Imidazole in Aqueous Solution: Hydrogen Bond Interactions and Structural Reorganization with Concentration

The structural and dynamic properties of imidazole in aqueous solution have been studied by means of classical and ab initio molecular dynamics simulations. We developed a new force field for the imidazole molecule with improved modeling of the electrostatic interactions, specifically tailored to address the well-known drawbacks of existing force fields based on the atomic fractional charge approach. To this end, we reparametrized the charge distribution on the heterocyclic ring, introducing an extra site accounting for the lone pair on the deprotonated nitrogen. The accuracy of the model in describing the hydrogen bond pattern in the aqueous solvent has been confirmed by comparing the classical results on imidazole–water interactions to accurate Car–Parrinello molecular dynamics simulations. It reproduces satisfactorily the experimental water/octanol partition coefficient of imidazole, as well as the structure of the imidazole molecular crystal. The force field has been finally applied to simulate aqueous solutions at various imidazole concentrations to obtain information on both imidazole–water and imidazole–imidazole interactions, providing a description of the different molecular arrangements in solution