Crystal structure, Hirshfeld surface analysis, DFT investigation and molecular docking study of 5-(thiophen-2-yl)-1,3,4-thiadiazol-2-amine

The present study investigates 5-(thiophen-2-yl)-1,3,4-thiadiazol-2-amine using an integrated crystallographic, electronic, and molecular interaction approach. Single-crystal X-ray diffraction reveals an orthorhombic crystal system ( Pccn ) with two independent molecules (Z′ = 2). Crystal packing is governed by N-H···N and N-H···S hydrogen bonds forming centrosymmetric dimers, supported by π–π interactions and dispersive forces. Hirshfeld surface analysis shows that H···H (22.2%), H···N (26.6%), and H···S (24.1%) contacts dominate the intermolecular interactions. Density Functional Theory calculations indicate a HOMO-LUMO energy gap of 4.22 eV, suggesting moderate chemical hardness and stability. Frontier molecular orbital and electrostatic potential analyses revealed distinct regions of charge distribution, consistent with the observed intermolecular interactions. Molecular docking against lanosterol 14-α-demethylase (CYP51) demonstrates favourable binding (-6.59 kcal mol −1 ), driven by hydrogen bonding and hydrophobic interactions. These results establish a clear structure-interaction relationship and provide a basis for further exploration of thiadiazole-based systems.