Computational Study of the Deamination Reaction of Cytosine with H₂O and OH^-

Abstract

The mechanism for the deamination reaction of cytosine with H(2)O and OH(-) to produce uracil was investigated using ab initio calculations. Optimized geometries of reactants, transition states, intermediates, and products were determined at RHF/6-31G(d), MP2/6-31G(d), and B3LYP/6-31G(d) levels and for anions at the B3LYP/6-31+G(d) level. Single-point energies were also determined at B3LYP/6-31+G(d), MP2/GTMP2Large, and G3MP2 levels of theory. Thermodynamic properties (DeltaE, DeltaH, and DeltaG), activation energies, enthalpies, and free energies of activation were calculated for each reaction pathway that was investigated. Intrinsic reaction coordinate analysis was performed to characterize the transition states on the potential energy surface. Two pathways for deamination with H(2)O were found, a five-step mechanism (pathway A) and a two-step mechanism (pathway B). The activation energy for the rate-determining steps, the formation of the tetrahedral intermediate for pathway A and the formation of the uracil tautomer for pathway B, are 221.3 and 260.3 kJ/mol, respectively, at the G3MP2 level of theory. The deamination reaction by either pathway is therefore unlikely because of the high barriers that are involved. Two pathways for deamination with OH(-) were also found, and both of them are five-step mechanisms. Pathways C and D produce an initial tetrahedral intermediate by adding H(2)O to deprotonated cytosine which then undergoes three conformational changes. The final intermediate dissociates to product via a 1-3 proton shift. Deamination with OH(-), through pathway C, resulted in the lowest activation energy, 148.0 kJ/mol, at the G3MP2 level of theory.

High level ab initio, DFT, and RRKM calculations for the unimolecular decomposition reaction of ethylamine

“…A c c e p t e d M a n u s c r i p t 4 It is produced on a large scale by combining ethanol and ammonia in the presence of an oxide catalyst [6]. Ethylamine is miscible with virtually all solvents and considered a good solvent for lithium metal, which is used for the reduction of unsaturated organic compounds [7].…”

“…4. In this pathway, a 1,3-proton shift occurs in the opposite direction where the proton transfers from the amino group to the methyl group to yield CH 2 =NH and CH 4 .…”

Theoretical study of water-assisted hydrolytic deamination mechanism of adenine

“…The base deamination has been studied extensively [1][2][3][4][5], in which few are about the water-assisted hydrolytic deamination. Zhang et al [4] have studied the hydrolytic deamination of adenine with 1-4 water molecules at B3LYP/6-31G(d,p) level.…”

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.…”