Electron transfer oxidation of DNA radicals by paranitroacetophenone

The reaction of a typical electron-affinic sensitizer, paranitroacetophenone (PNAP) with the model compounds thymine, thymidine, thymidylic acid, deoxyribose and single and double-stranded DNA has been investigated by pulse radiolysis. Radicals formed by one-electron reduction of the bases and of DNA react rapidly and efficiently with PNAP by electron transfer. A small yield of transfer (less than 10 per cent) is also observed arising from oxidation of the radicals formed by the small proportion of OH which react at the sugar moieties in DNA. In contrast, electron transfer oxidation by PNAP of radicals formed by the addition of OH to the base moieties, e.g. thymine, is not an efficient process. Further, addition of the sensitizer to the thymine OH-adduct proceeds at a rate that is too low to measure by pulse radiolysis. We conclude that, since the major sites of OH reaction with DNA are the heterocyclic bases (greater than 80 per cent), oxidation of the resultant radicals is unlikely to be a major step in the mechanism of sensitization by this typical hypoxic-cell sensitizer.