Ab Initio Study of 4(5)-Methylimidazole in Aqueous Solution

Abstract

The properties of the two tautomers of 4(5)-methylimidazole in aqueous solution have been studied through theoretical calculations using ab initio methods and various solvent models. We focus this study on the environmental effects due to cooperative solute−solvent interactions. The modifications of the tautomeric equilibrium and pKa value through hydrogen-bond formation and electrostatic solvation effects are discussed. The computations show that the polarizable continuum model of the solvent is able to give reasonable results for these properties. The prediction of absolute values of pKa is difficult, but relative values are reproduced quite well. We also consider a discrete-continuum model for the solution, but we show that this model leads to slightly stable (or unstable) complexes. Our results stress the importance of nonadditive energy contributions, which are presumably fundamental in order to explain the mechanism of several biological processes involving histidine residues.