Relationship between quantum-chemical descriptors of proton dissociation and experimental acidity constants of various hydroxylated coumarins. Identification of the biologically active species for xanthine oxidase inhibition

Quantum-chemical descriptors related to proton dissociation constants of a set of coumarins hydroxylated in various positions have been computed and related to the experimental pKa values. An excellent correlation was found between the computed deprotonation energies of hydroxycoumarins in water and their experimental pKa values, and the results were used to predict the pKa of other hydroxycoumarins. Then, predicted and experimental pKa values were used as a basis for interpreting and discussing the variation of xanthine oxidase inhibitory activities within a subset of coumarins, with the aim of identifying the molecular species most relevant for enzyme inhibition.

Graphical abstractDeprotonation energies of hydroxycoumarins in water were used to identify the biologically relevant species for xanthine oxidase inhibition.Figure optionsDownload full-size imageDownload as PowerPoint slide