Monte Carlo investigations of solvent effects on the decarboxylation reaction of neutral N-carboxy-2-imidazolidinone in aqueous solution

The solvent effects on the decarboxylation reaction of neutral N-carboxy-2-imidazolidinone in aqueous solution have been investigated by a combined quantum mechanical and molecular mechanical (QM/MM) Monte Carlo simulation method. In the present approach, the gas-phase intrinsic reaction coordinate of the reaction was first obtained by ab initio molecular orbital calculations at the RHF/6-31+G(d) level. Then, the potential of mean force for the decarboxylation reaction was determined via statistical perturbation theory using the combined QM/MM-AM1/TIP3P potential in Monte Carlo simulations. A two-stage mechanism consisting of the intramolecular proton transfer and N-C bond cleavage with the N-C bond breaking as the rate-limiting step was found. The computed free energy of activation in water is 21.0 +/- 0.2 kcal/mol, in good agreement with the experimental value of 20.7 kcal/mol. Analyses of the structural and energetic nature of the differential solvation along the reaction coordinate are presented.