Insights into the weak Csp(3)-H center dot center dot center dot H-Csp(3) 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

摘要

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 center dot center dot center dot O chalcogen bond and N-H center dot center dot center dot O and C-H center dot center dot center dot O hydrogen bonding interactions. The crystal structure is primarily stabilized by C-H center dot center dot center dot S, C-H center dot center dot center dot pi, C-H center dot center dot center dot O, Csp(3)-Br center dot center dot center dot O-C, C-H center dot center dot center dot Br and Csp(3)-H center dot center dot center dot H-Csp(3) interactions. The relative stability of the Csp(3)-Br center dot center dot center dot O=C halogen bond is stronger in the crystal structure. Analysis of intermolecular interactions and topological properties show that the Csp(3)-H center dot center dot center dot H-Csp(3) 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. (C) 2019 Elsevier B.V. All rights reserved.