Comprehensive structural, electronic, and in-silico characterization of 1-phenyl-5-(m-tolyl)-1H-tetrazole as a potential steroidogenic factor-1 (SF-1) inhibitor candidate

Dhanushchandraguru, H. M. and Hemaraju, B. C. and Chandra and Vinay Kumar, D. C. and Chethan, B. S. and Akhileshwari, P. and Preetham, R. and Sadashiva, M. P. (2026) Comprehensive structural, electronic, and in-silico characterization of 1-phenyl-5-(m-tolyl)-1H-tetrazole as a potential steroidogenic factor-1 (SF-1) inhibitor candidate. Journal of Molecular Structure, 1349. p. 143859. ISSN 0022-2860

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Abstract

This investigation details the integrated experimental and computational characterization of 1-phenyl-5-(m-tolyl)-1H-tetrazole, a novel tetrazole derivative is synthesized for potential therapeutic targeting. For the synthesis of the compound a stepwise strategy involving initial Grignard reagent formation, subsequent reaction with phenyl isothiocyanate, and final S-methylation, with isolation and purification achieved via optimized silica gel column chromatography was employed. The structural elucidation through single-crystal X-ray diffraction (SCXRD), revealed that the molecule crystallized in monoclinic crystal system with P2�/n space group. The Hirshfeld surface analysis quantified intermolecular contacts, identifying H···H interactions (43.7) as the predominant force governing crystal packing, underscoring the critical stabilizing role of dispersive van der Waals interactions within the lattice. Further, the Density Functional Theory (DFT) calculations carried out at B3LYP/6-311++G(d,p) basis set revealed the HOMO-LUMO gap of the compound to be 5.23 eV indicating a significant kinetic stability and inherently limited chemical reactivity for this compound. Molecular Electrostatic Potential (MEP) mapping further delineated distinct electrophilic (positive) and nucleophilic (negative) regions. These electronic properties were rigorously contextualized through the Quantum Theory of Atoms in Molecules (QTAIM), which corroborated SCXRD findings by characterizing bond critical points and delineating the topology of electron density distributions associated with key intra- and intermolecular interactions.To assess biological relevance, in silico molecular docking simulations targeted the ligand-binding domain of Steroidogenic Factor 1 (SF-1). The compound demonstrated a substantial predicted binding affinity of -7.7 kcal/mol, forming stable complex.In addition, the HOMO-LUMO gap and molecular docking studies were extended for comparison with the standard medication drug doxorubicin. This strong predicted interaction profile, combined with the established structural integrity and favorable electronic properties,makes1-phenyl-5-(m-tolyl)-1H-tetrazole as a compelling SF-1 inhibitor candidate for adrenocortical carcinoma.

Item Type:	Article
Uncontrolled Keywords:	Crystal structure, Hirshfeld surface, DFT, QTAIM, Molecular docking
Subjects:	C Chemical Science > Chemistry
Divisions:	Department of > Chemistry
Depositing User:	C Swapna Library Assistant
Date Deposited:	12 Nov 2025 06:07
Last Modified:	12 Nov 2025 06:07
URI:	http://eprints.uni-mysore.ac.in/id/eprint/17915

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