Spectroscopic characterization of genotoxic chromium(V) peptide complexes: Oxidation of Chromium(III) triglycine, tetraglycine and pentaglycine complexes

Abstract

Evidence is growing that metabolites of Cr(III) dietary supplements are partially oxidized to carcinogenic Cr(VI) and Cr(V) in vivo. Hence, we examined oxidations of Cr(III) peptide (triglycine, tetraglycine and pentaglycine) complexes to Cr(VI) and Cr(V) by PbO2 at 37°C and physiological pH values between 3.85 and 7.4. The products were characterized by EPR and UV/Vis spectroscopies and electrospray mass spectrometry. At pH3.85, the monomeric Cr(V) complexes produced were relatively unstable and degraded over min to hr under the acidic conditions. The triglycine and tetraglycine Cr(V) complexes had five-line 14N-superhyperfine-coupled EPR signals; giso, (AN) values 1.9824 (2.44×10−4cm−1) and 1.9825 (2.43×10−4cm−1), respectively. The pentaglycine Cr(V) complex had a seven-line 14N-superhyperfine-coupled EPR signal: giso=1.9844; AN=2.27×10−4cm−1. In phosphate buffer (pH7.4 and 5.85), several Cr(V) intermediates were produced, but Cr(VI) was the end product. For the triglycine, tetraglycine and pentaglycine Cr(V) complexes, the giso (AN, 10−4cm−1) values were 1.9831 (2.17), 1.9843 (2.27) and 1.9844 (2.30), respectively. A second EPR signal with unresolved superhyperfine structure was observed at giso~1.966. At 1min, the tetraglycine and pentaglycine Cr(V) complexes, had another signal at giso~1.978, which decayed relative to the other signals with time. This chemistry has relevance to: (i) certain types of DNA damage produced by Cr carcinogens; (ii) the intracellular oxidation of Cr(III) to Cr(VI); and (iii) redox recycling of Cr(III) metabolites formed from both the intracellular reduction of carcinogenic Cr(VI) and from Cr(III) supplements.