Mechanisms and energetics for N-glycosidic bond cleavage of protonated adenine nucleosides: N3 protonation induces base rotation and enhances N-glycosidic bond stability

N3 protonation induces base rotation and stabilizes the syn orientation of the adenine nucleobase of [dAdo+H]+ and [Ado+H]+via formation of a strong intramolecular N3H+⋯O5′ hydrogen-bonding interaction, which in turn influences the mechanisms and energetics for N-glycosidic bond cleavage.

Mechanisms and energetics for N-glycosidic bond cleavage of protonated 2′-deoxyguanosine and guanosine

TCID thresholds of [dGuo/Guo+H]+ indicate that 2′-hydroxyl strengthens glycosidic bond stability but slightly weakens the competition between the two primary dissociation pathways of [Guo+H]+vs. [dGuo+H]+.

THE INFLUENCES OF OXIDATION AND CATIONIZATION ON THE N-GLYCOSIDIC BOND STABILITY OF 8-OXO-2′-DEOXYADENOSINE — A THEORETICAL STUDY

This work is an attempt to evaluate theoretically the influences of oxidation and cationization on the N-glycosidic bond stability and the proton and sodium affinities on 8-oxo-2′-deoxyadenosine (8-oxodA) by using the density functional theory (DFT) B3LYP with basis set 6-31++G(d,p). This work shows that the cation attachment to 8-oxodA may modify the equilibrium geometry and bond dissociation. In all modified forms, the length of the N9–C1′ bond in which there is no intramolecular interaction, i.e. O8–H(Na)⋯O4′, increases relative to the neutral system 8-oxodA but that of others decreases. The analysis for the proton and sodium affinity energies indicates that the N1 and N3 atoms are the favorable sites for proton while the N1 atom is the favorable site for Na+. From the dissociation energies of the N-glycosidic bond, it has been found that the homolytic dissociation becomes more difficult upon introducing positive charge in the base ring. In contrast, these systems favor the heterolytic dissociation significantly. The influence is most prominent with the monocation obtained by O8 cationization.

Effect of 2'-Deoxyguanosine Oxidation at C 8 Position on N-Glycosidic Bond Stability

8-Oxo-2′-deoxyguanosine, 8-Oxoguanine, 8 -Hydroxyguanine, Base Modification, DNA Oxidative Damage The influence of 2′-deoxyguanosine (dG) oxidation at the C-8 position on N-glycosidic bond stability was in­ vestigated. A kinetic analysis of dG and 8-oxo-2′-deoxy-guanosine (8-oxodG) depurination reactions was carried out in water solutions at pH ranging from 2 to 7.4 and temperature of 100 °C. The results indicate that N-glyco­ sidic bond of 8-oxodG is significantly more stable in comparison with dG at any pH applied. At pH 5.1 hy­drolysis rate of dG is 4.5-fold higher than that for 8-oxodG. The chemical stability of the modified nucleo­ side in oxidatively damaged DNA is one of important factors contributing to its mutagenic potential. Results of our experiments indicate that 8-oxodG, potentially mutagenic and carcinogenic nucleoside, is hardly suscep tible to spontaneous depurination and its removal from cellular DNA depends mostly on the activity of DNA repair enzymes.