Hirshfeld Surface Analysis, DFT Calculations and Molecular docking studies of 2-Amino-N-(2-Fluorophenyl)-4,5,6,7-Tetrahydro-1-Benzothiophene-3-Carboxamide

Abstract

Thiophene nucleus has been established as a potential entity in the heterocyclic compounds possessing promising pharmacological characteristics such as anti-HIV PR inhibitors and anti-breast cancer activities. Importantly, benzothiophene derivative shows significant antimicrobial and anti-inflammatory activities. The title compound, C₁₅H₁₅FN₂OS was characterized by single-crystal X-ray diffraction studies. The molecular conformation is consolidated by intramolecular N-H···F and N-H···O hydrogen bonds. The Hirshfeld surface analysis revealed that H···H and C···H contacts contribute significantly to the intermolecular interactions. Further, their structures were optimized by density functional theory (DFT) calculations using B3LYP hybrid functionals with 6-311G (d,p) level basis set. The transitions among the molecular orbital’s were investigated using time-dependent density functional theory (TD-DFT) and the UV–Vis spectra showed the absorption peak at 306 nm. In addition, natural bond orbital (NBO) analysis was carried out to explore inter/intra molecular electron delocalization and hyperconjugative interactions responsible for the molecular structure stability. Docking studies were carried out using Autodock-4.2 with Lamarckian Genetic Algorithm (LGA) computational method to rationalize the plausible best binded candidates. The title compound was found to have minimum binding energy of -7.17 kJ/mol with the protein target (PDB Code: 3FDN).