Activation of Molecular Oxygen during the Reactions of Chromium(VI/V/IV) with Biological Reductants:  Implications for Chromium-Induced Genotoxicities¹

The first systematic study on the roles of O 2 in the reactions of Cr(VI/V/IV) with major intracellular reductants, cysteine ( 1 ), glutathione ( 2 ), and ascorbic acid ( 3 ) as well as with vitamin E analogue Trolox ( 4 ), has been performed. The reactions of 1 − 3 with Cr(VI) (aqueous buffer solutions, pH = 4.5−7.5, 25 °C) led to a slow O 2 consumption (measured by a Clark oxygen electrode). The reactions of 1 − 3 with the relatively stable Cr(V) and Cr(IV) 2-ethyl-2-hydroxybutanoato complexes under the same conditions were accompanied by fast O 2 consumption. The O 2 consumption during the reactions of Cr(VI/V/IV) with 1 − 3 did not lead to a significant accumulation of H 2 O 2 (determined with catalase). No significant O 2 consumption was detected for the reactions of Cr(VI/V/IV) with 4 . To reveal the mechanisms of O 2 activation, the kinetics of the Cr(V/IV) reactions with 1 − 4 at pH 4.5 and 7.5 were studied by stopped-flow UV−visible spectrophotometry; and the kinetic data were processed by the global analysis method. The stoichiometries and products of these reactions were studied by UV−visible, CD, and EPR spectroscopies. The proposed mechanism of O 2 activation includes oxidations of 1 − 4 by Cr(V/IV) to produce organic radical intermediates, which then react with O 2 in chain processes. No evidence was found for the direct activation of O 2 by the Cr compounds. Implications of the proposed mechanism to the DNA damage induced by the Cr(VI) + reductant + O 2 systems have been discussed.