An ab initio quantum chemistry study on N-glycosidic bond stabilities of hydroxyl radical modified guanosine analogs

Abstract

Stabilities of N-glycosidic bond of N 9-methoxymethyl guanosine, 8-oxo-guanosine, xanthine and fapy-guanosine in its most abundant tautomeric forms were studied by means of ab inito quantum chemistry methods. Gibbs free energies were estimated for all possible mono- and double-protonated compounds based on B3LYP/6–31G** geometries with inclusion of water solvent effects. Estimated values of protonation probabilities as well as proton affinities allow for comparison of basicidies, N-glycosidic bond stabilities and hydrolysis mechanism for studied compounds. Significant changes of the protonation affinities of hydroxyl radical modified guanosine has been noticed. This in turn has impact on the N-glycosidic bond properties. The first protonation takes place mostly at N 3, N 7 and O 6 atoms, which seems to be most basic centers for guanosine analogs. However, depurination process for most probable protonated species is not thermodynamically favored. On the contrary, there was found strong thermodynamical stimulus in case of hydrolysis of directly protonated N 9 center. However, this center has very low basicidity, what practically prohibits spontaneous occurrence in acidic conditions. Thus, mechanism of N-glycosidic bond hydrolysis is not as straightforward as expected till now.