One-Electron Oxidation of DNA Oligomers That Lack Guanine: Reaction and Strand Cleavage at Remote Thymines by Long-Distance Radical Cation Hopping

Abstract

The anthraquinone (AQ) photosensitized one-electron oxidation of DNA introduces a radical cation (electron "hole") that migrates through the duplex by hopping. The radical cation normally is trapped irreversibly by reaction at guanine. We constructed AQ-linked DNA oligomers composed exclusively of A/T base pairs. Their irradiation led to reaction and strand cleavage primarily at thymines. Long-distance radical cation hopping to distant thymines was demonstrated by the distance dependence of the process and by experiments with DNA oligomers that contain a single remote GG step. The reaction of the radical cation at thymine was shown to involve its 5-methyl group by the replacement of selected thymines with uracils. These findings show that the reactivity of radical cations in DNA cannot be explained simply by exclusive reliance on the relative oxidation potential of the nucleobases. Instead, the site of reaction is determined in accord with the Curtin-Hammett principle for reactive species in rapid equilibrium.