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.

A computational mechanistic study of the deamination reaction of melamine

“…The activation energy of the 1,3‐proton shift for the deamination of cytosine and guanine with OH − are lower with the respective values of 97 and 87 kJ mol −1 at G3MP2. The 1,3‐proton shift for deamination of adenine has an activation energy of 112 kJ mol −1 at G4MP2, which is comparable with this work on melamine to within 2 kJ mol −1 .…”

“…In comparison, the activation energy of the rate‐determining step ( TS1A ) for the deamination of cytosine and guanine with OH − are slightly lower with values of 148 and 155 kJ mol −1 at G3MP2, respectively. However, the activation energy of the rate‐determining step ( TS1A ) for the deamination of adenine is significantly higher, 189 kJ mol −1 at G4MP2 . The activation energy of TS1A is 185 kJ mol −1 at M06/6‐31G(d).…”

“…However, using the PCM and SMD solvation models, there is very little change in the overall activation energy of Pathway A . Previous theoretical studies of the deamination reaction of cytosine, guanine, isoguanine, adenine, and glutamine with hydroxide anion, both in the vacuum and in the presence of water, have clearly indicated that the energy barrier can be significantly reduced if the reaction occurs in the presence of one water molecule …”

“…Thomas and Kulkarni have found that melamine can interact with nucleobases, such as uracil by hydrogen bonding . Almatarneh and coauthors studied the deamination reaction of different nucleobases (adenine, cytosine, and guanine) and glutamine at different levels of theory . Uddin et al studied the deamination of cytosine, its cyclobutane cytosine dimer, and 5,6‐saturated cytosine analogues.…”

A Computational Study of the Ozonolysis of Phenanthrene

“…The previous works of the 1,3-proton shift has shown that the barrier could drop significantly when the water molecule is involved, acting as a mediator [53][54][55][56][57][58][59][60][61][62][63][64][65]. Figure 5 shows the one-step nucleophilic addition mechanism for the monohydrated reaction between the methanol and CI.…”