Structural examination, theoretical calculations, and pharmaceutical scanning of a new tetralone based chalcone derivative

Abstract

A tetralone based chalcone compound, (2E)-2-(2,3,4-trimethoxybenzylidene)-3,4-dihydronaphthalen-1(2H)-one [TBDN] was synthesized, and crystals were grown by repeated crystallization in a mixture of acetone and ethyl methyl ketone (EMK) [1:2] at room temperature. The crystal structure of the compound was derived by single-crystal X-ray diffraction studies (SXRD). The title compound was crystallized in a monoclinic crystal system with a P21/c space group and the crystal structure is stabilized by C-H…O type intermolecular hydrogen bonds. Hirshfeld surfaces and the associated 2D fingerprint plots were generated and their analysis provides information regarding the weak intermolecular interactions and the intra contacts contribution to the total Hirshfeld surface in the crystal structure. The pair-wise intermolecular interactions and their role in stabilizing the molecule were investigated via energy frameworks. The modes of vibrational frequencies were assigned through FTIR spectral analysis both experimentally and theoretically. In addition, Density functional theory (DFT) based calculations including HOMO-LUMO energies, Molecular Electrostatic potential surface (MEPs), Mulliken charges, and Fukui functions were also performed. The donor-acceptor interactions were studied with the help of natural bond orbital (NBO) analysis. Bioactivity assessment reveals that the compound obeys Lipinski's rule and showed good drug-likeness with the score -0.17 to -0.39. Molecular docking studies on the title compound complexed with Gram-negative (E. Coli) and Gram-positive (Staphylococcus aureus) bacteria reveal an excellent binding affinity between the ligand and the target protein. Thus, the title compound can be a promising antibacterial agent but require further biological and pharmaceutical investigation.