Supramolecular self-assembly built by weak hydrogen, chalcogen and unorthodox non-bonded motifs in 4-(4-chlorophenyl)-3-[(4-fluorobenzyl)sulfanyl]-5-(thiophen-2-yl)-4H-1,2,4-triazole, a selective COX-2 inhibitor: insights from X-ray and theoretical study

Abstract

A selective triazole-based COX-2 inhibitor, 4-(4-chlorophenyl)-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··· and S···C() contacts. These non-covalent interactions cooperatively generate the supramolecular self-assembly in the crystalline state. The Hirshfeld surface and its associated 2D-fingerprint plots were obtained to analyze the role of different non-covalent interactions in the crystal packing. Further, the enrichment ratio was obtained from different atom···atom pairs to calculate the propensity of these pairs to form non-covalent 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···F hydrogen bond, C–S···Cl chalcogen bond, and unorthodox non-bonded contacts (F··· and S···C()) is presented. The title compound possesses selective inhibitory activity against human COX-2 enzyme rather than COX-1. The QM polarized ligand docking analysis was used to predict the binding pose and study the title compound’s selectivity against COX-1/2 enzymes.