The Influence of 2'-Deoxyguanosine Lesions on the Electronic Properties of OXO G:::C Base Pairs in Ds-DNA: A Comparative Analysis of Theoretical Studies.

DNA is continuously exposed to a variety of harmful factors, which, on the one hand, can force undesirable processes such as ageing, carcinogenesis and mutagenesis, while on the other hand, can accelerate evolutionary changes. Of all the canonical nucleosides, 2'-deoxyguanosine (dG) exhibits the lowest ionization potential, making it particularly prone to the one-electron oxidizing process. The most abundant type of nucleobase damage is constituted by 7,8-dihydro-8-oxo-2'-deoxyguanosine ( OXO dG), with an oxidation potential that is 0.56 V lower than that of canonical dG. All this has led to OXO dG, as an isolated lesion, being perceived as a sink for radical cations in the genome. In this paper, a comparative analysis of the electronic properties of an OXO GC base pair within the context of a clustered DNA lesion (CDL) has been conducted. It is based on previous DFT studies that were carried out at the M06-2x/6-31++G** level of theory in non-equilibrated and equilibrated condensed phases. The results of the comparative analysis presented here reveal the following: (A) The ionization potentials of OXO G 4 C 2 were largely unaffected by a second lesion. (B) The positive charge and spin were found predominantly on the OXO G 4 C 2 moiety. (C) The electron-hole transfers A 3 T 3 →G 4 C 2 and G 4 C 2 ←A 5 T 1 were found in the Marcus inverted region and were resistant to the presence of a second DNA lesion in close proximity. It can therefore be reasonably postulated that OXO GC becomes the sink for a radical cation migrating through the double helix, irrespective of the presence of other 2'-deoxyguanosine lesions in the CDL structure.