MECHANISMS OF FORMATION AND DECOMPOSITION OF HYPERVALENT CHROMIUM METABOLITES IN THE GLUTATHIONE CHROMIUM(VI) REACTION

A long-lived chromium(IV) intermediate is generated during the reactio n between Cr(VI) and glutathione in glycine below pH 3. The intermedia te reacts with the tripeptide to produce Cr(III) and oxidized glutathi one. A dynamic magnetic susceptibility measurement based on a nuclear magnetic resonance method yielded a 2.8 mu(B) magnetic movement for th e chromium(IV) species. The intermediate is formed by parallel third-o rder and second-order processes. The third-order process (k = 5.9 x 10 (2) M(-2) s(-1)) involves first-order participation by each of the oxi dant, reductant, and hydrogen ions. A hydrogen ion independent pathway leads to a sluggish second-order process (k = 0.11 M(-1) s(-1)) that is first order with respect to reduced glutathione [GSH] and [Cr(VI)]. Chromium(IV) species is reduced to Cr(III) by a second-order process (k = 0.13 M(-1) s(-1)) that is first order in each of [Cr(IV)] and [GS H] and does not depend on [H+]. At pH 3.4, a chromium(V) species was d etected as a minor intermediate as well. In the pH range 6.5-7.5, thre e dominant chromium(V) intermediates were detected. The existence of C r(IV) in low pH offers an opportunity to examine the mechanism of DNA damage by this rare oxidation state.