Insight into (Z)-Ethyl-2-(2-((E)-2,4-dinitro benzylidene amino)-4-oxo-3-phenylthiazolidin-5-ylidene) acetate in-silico anti-SARS-CoV-2 performance: Synthesis, structural-spectral characterizations and DFT computations

This study reports on the synthesis of a 4-thiazolidinone derivative (EN2Th), namely, (Z)-Ethyl-2-(2-((E)-2,4-dinitro benzylidene amino)-4-oxo-3-phenylthiazolidin-5-ylidene) acetate. Its crystal structure has been determined by single crystal X-ray diffraction and the spectral characterizations were carried out by means of 1H and 13C NMR, and FT-IR techniques. The molecule of EN2Th crystallizes in the monoclinic P21/c symmetry and its crystal structure consists of a herringbone packing along [100]. The density functional theory (DFT) at the B3LYP/6-311G (d,p) level has been employed for structure optimization, the results confirm a good consistency between the theoretical and the experimental geometrical data. Hirshfeld surface and 2D fingerprints indicate C−H···O (29.7%) and H···H (24.5%) as the most relevant intermolecular interactions in the crystal packing of EN2Th. According to the reduced density gradient (RDG) analysis, EN2Th exhibits vdW to weak repulsive regions with low electron densities. The theoretical electronic circular dichroism (ECD) spectrum displays an exciton coupled transitions associated with the Z-configuration of the thiazolidin-4-one moiety reflecting the steric effect of the ester group. Charge transfer inside the 4-thiazolidinone derivative EN2Th was considered via the frontier molecular orbitals (FMOs) and natural bond orbital (NBO) investigations along with molecular electrostatic potential (MEP) distribution maps. The HOMO and LUMO energies allowed the estimation of the chemical reactivity descriptors. In accordance with the NBO results, the predicted hyperpolarizabilities indicate a strong donor to acceptor π-electrons delocalization in EN2Th. The anti-viral performance of EN2Th was evaluated in silico against SARS-CoV-2 main protease (MPro) via molecular docking simulations. Finally, ADMET (absorption, distribution, metabolism, excretion and toxicity) online software tools were utilized to uncover the title compound's potential cytotoxicity.