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

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journal contribution
posted on 05.11.2015, 00:00 by Shoushan Wang, Changzhe Zhang, Peiwen Zhao, Yuxiang Bu
Possible electron-induced ruptures of C3′–O3′, C5′–O5′, and N1–C1′ 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 C2′ site of 2′-deoxyribose to the C6 site and the C3′–O3′ 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–C1′ bond cleavage in [3′-dT­(O4H)­MPH]. However, essentially spontaneous N1–C1′ 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–C1′ cleavage arises readily at the 3′-end of single strand DNA with the strand ended by a thymine. The C5′–O5′ 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 (C3′–O3′) vs 16.18 kcal/mol (N1–C1′)), but not change their relative efficiencies.