Comparison of the reaction of ˙OH and of SO4–˙ radicals with pyrimidine nucleosides. An electron spin resonance study in aqueous solution

Reactions of photolytically generated ˙OH and SO4–˙ radicals with uridine, cytidine, 2′-deoxyuridine (dU) 2′-deoxycytidine (dC), and thymidine have been studied by e.s.r. spectroscopy under anoxic conditions. In the experiments with ˙OH, the spectra of the uracil compounds were dominated by the signals of radicals originating from ˙OH addition at the alkenic double bond of the nucleobase. No spectra were observed for the cytosine derivatives and thymidine. With SO4–˙, base radicals were generated from the deoxyribonucleosides [C(5)-OH-6-yl from dU, C(6)-OH-5-yl from thymidine, and a nitrogen-centred radical from dC] whereas the ribonucleosides lead to two different types of sugar radical. One of them is derived from the 2′-hydroxyalkyl radical by heterolytic elimination of the nucleobase and the other is the 3′-hydroxyalkyl radical which undergoes ring-opening by heterolytic cleavage of the C(4′)-oxygen bond at neutral and alkaline pH. Both the ˙OH and SO4–˙ radicals add to the base moieties in the primary step. The adduct radicals formed with ˙OH from uridine and dU are stable on the millisecond time-scale of the e.s.r. experiment whereas the sulphate adducts are too short-lived to be detected by e.s.r. In the deoxyribose derivatives they either hydrolyse (dU and thymidine) or eliminate SO42– and a proton (dC) whereas in the ribonucleosides they induce intramolecular H abstraction from positions 2′ and 3′ of the sugar residues.