Quantum theoretical study of mechanism of the reaction between guanine radical cation and carbonate radical anion: Formation of 8‐oxoguanine

Abstract

ABSTRACT:The reaction between guanine radical cation (G þÁ ) and carbonate radical anion (CO 3 ÀÁ ) producing the mutagenic product 8-oxoguanine that has been observed experimentally was investigated using density functional and second-order Møller-Plesset perturbation (MP2) theories. The structures of reactant, intermediate, and product complexes as well as those of the transition states were fully optimized at the B3LYP/6-31G**, B3LYP/AUG-cc-pVDZ, and BHandHLYP/AUG-cc-pVDZ levels of density functional theory in gas phase. Single point energy calculations were performed at the MP2/AUG-cc-pVDZ level using the BHandHLYP/AUG-cc-pVDZ level gas-phase optimized geometries. To obtain the equivalent solvent that would approximately represent the complex medium used in the experimental study, bulk solvent effect on the stability of the reactant complex was studied by single point energy calculations in various solvent media (toluene, chlorobenzene, dichloroethane, acetone dimethylsulfoxide, and water) using the polarizable continuum model. Thus, chlorobenzene was found to represent the experimental medium fairly closely. The calculated Gibbs free barrier and released energies show that the reaction under consideration would occur efficiently. V

Computational Study of the Formation of C8, C5, and C4 Guanine:Lysine Adducts via Oxidation of Guanine by Sulfate Radical Anion

“…The oxidation of guanine and subsequent reactions of guanine radical have been investigated computationally by a number of groups. − Sevilla and co-workers have studied guanine oxidation and reduction, protonation and deprotonation of guanine radical, and hydroxyl radical addition to guanine. − We have examined the reactions of guanine radical to form 8-oxoG , Sp , Gh , and FAPyG − and the p K a ’s and redox potentials of the intermediates in these pathways. − We have also studied the formation of guanine–thymine cross-links during oxidation by carbonate radical anion and the formation of guanine–lysine cross-links resulting from oxidation mediated by type I and type II photosensitizers. , Dumont and co-workers have investigated DNA–polyamine binding modes and cross-link formation, peroxy radical addition to guanine, and singlet oxygen reactions with guanine. − Liu and co-workers have used electronic structure calculations and guided ion beam mass spectrometry to examine water addition and singlet oxygen addition to guanine and its subsequent reactions. − The formation of 8-aminoguanine and its oxidized and reduced forms have been studied both computationally and experimentally…”

“…Wetmore, Boyd, and co-workers have calculated OH and NO 2 radical addition to nucleobases, as well as ionization potentials and electron affinities of individual nucleobases. − Rothlisberger and co-workers have computed ionization energies and electron affinities of guanine and 8-oxoG in two and three base pair fragments of DNA . Mishra and co-workers have published numerous studies of guanine oxidation by reactive oxygen species. − Nevertheless, computational studies of the formation of guanine–lysine cross-links are rather limited. ,,, …”

Computational Study of the pH-Dependent Competition between Carbonate and Thymine Addition to the Guanine Radical

“…32−35 Wetmore, Boyd, and co-workers have calculated ionization potentials and electron affinities of nucleobases, 64 NO 2 radical addition to guanine radical, 65 and hydroxyl radical addition to nucleobases. 66 Mishra and co-workers have published numerous studies of guanine oxidation by reactive oxygen species, 67−82 including the oxidation of guanine and 8oxoG with carbonate radical, 67 addition of carbonate radical to guanine radical, 68,69 as well as NO 2 and OH radical reactions with guanine. 70,71 Ding and co-workers have used molecular dynamics to investigate the structure and stability of guaninethymine cross-link products in double strand DNA.…”

“…A number of computational studies have addressed the reactions of guanine radical. ,,,− Sevilla and co-workers have investigated guanine oxidation and reduction, protonation and deprotonation of guanine radical, and hydroxyl radical adding to guanine. − We have used DFT calculations to examine the mechanisms for the formation of 8oxoG, Sp, Gh, and FAPyG from guanine radical, , the formation of guanine-lysine cross-links during oxidation mediated by type I and type II photosensitizers, , and the p K a ’s and redox potentials of nucleobases and intermediates in the pathway from guanine radical to Sp and Gh. − Dumont and co-workers have investigated the addition of singlet oxygen to guanine to form 8oxoG and Sp. − Liu and co-workers have used guided ion beam mass spectrometry and density functional calculations to examine gas-phase singlet oxygen reactions with guanine and its oxidation products. − Wetmore, Boyd, and co-workers have calculated ionization potentials and electron affinities of nucleobases, NO 2 radical addition to guanine radical, and hydroxyl radical addition to nucleobases . Mishra and co-workers have published numerous studies of guanine oxidation by reactive oxygen species, − …”