Molecular electrostatic potential analysis: A powerful tool to interpret and predict chemical reactivity

Abstract The molecular electrostatic potential (MESP) V ( r ) data derived from a reliable quantum chemical method has been widely used for the interpretation and prediction of various aspects of chemical reactivity. A rigorous mapping of the MESP topology is achieved by computing both ∇ V ( r ) data and the elements of the Hessian matrix at the critical points where ∇ V ( r ) = 0. In the MESP topology, intra‐ and inter‐molecular bonded regions show the characteristic (3, −1) bond critical points (BCPs) while the electron‐rich regions such as lone pair and π ‐bonds show (3, +3) minimum ( V min ) CPs. The V min analysis provides a simple and powerful technique to characterize the electron‐rich region in a molecular system as it corresponds to the condensed information of the wave function at this point due to the nuclei and electronic distribution through the Coulomb's law. The V min analysis has been successfully applied to explain the phenomena related to chemical reactivity such as π ‐conjugation, aromaticity, substituent effect, ligand electronic effects, trans‐influence, redox potential, activation energy, cooperativity, noncovalent interactions, and so on. The MESP parameters ∆ V min and ∆ V n , derived for arene systems have been used as powerful measures of substituent effects while V min at the lone pair region of ligands has been used as a reliable electronic parameter to assess their σ‐donating ability to metal centers. Furthermore, strong predictions on the intermolecular interactive behavior of molecular systems can be made from MESP topology studies. This review summarizes the chemical reactivity applications offered by MESP topology analysis for a large variety of organic, organometallic, and inorganic molecular systems. This article is categorized under: Molecular and Statistical Mechanics > Molecular Interactions Structure and Mechanism > Reaction Mechanisms and Catalysis Structure and Mechanism > Molecular Structures