Molecular Similarity Based on Atomic Electrostatic Potential

Abstract

We propose a new similarity measure operating in the space spanned by the potential values, evaluated at atoms constituting the benzene ring and the COOH group in para-substituted benzoic acids and at benzene ring atoms in monosubstituted benzenes. The similarity measures are equivalent to the Euclidean distance between points in that space. Only the distances between the potentials at corresponding atoms in different molecules are included. The distances for benzene rings were very similar, regardless of whether they were calculated in para-substituted acids or in monosubstituted benzenes. As reference reactions, dissociation of benzoic acids and nitration of monosubstituted benzenes have been used. The effects of reduction of dimensionality of the potential space on the comparison of similarity measures with the free energies of the reference reactions have been investigated. It became obvious that the potentials at individual atoms in molecules of the acids and monosubstituted benzenes are mutually correlated to a high degree.