Mechanistic Study of the Deamination Reaction of Guanine: A Computational Study

The mechanism for the deamination of guanine with H2O, OH-, H2O/OH- and for GuaH(+) with H2O has been investigated using ab initio calculations. Optimized geometries of the reactants, transition states, intermediates, and products were determined at RHF/6-31G(d), MP2/6-31G(d), B3LYO/6-31G(d), B3LYP/6-31+G(d) levels of theory. Energies were also determined at G3MP2, G3MP2B3, G4MP2, and CBS-QB3 levels of theory. Intrinsic reaction coordinate (IRC) calculations were performed to characterize the transition states on the potential energy surface. Thermodynamic properties (Delta E, Delta H, and Delta G), activation energies, enthalpies, and Gibbs free energies of activation were also calculated for each reaction investigated. All pathways yield an initial tetrahedral intermediate and an intermediate in the last step that dissociates to products via a 1,3-proton shift. At the G3MP2 level of theory, deamination with OH- was found to have an activation energy barrier of 155 kJ mol(-1) compared to 187 kJ mol(-1) for the reaction with H2O and 243 kJ mol(-1) for GuaH(+) with H2O. The lowest overall activation energy, 144 kJ mol(-1) at the G3MP2 level, was obtained for the deamination of guanine with H2O/OH-. Due to a lack of experimental results for guanine deamination, a comparison is made with those of cytosine, whose deamination reaction parallels that of guanine.