Molecular Electrostatic Potential Reorganization Theory to Describe Positive Cooperativity in Noncovalent Trimer Complexes

Abstract

Supramolecular self-assembly and molecular recognition processes are driven mainly by positive cooperativity in noncovalent interactions. Here, we report a large variety of hydrogen-, tetrel-, chalcogen-, pnicogen-, halogen-, aerogen-, and dihydrogen-bonded dimer and trimer complexes, computed using the MP2/6-311++G(d,p) level ab initio theory. The dimer to trimer change is associated with a positive cooperativity in all the complexes. Significant electron density reorganization occurs in monomers because of noncovalent bond formation which is quantified using the change in the molecular electrostatic potential (MESP) at bonded atoms. For a noncovalent dimer X D Y A , an electron density flow is observed from the donor molecule X D to acceptor molecule Y A . As a result, YA in dimer showed a tendency to form a stronger noncovalent bond with an electron-deficient center of a third molecule, whereas X D in the dimer showed a tendency to form a stronger noncovalent bond with an electron-rich center of a third molecule. The change in change-of-MESP at the donor and acceptor atoms involved in bond formation (ΔΔV n ) is used as a parameter to assess the extent of electron donor− acceptor (eDA) interaction in dimers and trimers and found that ΔΔV n is directly proportional to the total binding energy. A cooperativity rule has emerged from this study which states that the electron reorganization in the dimer due to the eDA interaction always enhances its donor−acceptor interactive behavior with a third molecule toward the formation of a noncovalent trimer complex.

The use of electrostatic potential at nuclei in the analysis of halogen bonding

“…Furthermore, it suggests that the halogen bond is a weak electron donor-acceptor (eDA) interaction wherein the halogen center accepts electron density from the base partner. 47,56 The loss of electron density from the base partner is reflected in the positive DV n-D , while the electron-accepting ability of the halide system is seen in the negative DV n-A . In other words, DDV n gives the 'width' of eDA interaction.…”

“…Very recently, Bijina and Suresh derived a cooperativity rule for non-covalent trimer complexes from MESP analysis, which states that electron reorganization in the dimer complex X D Y A due to non-covalent bond formation always enhances both the acceptor character of X D and donating character of Y A in the dimer, which improves the strength of non-covalent binding of the dimer with a third molecule. 56 According to Suresh and Bijina, the changes in MESP observed on the donor atom (Δ V n-D ) and acceptor atom (Δ V n-A ) are proportional to the electron-donating and accepting power of the donor and acceptor, respectively. Also, the difference between Δ V n-D and Δ V n-A referred to as ΔΔ V n showed a strong linear correlation with the interaction energy ( E int ) of the non-covalent complex.…”

Drug and Drug-like Molecule Binding to Interface of SARS-CoV-2 Sprotein:human ACE2 Complex: A Density Functional Theory Study

“…All Ls were optimized at B3LYP/6-31G* level to obtain their energy E0. The binding energy (Eb) is calculated as Eb = E2 -(E0 + E1) Further, the molecular electrostatic potential (MESP) calculation [33][34][35] is done at B3LYP/6-31G* level to understand the electron distribution features of M. The MESP analysis is useful for the interpretation of the noncovalent bonding features of molecular complexes.…”

Studying the Chemical Reactivity Properties of Cytosine and its Antiviral Analogues: Zebularine, 5-Aza-Cytosine And 5-Aza-5,6-Dihydro-Cytosine through Density Functional Theory

“…Electrostatic potential is an important property that plays a key role in the interaction of molecules and is well established as an effective tool for interpreting and predicting molecular reactive behaviour [20][21][22]. The electronic potential of a molecule is an expression of Coulomb's law: where Z A is the charge on nucleus A, located at R A .…”