CHROMIUM(VI) FORMS A THIOLATE COMPLEX WITH GLUTATHIONE

Reaction of potassium dichromate with the tripeptide glutathione resulted in the formation of a 1:1 complex of Cr(VI) with glutathione. The red Cr(VI)-glutathione adduct was stable for approximately 60 min at 4-degrees-C and I = 1.5 M. H-1, C-13, and O-17 NMR studies showed that glutathione acts as a monodentate ligand and binds to Cr(VI) through the cysteinyl thiolate group, forming a GSCrO3- complex. No evidence was obtained for involvement of the other possible ligating groups, e.g., glutamyl amino and carboxylate, glycinyl carboxylate, or peptide backbone, in binding to Cr(VI); however, Cr(VI)-induced conformational changes in the glutamyl and cysteinyl side chains of the tripeptide. EPR studies showed that two chromium(V) species (g = 1.987 and g = 1.973) are formed upon reaction of potassium dichromate with glutathione. Chromium-glutathione complexes may be involved in producing the high levels of chromium(VI)-induced DNA damage in cells having high concentrations of glutathione and may play an important role in the carcinogenicity of chromium(VI) compounds.