Comprehensive analysis of hydrazone Schiff bases: synthesis, structural characterization, DFT studies, molecular docking insights and bioactivity assessment

Abstract

The four new hydrazone Schiff bases have been synthesized in absolute ethanol at the reflux of 78 °C. These hydrazones are named as: (E)-1-(2,4-dinitrophenyl)-2-(2-ethoxy benzylidene) hydrazine(2-EDNPH) (L1), (E)-1-(2,4-dinitrophenyl)-2-(4-ethoxy benzylidene) hydrazine(4-EDNPH) (L2), (E)-3-chloro-2-((2-(2,4-dinitrophenyl) hydrazinylidene) methyl) phenol(3-Cl-2-OH-DNPH) (L3) and (E)-1-(2,4-dinitrophenyl)-2-(thiophen-3-ylmethylene) hydrazine (3-Thiophene Carbaldehyde-DNPH) (L4). Spectroscopic and physicochemical techniques were employed to validate these compound's structure, including 1H NMR, 13C NMR spectra, UV–Vis, IR, and melting point. A solubility test is also carried out on all the Schiff bases, indicating that all four ligands are soluble in THF and DMF. The thermal breakdown behavior of all ligands is being examined by thermogravimetric analysis (TGA/DTG) at a heating rate of 10 °C min−1 under a nitrogen environment. The crystalline structure of L1 was also investigated in an XtaLAB AFC12 (RINC): Kappa single diffractometer, which included unit cell computation and data collecting. The radioactive photon was created with MoKα (λ = 0.7107Å). In addition, density functional theory (DFT) is utilized to compute the optimized molecular structures, stability, reactivity, and numerous chemical characteristics of the synthesized ligands. The in-silico prediction of ADME features revealed that synthesized compounds gain notable drug-like characteristics. Also, molecular docking was enforced to predict the inhibitory action of the β-ketoacyl acyl carrier (KAS1) protein of E. Coli (PDB Id: 6TZF) on the examined hydrazones. Finally, all ligands were to assess the anti-bacterial properties against gram-positive (B. subtilis and MRSA) and gram-negative (P. mirabilis and E. coli) infections; only L1 and L2 showed activity against these pathogens.