Does the Molecular Electrostatic Potential Reflect the Effects of Substituents in Aromatic Systems?

A detailed analysis of the molecular electrostatic potential (MEP) at selected positions in molecular space was performed for a series of substituted benzene derivatives. We show that appropriately selected MEP values can quantitatively reflect the regiospecific effects of substituents on the aromatic ring. Theoretically evaluated electrostatic potentials in close proximity to the ring carbon atoms reflect well both through-space and resonance effects and excellent correlation is established between the MEP values and substituent constants. The best descriptor of the local properties at different ring positions is the electrostatic potential at nuclei (EPN).