Release of superoxide from nucleoside peroxyl radicals, a double-edged sword?

5,6-Dihydrothymidin-5-yl (1) and 2'-deoxyuridin-1'-yl (3) were independently generated in solution under aerobic conditions. The release of superoxide (O₂^.-) from the respective peroxyl radicals derived from 1 and 3 was determined spectrophotometrically. Competition studies enable one to estimate that the rate constant for elimination of O₂^.- from the peroxyl radical (4) derived from 3 is ~1 s^-1. This process is competitive with the anticipated rate of trapping of 4 in DNA by glutathione. Relative rate studies indicate that O₂^.- generation reslting from the formation of 1 under aerobic conditions competes effectively with trapping of the peroxyl radical by Bu₃SnH. Superoxide elmination from the peroxyl radical of 1 (2) restores the damaged nucleoside to its unaltered form, implying that this reactive intermediate has a naturally occurring detoxification pathway available to it. However, the freely diffusible superoxide can react further to generate other reactive species capable of damaging nucleic acids, suggesting that the eliminations of O₂^.- from 2 is a potential double- edged sword.