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 (O-2(.-)) 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 O-2(.-) from the peroxyl radical (4)derived from 3 is similar to 1 s(-1). This process is competitive with the anticipated rate of trapping of 4 in DNA by glutathione. Relative rate studies indicate that O(2)(.-)generation resulting from the formation of 1 under aerobic conditions competes effectively with trapping of the peroxyl radical by Bu3SnH. Superoxide elimination 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 elimination of O-2(.-) from 2 is a potential double-edged sword.