Insights into the structural and interactional aspects of 1-phenyl-5-(thiophen-2-yl)-1H-tetrazole: crystallographic, Hirshfeld surface, computational, and docking analyses

Tetrazoles are the bioisoster of carboxylic acid, and their derivatives demonstrated promising anticancer activity. Hybridization of tetrazole moiety with other anticancer pharmacophores may provide novel candidates with anticancer potency. In this regard, the 1-phenyl-5-(thiophen-2-yl)-1H-tetrazole (C₁₁H₈N₄S) is characterized by LC–MS, C¹³ NMR analysis, and single-crystal X-ray diffraction. The molecule crystallizes in the monoclinic crystal system with the space group P2₁/n. Hirshfeld surface analysis was carried out to quantify the intermolecular interactions and crystal packing. Hirshfeld surface analysis indicates that the most important contributions to the crystal packing are from N–H/H-N (30.7%) interaction. Geometry optimization of the molecule is done using density functional theory (DFT) at the B3LYP hybrid functional. Theoretical structure parameters are compared with the experimentally determined structure. The computed energy gap between the frontier molecular orbitals is 4.81 eV. The RDG calculations revealed the presence of C-H…S and C-H…N noncovalent interaction in the molecule. Molecular docking studies show that the binding affinity between protein and ligand is − 8.03 kcal/mol.