Independent generation and study of 5,6-dihydro-2′-deoxyuridin-6-yl, a member of the major family of reactive intermediates formed in DNA from the effects of γ-radiolysis

Nucleobase radicals are the major family of reactive intermediates formed when nucleic acids are exposed to gamma-radiolysis. Elucidation of their reactivity is complicated by the formation of multiple species randomly throughout the biopolymers. 5,6-Dihydro-2'-deoxyuridin-6-yl (1) was generated upon photolysis (350 nm) of the respective tert-butyl ketone (2). The radical abstracts hydrogen atoms from beta-mercaptoethanol (k = 8.8 +/- 0.5 x 10(6) M-1 s(-1)) and 2,5-dimethyltetrahydrofuran (k = 31 +/- 2.5 M-1 s(-1)). The latter was used as a model for the 2-deoxyribose component of DNA. The major product formed in the presence of O-2 was 6-hydroxy-5,6-dihydro-2'-deoxyuridine (11), which is believed to be formed directly from the peroxy precursor and not via elimination of superoxide. Small amounts of 2-deoxyribonolactone (13) were also formed under aerobic conditions. This product is believed to result from intramolecular hydrogen atom abstraction by the C6-peroxyl radical (14) and suggests that gamma-radiolysis may indirectly result in oxidation of the Cl'-position of nucleotides, despite the inaccessibility of this hydrogen in duplex DNA.