Theoretical study of proton-catalyzed hydrolytic deamination mechanism of adenine

Water-assisted proton-catalyzed hydrolytic deamination of adenine to produce hypoxanthine has been studied using density functional theory method. Because adenine could be protonated at N1, N3, N7 and N10, four pathways initiated from the four different protonated adenines have been investigated. The first step of the four pathways is the nucleophilic attack of water with an assistant water to form a tetrahedral structure complex, and this is the rate-determining step. Including solvent effects decreased the relative energies of stationary points but have little effect on the structures. Pathway A is preferred due to the lowest energy barrier, and the relative free energy is 28.9 kcal/mol in vacuo. The outcomes show that adenine deamination under acidic condition is much easier to occur than under neutral condition due to lower energy barriers. The total atomic charge of C5 in the initial intermediate is correlated with the ease of deamination reaction. The more positive C5 atom is, the easier the deamination reaction is.