Role of the guanine N1 imino proton in the migration and reaction of radical cations in DNA oligomers.

Oxidation of a guanine nucleobase to its radical cation in DNA oligomers causes an increase in the acidity of the N1 imino proton that may lead to its spontaneous transfer to N3 of the paired cytosine. This proton transfer is suspected of playing an important role in long-distance radical cation hopping in DNA and the decisive product-determining role in the reaction of the radical cation with H2O or O2. We prepared and investigated DNA oligomers in which certain deoxycytidines are replaced by 5-fluoro-2'-deoxycytidines (F5dC). The pKa of F5C was determined to be 1.7 units below that of dC, which causes proton transfer from the guanine radical cation to be thermodynamically unfavorable. Photoinitiated one-electron oxidation of the DNA by UV irradiation of a covalently attached anthraquinone derivative introduces a radical cation that hops throughout the oligomer and is trapped selectively at GG steps. The introduction of F5dC does not affect the efficiency of charge hopping, but it significantly reduces the amount of reaction at the GG sites, as revealed by subsequent reaction with formamidopyrimidine glycosylase. These findings suggest that transfer of the guanine radical cation N1 proton to cytosine does not play a significant role in long-range charge transfer, but this process does influence the reactions with H2O and/or O2.