Regioselectivity and reversibility of the glutathione conjugation of quercetin quinone methide

The chemical reactivity, isomerization, and glutathione conjugation of quer cetin o-quinone were investigated. Tyrosinase was used to generate the unst able quercetin o-quinone derivative which could be observed upon its subseq uent scavenging by glutathione. Identification of the products revealed for mation of 6-glutathionyl-quercetin and 8-glutathionyl-quercetin adducts. Th us, in particular, glutathione adducts in the A ring of quercetin were form ed, a result which was not expected a priori. Quantum mechanical calculatio ns support the possibility that the formation of these glutathione adducts can be explained by an isomerization of quercetin o-quinone to p-quinone me thides. Surprisingly, additional experiments of this study reveal the adduc t formation to be reversible, leading to interconversion between the two qu ercetin glutathione adducts and possibilities for release and further elect rophilic reactions of the quercetin quinone methide at cellular sites diffe rent from those of its generation.