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 pK(a) values. An excellent correlation was found between the computed deprotonation energies of hydroxycoumarins in water and their experimental pK(a) values, and the results were used to predict the pK(a) of other hydroxycoumarins. Then, predicted and experimental pK(a) 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.