Efficient and Substantial DNA Lesions From Near 0 eV Electron-Induced Decay of the O₄‑Hydrogenated Thymine Nucleotides: A DFT Study

Possible electron-induced ruptures of C_3′–O_3′, C_5′–O_5′, and N₁–C_1′ bonds in O₄-hydrogenated 2′-deoxythymidine-3′-monophosphate (3′-dT­(O4H)­MPH) and 2′-deoxythymidine-5′-monophosphate (5′-dT­(O4H)­MPH) are investigated using density functional theory calculations, and efficient pathways are proposed. Electron attachment causes remarkable structural relaxation in the thymine C₆ site. A concerted process of intramolecular proton transfer (IPT) from the C_2′ site of 2′-deoxyribose to the C₆ site and the C_3′–O_3′ bond rupture is observed in [3′-dT­(O4H)­MPH]⁻. A low activation barrier (9.32 kcal/mol) indicates that this pathway is the most efficient one as compared to other known pathways leading to backbone breaks of a single strand DNA at the non-3′-end thymine, which prevents the N₁–C_1′ bond cleavage in [3′-dT­(O4H)­MPH]⁻. However, essentially spontaneous N₁–C_1′ bond cleavage following similar IPT is predicted in [5′-dT­(O4H)­MPH]⁻. A moderate activation barrier (13.02 kcal/mol) for the rate-controlling IPT step suggests that base release from the N₁–C_1′ cleavage arises readily at the 3′-end of single strand DNA with the strand ended by a thymine. The C_5′–O_5′ bond has only an insignificant change in the IPT process. Solvent effects are found to increase slightly the energy requirements for either bond ruptures (11.23 kcal/mol (C_3′–O_3′) vs 16.18 kcal/mol (N₁–C_1′)), but not change their relative efficiencies