DFT Study of the Hydroxyl Radical Addition to 2'-Deoxyguanosine and the Guanine Base in Four Double-Stranded B-Form Dimers.

Abstract

Density functional theory (DFT) calculations of reactions between 2'-deoxyguanosine (dR-Gua) and hydroxyl radical (HO•) with water molecules (H2O)n, n = 0, 1, and 2, were carried out. The HO• addition to three carbon sites, C(4), C(5), and C(8), and the subsequent ring cleavage of the three HO adducts were investigated. The addition to C(5) is of the smallest activation energy according to the largest lobe of the dR-Gua highest occupied molecular orbital (HOMO) at C(5). However, its adduct has small stability, and the C(8) adduct has the largest one. The C(8) adduct and the ring-opened amide have similar stability, which would lead to the apparent small yield of the former. Calculations were also performed on HO• additions to the C(4) and C(8) sites of the guanine moiety of four dimer sequence models of B-form DNA with nucleotide moieties (a) 5'-GA-3', (b) 5'-GG-3', (c) 5'-GT-3', and (d) 5'-GC-3'. For instance, the (a) 5'-GA-3' model has a molecular formula C39H50N15Na2O21P2. The HO• attack to C(4) is ruled out owing to the reinforced deformation of the parallel stacking of base pairs. The clear selectivity that the (b) 5'-GG-3' sequence is most reactive was found with the inclusion of the water dimer.