2 Bifunctional catalysts for nucleophilic addition/elimination 811 7.3.3 σ- and π-Nucleophiles as catalysts for nucleophilic additions to aldehydes and ketones 812 7.3.4 Catalysis by self-assembled encapsulation 813 7.3.5 Catalysis of 1,4-additions (conjugate additions) 814 7.4 Anionic nucleophilic displacement reactions 815 7.4.1 Pulling on the leaving group 815 7.4.2 Phase transfer catalysis 816 7.5 Catalytical Umpolung C—C bond forming reactions 818 7.5.1 Benzoin condensation: Umpolung of aldehydes 819 7.5.2 Stetter reaction: Umpolung of aldehydes 821 7.5.3 Umpolung of enals 822 7.5.4 Umpolung of Michael acceptors 823 7.5.5 Rauhut–Currier reaction 826 7.5.6 Morita–Baylis–Hillman reaction 826 7.5.7 Nucleophilic catalysis of cycloadditions 828 7.5.8 Catalysis through electron-transfer: hole-catalyzed reactions 831 7.5.9 Umpolung of enamines 834 7.5.10 Catalysis through electron-transfer: Umpolung through electron capture 836 7.6 Brønsted and Lewis acids as catalysts in C—C bond forming reactions 836 7.6.1 Mukaiyama aldol reactions 839 7.6.2 Metallo-carbonyl-ene reactions 843 7.6.3 Carbonyl-ene reactions 846 7.6.4 Imine-ene reactions 847 7.6.5 Alder-ene reaction 848 7.6.6 Diels–Alder reaction 849 7.6.7 Brønsted and Lewis acid-catalyzed hetero-Diels-Alder reactions 851 7.6.8 Acid-catalyzed (2+2)-cycloadditions 853 7.6.9 Lewis acid catalyzed (3+2)- and (3+3)-cycloadditions 855 7.6.10 Lewis acid promoted (5+2)-cycloadditions 857 7.7 Bonding in transition metal complexes and their reactions 858 7.7.1 The π-complex theory 858 7.7.2 The isolobal formalism 860 7.7.3 σ-Complexes of dihydrogen 863 7.7.4 σ-Complexes of C—H bonds and agostic bonding 866 7.7.5 σ-Complexes of C—C bonds and C—C bond activation 867 7.7.6 Reactions of transition metal complexes are modeled by reactions of organic chemistry 869 7.7.7 Ligand exchange reactions 869 7.7.8 Oxidative additions and reductive eliminations 873 7.7.9 α-Insertions/α-eliminations 880 7.7.10 β-Insertions/β-eliminations 883 7.7.11 α-Cycloinsertions/α-cycloeliminations: metallacyclobutanes, metallacyclobutenes 886 7.7.12 Metallacyclobutenes: alkyne polymerization, enyne metathesis, cyclopentadiene synthesis 887 7.7.13 Metallacyclobutadiene: alkyne metathesis 889 7.7.14 Matallacyclopentanes, metallacyclopentenes, metallacyclopentadienes: oxidative cyclizations (β-cycloinsertions) and reductive fragmentations (β-cycloeliminations) 890 7.8 Catalytic hydrogenation 891 7.8.1 Heterogeneous catalysts for alkene, alkyne, and arene hydrogenation 892 7.8.2 Homogeneous catalysts for alkene and alkyne hydrogenation 894 7.8.3 Dehydrogenation of alkanes 897 7.8.4 Hydrogenation of alkynes into alkenes 897 7.8.5 Catalytic hydrogenation of arenes and heteroarenes 899 7.8.6 Catalytic hydrogenation of ketones and aldehydes 899 7.8.7 Catalytic hydrogenation of carboxylic acids, their esters and amides 902 7.8.8 Hydrogenation of carbon dioxide 903 7.8.9 Catalytic hydrogenation of nitriles and imines 904 7.8.10 Catalytic hydrogenolysis of C–halogen and C–chalcogen bonds 906 7.9 Catalytic reactions of silanes 906 7.9.1 Reduction of alkyl halides 906 7.9.2 Reduction of carbonyl compounds 907 7.9.3 Alkene hydrosilylation 909 7.10 Hydrogenolysis of C—C single bonds 910 7.11 Catalytic oxidations with molecular oxygen 911 7.11.1 Heme-dependent monooxygenase oxidations 912 7.11.2 Chemical aerobic C—H oxidations 914 7.11.3 Reductive activation of molecular oxygen 917 7.11.4 Oxidation of alcohols with molecular oxygen 918 7.11.5 Wacker process 920 7.12 Catalyzed nucleophilic aromatic substitutions 922 7.12.1 Ullmann–Goldberg reactions 923 7.12.2 Buchwald–Hartwig reactions 926 References 927 8 Transition-metal-catalyzed C—C bond forming reactions 1029 8.1 Introduction 1029 8.2 Organic compounds from carbon monoxide 1030 8.2.1 Fischer–Tropsch reactions 1030 8.2.2 Carbonylation of methanol 1032 8.2.3 Hydroformylation of alkenes 1034 8.2.4 Silylformylation 1039 8.2.5 Reppe carbonylations 1041 8.2.6 Pd(II)-mediated oxidative carbonylations 1042 8.2.7 Pauson–Khand reaction 1043 8.2.8 Carbonylation of halides: synthesis of carboxylic derivatives 1047 8.2.9 Reductive carbonylation of halides: synthesis of carbaldehydes 1049 8.2.10 Carbonylation of epoxides and aziridines 1050 8.2.11 Hydroformylation and silylformylation of epoxides 1053 8.3 Direct hydrocarbation of unsaturated compounds 1053 8.3.1 Hydroalkylation of alkenes: alkylation of alkanes 1054 8.3.2 Alder ene-reaction of unactivated alkenes and alkynes 1056 8.3.3 Hydroarylation of alkenes: alkylation of arenes and heteroarenes 1057 8.3.4 Hydroarylation of alkynes: alkenylation of arenes and heteroarenes 1060 8.3.5 Hydroarylation of carbon-heteroatom multiple bonds 1062 8.3.6 Hydroalkenylation of alkynes, alkenes, and carbonyl compounds 1062 8.3.7 Hydroacylation of alkenes and alkynes 1063 8.3.8 Hydrocyanation of alkenes and alkynes 1066 8.3.9 Direct reductive hydrocarbation of unsaturated compounds 1067 8.3.10 Direct hydrocarbation via transfer hydrogenation 1069 8.4 Carbacarbation of unsaturated compounds and cycloadditions 1070 8.4.1 Formal [𝜎2+𝜋2]-cycloadditions 1072 8.4.2 (2+1)-Cycloadditions 1072 8.4.3 Ohloff–Rautenstrauch cyclopropanation 1077 8.4.4 [𝜋2+𝜋2]-Cycloadditions 1078 8.4.5 (3+1)-Cycloadditions 1080 8.4.6 (3+2)-Cycloadditions 1081 8.4.7 (4+1)-Cycloadditions 1087 8.4.8 (2+2+1)-Cycloadditions 1089 8.4.9 [𝜋4+𝜋2]-Cycloadditions of unactivated cycloaddents 1090 8.4.10 (2+2+2)-Cycloadditions 1096 8.4.11 (3+3)-Cycloadditions 1101 8.4.12 (3+2+1)-Cycloadditions 1102 8.4.13 (4+3)-Cycloadditions 1103 8.4.14 (5+2)-Cycloadditions 1105 8.4.15 (4+4)-Cycloadditions 1108 8.4.16 (4+2+2)-Cycloadditions 1109 8.4.17 (6+2)-Cycloadditions 1110 8.4.18 (2+2+2+2)-Cycloadditions 1111 8.4.19 (5+2+1)-Cycloadditions 1112 8.4.20 (7+1)-Cycloadditions 1112 8.4.21 Further examples of high-order catalyzed cycloadditions 1112 8.4.22 Annulations through catalytic intramolecular hydrometallation 1115 8.4.23 Oxidative annulations 1115 8.5 Didehydrogenative C—C-coupling reactions 1116 8.5.1 Glaser–Hay reaction: oxidative alkyne homocoupling 1116 8.5.2 Oxidative C—C cross-coupling reactions 1117 8.5.3 Oxidative aryl/aryl homocoupling reactions 1119 8.5.4 Oxidative aryl/aryl cross-coupling reactions 1121 8.5.5 TEMPO-cocatalyzed oxidative C—C coupling reactions 1122 8.5.6 Oxidative aminoalkylation of alkynes and active C—H moieties 1123 8.6 Alkane, alkene, and alkyne metathesis 1124 8.6.1 Alkane metathesis 1125 8.6.2 Alkene metathesis 1126 8.6.3 Enyne metathesis: alkene/alkyne cross-metathesis 1131 8.6.4 Alkyne metathesis 1133 8.7 Additions of organometallic reagents 1134 8.7.1 Additions of Grignard reagents 1136 8.7.2 Additions of alkylzinc reagents 1142 8.7.3 Additions of organoaluminum compounds 1143 8.7.4 Additions of organoboron, silicium , and zirconium compounds 1145 8.8 Displacement reactions 1148 8.8.1 Kharash cross-coupling and Kumada–Tamao–Corriu reaction 1148 8.8.2 Negishi cross-coupling 1154 8.8.3 Stille cross-coupling and carbonylative Stille reaction 1157 8.8.4 Suzuki–Miyaura cross-coupling 1161 8.8.5 Hiyama cross-coupling 1166 8.8.6 Tsuji–Trost reaction: allylic alkylation 1168 8.8.7 Mizoroki–Heck coupling 1171 8.8.8 Sonogashira–Hagihara cross-coupling 1179 8.8.9 Arylation of arenes(heteroarenes) with aryl(heteroaryl) derivatives 1182 8.8.10 α-Arylation of carbonyl compounds and nitriles 1187 8.8.11 Direct arylation and alkynylation of nonactivated C—H bonds in alkyl groups 1189 8.8.12 Direct alkylation of nonactivated C—H bonds in alkyl groups 1190 References 1191 Index 1317

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Book SynopsisBasic Electrochemistry for Biotechnology Understand the basics of a thriving interdisciplinary research field Microbial electrochemistry is a subfield of bioelectrochemistry which concerns interactions between microbial organisms and electrically active surfaces such as electrodes. Its growth as a subject of research has been rapid in recent years, and its technological applications are many, particularly as the race to find sustainable organic energy sources accelerates. Basic Electrochemistry for Biotechnology offers an accessible overview of this interdisciplinary subject and its potential applications. Moving smoothly from the general to the specific, it offers both fundamental principles and some of the most relevant specific examples, such as biofilm electrodes, microbial fuel cells or microbial electrosynthesis cells, making it the ideal choice for building a working knowledge of this exciting new field. Its solid foundation of microbial electrochemical technologies also serves as a starting point for a wide range of applied research areas. Basic Electrochemistry for Biotechnology readers will also find: Carefully designed artistic illustrations Hands-on exercises throughout to facilitate entry into laboratory work Numerous illustrative examples and calculations designed to demonstrate and reinforce key principles Basic Electrochemistry for Biotechnology is the perfect point of entry into this growing field for both students and researchers.Table of ContentsList of Figures ix List of Boxes xxi Preface xxiii 1 A Reader’s Guide to Basic Electrochemistry for Biotechnology 1 2 A Basic Introduction to Microbial Electrochemical Technologies 3 2.1 Introduction to Microbial Energy Conversion and Microbial Electrochemical Technologies 3 2.1.1 Microbial Conversions 3 2.1.2 Microbial Fuel Cells and Microbial Electrolysis Cells 5 2.2 Electroactive Microorganisms and Mechanisms of Extracellular Electron Transfer 7 2.2.1 Extracellular Electron Transfer Mechanisms: The Role Models of Electroactive Microorganisms 7 2.2.2 A Snapshot on Electroactive Microorganisms 8 2.3 Energetics: The Redox Tower and a Water Analogy 9 2.4 Wastewater Characteristics 13 2.4.1 Physical Wastewater Characteristics 14 2.4.2 Chemical Wastewater Characteristics 14 2.4.3 Organic Constituents in Wastewater 15 2.4.4 Biological Wastewater Characteristics 16 2.5 Microbial Electrochemical Technologies: Systems and Design 17 2.5.1 Main Components and Design 17 2.5.2 Operational Modes 18 2.5.3 Electrodes and Current Collectors 19 2.5.4 Ionic Charge Transport and Membranes 21 2.5.5 Lab Measurements and Criteria for Normalization 22 2.6 Short Alert on Terminology 23 Questions 24 References 25 3 Electrochemical Potential, Electrode Potential, and the Need for Reference Electrodes 27 3.1 Introduction to Electrochemical Potentials 27 3.1.1 A Physical-Chemical Approach Toward Electrochemical Potentials 28 3.2 Electrodes and Electrode Reactions 36 3.2.1 Definition of Electrodes and Electrochemical Half-Cells 36 3.2.2 Scientific Notation of Electrochemical Cells 37 3.2.3 Types of Electrodes 38 3.3 The Relative Electrode Potential and the Need for Reference Electrodes 40 3.3.1 Point of Reference for Electrode Potentials 42 3.3.2 Reference Electrodes Explained via the Water Analogy 45 Questions 46 References 47 4 Reaction Equations and Thermodynamics of Electrochemical Reactions 49 4.1 Introduction to Oxidation and Reduction Reactions and Thermodynamic Limits 49 4.2 How to Write and Balance Reaction Equations of (Bio)electrochemical Reactions 50 4.2.1 Reaction Equations for the Hydrogen Fuel Cell 51 4.2.2 Reaction Equations for a Microbial Electrolysis Cell 53 4.3 Thermodynamics of Electrochemical Conversions 57 4.3.1 Calculations Assuming Standard Conditions 57 4.3.2 The Effect of Actual Concentrations on Gibbs Free Energy Change 62 4.3.3 The Effect of Temperature on Gibbs Free Energy Change 65 Questions 68 References 68 5 Static Electrochemical Methods 69 5.1 Introduction to Static Electrochemical Methods 69 5.2 What Is a Three-Electrode Arrangement, a Potentiostat or Power Supply, and for What Are They Needed? 70 5.3 The Electrochemical Double Layer and Capacitive Current 74 5.4 Potentiometry, Amperometry, Coulometry, and Constant Current Measurements 78 5.5 Chronoamperometry 82 Questions 87 References 88 6 Electrochemical Kinetics 89 6.1 Introduction to Electrochemical Kinetics 89 6.2 Basics of Electrochemical Kinetics 90 6.3 Electrochemical Reversibility 91 6.4 Overpotentials 94 6.5 The Overpotential Due to Mass Transfer 98 6.6 Potential-Current Plots and Electrode Kinetics 101 6.7 The Butler–Volmer Equation 103 6.8 Tafel Equation and Tafel Plots 106 6.9 Electrocatalysis 108 Questions 113 References 114 7 Dynamic Electrochemical Methods 115 7.1 Introduction to Electrochemical Methods with Changing Electrode Potential 115 7.2 Voltammetry 117 7.3 Performing Dynamic Electrochemical Methods Using Potentiostats: Discriminating Capacitive and Faradaic Current 117 7.3.1 The Principles of Linear Sweep Voltammetry 120 7.4 Cyclic Voltammetry 123 7.4.1 General Considerations and Basic Data Analysis 123 7.4.2 Studying Biofilm Electrodes Using Cyclic Voltammetry 131 7.4.3 Experimental Design and Limits of Information from Data 134 7.5 Redox-Active Components in Microorganisms 136 7.6 Acquisition of Polarization and Power Curves Using Stepwise Chronoamperometry and Chronopotentiometry 139 7.7 Acquisition of Polarization Curves Using External Resistance 145 7.8 Electrochemical Impedance Spectroscopy 147 Questions 152 References 152 8 Electrochemical Analysis of Reactors 155 8.1 Introduction to Characterization of Microbial Electrochemical Cells 155 8.2 Mass and Electron Balances and Efficiency of Conversions 157 8.2.1 Establishing Balances for Mass and Electrons 157 8.2.2 Removal Efficiency 158 8.2.3 Coulombic Efficiency 159 8.3 Polarization and Power Curves: Analysis of Measured Data 161 8.4 Internal Resistance and Potential Losses 168 8.5 Energy Efficiency and Voltage Efficiency 174 8.6 Ionic Current and Transport Numbers 176 8.6.1 Ionic Current for the Specific Removal and Recovery of Ions 176 8.6.2 Ionic Current and pH Gradients 177 Questions 178 References 179 9 Seizing the Beauty and Acknowledging the Complexity of Basic Electrochemistry for Biotechnology 181 Appendix A Abbreviations 185 Appendix B Symbols with Definition and Unit 187 Appendix C Solutions to Exercises 193 Appendix D Tabulated Values 217 Index 219

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Book SynopsisFourth volume of a classic in the field of organic synthesis, describing retrosynthetic analysis and total synthesis of important molecules Classics in Total Synthesis IV is a compilation of highly important synthetical methods which lead to a complex molecule with valuable properties. From the complex architectures of natural products to the streamlined synthesis of functional molecules, each chapter in Classics in Total Synthesis IV unfolds a unique story. The interplay of mechanisms, reactivity, selectivity, and stereochemical aspects is thoroughly examined, echoing the pedagogical format that has become synonymous with this series. Well-designed graphics are included throughout, and the most important parts of the reaction sequences are highlighted. This volume encapsulates the culmination of new methodologies, emerging trends, and a selection of significant total syntheses undertaken from 2009 to 2022 while additionally including two earlier syntheses from 1979 and 1992 for comparison and to highlight the development of organic synthesis over the past decades. The careful balance between historical context, comments on the molecules'' impact to humankind, and the design and execution aspects of each synthesis creates a narrative that is not only clear but also intellectually stimulating. Written by K.C. Nicolaou and co-workers, Classics in Total Synthesis IV includes 16 chapters covering: Coupling and rearrangement reactions Recent advances in nonenzymatic enantioselective cyclization Cycloaddition and annulation reactions C-H functionalization and transition metal-mediated C-H activation Electroorganic chemistry and visible-light photoredox catalysis HAT-initiated olefin hydrogenation, isomerization and hydrofunctionalization Joining its predecessors in weaving together the threads of scientific discovery, challenge, and intellectual pursuit and establishing strong connections with biology and medicine, Classics in Total Synthesis IV is an essential reference for all future and present organic chemists.

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Book SynopsisEnzyme Engineering An authoritative and up-to-date discussion of enzyme engineering and its applications In Enzyme Engineering: Selective Catalysts for Applications in Biotechnology, Organic Chemistry, and Life Science, a team of distinguished researchers deliver a robust treatment of enzyme engineering and its applications in various fields such as biotechnology, life science, and synthesis. The book begins with an introduction to different protein engineering techniques, covers topics like gene mutagenesis methods for directed evolution and rational enzyme design. It includes industrial case studies of enzyme engineering with a focus on selectivity and activity. The authors also discuss new and innovative areas in the field, involving machine learning and artificial intelligence. It offers several insightful perspectives on the future of this work. Readers will also find: A thorough introduction to directed evolution and rational design as protein engineering techniques Comprehensive explorations of screening and selection techniques, gene mutagenesis methods in directed evolution, and guidelines for applying gene mutagenesis in organic chemistry, pharmaceutical applications, and biotechnology Practical discussions of protein engineering of enzyme robustness relevant to organic and pharmaceutical chemistry Treatments of artificial enzymes as promiscuous catalysts Various lessons learned from semi-rational and rational directed evolution A transdisciplinary treatise, Enzyme Engineering: Selective Catalysts for Applications in Biotechnology, Organic Chemistry, and Life Science is perfect for protein engineers, theoreticians, organic, and pharmaceutical chemists as well as transition metal researchers in catalysis and biotechnologists.Table of ContentsIntroduction to Directed Evolution and Rational Design as Protein Engineering Techniques -Methods and Aims of Directed Enzyme Evolution -Short History of Directed Enzyme Evolution -Methods and Aims of Rational Design of Enzymes Screening and Selection Techniques Gene Mutagenesis Methods Guidelines for Applying Gene Mutagenesis Methods in Organic Chemistry, Pharmaceutical Applications and Biotechnology Case Studies of Protein Engineering of Activity and Selectivity -Epoxide Hydrolase -Transaminase as an Industrial Example with Pharmaceutical Application -Geranylgeranyl Diphosphate Synthase for Efficient Carotenoid Production -Cytochrome P450 Monooxygenases for Synthesis of Hydroxylation of Steroids Needed in the Preparation of Pharmaceuticals -Lipase for Stereocomplementary Production of Organic Compounds with Two Chirality Centers -Further Examples Using Other Enzyme Types Protein Engineering of Enzyme Robustness -Examples of Relevance to Organic and Pharmaceutical Applications -Examples of Relevance to Biotechnology Artificial Metallo-Enzymes for Promiscuous Transformations Using Known Organic Reaction Types as a Guide Learning Lessons from Protein Engineering Perspectives for Future Work -In Extending Applications in Organic and Pharmaceutical Chemistry -In Extending Biotechnological Contributions to Ecology

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Book Synopsis

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Book Synopsis

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Book SynopsisConnects principles, processes, and experimental techniques with current research in the continuously expanding field of photochemistry and photophysics Photochemistry and Photophysics covers a wide spectrum of concepts in photochemistry and photophysics, introducing principles, processes, and experimental techniques, with a wealth of examples of current applications and research spanning natural photosynthesis, photomedicine, photochromism, luminescent sensors, energy conversion and storage, and sustainability issues. In this Second Edition, several chapters have been revised considerably and others have been almost entirely rewritten. A number of schemes and figures have been added, and the reference list at the end of each chapter has been extended and updated. Clearly structured, the first part of the text discusses the formation, properties, and reactivity of excited states of inorganic and organic molecules and supramolecular species, and the second part focuses on photochemical and photophysical processes in natural and artificial systems. Readers will learn how photochemical and photophysical processes can be exploited for novel, unusual, and unexpected applications. Written by world-renowned experts in the field, Photochemistry and Photophysics includes information on: Formation, electronic structure, properties, chemical reactivity, and radiative and nonradiative decay of electronically excited states Fundamental concepts and theoretical approaches concerning energy transfer and electron transfer Peculiar light absorption/emission spectra and the photochemical properties of the various families of organic molecules and metal complexes Equipment, techniques, procedures, and reference data concerning photochemical and photophysical experiments, including warnings to avoid mistakes and misinterpretations Relationships between photochemical, photophysical, and electrochemical properties of molecules that enable interconversion between light and chemical energy With an appropriate mix of introductory, intermediate, and advanced content, this is an ideal textbook resource for related undergraduate and postgraduate courses. The text is also valuable for scientists already active in photochemical and photophysical research who will find helpful suggestions to undertake novel scientific projects.

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Book Synopsisoffers the theory and mechanism of wetting-controlled surfaces, model of physics and chemistry, idea of design, methods of fabrication to realize wetting functions.

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Book SynopsisPhysics and Chemistry of Interfaces Comprehensive textbook on the interdisciplinary field of interface science, fully updated with new content on wetting, spectroscopy, and coatings Physics and Chemistry of Interfaces provides a comprehensive introduction to the field of surface and interface science, focusing on essential concepts rather than specific details, and on intuitive understanding rather than convoluted math. Numerous high-end applications from surface technology, biotechnology, and microelectronics are included to illustrate and help readers easily comprehend basic concepts. The new edition contains an increased number of problems with detailed, worked solutions, making it ideal as a self-study resource. In topic coverage, the highly qualified authors take a balanced approach, discussing advanced interface phenomena in detail while remaining comprehensible. Chapter summaries with the most important equations, facts, and phenomena are included to aid the reader in information retention. A few of the sample topics included in Physics and Chemistry of Interfaces are as follows: Liquid surfaces, covering microscopic picture of a liquid surface, surface tension, the equation of Young and Laplace, and curved liquid surfaces Thermodynamics of interfaces, covering surface excess, internal energy and Helmholtz energy, equilibrium conditions, and interfacial excess energies Charged interfaces and the electric double layer, covering planar surfaces, the Grahame equation, and limitations of the Poisson-Boltzmann theory Surface forces, covering Van der Waals forces between molecules, macroscopic calculations, the Derjaguin approximation, and disjoining pressure Physics and Chemistry of Interfaces is a complete reference on the subject, aimed at advanced students (and their instructors) in physics, material science, chemistry, and engineering. Researchers requiring background knowledge on surface and interface science will also benefit from the accessible yet in-depth coverage of the text.Table of Contents1. Introduction 2. Liquid Surfaces 2.1 Microscopic Picture of a Liquid Surface 2.2 Surface Tension 2.3 Equation of Young and Laplace 2.3.1 Curved Liquid Surfaces 2.3.2 Derivation of Young?Laplace Equation 2.3.3 Applying the Young?Laplace Equation 2.4 Techniques to Measure Surface Tension 2.5 Kelvin Equation 2.6 Capillary Condensation 2.7 Nucleation Theory 2.8 Summary 2.9 Exercises 3. Thermodynamics of Interfaces 3.1 Thermodynamic Functions for Bulk Systems 3.2 Surface Excess 3.3 Thermodynamic Relations for Systems with an Interface 3.3.1 Internal Energy and Helmholtz Energy 3.3.2 Equilibrium Conditions 3.3.3 Location of Interface 3.3.4 Gibbs Energy and Enthalpy 3.3.5 Interfacial Excess Energies 3.4 Pure Liquids 3.5 Gibbs Adsorption Isotherm 3.5.1 Derivation 3.5.2 System of Two Components 3.5.3 Experimental Aspects 3.5.4 Marangoni Effect 3.6 Summary 3.7 Exercises 4. Charged Interfaces and the Electric Double Layer 4.1 Introduction 4.2 Poisson?Boltzmann Theory of Diffuse Double Layer 4.2.1 Poisson?Boltzmann Equation 4.2.2 Planar Surfaces 4.2.3 The Full One-Dimensional Case 4.2.4 The Electric Double Layer around a Sphere 4.2.5 Grahame Equation 4.2.6 Capacitance of Diffuse Electric Double Layer 4.3 Beyond Poisson?Boltzmann Theory 4.3.1 Limitations of Poisson?Boltzmann Theory 4.3.2 Stern Layer 4.4 Gibbs Energy of Electric Double Layer 4.5 Electrocapillarity 4.5.1 Theory 4.5.2 Measurement of Electrocapillarity 4.6 Examples of Charged Surfaces 4.7 Measuring Surface Charge Densities 4.7.1 Potentiometric Colloid Titration 4.7.2 Capacitances 4.8 Electrokinetic Phenomena: the Zeta Potential 4.8.1 Navier?Stokes Equation 4.8.2 Electro-Osmosis and Streaming Potential 4.8.3 Electrophoresis and Sedimentation Potential 4.9 Types of Potential 4.10 Summary 4.11 Exercises 5. Surface Forces 5.1 Van der Waals Forces between Molecules 5.2 Van der Waals Force between Macroscopic Solids 5.2.1 Microscopic Approach 5.2.2 Macroscopic Calculation ? Lifshitz Theory 5.2.3 Retarded Van der Waals Forces 5.2.4 Surface Energy and the Hamaker Constant 5.3 Concepts for the Description of Surface Forces 5.3.1 The Derjaguin Approximation 5.3.2 Disjoining Pressure 5.4 Measurement of Surface Forces 5.5 Electrostatic Double-Layer Force 5.5.1 Electrostatic Interaction between Two Identical Surfaces 5.5.2 DLVO Theory 5.6 Beyond DLVO Theory 5.6.1 Solvation Force and Confined Liquids 5.6.2 Non-DLVO Forces in Aqueous Medium 5.7 Steric and Depletion Interaction 5.7.1 Properties of Polymers 5.7.2 Force between Polymer-Coated Surfaces 5.7.3 Depletion Forces 5.8 Spherical Particles in Contact 5.9 Summary 5.10 Exercises 6. Contact Angle Phenomena and Wetting 6.1 Young?s Equation 6.1.1 Contact Angle 6.1.2 Derivation 6.1.3 Line Tension 6.1.4 Complete Wetting and Wetting Transitions 6.1.5 Theoretical Aspects of Contact Angle Phenomena 6.2 Important Wetting Geometries 6.2.1 Capillary Rise 6.2.2 Particles at Interfaces 6.2.3 Network of Fibers 6.3 Measurement of Contact Angles 6.3.1 Experimental Methods 6.3.2 Hysteresis in Contact Angle Measurements 6.3.3 Surface Roughness and Heterogeneity 6.3.4 Superhydrophobic Surfaces 6.4 Dynamics of Wetting and Dewetting 6.4.1 Spontaneous Spreading 6.4.2 Dynamic Contact Angle 6.4.3 Coating and Dewetting 6.5 Applications 6.5.1 Flotation 6.5.2 Detergency 6.5.3 Microfluidics 6.5.4 Electrowetting 6.6 Thick Films: Spreading of One Liquid on Another 6.7 Summary 6.8 Exercises 7. Solid Surfaces 7.1 Introduction 7.2 Description of Crystalline Surfaces 7.2.1 Substrate Structure 7.2.2 Surface Relaxation and Reconstruction 7.2.3 Description of Adsorbate Structures 7.3 Preparation of Clean Surfaces 7.3.1 Thermal Treatment 7.3.2 Plasma or Sputter Cleaning 7.3.3 Cleavage 7.3.4 Deposition of Thin Films 7.4 Thermodynamics of Solid Surfaces 7.4.1 Surface Energy, Surface Tension, and Surface Stress 7.4.2 Determining Surface Energy 7.4.3 Surface Steps and Defects 7.5 Surface Diffusion 7.5.1 Theoretical Description of Surface Diffusion 7.5.2 Measurement of Surface Diffusion 7.6 Solid?Solid Interfaces 7.7 Microscopy of Solid Surfaces 7.7.1 Optical Microscopy 7.7.2 Electron Microscopy 7.7.3 Scanning Probe Microscopy 7.8 Diffraction Methods 7.8.1 Diffraction Patterns of Two-Dimensional Periodic Structures 7.8.2 Diffraction with Electrons, X-Rays, and Atoms 7.9 Spectroscopic Methods 7.9.1 Optical Spectroscopy of Surfaces 7.9.2 Spectroscopy Using Mainly Inner Electrons 7.9.3 Spectroscopy with Outer Electrons 7.9.4 Secondary Ion Mass Spectrometry 7.10 Summary 7.11 Exercises 8. Adsorption 8.1 Introduction 8.1.1 Definitions 8.1.2 Adsorption Time 8.1.3 Classification of Adsorption Isotherms 8.1.4 Presentation of Adsorption Isotherms 8.2 Thermodynamics of Adsorption 8.2.1 Heats of Adsorption 8.2.2 Differential Quantities of Adsorption and Experimental Results 8.3 Adsorption Models 8.3.1 Langmuir Adsorption Isotherm 8.3.2 Langmuir Constant and Gibbs Energy of Adsorption 8.3.3 Langmuir Adsorption with Lateral Interactions 8.3.4 BET Adsorption Isotherm 8.3.5 Adsorption on Heterogeneous Surfaces 8.3.6 Potential Theory of Polanyi 8.4 Experimental Aspects of Adsorption from Gas Phase 8.4.1 Measuring Adsorption to Planar Surfaces 8.4.2 Measuring Adsorption to Powders and Textured Materials 8.4.3 Adsorption to Porous Materials 8.4.4 Special Aspects of Chemisorption 8.5 Adsorption from Solution 8.6 Summary 8.7 Exercises 9. Surface Modification 9.1 Introduction 9.2 Physical and Chemical Vapor Deposition 9.2.1 Physical Vapor Deposition 9.2.2 Chemical Vapor Deposition 9.3 Soft Matter Deposition 9.3.1 Self-Assembled Monolayers 9.3.2 Physisorption of Polymers 9.3.3 Polymerization on Surfaces 9.3.4 Plasma Polymerization 9.4 Etching Techniques 9.5 Lithography 9.6 Summary 9.7 Exercises 10. Friction, Lubrication, and Wear 10.1 Friction 10.1.1 Introduction 10.1.2 Amontons? and Coulomb?s Law 10.1.3 Static, Kinetic, and Stick-Slip Friction 10.1.4 Rolling Friction 10.1.5 Friction and Adhesion 10.1.6 Techniques to Measure Friction 10.1.7 Macroscopic Friction 10.1.8 Microscopic Friction 10.2 Lubrication 10.2.1 Hydrodynamic Lubrication 10.2.2 Boundary Lubrication 10.2.3 Thin-Film Lubrication 10.2.4 Superlubricity 10.2.5 Lubricants 10.3 Wear 10.4 Summary 10.5 Exercises 11. Surfactants, Micelles, Emulsions, and Foams 11.1 Surfactants 11.2 Spherical Micelles, Cylinders, and Bilayers 11.2.1 Critical Micelle Concentration 11.2.2 Influence of Temperature 11.2.3 Thermodynamics of Micellization 11.2.4 Structure of Surfactant Aggregates 11.2.5 Biological Membranes 11.3 Macroemulsions 11.3.1 General Properties 11.3.2 Formation 11.3.3 Stabilization 11.3.4 Evolution and Aging 11.3.5 Coalescence and Demulsification 11.4 Microemulsions 11.4.1 Size of Droplets 11.4.2 Elastic Properties of Surfactant Films 11.4.3 Factors Influencing the Structure of Microemulsions 11.5 Foams 11.5.1 Classification, Application, and Formation 11.5.2 Structure of Foams 11.5.3 Soap Films 11.5.4 Evolution of Foams 11.6 Summary 11.7 Exercises 12. Thin Films on Surfaces of Liquids 12.1 Introduction 12.2 Phases of Monomolecular Films 12.3 Experimental Techniques to Study Monolayers 12.3.1 Optical Microscopy 12.3.2 Infrared and Sum Frequency Generation Spectroscopy 12.3.3 X-Ray Reflection and Diffraction 12.3.4 Surface Potential 12.3.5 Rheologic Properties of Liquid Surfaces 12.4 Langmuir?Blodgett Transfer 12.5 Summary 12.6 Exercises 13. Solutions to Exercises 14. Analysis of Diffraction Patterns 14.1 Diffraction at Three-Dimensional Crystals 14.1.1 Bragg Condition 14.1.2 Laue Condition 14.1.3 Reciprocal Lattice 14.1.4 Ewald Construction 14.2 Diffraction at Surfaces 14.3 Intensity of Diffraction Peaks Appendix A Symbols and Abbreviations References Index

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Book SynopsisThis volume is intended as a systematic introduction to gauge field theory for advanced undergraduate and graduate students in high energy physics. The discussion is restricted to the classical (non-quantum) theory in Minkowski spacetime. Particular attention has been given to conceptual aspects of field theory, accurate definitions of basic physical notions, and thorough analysis of exact solutions to the equations of motion for interacting systems.Trade ReviewFrom the reviews: "Russian physicist Kosyakov has written an introduction to classical gauge theory for students of high energy or particle physics. … Extensive reference list. A valuable addition to a university library supporting a program in high energy theory; highly mathematical, so most useful as a resource for undergraduate programs. Summing Up: Recommended. Graduate students; professionals." (R. L. Stearns, CHOICE, Vol. 44 (10), June, 2007) "The classical theory of gauge fields is an important subject that has numerous applications in modern physics. … A nice feature of this book is that this is self contained. All the necessary definitions as well as the technical tools are provided by the author in the main body of the book. … I enjoyed reading the book. … Overall the monograph … can be warmly recommended to any serious student of electrodynamics and gauge theory and to their instructors alike." (Yuri N. Obukhov, Annalen der Physik, Vol. 16 (12), 2007) "Each chapter contains problems and final notes, a useful guide to the history of the subject. … The volume is intended to be an introduction for advanced undergraduate and graduate students in high energy physics. … We mention that it is timely elaborate a unified view of the classical self-interaction problems in classical gauge theories with particular reference to the electrodynamics of point electrons and Yang-Mills interaction of point quarks. The present work is a valuable contribution to this task." (Petre P. Teodorescu, Zentralblatt MATH, Vol. 1114 (16), 2007) "This book is an introduction to classical field theory. Although it was designed for advanced undergraduate and graduate students, researchers could also benefit from this book. It is intended for mathematical physicists and theoretical physicists. Classical gauge theories are discussed in detail, with great emphasis on self-interactions. … In summary, this is a useful introduction to classical gauge theories that can be recommended both to students (theoretical or mathematical physics), and to specialists and researchers, as a reference book." (Giuseppe Nardelli, Mathematical Reviews, Issue 2008 c)Table of ContentsGeometry of Minkowski Space.- Relativistic Mechanics.- Electromagnetic Field.- Solutions to Maxwell's Equations.- Lagrangian Formalism in Electrodynamics.- Self-Interaction in Electrodynamics.- Lagrangian Formalism for Gauge Theories.- Solutions to the Yang?Mills Equations.- Self-Interaction in Gauge Theories.- Generalizations.- Mathematical Appendices.

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Book SynopsisThis book is the second edition of an excellent undergraduate-level overview of classical and modern physics, intended for students of physics and related subjects, and also perfectly suited for the education of physics teachers. The twelve-chapter book begins with Newton’s laws of motion and subsequently covers topics such as thermodynamics and statistical physics, electrodynamics, special and general relativity, quantum mechanics and cosmology , the standard model and quantum chromodynamics. The writing is lucid, and the theoretical discussions are easy to follow for anyone comfortable with standard mathematics.An important addition in this second edition is a set of exercises and problems, distributed throughout the book. Some of the problems aim to complement the text, others to provide readers with additional useful tools for tackling new or more advanced topics. Furthermore, new topics have been added in several chapters; for example, the discovery of extra-solar planets from the wobble of their mother stars, a discussion of the Landauer principle relating information erasure to an increase of entropy, quantum logic, first order quantum corrections to the ideal gas equation of state due to the Fermi-Dirac and Bose-Einstein statistics. Both gravitational lensing and the time-correction in geo-positioning satellites are explained as theoretical applications of special and general relativity. The discovery of gravitational waves, one of the most important achievements of physical sciences, is presented as well. Professional scientists, teachers, and researchers will also want to have this book on their bookshelves, as it provides an excellent refresher on a wide range of topics and serves as an ideal starting point for expanding one’s knowledge of new or unfamiliar fields. Readers of this book will not only learn much about physics, they will also learn to love it.Trade ReviewFrom the reviews of the first edition:Selected by Choice magazine as an "Outstanding Academic Title" for 2014“This is a very high-quality presentation. The writing is lucid, and the theoretical discussions are easy to follow for anyone comfortable with the mathematics. … the work is a valuable addition to college libraries. Professionals and researchers will also want it on their bookshelves; it provides an excellent refresher on a wide range of topics and can serve as a good starting point for expanding knowledge of new or unfamiliar subjects. Summing Up: Highly recommended. Lower-division undergraduates and above.” (A. Spero, Choice, Vol. 51 (9), May, 2014)“It describes all the major developments and theories regarding the description of the universe we live on, from the very small to the very large. … I highly recommend this book to any physicist. It will not only be a fun and an easy read but also a useful revision of all the main concepts in physics. Undergraduate and graduate physics students definitely should read it. … appropriate for scientists in other fields who have a genuine interest for physics.” (Monica Pierri-Galvao, Contemporary Physics, April, 2014)Table of ContentsGravitation and Newton Laws.- Entropy, Statistical Physics and Information.- Electromagnetism and Maxwell's Equations.- Electromagnetic Waves.- Special Theory of Relativity.- Atoms and Quantum Theory.- Quantum Electrodynamics.- Fermi-Dirac and Bose-Einstein Statistics.- Four Fundamental Forces.- General Relativity and Cosmology.- Unification of the Forces of Nature.- Physics and Life.

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Book SynopsisThis open access book offers a concise overview of how data from large scale experiments are analyzed and how technological tools are used in practice, as in the search for new elementary particles. It focuses on interconnects between physics and detector technology in experimental particle physics, and includes descriptions of mathematical approaches. Readers find all the important steps in analysis, including reconstruction of the momentum and energy of particles from detector information, particle identification, and also the general concept of simulating particle production from collisions and detector responses. As the scale of scientific experiments becomes larger and data-intensive science emerges, the techniques used in the data analysis become ever more complicated, making it difficult for beginners to grasp the overall picture. The book provides an explanation of the idea and concepts behind the methods, helping readers understand journal articles on high energy physics. This book is engaging as it does not overemphasize mathematical formalism and it gives a lively example of how such methods have been applied to the Higgs particle discovery in the Large Hadron Collider (LHC) experiments, which led to Englert and Higgs being awarded the Nobel Prize in Physics for 2013.Graduate students and young researchers can easily obtain the required knowledge on how to start data analyses from these notes, without having to spend time in consulting many experts or digesting huge amounts of literature.Table of ContentsIntroduction.- Basic Idea of Measurements in Particle Collisions.- Apparatus.- Statistics.- Detector Calibration.- Particle Identification.- Event Simulation.- Examples of Physics Analysis.

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Book SynopsisEl volumen 9 completa la colección del Handbook of Mammals of the World y está dedicado a los murciélagos, la orden Chiroptera. En las últimas dos décadas, nuestro conocimiento sobre los murciélagos ha experimentado un notable incremento que queda plasmado en este volumen. Durante este periodo, las especies reconocidas han aumentado en más de 400, un número que sigue creciendo. Los murciélagos ocupan casi todos los hábitats de los seis continentes y su ecología es extraordinariamente diversa. Polinizadores y dispersores de semillas de miles de especies de plantas, los murciélagos son críticos para el mantenimiento de los ecosistemas tropicales.

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Book SynopsisPresents views on current developments in heat and mass transfer research related to the modern development of heat exchangers. Devotes special attention to the different modes of heat and mass transfer mechanisms in relation to the new development of heat exchangers design. Dedicates particular attention to the future needs and demands for further development in heat and mass transfer. GaN and related materials are attracting tremendous interest for their applications to high-density optical data storage, blue/green diode lasers and LEDs, high-temperature electronics for high-power microwave applications, electronics for aerospace and automobiles, and stable passivation films for semiconductors. In addition, there is great scientific interest in the nitrides, because they appear to form the first semiconductor system in which extended defects do not severely affect the optical properties of devices. This series provides a forum for the latest research in this rapidly-changing field, offering readers a basic understanding of new developments in recent research. Series volumes feature a balance between original theoretical and experimental research in basic physics, device physics, novel materials and quantum structures, processing, and systems.Table of Contents1. Plate Type Exchangers 2. Dynamic Systems 3. A Historical Survey of Research on Gallium Nitride 4. Growth of Group III Nitrides from Molecular Beams 5. Ternary Alloys 6. Optical Characterization of GaN and Related Materials 7. Theoretical Studies in GaN 8. GaAsN Alloys and GaN/GaAs Thin Layer Structures 9. The Contribution of Defects to the Electrical and Optical Properties of GaN 10. Growth of GaN Single Crystals Under High Nitrogen Pressure 11.Ion Implantation Doping and Isolation of III-Nitride Materials 12. High-Density ECR Etching of Group-III Nitrides 13. Contacts on III-Nitrides 14. III-V Nitride Based LEDs 15. III-V Nitride Electronic Devices 16. Physical Properties of the Bulk GaN Crystals Grown by the High-Pressure, High Temperature Method 17. Microstructure of Epitaxial III-V Nitride Thin Films 18. The Role of Hydrogen in GaN and Related Compounds

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Book SynopsisBased on presentations made during the 6th International Symposium on Natural Product Chemistry, this book is divided into two sections. Section A has articles on synthetic routes developed to complex natural products, whilst Section B is a compilation of discoveries of new natural products and their pharmacological properties. There are several chapters in this volume devoted to advances in the quest for improved anticancer agents from natural resources - be they plants, marine organisms or micro-organisms. Additionally, approaches to the development of antimalarial agents are reviewed, as are strategies for cancer chemopreventive agents.Table of ContentsPart 1 Open chain 1,3-stereocontrol: synthetic studies on anti-tumor alkaloids; synthetic studies in the alkaloid field - synthesis of epibatidine; synthetic studies on antitumor antibiotics and enzyme inhibitors; epoxy sulfonate pyranoses, valuable intermediates in carbohydrate syntheses. Part 2 Recent studies on biologically active natural products: novel strategies for the discovery of plant-derived anticancer agents; discovery and characterization of natural product cancer chemopreventive agents; logical approach to structure elucidation of natural compounds; new natural products from indigenous medicinal plants; bioactive compounds fom the leaves and pods of moringa oleifera; new alkaloids and biological activities of Turkish amaryllidiceae plants; malarial vaccine candidate - the nature of the carbohydrate-peptide linkage in the 42-53 KDA glycoprotein; effect of the imidazoline compounds on sympathomimetic responses and its pharmacological implications. (Part contents).

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