Hydrogen bonding, steric effects and thermodynamics of partitioning

Abstract

The descriptors in the Abraham solvation equation, especially the solute hydrogen bond acidity descriptor, A, have been compared to values of DH o and DS o for partitioning in the water-cyclohexane and wateroctanol systems obtained by Dearden and Bresnen. It is shown that effects on DH o and DS o due to internal hydrogen bonding parallel very closely effects on A values for substituted phenols and substituted benzoic acids, thus suggesting a common structural origin. Steric effects of ortho-substituted methyl groups in phenols, benzoic acids and acetanilides on DH o and DS o also parallel effects on the Abraham solvation parameters. Some of these steric effects, such as those in 2,6-dimethylacetanilide, can be very large. Both the thermodynamics of partitioning and the Abraham descriptors suggest that in 2,6-dihydroxybenzoic acid there is only one internal hydrogen bond, and that 2-nitroresorcinol behaves as though it had two internal hydrogen bonds.

Genetic profile of second primary tumors and recurrences in head and neck squamous cell carcinomas

“…Based on the above structural analysis, 26DHBA co‐crystal formation may be inhibited by two factors: First, both 2‐ and 6‐hydroxy groups have a steric hindrance on the approach of piracetam. This steric effect was observed in several studies 11, 12. Second, both the 2‐ and 6‐hydroxy groups may form an intramolecular hydrogen bond with 1‐carboxylic acid group (Fig.…”

Effect of position isomerism on the formation and physicochemical properties of pharmaceutical co-crystals

“…4). This reduces intermolecular hydrogen bonding ability,11 thus eliminate the chance of carboxylic acid–amide synthon formation.…”

Binding Mechanisms in Supramolecular Complexes

“…[382] Hydrogen bonds are especially sensitive to media that can function as both a donor and an acceptor. [384] Ab initio/DFT calculations suggest, however, that binding strengths seldom correlate with the pK values of proton donors. Exothermic reactions are found for complexes of dicarboxylates with urea derivatives in DMSO, with TDS values near zero.…”