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 gamma-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 C1'-position of nucleotides, despite the inaccessibility of this hydrogen in duplex DNA.
Carter
K Nolan
KN
Department of Chemistry, Johns Hopkins University, 3400 N. Charles St., Baltimore, Maryland 21218, USA.
Greenberg
Marc M
MM
D004247:DNA / Q000737:chemistry / Q000187:drug effects / Q000528:radiation effects; D004249:DNA Damage; D003857:Deoxyuridine / Q000031:analogs & derivatives / Q000737:chemistry*; D005609:Free Radicals / Q000737:chemistry*; D007700:Kinetics; D008956:Models, Chemical; D015394:Molecular Structure; D010100:Oxygen / Q000737:chemistry; D010782:Photolysis
C479982:5,6-dihydro-2'-deoxyuridin-6-yl; D005609:Free Radicals; D004247:DNA; D010100:Oxygen; D003857:Deoxyuridine