Adducts across the 5,6-double bond of pyrimidines. The mechanism of dehydration of 1-substituted uracil photohydrates.

The mechanism of dehydration of 1-substituted 6-hydroxy-5,6-dihydrouracils has been studied using kinetic methods and hydrogen isotope effects. The reaction is catalyzed by hydronium and hydroxide ions and, depending upon the 1-substituent, may undergo a spontaneous uncatalyzed reaction. The acid-catalyzed dehydration involves pre-equilibrium protonation of the 6-hydroxyl group and loss of water from the 6-carbon, followed by rate-determining loss of a proton from the 5-position. In basic media, there is first a rate-determining proton loss from the 5-position to form a carbanionic intermediate, followed by elimination of hydroxide ion at the 6-carbon to give the parent pyrimidine. By microscopic reversibility, the results described here provide an accurate description of the mechanisms of the acid- and base-catalyzed formation of 6-hydroxy-5,6-dihydropyrimidines which are involved in cleavage of the N-glycosidic bond of uridine (Prior, J. J., and Santi, D. V. (1984) J. Biol. Chem. 259, 2429-2434) and are related to covalent adducts which are important in the catalysis of certain enzymic reactions as well as interactions between certain proteins and nucleic acids.