THE STRENGTH OF THE H-BOND: DEFINITIONS AND THERMODYNAMICS
This chapter analyzes thermodynamic parameters (ΔG°, ΔH°, ΔS°, and ΔCp°) of the H-bond association equilibrium in gas-phase, crystalline solids, and non-polar and aqueous solvents. The key feature is the extrathermodynamic enthalpy-entropy compensation relationship, ΔH° = βS°, induced by the loss of degrees of freedom during H-bond formation and inducing a considerable reduction of the association constants (e.g., ΔG° ≅ 2/3 Δ/H° in gas-phase and ≅ 1/3 Δ/H° in non-polar solvents). H-bonds in aqueous solutions are mostly studied through drug-receptor binding thermodynamic data. A distinction is made between hydrophobic binding to cytoplasmic and hydrophilic binding to membrane receptors, respectively characterized by negative or nearly zero ΔCp° values. The unifying aspect of all drug-receptor phenomena remains enthalpy-entropy compensation. This is interpreted in terms of solvent reorganization by the Grunwald and Steel (1995) theoretical model showing that solvent effects do not significantly affect the intrinsic ΔG° of the H-bonds which directly connect the drug to the receptor binding site.
Keywords: H-bond association equilibrium, enthalpy-entropy compensation, gas-phase, non-polar solvents, aqueous solutions, drug-receptor binding, drug-receptor thermodynamics, hydrophobic binding, hydrophilic binding, Grunwald and Steel model
Oxford Scholarship Online requires a subscription or purchase to access the full text of books within the service. Public users can however freely search the site and view the abstracts and keywords for each book and chapter.
If you think you should have access to this title, please contact your librarian.