Hydrogen-Abstracted Adenine−Thymine Radicals with Interesting Transferable Properties

The formation of radicals on DNA bases through various pathways can lead to harmful structural alterations. Such processes are of interest for preventing alteration of healthy DNA and, conversely, to develop more refined methods for inhibiting the replication of unwanted mutagenic DNA. In the present work, we explore theoretically the energetic and structural properties of the nine possible neutral radicals formed via hydrogen abstraction from the adenine−thymine base pair. The lowest energy radical is formed by loss of a hydrogen atom from the methyl group of thymine. The next lowest energy radicals, lying 8 and 9 kcal mol-1 higher than the global minimum, are those in which hydrogens are removed from the two nitrogens that would join the base pair to 2-deoxyribose in double-stranded DNA. The other six radicals lie between 16 and 32 kcal mol-1 higher in energy. Unlike the guanine−cytosine base pair, adenine−thymine (A−T) exhibits only minor structural changes upon hydrogen abstraction, with all A−T derived radicals maintaining planarity. Moreover, the energetic ordering for the radicals of the two isolated bases (adenine and thymine) is preserved upon formation of the base pair, though with a wider spread of energies. Even more significantly, the energetic interleaving of the (A−H)•−T and A−(T−H)• radicals is correctly predicted from the X−H bond dissociation energies of the isolated adenine and thymine. This suggests that the addition of the hydrogen-bonded complement base only marginally affects the bond energies.