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

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.

Crystal and geometry-optimized structure of an anthracene-based Diels-Alder adduct.

Computational calculations of an anthracene-based Diels-Alder adduct, namely, 17-ethyl-1-hydroxymethyl-17-azapentacyclo[6.6.5.02,7.09,14.015,19]nonadeca-2,4,6,9,11,13-hexaene-16,18-dione, C21H19NO3, predicting density functional theory (DFT) optimized geometries in the gas phase are compared in terms of accuracy relative to the solid-state crystal structure and computational cost. Crystal structure determination and Hirshfeld surface analysis of the racemic product reveal that the molecules are linked by O-H...O=C hydrogen bonds between the hydroxy and carbonyl groups, accounting for 9.5% of the intermolecular contacts, while H...H contacts represent 56.9% of the total. Boltzmann population analysis of computed relative rotamer abundances in the gas phase are based on lower-level geometry optimization and thermochemical corrections coupled with higher-level electronic energy calculations using the B2PLYP double-hybrid functional. As expected, the choice of density functional has a greater effect than the basis set on accuracy for all levels of theory. For any given functional, increasing the basis set size did not always correlate with increasingly accurate structures. The hybrid functional B3LYP without dispersion correction routinely gave the closest approximations to the crystal structure where the B3LYP/aug-cc-pVDZ combination afforded the best structure (r.m.s. deviation = 0.1314 Å). However, the B3LYP/6-31+G(d,p) level of theory represents the best compromise between accuracy (r.m.s. deviation = 0.1388 Å) and cost as it yielded appreciably accurate results in a fraction of the time compared to other method combinations.