Identification of the Oxidized Products Formed upon Reaction of Chromium(V) with Thymidine Nucleotides

Abstract

Two pathways have been observed for Cr(V)-mediated nucleotide oxidation in reactions of bis(2-ethyl-2-hydroxybutyrato)oxochromate(V) [CrO(ehba)2]- with thymidine nucleotides dTMP, dTDP, and dTTP. The extent of Cr(V)-induced nucleotide oxidation was greatest for thymidine diphosphate (dTDP), as measured by the production of thiobarbituric acid reactive species (TBARS; indicative of pathway 1) and thymine release (indicative of pathway 2). The nucleoside thymidine showed no reaction, suggesting a phosphate-dependent oxidation. Amounts of TBARS and thymine were maximal at a pH range of 6.0−6.5, and both TBARS formation and thymine release correlated with decay of the Cr(V) EPR signal. Formation of TBARS was maximal in 100% O2 but decreased markedly under argon, whereas thymine release was maximal under argon, but remained the major product observed under aerobic conditions. Pathway 1 for the reaction of Cr(V) with dTDP led to formation of glycolic acid and trans-thymine propenal at approximately equimolar am...