The Autoxidation of 5-Mercaptouracil and 5-Mercaptodeoxyuridine

5-Mercaptouracil (I) and its Ni deoxyribosides (III) undergo rapid autoxidation in aqueous solutions to the corresponding disulfides. This reaction was found to be dependent on the presence of trace amount of Fe³⁺ in the buffer solution. Addition of EDTA inhibited the oxidation and changed its over-all kinetic order. Addition of Fe salts at low substrate concentrations resulted in an initial rate increase, up to a certain “saturation” concentration of iron which was dependent upon, but much smaller than, the substrate concentration. The pH dependence of the oxidation rate closely paralleled that of the ionization of the SH group; ionization of the second proton of I (N₁-H) further increased, while that of III (N₃-H) decreased the rate. The kinetic data are consistent with the assumption that the autoxidation reactions depend on the formation of a 1:3 chelate between the Fe³⁺ and the thiolate ions and on its subsequent homolytic breakdown, to a Fe^II complex and a thiyl radical, the latter process being significantly promoted by the ionization of the N₁-H proton. Based on the proposed mechanistic scheme, it was possible to derive for the autoxidation reactions a general rate equation which satisfies all kinetic results.