Valence Anion of Thymine in the DNA π-Stack

Abstract

Most of theoretical data on the stability of radical anions supported by nucleic acid bases have been obtained for anions of isolated nucleobases, their nucleosides, or nucleotides. This approach ignores the hallmark forces of DNA, namely, hydrogen bonding and pi-stacking interactions. Since these interactions might be crucial for the electron affinities of nucleobases bound in DNA, we report for the first time on the stability of the thymine valence anion in trimers of complementary bases possessing the regular B-DNA geometry but differing in base sequence. In order to estimate the energetics of electron attachment to a trimer, we developed a thermodynamic cycle employing all possible two-body interaction energies in the neutral and anionic duplex as well as the adiabatic electron affinity of isolated thymine. All calculations were carried out at the MP2 level of theory with the aug-cc-pVDZ basis set. The two-body interaction energies were corrected for the basis set superposition error, and in benchmark systems, they were extrapolated to the basis set limit and supplemented with correction for higher order correlation terms calculated at the CCSD(T) level. We have demonstrated that the sequence of nucleic bases has a profound effect on the stability of the thymine valence anion: the anionic 5'-CTC-3' (6.0 kcal/mol) sequence is the most stable configuration, and the 5'-GTG-3' (-8.0 kcal/mol) trimer anion is the most unstable species. On the basis of obtained results, one can propose DNA sequences that are different in their vulnerability to damage by low energy electron.

Electron transfer in DNA

“…The orbital energies of LUMO (lowest unoccupied molecular orbital) and LUMO+1 of neutral stacks may be used to estimate the driving force of EET44,47 The effect of neighboring basepairs on EA values in DNA stacks was studied using the AM1 method 64. The adiabatic EAs of short DNA stacks recently derived from MP2 calculations 65. It was shown that pyrimidine triplets, such as 5′‐T T T‐3′ or 5′‐C T C‐3′, are most easily reduced and their radical anion states should be nearly in resonance favoring efficient transport of the excess electron.…”

Electron Attachment to Hydrated Oligonucleotide Dimers: Guanylyl‐3′,5′‐Cytidine and Cytidylyl‐3′,5′‐Guanosine

“…[56][57][58][59][60][61][62][63][64][65][66][67][68][69] Recently, the electron affinities of the thymine-adenine base-pair stacking between different bases were studied by the "resolution of identity formulation of MP2" (RI-MP2) approach. [70] These investigations suggest that the pyrimidines in DNA fragments have a strong tendency to capture low-energy electrons and to form electronically stable radical anions. Both the presence of the ribose and phosphate backbones in DNA strands and water microsolvation greatly increase the electron affinities of the nucleobases.…”

Microsolvation of uracil anion radical in aqueous solution: a QM/MM study

“…Concerning the isomeric form of the uracil anion radical in aqueous solution, in a recent study [15] we have shown that the experimentally generated radical as observed by ESR spectroscopy [16] does correspond unequivocally to the canonical form, whereas a previous theoretical study [14] suggested that other tautomers would have been thermodynamically more favourable. Furthermore, there is a great interest on the identification of the structural factors that concur to stabilize/destabilize the excess electron on NAB radicals in complex environments and in DNA chains [17,18].…”