Formation of S-[5-(2'-Deoxyuridyl)] thiol Compounds in the Dehalogenation of 5-Bromo- and 5-Iodo-2'-deoxyuridine with Cysteine Derivatives

Dehalogenations of 5-bromo- and 5-iodo-2'-deoxyuridine by thiol compounds in aqueous solutions were studied. The thiols used were cysteine, cysteine methyl- and ethyl-esters, cysteamine, homocysteine, glutathione, 2-mercaptoethanol, and 2-mercaptopropionic acid. The products of these reactions and the rate constants were determined. At pH 8 and 37°, the dehalogenation rates by these thiols decreased in above-mentioned order. 5-Alkylthiouracil derivatives were found in products of the reactions between 5-bromo-2'-deoxyuridine and cysteine, cysteine ethyl ester, cysteamine, homocysteine and glutathione, as well as of the reaction between 5-iodo-2'-deoxyuridine and cysteine. This indicated that the SN2 mechanism proposed in a previous paper (Y. Wataya, K. Negishi and H. Hayatsu, Biochemistry, 12, 3992 (1973)) is generally operating in the dehalogenations of these compounds with thiols.