Title: Nonenzymatic displacement of chlorine and formation of free radicals upon the reaction of glutathione with PCB quinones.

Authors: Song, Yang; Wagner, Brett A; Witmer, Jordan R; Lehmler, Hans-Joachim; Buettner, Garry R

Published In Proc Natl Acad Sci U S A, (2009 Jun 16)

Abstract: The reactions of glutathione (GSH) with polychlorinated biphenyl (PCB) quinones having different degrees of chlorination on the quinone ring were examined. EPR spectroscopy and MS revealed 2 types of reactions yielding different products: (i) a nonenzymatic, nucleophilic displacement of chlorine on the quinone ring yielding a glutathiylated conjugated quinone and (ii) Michael addition of GSH to the quinone, a 2-electron reduction, yielding a glutathiylated conjugated hydroquinone. The pK(a) of parent hydroquinone decreased by 1 unit as the degree of chlorination increased. This resulted in a corresponding increase in the oxidizability of these chlorinated hydroquinones. The reaction with oxygen appears to be first-order each in ionized hydroquinone and dioxygen, yielding hydrogen peroxide stoichiometrically. The generation of semiquinone radicals, superoxide, and hydroxyl radicals was observed by EPR; however, the mechanisms and yields vary depending on the degree of the chlorination of hydroquinone/quinone and the presence or absence of GSH. Our discovery that chlorinated quinones undergo a rapid, nonenzymatic dechlorination upon reaction with GSH opens a different view on mechanisms of metabolism and the toxicity of this class of compounds.

PubMed ID: 19497881

MeSH Terms: Chlorine/chemistry*; Electron Spin Resonance Spectroscopy; Glutathione/chemistry*; Polychlorinated Biphenyls/chemistry*; Quinones/chemistry*