Photolabile N-hydroxypyrid-2(1H)-one derivatives of guanine nucleosides: a new method for independent guanine radical generation.

One-electron oxidized guanine is an important reactive intermediate in the formation of oxidatively generated damage in DNA and a variety of methods have been utilized for the abstraction of a single electron from the guanine moiety. In this study, an alternative approach for the site specific, independent generation of the guanine radical, utilizing N-hydroxypyrid-2(1H)-one as a photolabile modifier of guanine, is proposed. Novel photolabile 6-[(1-oxido-2-pyridinyl)oxo]-6-deoxy- and 2',6-dideoxy-guanosine derivatives capable of generating the neutral guanine radical (G(-H)*) upon photolysis were synthesized and characterized. The generation of G(-H)* proceeds through homolysis of the N-O bond and was confirmed through continuous photolysis product analysis and trapping studies, as well as laser flash photolysis experiments.