Direct measurement of pyrimidine C6-hydrate stability

Pyrimidine C6-hydrates are produced via UV-irradiation and undergo dehydration upon standing. The stability of these compounds has a direct bearing on their genotoxicity. The rate constants for elimination from 5'-benzyoylated derivatives of 5,6-dihydro-5-hydroxythymidine (6) and 5,6-dihydro-5-hydroxy-2'-deoxyuridine (9) were measured directly via HPLC. The rate constants for dehydration increase from pH 6.0 to 8.0. The half-lives for 6 and 9 at pH 7.4 and 37 degrees C are 46.5 and 24.4h, respectively. Deglycosylation is not observed, even upon heating at 90 degrees C. These observations reinforce proposals that pyrimidine hydrates are sufficiently long-lived that they can exert significant effects on biological systems.