Hydrolysis of adenosine. A semiempirical and ab initio study

Abstract

The electron distributions, proton affinities and energies of the heterolytic fission of the N-glycosidic bond of adenosine, 3-methyladenosine and a set of related model compounds have been calculated by semiempirical and ab initio methods. In the gas phase the preferred site of protonation in adenosine is nitrogen N3 of the adenine ring, the N1 site being almost as basic. In solution solvent effects change the order, making N7 the preferred protonation site. The 3-methyladenosinium ion is most likely protonated at N7. The net atomic charges of the skeleton atoms, in particular in the N-glycosidic bond, are not markedly affected by protonation (or by N3 methylation). Yet the electron density of this bond is decreased and the bond is hence weakened. The influence is most prominent with the monocations obtained by N7 protonation or N3 methylation. The previously reported variations of reaction rates are discussed on the basis of these results.