π- vs σ-Radical States of One-Electron-Oxidized DNA/RNA Bases: A Density Functional Theory Study

Abstract

As a result of their inherent planarity, DNA base radicals generated by one electron oxidation/reduction or bond cleavage form π- or σ-radicals. While most DNA base systems form π-radicals there are a number of nucleobase analogs such as one-electron oxidized 6-azauraci1, 6-azacytosine, and 2-thiothymine or one-electron reduced 5-bromouracil that form more reactive σ-radicals. Elucidating the availability of these states within DNA, base radical electronic structure is important to the understanding of the reactivity of DNA base radicals in different environments. In this work, we address this question by the calculation of the relative energies of π- and σ-radical states in DNA/RNA bases and their analogs. We used density functional theory B3LYP/6-31++G** method to optimize the geometries of π- and σ-radicals in Cs symmetry (i.e., planar) in the gas phase and in solution using the polarized continuum model (PCM). The calculations predict that σ- and π-radical states in one electron oxidized bases of thymine, T(N3-H)•, and uracil, U(N3-H)• are very close in energy, i.e., the π-radical is only ca. 4 kcal/mol more stable than the σ-radical. For the one electron oxidized radicals of cytosine, C•+, C(N4-H)•, adenine, A•+, A(N6-H)•, and guanine, G•+, G(N2-H)•, G(N1-H)• the π-radicals are ca. 16 to 41 kcal/mol more stable than their corresponding σ-radicals. Inclusion of solvent (PCM) is found to stabilize the π- over σ-radical of each of the systems. U(N3-H)• with three discrete water molecules in the gas phase, is found to form a three-electron σ bond between N3 atom of uracil and O atom of a water molecule but on inclusion of full solvation and discrete hydration the π-radical remains most stable..

Electron-Induced Repair of 2′-Deoxyribose Sugar Radicals in DNA: A Density Functional Theory (DFT) Study

“…The ωB97XD-PCM/6-31++G**-calculated spin density plots of sugar radicals of 2′-dG and highest occupied molecular orbital (HOMO) of their corresponding anions are presented in Figure 1 and of those of 2′-dT are presented in the supporting information as Figure S1 . For a radical species (odd electron system) the spin density distributions presented as a 3-dimensional visual plot characterize the nature of odd electron distributions [ 88 ] within the molecule. The anion, produced by one-electron reduction of a radical, is an even electron system and HOMO plot of anion gives the visual information about the perturbation induced to the radical after an excess electron attachment.…”

Gamma and ion-beam irradiation of DNA: Free radical mechanisms, electron effects, and radiation chemical track structure

“…We note here that experiments and calculations employing density functional theory (DFT) show that π-type DNA-base cation radicals from a DNA base (G• + , A• + , C• + , T• + ) or modified analog are almost always lower in energy than the σ-type radical (Adhikary et al, 2015; Kumar and Sevilla, 2013). However, the σ-states of C• + and T• + are predicted to be energetically closer to their lower-lying π-states than the σ-states of G• + and A• + are to their respective low lying π-states (Adhikary et al, 2015; Kumar and Sevilla, 2013).…”

“…However, the σ-states of C• + and T• + are predicted to be energetically closer to their lower-lying π-states than the σ-states of G• + and A• + are to their respective low lying π-states (Adhikary et al, 2015; Kumar and Sevilla, 2013). …”

Radiation Induced One-Electron Oxidation of 2-Thiouracil in Aqueous Solutions

“…A series of papers was published in recent five years addressing the dissociative electron attachment to 2-thiouracil (2-TU) and 2-thiothymine in gas-phase and showing that the fragmentation of these molecules arises mainly at the sulfur site [35,36,37,38,39,40]. Some attention was also paid to electron paramagnetic resonance (EPR) studies [41,42,43,44,45,46,47,48,49] combined with DFT calculations [50,51,52] of radicals derived from γ-irradiated single crystals of sulfur-substituted nucleobases.…”