| Abstract
| - The mechanism for the deamination reaction of cytosine with H2O and OH- to produce uracil was investigatedusing ab initio calculations. Optimized geometries of reactants, transition states, intermediates, and productswere 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, andG3MP2 levels of theory. Thermodynamic properties (ΔE, ΔH, and ΔG), activation energies, enthalpies, andfree energies of activation were calculated for each reaction pathway that was investigated. Intrinsic reactioncoordinate analysis was performed to characterize the transition states on the potential energy surface. Twopathways for deamination with H2O 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 intermediatefor 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 ofthe high barriers that are involved. Two pathways for deamination with OH- were also found, and both ofthem are five-step mechanisms. Pathways C and D produce an initial tetrahedral intermediate by adding H2Oto deprotonated cytosine which then undergoes three conformational changes. The final intermediate dissociatesto product via a 1−3 proton shift. Deamination with OH-, through pathway C, resulted in the lowest activationenergy, 148.0 kJ/mol, at the G3MP2 level of theory.
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