Abstract
A selective triazole-based COX-2 inhibitor, 4-(4chlorophenyl)-3-[(4-fluorobenzyl)sulfanyl]-5-(thiophen-2-yl)-4H- 1,2,4-triazole, C19H13ClFN3S2, has been synthesized, and its crystal structure was determined at 150 K. Single-crystal X-ray diffraction analysis revealed that the thiophene ring was disordered over two orientations. The crystal structure is stabilized by weak hydrogen and chalcogen bonds and unorthodox F center dot center dot center dot pi and S center dot center dot center dot C(pi) contacts. These noncovalent interactions cooperatively generate the supramolecular self-assembly in the crystalline state. The Hirshfeld surface and its associated two-dimensional (2D)-fingerprint plots were obtained to analyze the role of different noncovalent interactions in the crystal packing. Further, the enrichment ratio was obtained from different atom center dot center dot center dot atom pairs to calculate the propensity of these pairs to form noncovalent interactions. The strength of different dimeric motifs formed in the crystal structure and lattice energies was calculated by the PIXEL method. Furthermore, the topological analysis of the charge density of intermolecular interactions was described. A CSD survey of C-H center dot center dot center dot F hydrogen bond, C-S center dot center dot center dot Cl chalcogen bond, and unorthodox nonbonded contacts (F center dot center dot center dot pi and S center dot center dot center dot C(pi)) is presented. The title compound possesses selective inhibitory activity against human COX-2 enzyme rather than COX-1. The quantum mechanics (QM) polarized ligand docking analysis was used to predict the binding pose and study the title compound's selectivity against COX-1/2 enzymes.