Molecular structures and energetics associated with hydrogen atom addition to the guanine-cytosine base pair

The radicals generated by hydrogen-atom addition to the Watson-Crick guanine-cytosine (G-C) DNA base pair were studied theoretically using an approach that has proved effective in predicting molecular structures and energetics. All optimized structures were confirmed to be minima via vibrational frequency analysis. The dissociation energies of the base-pair radicals are predicted and compared with that of the neutral G-C base pair. The lowest-energy base-pair radical is that with the hydrogen atom attached to the C8 position of guanine, resulting in the nitrogen radical designated G(C8)-C. In this, the most favorable radical, the G-C pair C8N7 distance of 1.310 A increases to 1.453 A when the pi bond is broken upon hydrogen-atom addition. This radical has a dissociation energy of 28 kcal/mol, which may be compared with 27 kcal/mol for neutral G-C. The other (GC + H)(center dot) radical dissociation energies range downward to 8 kcal/mol. Significant structural changes were observed when the hydrogen was added to the sites where the interstrand hydrogen bonds are formed. For example, "butterfly"-shape structures were found when the hydrogen atom was added to the C4 or C5 sites of guanine. The formation of radical G(C2)-C may cause a single-strand break because of significant strain in the closely stacked base pairs. Radical G(C8)-C is of biological importance because it may be an intermediate in the formation of 8-oxo guanine.