Spectrophotometric and chemical studies of 5‐mercaptouracil, 5‐mercaptodeoxyuridine, and their S‐substituted derivatives

5‐Mercaptouracil (1) and 5‐mercaptodeoxyuridine (II), structural analogs of thymine and thymidine, respectively, are effective growth inhibitors in various biological systems and under study as potential antineoplastic and antiviral agents. Both compounds were found to be extremely unstable in aqueous solutions as they undergo rapid autoxidation to the corresponding disulfides. Determination of the ultraviolet spectra and pKa values of the thiols was possible only by special techniques, using dithiothreitol (DTT) as a “protecting” agent. Both I and II have very low pKa's, and their anionic forms show characteristic absorption maxima in the 330‐mμ region. These results are discussed in comparison with the spectra and ionization equilibria of related compounds including some new S‐substituted derivatives of I and II. DTT was found to be also a uniquely suitable reagent for the preparation of pure I and II by stoichiornetric reduction of the corresponding disulhdes. A special technique was developed for the quantitative determination of the free thiols.