Computational study on the deamination reaction of adenine with OH−/nH2O (n = 0, 1, 2, 3) and 3H2O

Abstract

Deamination of adenine is one of several forms of premutagenic lesions occurring in DNA. In the present study, mechanisms for the deamination reaction of adenine with OH−/nH2O (n = 0, 1, 2, 3) and 3H2O were investigated. HF/6-31G(d), B3LYP/6-31G(d), MP2/6-31G(d), and B3LYP/6-31+G(d) levels of theory were employed to search for and optimize all geometries. Energies were calculated at the G3MP2B3 and CBS-QB3 levels of theory. The effect of solvent (water) was computed using the polarizable continuum model (PCM). Intrinsic reaction coordinate (IRC) calculations were performed for all transition states. Five pathways were investigated for the deamination reaction of adenine with OH−/nH2O and 3H2O. The first four pathways (A–D) are initiated by deprotonation at the amino group of adenine by OH−, while pathway E is initiated by tautomerization of adenine. For all pathways the next two steps involve formation of a tetrahedral intermediate followed by dissociation to products via a 1,3-proton shift. Deamination with a single OH− has a high activation barrier (190 kJ mol−1 using the G3MP2B3 level) for the rate-determining step. The addition of one water molecule reduces this barrier by 68 kJ mol−1 at the G3MP2B3 level. Adding additional water molecules decreases the overall activation energy of the reaction, but the effect becomes smaller with each additional water molecule. The most plausible mechanism is pathway E, the deamination reaction of adenine with 3H2O, with an overall G3MP2B3 activation energy of 139 and 137 kJ mol−1 for the gas phase and PCM, respectively. This barrier is lower than that for the deamination with OH−/3H2O by 6 and 2 kJ mol−1 for the gas phase and PCM, respectively.