Evidence for intrastrand C2' hydrogen abstraction in photoirradiation of 5-halouracil-containing oligonucleotides by using stereospecifically C2'-deuterated deoxyadenosine

In order to investigate the nature of deoxyribose C1' and C2' H abstraction by uracilyl-5-yl radical in DNA, we have examined the photoreaction of hexanucleotides d(GCA(Br)UGC)(2) in which one of the C2' hydrogens of the deoxyribose moiety was stereospecifically deuterated. Irradiation of (2'R)-[2'-H-2]-2'-deoxyadenosine-containing hexamer (1) gave only a smaller amount of 8 compared to that of the unlabeled hexamer, whereas (2'S)-[2'-H-2]-2'-deoxyadenosine-containing hexamer (2) gave essentially the same amount of 8 as that obtained for the unlabeled hexamer. The results indicated that the formation of C2' oxidation product 8 occurs via a rate-limiting abstraction of (2'alpha)-H of the deoxyribose moiety by uracilyl-5-yl radical. The kinetic isotope effects (k(H)/k(D)) obtained for the formation of 8 by photoirradiation of U-Br- and U-I-containing hexamers were 7.5 and 7.2, respectively.