An ab initio theoretical study of electronic structure and properties of 2′‐deoxyguanosine in gas phase and aqueous media

Abstract

Molecular geometries of two structural forms of 2'-deoxyguanosine (keto-N9R and keto-N7R, R = the sugar moiety) considering both the C2'-endo and C3'-endo conformations of the sugar ring and those of the complexes of these species with two water molecules each were optimized employing the ab initio RHF procedure. A mixed basis set consisting of the 6-311+G* basis set for the nitrogen atom of the amino group and the 4-31G basis set for all the other atoms was used. The RHF calculations were followed by correlation correction of the total energy at the MP2 level. Both the structural forms of 2'-deoxyguanosine were solvated using the polarized continuum model (PCM) of the self-consistent reaction field (SCRF) theory and the corresponding RHF optimized geometries at the RHF and MP2 levels. Geometry optimization was also performed in aqueous media using the Onsager model at the RHF level using the above-mentioned mixed basis set, and subsequently, using the reoptimized geometries, single-point MP2 calculations were performed. It is found that both the keto-N9R and keto-N7R forms of 2'-deoxyguanosine as well as their complexes with two water molecules each would occur, particularly at the water-air interface. Though the normal Watson-Crick-type base pairing would not be possible with the keto-N7R form of 2'-deoxyguanosine(G*), two other (G*-C and G*-T) base pairing schemes may occur with this form of the nucleoside, which may cause mutation. The present calculated geometry of the keto-N9R form of the anti-conformation of 2'-deoxyguanosine including the dihedral angle chi(CN) agree satisfactorily with the available crystallographic results. The present results also agree satisfactorily with those obtained by other authors earlier for the keto-N9R form of 2'-deoxyguanosine using B3LYP and MP2 methods employing the 6-31G* basis set. Using transition state calculations, it is shown that tautomerism of guanine and other similar molecules where the tautomers would coexist would be facilitated by the occurrence of the H(+) and OH(-) fragments of water molecules. Further, this coexistence of the two tautomers appears to make the C8 carbon atom located between the N7 and N9 nitrogen atoms susceptible to attack by the OH(-) group. Thus, an explanation is obtained for the efficient formation of the reaction product 8-hydroxy-2'-deoxyguanosine, which serves as a biomarker for oxidative damage to DNA in biological systems.

Flexible 5-Guanidino-4-nitroimidazole DNA Lesions: Structures and Thermodynamics

“…The same method as in the base level study was employed to perform QM geometry-optimization. The gas phase geometry-optimized structures produced a non-planar NI amino group, as is usually the case for such computed structures (44,45). However, in all crystal structures of guanines and adenines, these groups are planar (46)(47)(48), and we therefore remodeled them to be planar for the next stage of our studies involving the modified DNA duplexes.…”

Reactivities of radicals of adenine and guanine towards reactive oxygen species and reactive nitrogen oxide species: OH and NO2

“…Modified DNA bases e.g. 8-oxo and 8-nitro derivatives of guanine and adenine are formed due to attack of OH Å , NO 2 Å or other ROS or RNOS on the bases or due to their ultraviolet or high energy irradiation [12,[20][21][22][23][24][25][26][27][28][29]. Oxidative modifications of DNA bases can also be produced due to nucleophilic attack of water molecule at the C8 site of the guanine radical cation leading to the formation of 8-hydroxyguanine radical which can transform to 8-oxoG [30].…”

Nuclear localization of the zebrafish tight junction protein nagie oko

“…Deoxyribonucleosides as the fundamental building blocks of DNA have attracted considerable attentions in recent years. A number of experimental studies 1–12 and theoretical investigations 13–35 have been carried out to explore ground‐state properties of isolated nucleosides, such as structural features, relative energies, electron and proton affinities both in the gas phase and in the condensed phase.…”