THEORETICAL CALCULATION OF TAUTOMER EQUILIBRIA OF 4-SUBSTITUTED IMIDAZOLES IN THE GAS-PHASE AND IN SOLUTION

The tautomer equilibrium of a number of 4-substituted imidazoles in the gas phase and in aqueous solution was calculated by combining quantum chemical ab initio calculations on the tautomers in the gas phase with classical electrostatics calculations (a continuum model and a Monte Carlo method with a limited number of discrete solvent molecules) to evaluate the solvation energy. The results were in good agreement with experimental data from N-15-NMR studies. It was found to be important to include counter ions in the calculations for imidazoles with a charged side chain. The methods for evaluation of the solvation energy were compared.