Abstract
In this work, we used ωB97XD density functional and 6-31++G** basis set to study the structure, electron affinity, populations via Boltzmann distribution, and one-electron reduction potentials (E°) of 2′-deoxyribose sugar radicals in aqueous phase by considering 2′-deoxyguanosine and 2′-deoxythymidine as a model of DNA. The calculation predicted the relative stability of sugar radicals in the order C4′• > C1′• > C5′• > C3′• > C2′•. The Boltzmann distribution populations based on the relative stability of the sugar radicals were not those found for ionizing radiation or OH-radical attack and are good evidence the kinetic mechanisms of the processes drive the products formed. The adiabatic electron affinities of these sugar radicals were in the range 2.6–3.3 eV which is higher than the canonical DNA bases. The sugar radicals reduction potentials (E°) without protonation (−1.8 to −1.2 V) were also significantly higher than the bases. Thus the sugar radicals will be far more readily reduced by solvated electrons than the DNA bases. In the aqueous phase, these one-electron reduced sugar radicals (anions) are protonated from solvent and thus are efficiently repaired via the “electron-induced proton transfer mechanism”. The calculation shows that, in comparison to efficient repair of sugar radicals by the electron-induced proton transfer mechanism, the repair of the cyclopurine lesion, 5′,8-cyclo-2′-dG, would involve a substantial barrier.
Highlights
Cellular DNA is damaged by ionizing radiation [1,2,3,4,5,6,7,8,9,10,11] as well as by reactive oxygen species (ROS) [12,13] such as O2, 1 O2, O2 −, OH, NO, NO2, ONOO−, H2 O2, and peroxy radicals (ROO )
Since these sugar radicals were formed predominantly along the ion track, where excitations and ionizations are in proximity, it was proposed that base cation radicals in excited states could be the direct precursors of the neutral sugar radicals [14,15]
To test the proposed repair mechanism of Razskazovskii et al [59], we explored the reaction of one-electron reduced sugar radicals with water and found that these reduced sugar radicals are protonated from solvent
Summary
Cellular DNA is damaged by ionizing radiation [1,2,3,4,5,6,7,8,9,10,11] as well as by reactive oxygen species (ROS) [12,13] such as O2 , 1 O2 , O2 •− , OH• , NO• , NO2 • , ONOO− , H2 O2 , and peroxy radicals (ROO• ). Radiation and ROS act synergistically to cause far more damage than each separately [10]. Initially, radiation randomly ionizes each building block of DNA (bases, deoxyribose, and phosphate) and the surrounding water molecules randomly to produce highly reactive ion radicals [2,4,5,6,7,8,9,10,11]. The study of the mechanisms of formation and subsequent reaction of these transient ion radicals is of fundamental importance to the understanding of the extent of DNA damage and related consequences. As an example, irradiations of DNA by a high-energy argon ion-beam (high linear-energy-transfer (LET)radiation) and γ-irradiation (a low LET radiation) both produced significant fractions of sugar radicals with the ion-beam irradiated DNA showing a greater fraction than γirradiation [14]. Since these sugar radicals were formed predominantly along the ion track, where excitations and ionizations are in proximity, it was proposed that base cation radicals in excited states could be the direct precursors of the neutral sugar radicals [14,15].
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