An application of the Miertus-Scrocco-Tomasi solvation model in molecular mechanics and dynamic simulations

The point-chart approximation of the Miertus-Scrocco-Tomasi solvation model (MST-PC) based on a continuum representation of the solvent has been incorporated in force field calculations. Application in molecular mechanics (MM) involves conformational equilibria in solution: rotational isomers of ethylene glycol (I), 1,2-difluoreothane (II), fluoroacetic acid (III), and representative conformers of macrocyclic receptors such as 18-crown-6 (IV), cryptand 2.2.2 (V), and t-butyl-calix[4]arenetetraamide (VI). Assessment of the MST-PC results is based on the comparison with ab initio reactive field calculations (for I-III), with the continuum model of Still (W. C. Still et al., J. Am. Chem. Soc., 1990, 112, 6127) (for I-VI), and with average solute-solvent interaction energies obtained from molecular dynamics (MD) simulations with explicit solvent in water (I-VI) and in acetonitrile (IV-VI). It is demonstrated that the continuum solvent model qualitatively reproduces the trends in solvation energies in water. The few exceptions may be related to particular topological features of the solute. An improved discrete/continuum approach in which some first-shell solvent molecules are considered as a part of the solute embedded in the dielectric continuum provides more realistic results, as is shown for VI in water. The MST-PC model which mimics the solute-solvent electrostatic interaction only fails to reproduce conformationally dependent solvation energies in acetonitrile, in which the electrostatic contribution is relatively small compared to van der Waals interactions. Exploratory MD simulations within the continuum model in water are reported on urea and 18-crown-6.