1,4-Reductive addition of glutathione to quinone epoxides. Mechanistic studies with h.p.l.c. with electrochemical detection under anaerobic and aerobic conditions. Evaluation of chemical reactivity in terms of autoxidation reactions.
The nucleophilic addition of GSH to quinonoid compounds, characterized as a 1,4-reductive addition of the Michael type, was studied with p-benzoquinone- and 1,4-naphthoquinone epoxides with different degree of methyl substitution. Identification and evaluation of molecular products from the above reaction were assessed by h.p.l.c. with either reductive or oxidative electrochemical detection, based on the redox properties retained in the molecular products formed. It was found that the degree of methyl substitution of the quinone epoxide, from either the 1,4-naphthoquinone- or p-benzoquinone epoxide series, determined their rate of reaction with GSH. The reductive addition implied the rearrangement of the quinone structure with opening of the epoxide ring yielding as the primary product a hydroxy-glutathionyl substituted adduct of either p-benzohydroquinone or 1,4-naphthohydroquinone. The primary product undergoes elimination reactions and redox transitions which bring about a number of secondary molecular products. The distribution pattern of the latter depends on the degree of methyl substitution of the quinone epoxide studied and on the concentration of O2 in the solution. The occurrence of the hydroxy-substituent in position alpha, adjacent to the carbonyl group, enhances the autoxidation properties of the compound resulting in an augmented O2 consumption and H2O2 production. Therefore, it could be expected that the chemical reactivity of the products originating from the thiol-mediated nucleophilic addition to quinone epoxides would be of toxicological interest.
Brunmark
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Department of Pathology II, University of Linköping, Sweden.
Cadenas
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D016227:Benzoquinones; D055598:Chemical Phenomena; D002621:Chemistry; D002851:Chromatography, High Pressure Liquid; D004852:Epoxy Compounds; D004988:Ethers, Cyclic; D005609:Free Radicals; D005978:Glutathione; D006861:Hydrogen Peroxide; D007700:Kinetics; D009285:Naphthoquinones; D010084:Oxidation-Reduction; D010100:Oxygen / Q000494:pharmacology; D011809:Quinones; D014812:Vitamin K
D016227:Benzoquinones; D004852:Epoxy Compounds; D004988:Ethers, Cyclic; D005609:Free Radicals; D009285:Naphthoquinones; D011809:Quinones; D014812:Vitamin K; C004532:quinone; D006861:Hydrogen Peroxide; D005978:Glutathione; C035342:1,4-naphthoquinone; D010100:Oxygen