(G-H)*-C and G-(C-H)* radicals derived from the guanine.cytosine base pair cause DNA subunit lesions.

The radicals generated by the homolytic cleavage of an X-H bond from the guanine.cytosine (G.C) base pair were studied by using carefully calibrated theoretical methods. The gradient-corrected density functional B3LYP was applied in conjunction with double-zeta plus polarization and diffuse function basis sets. Optimized geometries, energies, and vibrational frequencies were obtained for all of the radicals considered. Structural perturbations along with energy relaxation due to radical formation were investigated. Dissociation energies of the G.C base pair and all of the radicals are predicted and compared with the dissociation energy of neutral G.C. The three lowest-energy base pair radicals all involve removal of an H atom from one of the N atoms in G.C. The lowest-energy base pair radical has the hydrogen atom removed from the guanine nitrogen atom used for the sugar phosphate linkage in DNA. This (G-H)(*)-C radical has a dissociation energy (to G-H(*) + C) of 30 kcal/mol, which may be compared with 27 kcal/mol for G.C. All of the radicals that are possible outcomes of direct ionizing radiation or oxidizing species were investigated for the presence of local minima with significant structural changes. Major structural deformations cause strain in the interstrand hydrogen bonding in the DNA double helix. Severe geometry changes were observed when the hydrogen was abstracted from interstrand hydrogen bonding sites, along with sizeable energy changes, indicating the potentially serious consequences to the G.C base pair.