Optimization of molecular cavities in the PCM of neutral molecules using charge dependent atomic radii: applications to the semi-empirical AM1 and MNDO/PM3 methods

An improvement in the results from the polarizable continuum model (PCM), when coupled to the AM1 and MNDO/PM3 semi-empirical methods, has been obtained by an optimization of the molecular cavities using charge-dependent atomic radii. A set of neutral molecules, containing different functional groups, was used to parametrize functions relating Mulliken atomic net charges to atomic radii. Another set of neutral molecules was utilized to test these functions. The RMS errors in free energy of hydration were 0.47 kcal mol−1 for AM1 and 0.74 kcal mol−1 for MNDO/PM3.