Face-to-Face Arene−Arene Binding Energies: Dominated by Dispersion but Predicted by Electrostatic and Dispersion/Polarizability Substituent Constants

Abstract

Parallel face-to-face arene-arene complexes between benzene and substituted benzenes have been investigated at the MP2(full)/6-311G** and M05-2X/6-311G** levels of theory. A reasonably good correlation was found between the binding energies and the ∑|σ(m)| values of the substituted aromatics. It is proposed that a substituent |σ(m)| value informs on both the aromatic substituent dispersion/polarizability and the effect the substituent has on the aromatic electrostatics. Supporting this hypothesis, a combination of electrostatic (∑σ(m)) and dispersion/polarizability (∑M(r)) substituent constant terms gives an excellent, and statistically significant, correlation with the benzene-substituted benzene binding energy. Symmetry adapted perturbation theory energy decomposition calculations show the dominant attractive force is dispersion; however, the sum of all nonelectrostatic forces is essentially a constant, while the electrostatic component varies significantly. This explains the importance of including an electrostatic term when predicting benzene-substituted benzene binding energies.

Predicting DNA–intercalator binding: the development of an arene–arene stacking parameter from SAPT analysis of benzene‐substituted benzene complexes

“…[3,51,52] Recent work has suggested that dispersion and electrostatics are important contributing forces in aromatic stacking interactions. [38,53,54] Scheme 1. Reduction of 3-nitro-1,8-naphthalic anhydride and condensation reaction for formation of 3-substituted naphthalimides [39] Scheme 2.…”

“…In parallel face-to-face conformations of benzene-substituted benzene dimers, electrostatics and dispersion have been shown to contribute most significantly. [38,53,54,68,[73][74][75][76] The Π π parameter was developed from benzene-monosubstituted benzene dimers (Fig. 3) where the substituted benzene substituent corresponds to the naphthalimide substituents in intercalators 1b -3b, 4 -9, and 11.…”

“…[26,27] Sherrill and coworkers have extensively used SAPT to investigate the non-covalent binding of arene-arene interactions, [28][29][30][31][32][33][34] other research groups have studied such interactions using other energy decomposition methods, [35][36][37] and we have recently employed SAPT to comment on the non-covalent binding of substituted benzene-benzene binding energies. [38] The SAPT method is computationally demanding, and it has only been in recent years, with advances in computational hardware and software, that the calculations have been possible on systems as large as benzene dimers. Given that numerous QSAR parameters have been developed to describe the effects of electrostatics, dispersion, and induction on the biological properties of pharmaceutically active compounds and that SAPT calculates the energies associated with these forces, this is a logical area of application for the theory.…”

Energetic factors determining the binding of type I inhibitors to c-Met kinase: experimental studies and quantum mechanical calculations

“…The model combining dispersion and electrostatics may better reflect the nature of π-π interactions. Recently, several groups have identified substituent effects that can be correlated to the Hammett σ m parameters [15,32,36] . This ultimately led to the proposal of a local direct interaction model for π-π stacking [37,38] .…”

Pyrazolo[3,4-d]pyrimidines as inhibitor of anti-coagulation and inflammation activities of phospholipase A 2 : insight from molecular docking studies

“…Intermolecular interactions minimize the energy of the complexes and play an important role in drug-receptor, protein-DNA, protein-protein interactions, etc., while intramolecular interactions minimize the energy of a molecule and are responsible for tertiary structure of proteins, DNA, RNA etc. [13][14][15][16]. In the literature, to facilitate arene interactions, several models have been proposed [17].…”