title: Nonenzymatic displacement of chlorine and formation of free radicals upon the reaction of glutathione with PCB quinones.
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.
authors.affiliation: Department of Occupational and Environmental Health, University of Iowa, 100 Oakdale Campus, 124 IREH, Iowa City, IA 52242-5000, USA.
authors.forename: Yang
authors.initials: Y
authors.lastname: Song
authors.forename: Brett A
authors.initials: BA
authors.lastname: Wagner
authors.forename: Jordan R
authors.initials: JR
authors.lastname: Witmer
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Lehmler
authors.forename: Garry R
authors.initials: GR
authors.lastname: Buettner
mesh_terms: D002713:Chlorine / Q000737:chemistry*; D004578:Electron Spin Resonance Spectroscopy; D005978:Glutathione / Q000737:chemistry*; D011078:Polychlorinated Biphenyls / Q000737:chemistry*; D011809:Quinones / Q000737:chemistry*
chemical_list: D011809:Quinones; D002713:Chlorine; D011078:Polychlorinated Biphenyls; D005978:Glutathione