Design, synthesis and spectroscopic and structural characterization of novel N-(2-hydroxy-5-methylphenyl)-2,3-dimethoxybenzamide: DFT, Hirshfeld surface analysis, antimicrobial activity, molecular docking and toxicology.

The novel compound N-(2-hydroxy-5-methylphenyl)-2,3-dimethoxybenzamide, CHNO, I, was prepared by a two-step reaction and then characterized by elemental analysis and X-ray diffraction (XRD) methods. Moreover, its spectroscopic properties were investigated by FT-IR and H and C NMR. Compound I crystallized in the monoclinic space group P2/c and the molecular geometry is not planar, being divided into three planar regions. Supramolecular structures are formed by connecting units via hydrogen bonds. The ground-state molecular structure of I was optimized by the DFT-B3LYP/6-31G(d,p) method and the theoretical structure was compared with that obtained by X-ray diffraction. Intermolecular interactions in the crystal network were studied by two-dimensional (2D) and three-dimensional (3D) Hirshfeld analyses. The calculated electronic transition results were examined and the molecular electrostatic potentials (MEPs) were also determined. The in vitro antimicrobial activities of I against three Gram-positive bacteria, three Gram-negative bacteria and two fungi were determined. The compound was compared with several control drugs and showed better activity than the amoxicillin standard against Gram-positive bacteria B. subtilis, S. aureus and E. faecalis, and Gram-negative bacteria E. coli, K. pneumoniae and P. aeruginosa. The density functional theory (DFT)-optimized structure of the small molecule was used to perform molecular docking studies with proteins from experimentally studied bacterial and fungal organisms using AutoDock to determine the most preferred binding mode of the ligand within the protein cavity. A druglikeness assay and ADME (absorption, distribution, metabolism and excretion) and toxicology studies were carried out and predict a good drug-like character.