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

Hydrogen bond (H-bond) effects are known: it makes sea water liquid, joins cellulose microfibrils in trees, shapes DNA into genes and polypeptide chains into wool, hair, muscles or enzymes. Its true nature is less known and we may still wonder why O-H...O bond energies range from less than 1 to more than 30 kcal/mol without apparent reason. This H-bond puzzle is re-examined here from its very beginning and presented as an inclusive compilation of experimental H-bond energies and geometries. New concepts emerge from this analysis: new classes of systematically strong H-bonds (CAHBs and RAHBs: charge- and resonance-assisted H-bonds); full H-bond classification in six classes (the six chemical leitmotifs); and assessment of the covalent nature of strong H-bonds. This leads to three distinct but inter-consistent models able to rationalize the H-bond and predict its strength, based on classical VB theory, matching of donor-acceptor acid-base parameters (PA or pKa), or shape of the H-bond proton-transfer pathway. Applications survey a number of systems where strong H-bonds play an important functional role, namely drug-receptor binding, enzymatic catalysis, ion-transport through cell membranes, crystal design and molecular mechanisms of functional materials. Contents......Page 8 Introduction......Page 14 1.1 The discovery of the H-bond......Page 19 1.2 The theoretical understanding of the H-bond......Page 20 1.3 The experimental approach to the H-bond......Page 26 1.4 Significant books and reviews......Page 32 2.2 Formal H-bond definitions......Page 36 2.3 The H-bond as a shared-proton interaction: A chemical classification......Page 41 2.4 H-bonds involving main-group elements (Class 1)......Page 43 2.4.1 Conventional H-bonds (Group 1.1)......Page 44 2.4.2 Weak H-bonds: General properties (Groups 1.2–4)......Page 45 2.4.3 Weak H-bond donors (Group 1.2)......Page 51 2.4.4 Weak H-bond acceptors (Group 1.3)......Page 57 2.4.5 Weak π-acceptors (Group 1.4)......Page 60 2.5 H-bonds involving metal centers (Class 2)......Page 62 2.5.1 Metals as H-bond donors (Group 2.1)......Page 63 2.5.3 Metal hydrides as H-bond acceptors or dihydrogen bond (DHB) (Group 2.3)......Page 66 2.5.4 Metal ligands as H-bond donors or acceptors (Groups 2.4–5)......Page 69 2.6 H-bond classification by physical properties: Weak, moderate, and strong H-bonds......Page 72 2.7 Correlation among physical descriptors: The problem of the driving variable......Page 73 3.1.1 A survey of structural databases......Page 78 3.1.2 Crystal–structure correlation (CSC) methods......Page 81 3.1.3 Bond lengths, bond energies and bond-number conservation rule......Page 84 3.2.1 Cooperative H-bonds: An introduction......Page 94 3.2.2 Evidence for RAHB from CSC studies of ß-diketone enols......Page 97 3.2.3 RAHB generalization and systematics......Page 121 3.3.1 A full H-bond classification from the systematic analysis of the O–H···O system......Page 160 3.3.2 CAHB generalization to other homonuclear X–H···X bonds......Page 174 3.3.4 CAHB geometry–energy relationships......Page 176 4.2.1 PA and pK[sub(a)] definitions......Page 181 4.2.2 Proton-transfer and proton-sharing H-bonds......Page 183 4.2.3 Computing ΔPA and ΔpK[sub(a)] values: The problem of ΔPA evaluation......Page 184 4.2.4 The use of PA and pK[sub(a)] as predictors of the H-bond strength: A summary......Page 186 4.3.1 ΔH[sup(°)sub(DIS)] against ΔPA correlations......Page 187 4.3.2 A verification of the PA equalization principle......Page 188 4.4.2 The pK[sub(a)] slide rule......Page 190 4.4.3 Two projects for validating the pK[sub(a)] equalization principle......Page 193 4.5 Appendix. pK[sub(a)] tables arranged for chemical functionality......Page 197 5.1 Summary of chemical leitmotifs (CLs): The three main classes of H-bonds......Page 206 5.2 Summary of VB methods: The electrostatic-covalent H-bond model (ECHBM)......Page 209 5.3 Summary of the PA/pK[sub(a)] equalization principle......Page 212 5.4 On the chemical nature of the H-bond......Page 213 6.1 Empirical laws, models and scientific theories: An introduction......Page 216 6.2.2 Criteria for the choice of a suitable PT reaction......Page 219 6.3.2 Methods of study......Page 221 6.3.3 Analysis of crystallographic results......Page 223 6.3.4 DFT emulation......Page 224 6.3.5 Marcus analysis of DFT data......Page 226 6.3.6 Conclusions......Page 233 7.1.1 Enthalpy–entropy compensation and its influence on the H-bond strength......Page 235 7.1.2 H-bond strength in the gas phase......Page 236 7.1.3 H-bond strength in non-polar solvents......Page 237 7.2.1 Introduction: Drug–receptor binding as a sample system......Page 238 7.2.2 Hydrophilic and hydrophobic contributions to drug–receptor binding......Page 239 7.2.3 Hydrophobic binding: Thermodynamics of the steroid–nuclear receptor system......Page 241 7.2.4 Hydrophilic–hydrophobic binding: Thermodynamics of the adenosine A[sub(1)] membrane receptor......Page 245 7.2.5 Enthalpy–entropy compensation: A universal property of drug–receptor binding......Page 248 7.2.6 Solvent reorganization and enthalpy–entropy compensation in drug–receptor binding: The Grunwald and Steel model......Page 251 7.2.7 Thermodynamic discrimination in ligand-gated ion channels......Page 254 7.2.8 Enthalpy–entropy compensation in crown ethers and cryptands......Page 255 8.1.2 The concept of 'functional H-bonds'......Page 258 8.2.1 RAHB-activation of the carbon in α to a carbonyl......Page 260 8.2.3 RAHB-induced tautomerism in heteroconjugated systems......Page 261 8.2.4 RAHB cooperativity and anticooperativity in more complex cases......Page 262 8.3.1 The crystal packing of squaric acid and its anions......Page 264 8.4.1 Generalities......Page 266 8.4.2 RAHB and ferro/antiferroelectric behavior......Page 267 8.4.3 RAHB and excited-state proton transfer (ESPT)......Page 271 8.5.1 RAHB in the secondary structure of proteins and in DNA base pairing......Page 273 8.5.2 Charge-assisted H-bonds in enzymatic catalysis......Page 274 8.6.1 Cooperative and anticooperative water chains......Page 282 8.6.2 An example of cooperativity: The gramicidine A channel......Page 285 8.6.3 An example of anticooperativity: Water-without-proton transmission in aquaporin channels......Page 288 References......Page 290 H......Page 328 P......Page 329 X......Page 330

Hydrogen bond (H-bond) effects are known: it makes sea water iquid, joins cellulose microfibrils in trees, shapes DNA nto genes and polypeptide chains into wool, hair, muscles or enzymes. Its true nature is less known and we may still wonder why O-H...O bond energies range from less than 1 to more than 30 kcal/mol without apparent reason. This H-bond puzzle is re-examined here from its very beginning and presented as an inclusive compilation of experimental H-bond energies and geometries.

New concepts emerge from this analysis: new classes of systematically strong H-bonds (CAHBs and RAHBs: charge- and resonance-assisted H-bonds); full H-bond classification in six classes (the six chemical leitmotifs); and assessment of the covalent nature of strong H-bonds. This leads to three distinct but inter-consistent models able to rationalize the H-bond and predict its strength, based on classical VB theory, matching of donor-acceptor acid-base parameters (PA or pKa), or shape of the H-bond proton-transfer pathway.

Applications survey a number of systems where strong H-bonds play an important functional role, namely drug-receptor binding, enzymatic catalysis, ion-transport through cell membranes, crystal design and molecular mechanisms of functional materials.

Hydrogen bond (H-bond) effects are known: it makes sea water iquid, joins cellulose microfibrils in trees, shapes DNA nto genes and polypeptide chains into wool, hair, muscles or enzymes. Its true nature is less known and we may still wonder why O-H ... O bond energies range from less than 1 to more than 30 kcal/mol without apparent reason. This H-bond puzzle is re-examined here from its very beginning and presented as an inclusive compilation of experimental H-bond energies and geometries. New concepts emerge from this analysis: new classes of systematically strong H-bonds (CAHBs and RAHBs: charge- and resonance-assisted H-bonds); full H-bond classification in six classes (the six chemical leitmotifs); and assessment of the covalent nature of strong H-bonds. This leads to three distinct but inter-consistent models able to rationalize the H-bond and predict its strength, based on classical VB theory, matching of donor-acceptor acid-base parameters (PA or pKa), or shape of the H-bond proton-transfer pathway. Applications survey a number of systems where strong H-bonds play an important functional role, namely drug-receptor binding, enzymatic catalysis, ion-transport through cell membranes, crystal design and molecular mechanisms of functional materials This text defines the rules for predicting H-bond energies and geometries from the properties of the interacting molecules. This new knowledge is used to investigate the molecular mechanisms in systems relevant to chemistry, biochemistry, pharmacology, crystallography, and material sciences