Structural investigations and theoretical insights of a polymethoxy chalcone derivative: Synthesis, crystal structure, 3D energy frameworks and SARS CoV-2 docking studies

Abstract

Chalcone derivatives with various functional groups have shown potent pharmacological and non-linear optical properties. A multi‑methoxy substituted (E)-1-(3,4-dimethoxyphenyl)-3-(3,4,5-trimethoxyphenyl) prop‑2-en-1-one, chalcone derivative has been synthesized and spectroscopically characterized by 1H and 13C NMR, LC-MS and FT-IR techniques. A pale yellow colored rectangular shaped single crystals of the compound were obtained by slow evaporation method and the three dimensional structure was confirmed using X-ray diffraction studies. The compound crystallized in the monoclinic crystal system with P21/a space group. The crystal and molecular structure is stabilized by CH···O inter and intra molecular hydrogen bond interactions apart from the prominent CH···π and π···π stacking interactions. These interactions were studied using Hirshfeld surface analysis to understand the nature and strength of interactions; the 2D fingerprint plot quantifies each individual intermolecular contact and revealed that the H…H (49.2%) interactions have the major contribution to the molecular surface. The analysis of 3D molecular energy frameworks revealed that the dispersion energy (-208.16 kJ mol−1) dominates all other energies and their visualization identifies the packing order of the molecules in the crystalline environment. The lattice energy of the compound is found to be -398.1 kJ mol−1. The electronic properties of the compound were quantified using theoretical quantum chemical computations with DFT-B3LYP/6–311+G (d, p) level basis set. The electronic energy band gap of the chalcone molecule is found to be 3.6961 eV. The NBO and Mulliken atomic charges were computed and the molecular electrostatic potential map was plotted to identify the chemical reactive sites on the molecular surface. The second-order nonlinear optical properties of the molecule based on the first static hyperpolarizability (β) have been investigated. Further, the molecular docking studies of the chalcone derivative against corona virus 2 (SARS-CoV-2) protein have been carried out to shed light on the possible significant molecular interactions.