Insights into the weak Csp3–H···H–Csp3 mediated supramolecular architecture in ethyl 2-(5-bromopentanamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate, a probable selective COX-2 lead molecule: An integrated crystallographic and theoretical approach

Abstract

We report a detailed investigation of the weak noncovalent interactions exist in the crystal structure of the title benzo[b]thiophene derivative. It crystallizes in triclinic system with the centrosymmetric space group P-1. The planar conformation of the molecule is maintained by intramolecular 1,5-S···O chalcogen bond and N–H⋯O and C–H⋯O hydrogen bonding interactions. The crystal structure is primarily stabilized by C–H⋯S, C–H···π, C–H⋯O, Csp3–Br···O[dbnd]C, C–H⋯Br and Csp3–H···H–Csp3 interactions. The relative stability of the Csp3–Br···O[dbnd]C halogen bond is stronger in the crystal structure. Analysis of intermolecular interactions and topological properties show that the Csp3–H···H–Csp3 interactions play vital role in the construction of supramolecular architecture in the crystalline state. The structure based ligand docking and free energy calculation suggests that the title compound could display anti-inflammatory activity via selective inhibition of COX-2 enzyme. The selective inhibitory potential of the title molecule is further validated through theoretical charge density analysis.