Halogen Bonding in Solution

Long-awaited on the importance of halogen bonding in solution, demonstrating the specific advantages in various fields - from synthesis and catalysis to biochemistry and electrochemistry! Halogen bonding (XB) describes the interaction between an electron donor and the electrophilic region of a halogen atom. Its applicability for molecular recognition processes long remained unappreciated and has mostly been studied in solid state until recently. As most physiological processes and chemical reactions take place in solution, investigations in solutions are of highest relevance for its use in organic synthesis and catalysis, pharmaceutical chemistry and drug design, electrochemistry, as well as material synthesis. Halogen Bonding in Solution gives a concise overview of halogen bond interactions in solution. It discusses the history and electronic origin of halogen bonding and summarizes all relevant examples of its application in organocatalysis. It describes the use of molecular iodine in catalysis and industrial applications, as well as recent developments in anion transport and binding. Hot topic: Halogen bonding is an important interaction between molecules or within a molecule. The field has developed considerably in recent years, with numerous different approaches and applications having been published. Unique: There are several books on halogen bonding in solid state available, but this will be the first one focused on halogen bonding in solution. Multi-disciplinary: Summarizes the history and nature of halogen bonding in solution as well as applications in catalysis, anion recognition, biochemistry, and electrochemistry. Aimed at facilitating exciting future developments in the field, Halogen Bonding in Solution is a valuable source of information for researchers and professionals working in the field of supramolecular chemistry, catalysis, biochemistry, drug design, and electrochemistry.

Table of Contents:
Preface xi 1 Halogen Bonding: An Introduction 1 Daniel A. Decato, Eric A. John and Orion B. Berryman 1.1 Introduction 1 1.1.1 The Halogen Bond: Definition, Characteristics, Representations, and Parallels to the Hydrogen Bond 2 1.1.2 Parallels to the Hydrogen Bond 3 1.1.3 Notation and Terminology 4 1.1.4 Solid-state Halogen Bond Contacts 4 1.1.5 Halogen Bond Features 5 1.1.6 Additional Nomenclature 6 1.2 Historical Perspective 6 1.2.1 Rediscovery 10 1.3 Crystallographic Studies 11 1.3.1 CSD Evaluations 12 1.3.2 Fundamental Studies and Halogen Bond–Hydrogen Bond Interplay 13 1.3.3 Metal Complexes and Charge-assisted Halogen Bonding Systems 17 1.3.4 Alternative Motifs and Solid-state Reactivity 19 1.3.5 Crystallographic Studies Conclusion 20 1.4 Computational Studies 21 1.4.1 Introduction 21 1.4.2 Electrostatics of the Halogen Bond and the σ-Hole 21 1.4.3 Limitations on Electrostatic Potential 24 1.4.4 Atomic Orbital Theory and the σ-Hole 24 1.4.5 Charge Transfer 24 1.4.6 Dispersion and Polarization Component 25 1.4.7 Decomposition 26 1.4.8 Biological Computation of Halogen Bonding 26 1.4.9 Computational Conclusion 27 1.5 Materials 28 1.5.1 Introduction 28 1.5.2 Liquid Crystals 28 1.5.3 Supramolecular Polymers 29 1.5.3.1 LC Polymers 29 1.5.3.2 Light-sensitive Polymers 30 1.5.3.3 Block Polymers 30 1.5.3.4 Self-healing Polymers 31 1.5.4 Supramolecular Gels 31 1.5.5 Materials Conclusion 33 1.6 Conclusion 33 Acknowledgments 34 References 34 2 Thermodynamics of Halogen Bonding in Solution 43 Mark S. Taylor 2.1 Introduction 43 2.2 Molecular Halogens and Interhalogens 44 2.2.1 Uncharged Lewis Bases 44 2.3 N-Halo and N-Halonium Compounds 46 2.4 Haloalkynes 47 2.4.1 Uncharged Lewis Bases 47 2.5 Haloarenes 51 2.5.1 Uncharged Lewis Bases 51 2.5.2 Anionic Lewis Bases 58 2.6 Halogenated Heterocycles 61 2.6.1 Uncharged Lewis Bases 62 2.6.2 Anionic Lewis Bases 64 2.7 Haloalkanes and Haloalkenes 67 2.7.1 Uncharged Lewis Bases 67 2.7.2 Anionic Lewis Bases 71 2.8 Summary and Outlook 72 References 73 3 Recognition with Macrocycles and Interlocked Systems 83 Andrew Docker and Paul D. Beer 3.1 Introduction 83 3.2 Recognition by XB Macrocyclic Hosts 86 3.3 XB Interlocked Hosts for Recognition and Sensing 87 3.3.1 XB-Anion Templation of Interlocked Molecules 90 3.3.2 [2]Rotaxane Hosts for Anion Recognition 92 3.3.3 [2]Catenanes for Anion Recognition 97 3.3.4 XB Interlocked Hosts Constructed via Active Metal Template Methodology 100 3.3.5 Interlocked Host Molecules for Sensing Applications 107 3.4 Foldamer Architectures for Recognition 113 3.5 Summary and Conclusions 117 References 118 4 The Three-Center Halogen Bond 121 Lotta Turunen and Máté Erdélyi 4.1 Introduction 121 4.2 Three-Center Halogen Bond 122 4.2.1 Features of the Three-Center Halogen Bond 123 4.2.1.1 Symmetry and Dynamics of the Three-Center Halogen Bonds 123 4.2.1.2 The Influence of the Identity of Halonium Ions 126 4.2.1.3 The Influence of Lewis Basicity 128 4.2.1.4 The Influence of Solvent and Counterions 131 4.2.2 The Three-Center Halogen Bond of N-Halosuccinimides and N-Halosaccharins 132 4.2.3 Trihalide Ions 134 4.2.4 Stability of the Three-Center Halogen Bond 135 4.3 Synthetic Applications 137 4.3.1 Halonium Transfer Reactions 137 4.3.2 Oxidation Reactions 140 4.3.3 Enantioselective Halogenations 141 4.4 Three-Center Halogen Bonds in Supramolecular Chemistry 143 4.5 Summary and Conclusions 147 References 148 5 Spectroscopy of Halogen Bonding in Solution 153 Scott Wilcox, Wouter Herrebout and Mate Erdelyi 5.1 Introduction 153 5.2 Vibrational Spectroscopy 154 5.3 UV–vis Spectroscopy 158 5.4 NMR Spectroscopy 160 5.4.1 Solvent Effects 161 5.4.2 Entropic Effects on Halogen Bonding 165 5.4.3 NMR Titration Studies 168 5.4.3.1 Direct Detection Techniques 169 5.4.3.2 Indirect Detection Techniques 176 5.4.4 Nuclear Overhauser Effect (NOE) NMR Spectroscopy 178 5.4.4.1 Homonuclear NOE Spectroscopy 178 5.4.4.2 Heteronuclear NOE Spectroscopy 181 5.4.5 Diffusion NMR 182 5.4.6 The Isotopic Perturbation of Equilibrium Method 184 5.5 ESR Spectroscopy 185 5.6 Summary and Conclusions 187 Acknowledgments 189 References 189 6 Anion Transport in Lipid Bilayer Membranes Using Halogen Bonds 195 Andreas Vargas Jentzsch and Stefan Matile 6.1 Introduction 195 6.1.1 Halogen Bonding in the Context of Ion Transport 196 6.1.2 Organization of This Chapter 198 6.2 Macrocyclic Systems 198 6.2.1 Calix[4]arenes 198 6.2.1.1 Synthesis 199 6.2.1.2 Ion Transport 199 6.2.2 Oxacalix[2]arene[2]triazine 203 6.2.2.1 Synthesis 203 6.2.2.2 Anion Binding Studies 203 6.2.2.3 Crystallographic Studies 203 6.2.2.4 Ion Transport 204 6.2.2.5 Anticancer Activity 205 6.3 Small Molecules 209 6.3.1 Iodoperfluoroarenes 209 6.3.2 Iodoperfluoroalkanes 210 6.3.3 Conductance Experiments in Planar Lipid Bilayers with Small Molecules 215 6.3.4 Elucidating the Mechanism of Transport with Small Molecules 216 6.3.4.1 Membrane Composition in the HPTS Assay 216 6.3.4.2 Hill Coefficients 217 6.3.4.3 Molecular Modeling: DFT Calculations 217 6.3.4.4 Crystal Structures 218 6.4 Halogen Bonding Ion Channels 218 6.4.1 Halogen Bonding Cascades 219 6.4.1.1 Synthesis 219 6.4.1.2 Ion Transport 219 6.4.2 Halogen Bonding Self-Assembled Pores and Channels 222 6.4.2.1 Synthesis 222 6.4.2.2 Ion Transport 223 6.4.2.3 Conductance Experiments in Planar Lipid Bilayers 225 6.4.2.4 Molecular Dynamics Simulations 225 6.4.2.5 Anticancer Activity 225 6.5 Discussion and Perspectives 225 6.6 Summary 227 Acknowledgments 229 References 229 7 Catalysis by Molecular Iodine 233 Jonas J. Koenig and Martin Breugst 7.1 Introduction 233 7.2 Proposed Activation Mechanisms 234 7.2.1 Halogen-Bond Catalysis 235 7.2.2 Iodonium-Ion Catalysis 236 7.2.3 Brønsted-Acid Catalysis 238 7.3 Applications in Catalysis 239 7.3.1 Scope and Aim 239 7.3.2 Michael Additions 239 7.3.3 Knoevenagel Condensations 242 7.3.4 Cycloadditions and Related Reactions 243 7.3.5 Nazarov-type Reactions 247 7.3.6 Esterifications and Transesterifications 249 7.3.7 Acetalizations and Related Reactions 252 7.3.8 Etherification 254 7.3.9 Friedel–Crafts Alkylations and Arylations 255 7.3.10 Isomerization of Double Bonds 257 7.3.11 Polymerization 259 7.3.12 Cascade Reactions 259 7.4 Summary and Conclusions 263 References 263 8 Halogen Bonding in Organocatalysis 269 Revannath L. Sutar 8.1 Introduction 269 8.2 Organic Reactions Involving XB as Primary Interaction 270 8.2.1 Activation of Halocarbons 272 8.2.2 Activation of Organic Functional Groups 279 8.2.3 XB Organocatalysis Through π-Activation 289 8.2.4 Asymmetric Catalysis Through Halogen Bonding 292 8.3 Reactions Involving XB as Secondary Interaction 297 8.4 Conclusion 301 References 301 9 Halogen Bonding in Electrochemistry 307 Claire Fave and Bernd Schöllhorn 9.1 Introduction 307 9.2 Methods 309 9.3 Electrochemistry for Crystal Engineering: Mixed Valence Crystal Structures 311 9.4 Redox Switching in Homogeneous Solution 312 9.4.1 Concept 312 9.4.2 Redox-Active XB Acceptors 313 9.4.2.1 Quinones 313 9.4.3 Redox-Active XB Donors 315 9.4.3.1 Ferrocenes 315 9.4.3.2 Tetrathiafulvalenes 318 9.4.3.3 Viologens 323 9.5 Interfacial Halogen Bonding 324 9.5.1 Anion Detection on Self-Assembled Monolayers 324 9.5.2 Photovoltaic Systems 327 9.6 Activation of Covalent Bonds 328 9.6.1 XB-Mediated Redox Reactions: A Perspective 328 9.7 Conclusions 329 References 330 10 Halogen Bonds in Biomolecular Engineering 335 Pui S. Ho and Derek M. Anderson 10.1 Introduction to Biomolecular Engineering and Halogen Bonds 335 10.2 Halogen Bonds in Nucleic Acids 340 10.2.1 Controlling DNA Assembly and Structure 342 10.2.2 Controlling Conformation 344 10.2.3 Structure–Energy Relationships 344 10.3 Halogen Bonds in Peptides and Proteins 346 10.3.1 Halogen Bonds in Amino Acids and Peptides 347 10.3.2 Halogen Bonds Engineered into Proteins 350 10.4 Conclusions and Perspectives 353 10.4.1 Expanding the Genetic Alphabet 353 10.4.2 Multimeric Assemblies 353 10.4.3 New Catalysts 355 10.4.4 Need for Computational Tools 355 10.4.5 Conclusion 356 Acknowledgments 356 References 356 11 The Chalcogen Bond in Solution: Synthesis, Catalysis and Molecular Recognition 363 Kamran T. Mahmudov, Vusala A. Aliyeva, M. Fátima C. Guedes da Silva and Armando J. L. Pombeiro 11.1 Introduction 363 11.2 Chalcogen Bonding in Synthesis 367 11.3 Chalcogen Bonding in Catalysis 371 11.4 Chalcogen Bonding in Molecular Recognition 375 11.5 Conclusions 378 Acknowledgments 379 References 380 Index 383

About the Author :
Stefan Huber is Associate Professor of organic chemistry at Ruhr-University Bochum, Germany. His research interest is the development of applications for halogen bonding and chalcogen bonding in solution, with a strong focus on organocatalysis and molecular recognition. He has, inter alia, received an ERC Starting Grant, the Hoechst Dozentenpreis by the Aventis Foundation and the Robert-Sauer-Prize of the Bavarian Academy of Sciences.