Molecular Electrostatic Potential Topology Analysis of Noncovalent Interactions

Abstract

The topology of molecular electrostatic potential (MESP), V(r), derived from a reliable quantum chemical method has been used as a powerful tool for the study of intermolecular noncovalent interactions. The MESP topology mapping is achieved by computing both ∇V(r) data and the elements of the Hessian matrix at ∇V(r) = 0, the critical point. MESP minimum (Vmin) as well as MESP at a reaction center, specific to an atom (Vn), have been employed as electronic parameters to interpret the variations in the reactivity (activation/deactivation) of chemical systems with respect to the influence of substituents, ligands, π-conjugation, aromaticity, trans influence, hybridization effects, steric effects, cooperativity, noncovalent interactions, etc. In this Account, several studies involving MESP topology analysis, which yielded interpretations of various noncovalent interactions and also provided new insights in the area of chemical bonding, are highlighted. The existence of lone pairs in molecules is distinctly reflected by the topology features of the MESP minima (Vmin). The Vmin is able to probe lone pairs in molecules, and it has been used as a reliable electronic parameter to assess their σ-donating power. Furthermore, MESP topology analysis can be used to forecast the structure and energetics of lone pair π-complexes. The MESP approach to rationalize lone pair interactions in molecular systems has led to the design of cyclic imines for CO2 capture. The MESP topology analysis of intermolecular complexes revealed a hitherto unknown phenomenon in chemical bonding theory─formation of a covalent bond due to the influence of a noncovalent bond. The MESP-guided approach to intermolecular interactions provided a successful design strategy for the development of CO2 capture systems. The MESP parameters Vmin and MESP at the nucleus, Vn, derived for the molecular systems have been used as powerful measures for the extent of electron donor–acceptor (eDA) interactions in noncovalent complexes. Noncovalent bond formation leads to more negative MESP at the acceptor nucleus (VnA) and less negative MESP at the donor nucleus (VnD). The strong linear relationship observed between ΔΔVn = ΔVnD – ΔVnA and bond energy suggested that MESP data provide a clear evidence of bond formation. Furthermore, MESP topology studies established a cooperativity rule for understanding the donor–acceptor interactive behavior of a dimer D...A with a third molecule. According to this, the electron reorganization in the dimer due to the eDA interaction enhances electron richness at “A”, the acceptor, and enhances electron deficiency at “D”, the donor. Resultantly, D in D...A is more accepting toward trimer formation, while A in D...A is more donating. MESP topology offers promising design strategies to tune the electron-donating strength in various noncovalent interactions in hydrogen-, dihydrogen-, halogen-, tetrel-, pnicogen-, chalcogen-, and aerogen-bonded complexes and thereby to predict the interactive behavior of molecules. To sum up, MESP topology analysis has become one of the most effective modern techniques for understanding, interpreting, and predicting the intermolecular interactive behavior of molecules.