Stability of the guanine-cytosine radical cation in DNA base pairs triplets

To investigate the influence of flanking nucleic acid base pairs on the stability of the guanine-cytosine radical cation (GC+), ab initio Hartree-Fock calculations on 16 DNA base pair triplets were carried out using cc-pVDZ and cc-pVTZ basis sets. Furthermore, second order Møller-Plesset (MP2) correlation energy correction were computed using the cc-pVDZ basis set. The results from homodesmotic reactions suggest that GC+ is energetically most favored when being embedded by two neighboring GC base pairs, while the strongest destabilization of around 39 kJ mol−1 (9.2 kcal mol−1) occurs in the TGC triplet. The destabilization was also found to be dependent on the actual sequence where the nucleotide in 5′ position has a weaker influence than that in 3′ position. As effects from the DNA backbone and further environment are excluded, the results indicates that the strong localization of the positive charge on the middle GC base pair is dominated by electrostatic interactions. Consequences for the DNA in terms of susceptibility to mutations by oxidative damage and charge hopping are discussed.