Synthesis, Spectroscopic, DFT Study, and Molecular Modeling of Thiophene-Carbonitrile Against Enoyl-ACP Reductase Receptor

The studied compound was synthesized by the reaction of diazotized 4-Aminobenzene and 2-amino-4-(4-aminophenyl) thiophene-3-carbonitrile (AATC). The synthesized structure was experimentally characterized using FT-IR and GC-MS followed by detailed computational investigations of the experimental structure and a subsequent application for molecular docking against the InhA receptors. The density functional theory (DFT) and time-dependent DFT calculations were performed using the B3LYP/6-311++G(d,p) method. The experimental vibrational frequencies were compared with the theoretical vibrational wavenumbers and the entire vibrational assignments were made solely to characterize the potential energy distributions (PED) using the Veda04 programme. The Fukui functions, MEP, and ADCH analysis were used to describe the reactive sites of the studied structure. Conceptual density functional theory (CDFT) and Frontier molecular orbitals (FMO) were used to characterize the reactivity parameters of the whole molecule while the aromaticity index was used to identify the most aromatic fragment of the studied compound. Natural bond orbital (NBO) analysis aided in describing the interactions that lead to the highest stabilization of the molecule and the interactions that undergo Intra- and Intermolecular charge transfer. Nonlinear optical property (NLOP) of APTC was also studied in order to ascertain its importance in technology such as optoelectronic devices. The Molecular docking studies were used to study the inhibitory action of the studied structure against some InhA proteins [an NADH-dependent enoyl-acyl carrier protein reductase (enoyl-ACP reductase)] using Auto-Dock vina software. The absorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis was carried out using pq SCM to compare the drug physicochemical properties with standard drug isoniazid.

Automated summary

The studied compound was synthesized and characterized using experimental and computational methods. The research investigated various properties of the compound such as potential energy distribution, reactive sites, reactivity parameters, aromaticity, and intermolecular interactions. Additionally, the study examined the compound's nonlinear optical properties and inhibitory action through molecular docking.