Formation of 5′,8-cyclo-2′-deoxyadenosine in dA::T pairs as a model of double stranded DNA: A theoretical quantum mechanics study

Reactions of a hydroxyl radical with nucleotides may lead to the generation of radicals in DNA components. In this study emphasis was placed on the consideration of the possible reaction of 2′-deoxyadenosine radicals involved in the structure of dA::T nucleoside pairs leading to the formation of related 5′,8-cyclo-2′-deoxyadenosine (cdA) as part of a cdA::T pair. It has been shown by several authors that 5′R and 5′S diastereomers of the cdA are formed with different frequency in nucleoside, single and double-stranded DNA. In this theoretical quantum mechanics study, the (5′S)cdA::T was found to be the most stable; moreover, the investigated paths of the reaction showed the energetic preferential of (5′S)cdA::T nucleoside pairs formation in both the aqueous and gaseous phase. Therefore the presented results are in good agreement with experimental data. Additionally, the fluctuations of charge distribution and dipole moment as well as the strength of hydrogen bonds of the discussed cdA::T pairs are presented.