CATALYTIC EFFECTS OF GLUTATHIONE-PEROXIDASE MIMETICS ON THE THIOL REDUCTION OF CYTOCHROME-C

The reduction of ferric cytochrome c by various thiols was studied. It was found that L-cysteine, L-cysteine methyl ester and D-penicillamine were very efficient reductants for cytochrome c, whereas N-acetylated aminoacids (N-acetyl-L-cysteine and N-acetyl-D-cysteine) reacted considerably slower. A series of glutathione peroxidase mimetics and related compounds were studied as catalysts for the N-acetyl-L-cysteine reduction of ferric cytochrome c. Diphenyl diselenide, t-butylthio phenyl selenide, S-(phenylseleno)-glutathione, N-(phenylseleno)-phthalimide and alpha-(phenylselenenyl)-acetophenone were all efficient reduction catalysts. Diphenyl disulfide, Ebselen and several derivatives thereof were less potent catalysts whereas diaryl selenides and diphenyltelluride did not affect the rate of reduction when present in catalytic amounts. The catalysis of diphenyl diselenide, selenosulfides, alpha-(phenylselenenyl)acetophenone, N-(phenylseleno)-phthalimide and Ebselen and derived compounds was suggested to involve the formation of areneselenolate ions as redox-active species capable of transferring one electron to the ferric cytochrome c. The resulting selenium centered arylseleno radicals would then dimerize to regenerate the catalyst in the diselenide form. In the presence of diaryl ditellurides and N-acetyl-L-cysteine, ferric cytochrome c was also rapidly reduced. This reaction was stoichiometric with respect to the ditelluride reagent.