Multifaceted exploration of benzyl 5-(p-tolyl)-1,3,4-thiadiazole-2-carboxylate: Spectroscopic, structural, and computational insights into its drug-like potential

Karthik, V. and Santhosh, C. and Geetha, D․ V․ and Chandini, K․ M․ and Sindogi, Kishorkumar and Sridhar, M․ A․ and Sadashiva, M․ P. (2026) Multifaceted exploration of benzyl 5-(p-tolyl)-1,3,4-thiadiazole-2-carboxylate: Spectroscopic, structural, and computational insights into its drug-like potential. Journal of Molecular Structure, 1350. p. 143963. ISSN 0022-2860

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Abstract

The present research article delves into a comprehensive structural study of a thiadiazole derivative. The work begins with the synthesis by employing a multifaceted approach to unravel its molecular properties and potential biological significance of a novel thiadiazole derivative benzyl 5-(p-tolyl)-1,3,4-thiadiazole-2-carboxylate (C1) synthesized using cyclocondensation reaction. A single crystal X-ray diffraction study revealed that the compound (C1) crystallized in the triclinic crystal system with P 1¯ space group, revealing a non-planarity of the structure. The crystal packing is stabilized by a network of intermolecular interactions, including hydrogen bonds, CH…O, CH…π, and π-π stacking, Van der Waals force and other intra-intermolecular interaction. The Hirshfeld surface analysis was performed, in order to visualize, explore and quantify the inter molecular interactions that stabilize the crystal packing of the compound (C1), which reveals that H…H contacts are major contributors to the total Hirshfeld surface. Density Functional Theory (DFT) was employed using the B3LYP functional and 6–311++ G (d, p) basis set to explore the compound’s electronic structure and physicochemical properties. The energy gap of the compound C1 is found to be 4.272 eV. Molecular Electrostatic Potential (MEP) surfaces were performed to get additional insights into charge distribution, intermolecular interactions, and stabilization energies. Quantum theory of atoms in molecule (QTAIM) and non-covalent interactions (NCI) analysis provided insights into the topology of the compounds. Based on the Bader’s theory, reduced density gradient (RDG) analysis is exploited to visualize and quantify the concept of electronic compactness in supramolecular chemistry, and to investigate the nature and strength of the van der Waal interactions. Additionally, molecular docking studies are used to compare the titled compound (C1) with a standard drug. The binding energy of the complex 7WWK-C1 protein is found to be -8.73 kcal/mol. According to the in silico simulations, the molecule being studied may ultimately be a good inhibitor for SARS-CoV-2 virus main protease, and additional in vitro and in vivo research may reveal its therapeutic potential.

Item Type:	Article
Uncontrolled Keywords:	Thiadiazole derivative, Crystal structure, Hirshfeld surface, DFT, MEP, Molecular docking, Molecular dynamics simulation
Subjects:	C Chemical Science > Chemistry
Divisions:	Department of > Physics
Depositing User:	C Swapna Library Assistant
Date Deposited:	12 Nov 2025 05:57
Last Modified:	12 Nov 2025 05:57
URI:	http://eprints.uni-mysore.ac.in/id/eprint/17912

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