Modeling irradiative damage to DNA
Lind, Maria C.
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Hydrogen-abstracted and deprotonated structures of the two DNA base pairs, guanine-cytosine and adenine-thymine (G-C and A-T), have been studied using Density Functional Theory (DFT). Such structures are of interest as products created along the radiation track which results in damage to living cells. DFT is well-suited to provide reliable predictions both for optimized geometries for systems of this size, as well as electronic properties and relative energies. For the various deprotonated G-C base pair structures, the most stable pair results from the loss of a proton analogous to the glycosidic bond (which connects base to the sugar-phosphate backbone in double-stranded DNA) and corresponds to the hydrogen-abstracted radical with the greatest adiabatic electron affinity, 3.65 eV. The most stable A-T radical results from loss of a hydrogen atom from thymine's methyl group. The next two most stable structures, lying only about 1 kcal mol apart, result from a loss of hydrogen at the sites analogous to the two glycosidic bonds. In general, hydrogen-abstracted radicals of the A-T base pair exhibited fewer geometric perturbations than the G-C structures, despite having only two hydrogen bonds connecting the pair. The energetic interleaving of the H-abstracted individual bases adenine and thymine are found to be the same as those for the hydrogen bonded pair, suggesting that predictions made for smaller fragments may be extrapolated to larger systems. Additionally, the electronic ground states (X1 Sigma+) of HNSi, HSiN, and the transition state connecting the two isomers were systematically studied using highly correlated ab initio methods in conjunction with large correlation consistent type basis sets. The HNSi isomer has been confirmed to be the global minimum on the ground state HSiN-HNSi surface and is predicted to lie 65.4 kcal/mol below the HSiN isomer at the aug-cc-pCVQZ CCSD(T) level of theory. The barrier height for the isomerization reaction (HNSi - HSiN) is determined to be 79.6 kcal/mol.