Synthesis, structural elucidation, in vitro antibacterial activity, DFT calculations, and molecular docking aspects of mixed-ligand complexes of a novel oxime and phenylalanine

Abstract

An oxime ligand (HL) was synthesized by the condensation of 4-biphenylhydroxymoyl chloride with 2-amino-5-bromopyridine. The oxime ligand was reacted with l-phenylalanine and metal(II) acetate salts (Co(II), Ni(II), and Cu(II)) to synthesize mixed-ligand complexes. Structural elucidation of the newly synthesized ligand and complexes was performed by elemental analysis, 13C NMR, 1H NMR, FT-IR, ICP-OES, the measurements of molar conductivity and magnetic susceptibility. The thermal properties of the compounds were characterized by TG/DTA analyses. The antibacterial activities of the compounds were evaluated in vitro by the resazurin-aided broth microdilution method. Optimized molecular geometries of the HL and its metal complexes were calculated using the density functional theory (DFT) of the B3LYP method with 6-311G (d, p) and LANL2DZ basis sets. The NMR chemical shift values, vibrational frequencies, and HOMO-(LUMO or SOMO) energies were also computed using the mentioned level. A molecular docking study was performed to demonstrate the interactions of the synthesized compound with beta-ketoacyl-ACP synthase III (KAS III), an enzyme that has a key role in bacterial survival. Based on the MIC values and binding energy scores, both in vitro and in silico studies showed that the antibacterial activity of the Cu(II) complex was better than the other studied molecules.