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Book Details
Abstract
Multi-component crystalline systems or co-crystals have received tremendous attention from academia and industry alike in the past decade. Applications of co-crystals are varied and are likely to positively impact a wide range of industries dealing with molecular solids. Co-crystallization has been used to improve the properties and performance of materials from pharmaceuticals to energetic materials, as well as for separation of compounds.
This book combines co-crystal applications of commercial and practical interest from diverse fields in to a single volume. It also examines effective structural design of co-crystals, and provides insights into practical synthesis and characterization techniques. Providing a useful resource for postgraduate students new to applied co-crystal research and crystal engineering, it will also be of interest to established researchers in academia or industry.
Table of Contents
| Section Title | Page | Action | Price |
|---|---|---|---|
| Cover | Cover | ||
| Preface | v | ||
| Contents | vii | ||
| Chapter 1 Co-crystals: Introduction and Scope | 1 | ||
| 1.1 Rationale and Scope | 1 | ||
| 1.2 Covalent Versus Non-covalent Synthesis | 2 | ||
| 1.3 History | 3 | ||
| 1.3.1 Crystal Engineering | 4 | ||
| 1.4 Nomenclature | 5 | ||
| 1.4.1 Can We Make It Without a Definition? | 5 | ||
| 1.4.2 Salt or Co-crystal? | 6 | ||
| 1.5 Design of Co-crystals | 7 | ||
| 1.5.1 Etter's Rules and Graph Set Notation | 8 | ||
| 1.5.2 Supramolecular Synthons | 9 | ||
| 1.5.3 Binary Co-crystals | 9 | ||
| 1.5.4 Beyond Binary Co-crystals | 12 | ||
| 1.6 Cheminformatics and Co-crystals | 19 | ||
| 1.6.1 Intermolecular Contacts: IsoStar and Full Interaction Maps | 20 | ||
| 1.6.2 Hydrogen-bond Motif Searches | 21 | ||
| 1.6.3 Multi-component Hydrogen-bond Propensity | 22 | ||
| 1.7 Synthesis, Screening and Characterization of Co-crystals | 22 | ||
| 1.8 Applications of Co-crystals | 24 | ||
| 1.8.1 Pharmaceutical Co-crystals | 24 | ||
| 1.8.2 Co-crystals of Energetic Compounds | 25 | ||
| 1.9 Summary | 25 | ||
| References | 26 | ||
| Chapter 2 The Role of Hydrogen Bonding in Co-crystals | 33 | ||
| 2.1 Introduction | 33 | ||
| 2.2 Multicomponent Molecular Crystals | 35 | ||
| 2.2.1 Co-crystals: Definition, Classification and Synthesis | 36 | ||
| 2.2.2 Molecular Co-crystals (MCCs) | 37 | ||
| 2.2.3 Ionic Co-crystals (ICCs) | 37 | ||
| 2.2.4 Synthesis of Co-crystals | 38 | ||
| 2.3 Hydrogen Bonds: Discovery and Classification | 39 | ||
| 2.3.1 Geometry | 39 | ||
| 2.3.2 Classification | 40 | ||
| 2.4 Designing Co-crystals Based on Hydrogen Bonds | 41 | ||
| 2.4.1 Etter's Rules, Hydrogen Bond Patterns and Graph Sets | 41 | ||
| 2.4.2 Supramolecular Synthons and Tectons | 43 | ||
| 2.4.3 Supramolecular Synthon Hierarchy | 44 | ||
| 2.5 Other Aspects of Crystal Engineering of Co-crystals | 50 | ||
| 2.5.1 Design of 2D and 3D Hydrogen Bonded Networks | 50 | ||
| 2.5.2 Polymorphism in Co-crystals | 52 | ||
| 2.5.3 Co-crystal Solvates and Hydrates | 54 | ||
| 2.5.4 Crystalline Inclusion Compounds (CICs) | 56 | ||
| 2.5.5 Molecular Co-crystals with More Than Two Co-formers | 56 | ||
| 2.6 Applications of Co-crystals | 58 | ||
| 2.6.1 Pharmaceutical Co-crystals | 58 | ||
| 2.6.2 Ionic Co-crystals of Pharmaceutically Acceptable Metals | 62 | ||
| 2.6.3 Co-crystals of Agrochemicals | 65 | ||
| 2.6.4 Co-crystal Controlled Solid-state Synthesis (C3S3) | 66 | ||
| 2.6.5 Co-crystal Based NLO Materials | 69 | ||
| 2.7 Conclusions | 70 | ||
| Acknowledgements | 71 | ||
| References | 71 | ||
| Chapter 3 Design and Structural Chemistry of Halogen-bonded Co-crystals | 80 | ||
| 3.1 Introduction | 80 | ||
| 3.2 Dihalogen Donors | 82 | ||
| 3.3 Saturated Halocarbons | 88 | ||
| 3.4 Haloalkene Donors | 88 | ||
| 3.5 1-Haloalkyne Donors | 89 | ||
| 3.6 Aryl Halide Donors | 97 | ||
| 3.7 Perfluoroaromatic Donors | 99 | ||
| 3.8 Perfluoroaliphatic Donors | 104 | ||
| 3.9 Nitroaryl Donors | 112 | ||
| 3.10 N-Haloimide Donors | 115 | ||
| 3.11 Structural Equivalence of Donors and Acceptors | 123 | ||
| 3.12 Halogen Bonding Hierarchy | 127 | ||
| 3.13 Hydrogen and Halogen Bonding | 129 | ||
| 3.14 Conclusions and Outlook | 141 | ||
| References | 142 | ||
| Chapter 4 Mechanochemistry in Co-crystal Synthesis | 147 | ||
| 4.1 Introduction to Mechanochemistry | 147 | ||
| 4.1.1 Relationship Between Mechanochemistry and Supramolecular Synthesis | 147 | ||
| 4.1.2 Definition | 148 | ||
| 4.1.3 Techniques | 149 | ||
| 4.2 Advantages and Challenges of Mechanochemistry in Co-crystal Synthesis | 159 | ||
| 4.2.1 Structural Characterization of Mechanochemical Products | 159 | ||
| 4.2.2 Co-crystal Screening and Stoichiometric Control in Mechanochemistry | 160 | ||
| 4.2.3 Polymorphism Control in Liquid-assisted Mechanochemistry | 163 | ||
| 4.3 Advances in Mechanistic Studies of Mechanochemical Co-crystallization | 165 | ||
| 4.3.1 Qualitative Description of Mechanochemical Co-crystal Formation | 165 | ||
| 4.3.2 Real-time and In Situ Studies of Mechanochemical Co-crystallization | 167 | ||
| 4.4 Mechanochemical Synthesis of Complex Molecular Solids | 172 | ||
| 4.4.1 Mechanochemical Synthesis of Three-component Co-crystals | 172 | ||
| 4.4.2 Combining Different Types of Molecular Self-assembly | 176 | ||
| 4.5 Understanding Molecular and Biomolecular Recognition Through LAG Co-crystallization | 176 | ||
| 4.5.1 Screening for Molecular Recognition | 176 | ||
| 4.5.2 Screening for Recognition Motifs of Steroids | 180 | ||
| 4.6 Mechanochemical Synthesis of Halogen-bonded Co-crystals | 182 | ||
| 4.7 Co-crystal-catalyzed Photo-mechanochemical Reactions | 183 | ||
| 4.8 Mechanochemical Reactions of Co-crystals | 186 | ||
| 4.8.1 Supramolecular Metathesis and Co-crystal–Co-crystal Reactions | 186 | ||
| 4.9 Conclusions | 188 | ||
| References | 188 | ||
| Chapter 5 Pharmaceutical Co-crystals—Molecular Design and Process Development | 194 | ||
| 5.1 Introduction | 194 | ||
| 5.1.1 Role of Co-crystals in Drug Development | 196 | ||
| 5.1.2 Process Development and Scale-up of Co-crystallization | 197 | ||
| 5.2 Co-crystal Design | 198 | ||
| 5.2.1 Synthon-based Design Strategies | 199 | ||
| 5.2.2 Co-crystal Design for Molecules That AreDevoid of Hydrogen Bonding Sites: Trial and Error Methods | 200 | ||
| 5.2.3 Molecular Descriptor Based Strategy | 202 | ||
| 5.2.4 Knowledge-based Strategy | 203 | ||
| 5.2.5 Case Study—Design of Propyphenazone Co-crystals | 205 | ||
| 5.3 Process Development and Scale-up of Co-crystallization | 210 | ||
| 5.3.1 General Crystallization Development Procedure | 212 | ||
| 5.3.2 Case Study: Development of Caffeine–Glutaric Acid Co-crystallization | 218 | ||
| 5.4 Conclusions and Outlook | 226 | ||
| Acknowledgements | 227 | ||
| References | 227 | ||
| Chapter 6 Co-crystallization of Energetic Materials | 231 | ||
| 6.1 Introduction to Energetic Materials | 231 | ||
| 6.2 Co-crystals of TNT (2,4,6-Trinitrotoluene) | 234 | ||
| 6.3 Co-crystals of Benzotrifuroxan (BTF) | 239 | ||
| 6.4 Co-crystals of HMX and RDX | 240 | ||
| 6.5 Co-crystals of CL-20 | 244 | ||
| 6.6 Co-crystals of Azole Derivatives (NTO, DNBT, and DNPP) | 250 | ||
| 6.7 Co-crystals of Ethylenedinitramine (EDNA) | 252 | ||
| 6.8 Co-crystals of Diacetone Diperoxide (DADP) | 253 | ||
| 6.9 Stabilization of High-nitrogen Compounds | 254 | ||
| 6.10 A Melt-castable Co-crystal | 255 | ||
| 6.11 Co-crystals or Physical Mixtures? | 256 | ||
| 6.12 Novel Preparative Methods of Energetic Co-crystal RAM Mixing and Vacuum Freeze-drying | 257 | ||
| 6.13 Summary and Future Directions | 258 | ||
| References | 262 | ||
| Chapter 7 Paramagnetic Organic Co-crystals of Neutral or Ionic Radicals | 267 | ||
| 7.1 Introduction | 267 | ||
| 7.2 Radical Species and their Interactions | 268 | ||
| 7.3 Neutral Radical Species in Co-crystals | 269 | ||
| 7.3.1 Radical Co-crystals as Inclusion Adducts | 269 | ||
| 7.3.2 Radical Co-crystals Stabilized through π–π Interactions | 271 | ||
| 7.3.3 Radical Co-crystals Stabilized through Hydrogen Bonding | 273 | ||
| 7.3.4 Radical Co-crystals Stabilized through Halogen Bonding | 275 | ||
| 7.4 Cation (Anion) Radical Species in Co-crystal Salts | 277 | ||
| 7.4.1 Electron Transfer in TEMPO Radicals | 277 | ||
| 7.4.2 Mixed-Valence Anion Radical Co-crystal Salts | 278 | ||
| 7.4.3 Mixed-valence Cation Radical Co-crystal Salts | 280 | ||
| 7.5 Conclusion and Perspectives | 281 | ||
| References | 281 | ||
| Chapter 8 Hydrogen-bonded Semiconductor Co-crystals | 285 | ||
| 8.1 Introduction | 285 | ||
| 8.2 Supramolecular Construction and Co-crystals | 286 | ||
| 8.3 Co-crystals for Crystal Engineering Semiconductors | 287 | ||
| 8.3.1 Benefits of the Co-crystal Approach | 287 | ||
| 8.4 Finite Assemblies of Semiconductor Molecules in Co-crystals | 288 | ||
| 8.4.1 Polymorphism of Pure Thiophene Substrates | 289 | ||
| 8.4.2 Related Approaches for Hydrogen-bonded Semiconductors | 290 | ||
| 8.5 Solid-state Reactivity of Thiophene Substrates in Co-crystals | 291 | ||
| 8.5.1 Head-to-head Photodimerization | 292 | ||
| 8.5.2 Head-to-tail Photodimerization | 293 | ||
| 8.6 Metal-organic Approach | 293 | ||
| 8.6.1 Electrical Conductivity Before and After [2+2] Photodimerization | 294 | ||
| 8.6.2 Electrical Conductivity in Related Metal-organic Materials | 294 | ||
| 8.7 Summary and Outlook | 295 | ||
| Acknowledgements | 295 | ||
| References | 296 | ||
| Chapter 9 Co-crystallization as a Versatile Tool in Separations Technology | 302 | ||
| 9.1 Introduction | 302 | ||
| 9.2 Thermodynamics of Separation via Co-crystallization | 305 | ||
| 9.3 Industrial Separation and Co-crystallization | 309 | ||
| 9.4 Chiral Resolution via Co-crystallization | 317 | ||
| 9.5 Summary | 329 | ||
| References | 330 | ||
| Subject Index | 336 |