The Nature of the Hydrogen Bond: Outline of a Comprehensive Hydrogen Bond Theory Book

Introduction 1

1 A Century of the hydrogen bond (H-bond) 6

1.1 The discovery of the H-bond 6

1.2 The theoretical understanding of the H-bond 7

1.3 The experimental approach to the H-bond 13

1.4 Significant books and reviews 19

2 Generalities, definitions and preliminary classification 23

2.1 Basic H-bond nomenclature 23

2.2 Formal H-bond definitions 23

2.3 The H-bond as a shared-proton interaction: A Chemical classification 28

2.4 H-bonds involving main-group elements (Class 1) 30

2.4.1 Conventional H-bonds (Groups 1.1) 31

2.4.2 Weak H-bonds: General properties (Groups 1.2-4) 32)

2.4.2.1 Treatment of H...A contact distances 35

2.4.2.2 H-bond directionality 36

2.4.2.3 Importance of crystal-packing patterns 38

2.4.3 Weak H-bond donors (Group 1.2) 38

2.4.3.1 C-H... bonds 40

2.4.3.2 S-H... bonds 42

2.4.3.3 P-H... bonds 42

2.4.3.4 Si-H, As-H and Se-H... bonds 43

2.4.4 Weak H-bond acceptors (Group 1.3) 44

2.4.4.1 C-Hal (Hal=F, Cl, Br) as acceptors 44

2.4.4.2 S, Se and Te as acceptors 44

2.4.4.3 P, As and Sb as acceptors 45

2.4.4.4 C as acceptor 46

2.4.5 Weak acceptors (Group 1.4) 47)

2.5 H-bonds involving metal centers (Class 2) 49

2.5.1 Metals as H-bond donors (Group 2.1) 50

2.5.2 Metals as H-bond acceptors (Group 2.2) 53

2.5.3 Metal hydrides as H-bond acceptors or dihydrogen bond (DHB) (Group 2.3) 53

2.5.3.1 DHB to main-group hydrides 54

2.5.3.2 DHB to transition-metal hydrides 56

2.5.4 Metal ligands as H-bond donors or acceptors (Groups 2.4-5) 56

2.6 H-bond classification by physical properties: Weak, moderate, and strong H-bonds 59

2.7 Correlation among physical descriptors: The Problem of the drivingvariable 60

3 Modelling the H-bond by Crystallographic methods 65

3.1 Crystallographic databases and structural correlation 65

3.1.1 A survey of structural databases 65

3.1.2 Crystal-structure correlation (CSC) methods 68

3.1.3 Bond lengths, bond energies and bond-number conservation rule 71

3.1.3.1 Bond lengths, energies and numbers 71

3.1.3.2 Bond-number conservation rule 72

3.1.3.3 The Lippincott and Schroeder H-bond model (LS-HB) 75

3.2 A new class of H-bonds: An introduction 81

3.2.1 Cooperative H-bonds: An Introduction 81

3.2.2 Evidence for RAHB from CSC studies of ?-diketone enols 84

3.2.2.1 A survey of CSC results 84

3.2.2.2 RAHB interpretation: The ionic model 89

3.2.2.3 RAHB interpretation: The resonant model 91

3.2.2.4 Appendix 3A: RAHB as a cybernetic effector 100

3.2.2.5 Apendix 3B: RAHB as a state-correlation diagram 100

3.2.2.6 Appendix 3C: RAHB electron effective-mass model 103

3.2.3 RAHB generalization and systematics 108

3.2.3.1 RAHB generalization 108

3.2.3.2 Intra-and intermolecular O-H...O RAHB 111

3.2.3.3 Intramolecular N-H...N RAHB 121

3.2.3.4 Heteronuclear X-H...y RAHB 122

3.3 Completing the H-bond classification: The Chemical leitmotifs analysis of the O-H...O system 147

3.3.1 A full H-bond classification from the systematic analysis of the O-H...O system 147

3.3.1.1 A full CSD analysis of the O-H...O System 147

3.3.1.2 Interpreting the O-H...O system: The electrostatic-covalent H-bond model 155

3.3.1.3 Interpreting the O-H...O system: The PA/PKa equalization principle 159

3.3.2 CAHB generalization to other homnuclear X-H...X bonds 161

3.3.3 CAHB generalization to heteronuclear X-H...Y bonds 163

3.3.4 CAHB geometry-energy relationships 163

4 Modelling the H-bond by thermodynamic methods 168

4.1 Introduction 168

4.2 The use of ?PA and?OKa indicators in H-bond studies 168

4.2.1 PA and PKa definitions 168

4.2.2 Proton-transfer and proton-sharing H-bonds 170

4.2.3 Computing ?PA and ?PKa values: The problem of ?PA evaluation 171

4.2.4 The use of PA and PKa as predictors of the H-bond strength: A summary 173

4.3 Predicting (-)CAHB and (+)CAHB strengths from enthaply versus proton affinity correlations 174

4.3.1 ?H°DIS against ?PA correlations 174

4.3.2 A Verification of the PA equalization principle 175

4.4 Predicting H-bond strengths from crystal geometry versus PKa correlations 177

4.4.1 PKa tables for the most common H-bond donors and acceptors 177

4.4.2 The PKa slide rule 177

4.4.3 Two projects for validating the PKa equalization principle 180

4.4.3.1 First project. PKa equalization in CAHBs with ?PKa near zero 180

4.4.3.2 Second project. PKa equalization in the N-H-...O/O-H system 183

4.4.3.3 Conclusions 184

4.5 Appendix. PKa tables arranged for chemical funtionality 184

5 The empirical laws governing the H-bonds: A summary 193

5.1 Summary of chemical leitmotifs (CLs): The three main classes of H-bonds 193

5.2 Summary of VB methods: The electrostatic-covalent H-bond model (ECHBM) 196

5.3 Summary of the PA/Pka equalization principle 199

5.4 On the chemical nature of the h-bond 200

6 Outline a novel transition-state H-bond theory (TSHBT) 203

6.1 Empirical laws, models and scietific theories: An introduction 203

6.2 A new way of looking at the H-bond: The TSHBT 206

6.2.1 Introduction 206

6.2.2 Criteria for the choice of a suitable PT reaction 206

6.3 A practical verification of the TSHBT 208

6.3.1 A suitable reaction: The ketohydrazone?azoenol system 208

6.3.2 Methods of study 208

6.3.3 Analysis of crystallographic results 210

6.3.4 DFT emulation 211

6.3.5 Marcus analysis of DFT data 213

6.3.6 Conclusions 220

7 The Strength of the H-bond: Definitions and thermodynamics 222

7.1 The H-bond strength in gas-phase, non-polar solvents and molecular Crystals 222

7.1.1 Enthalphy-entrophy compensation and its influence on the H-bond strength 222

7.1.2 H-bond strength in the gas phase 223

7.1.3 H-bond strength in polar solvents 224

7.1.4 H-bond strength in molecular crystals 225

7.2 The H-bond strength in aqueous soulutions 225

7.2.1 Introduction: Drug-receptor binding as a sample system 225

7.2.2 Hydrophilic and Hydrophobic contributins to drug-receptor binding 226

7.2.3 Hydrophobic binding: Thermodynamics of the steriod-nuclear receptor system 228

7.2.4 Hydrophilic-hydrophobic binding: Thermodynamics of the adenosine A1 membrane receptor 232

7.2.5 Enthalphy-entropy compensation: A universal property of drug-receptor binding 235

7.2.6 Solvent reorganization and enthalpy-entrophy compensation in drug-receptor binging: The Grunward and Steel model 238

7.2.7 Thermodynamic discrimination in ligand-gated ion channels 241

7.2.8 Enthalpy-entrophy compensation in crown ethers and cryptands 242

8 The role of strong H-bonds in nature: A gallery of functional H-bonds 245

8.1 Introductin 245

8.1.1 Detecting strong H-bonds 245

8.1.2 The concept of 'functional H-bonds' 245

8.2 RAHB-driven prototropic tautomerism 247

8.2.1 RAHB-activation of the carbon in? to a carbonyl 247

8.2.2 RAHB-induced enolization in keto-enol tautomerism 248

8.2.3 RAHB-induced tautomerism in heterconjugated systems 248

8.2.4 RAHB cooperativity and anticooperativity in more complex cases 249

8.3 H-bond-controlled crystal packing 251

8.3.1 The crystal packing of squaric acid and its anions 251

8.4 Bistable H-bonds in fuctional molecular materials 253

8.4.1 Generalities 253

8.4.2 RAHB and ferro/antiferroelectric behavior 254

8.4.3 RAHB and excited-state proton transfer (ESPT) 258

8.5 Functional H-bonds in biological systems 260

8.5.1 RAHB in the secondary structure of protiens and in DNA base pairing 260

8.5.2 Charge-assisted H-bonds in enzumatic catalysis 261

8.5.2.1 Generalities 261

8.5.2.2 The catalytic triad of serine proteases 263

8.5.2.3 ?5-3-Ketosteroid isomerase 266

8.5.2.4 An aspartic protease: HIV-1 Protease 267

8.6 ?-bond cooperativity and anticooperative in PAHBs 269

8.6.1 Cooperative and anticooperative water chains 269

8.6.2 An example of cooperativity: The gramicidline A channel 272

8.6.3 An example of anticooperativity: Water-without-proton transmission in aquaporin channels 275

References 277

Index 315