Molecular Electrostatic Potential Topology Analysis of Noncovalent Interactions

Conspectus The topology of molecular electrostaticpotential (MESP), V(r), derived froma reliable quantum chemicalmethod has been used as a powerful tool for the study of intermolecularnoncovalent interactions. The MESP topology mapping is achieved bycomputing both backward difference V(r) data andthe elements of the Hessian matrix at backward difference V(r) = 0, the critical point. MESP minimum (V (min)) as well as MESP at a reaction center, specific toan atom (V (n)), have been employed as electronicparameters to interpret the variations in the reactivity (activation/deactivation)of chemical systems with respect to the influence of substituents,ligands, & pi;-conjugation, aromaticity, trans influence, hybridizationeffects, steric effects, cooperativity, noncovalent interactions,etc. In this Account, several studies involving MESP topology analysis,which yielded interpretations of various noncovalent interactionsand also provided new insights in the area of chemical bonding, arehighlighted. The existence of lone pairs in molecules is distinctlyreflected by the topology features of the MESP minima (V (min)). The V (min) is able toprobe lone pairs in molecules, and it has been used as a reliableelectronic parameter to assess their & sigma;-donating power. Furthermore,MESP topology analysis can be used to forecast the structure and energeticsof lone pair & pi;-complexes. The MESP approach to rationalize lonepair interactions in molecular systems has led to the design of cyclicimines for CO2 capture. The MESP topology analysis of intermolecularcomplexes revealed a hitherto unknown phenomenon in chemical bondingtheory formation of a covalent bond due to the influence ofa noncovalent bond. The MESP-guided approach to intermolecular interactionsprovided a successful design strategy for the development of CO2 capture systems. The MESP parameters V (min) and MESP at the nucleus, V (n), derived for the molecular systems have been used as powerful measuresfor the extent of electron donor-acceptor (eDA) interactionsin noncovalent complexes. Noncovalent bond formation leads to morenegative MESP at the acceptor nucleus (V (nA)) and less negative MESP at the donor nucleus (V (nD)). The strong linear relationship observed between & UDelta;& UDelta;V (n) = & UDelta;V (nD) -& UDelta;V (nA) and bond energy suggested thatMESP data provide a clear evidence of bond formation. Furthermore,MESP topology studies established a cooperativity rule for understandingthe donor-acceptor interactive behavior of a dimer D...A witha third molecule. According to this, the electron reorganization inthe dimer due to the eDA interaction enhances electron richness at"A", the acceptor, and enhances electron deficiencyat "D", the donor. Resultantly, D in D...A is more acceptingtoward trimer formation, while A in D...A is more donating. MESP topologyoffers promising design strategies to tune the electron-donating strengthin various noncovalent interactions in hydrogen-, dihydrogen-, halogen-,tetrel-, pnicogen-, chalcogen-, and aerogen-bonded complexes and therebyto predict the interactive behavior of molecules. To sum up, MESPtopology analysis has become one of the most effective modern techniquesfor understanding, interpreting, and predicting the intermolecularinteractive behavior of molecules.