Synthesis, DFT Studies, and Molecular Docking Analysis of a Novel Acylpyrazolone Schiff Base and Its Metal(II) Complexes

Novel Schiff base ligand 1,5-dimethyl-4-((1-(3-methyl-5-oxo-1-phenyl-1,5-dihydro-4H-pyrazol-4-ylidene)butyl)amino)-2-phenyl-1,2-dihydro-3H-pyrazol-3-one was synthesized by the condensation reaction between 4-acylpyrazol-5-one and 4-aminoantipyrine. Ni(II), Cu(II), Co(II), or Zn(II) complexes were synthesized by reactions of the ligand with respective metal chlorides. The ligand and complexes were characterized by conventional spectroscopic techniques: UV–Visible, FTIR, mass spec, ¹H and ¹³C NMR, and single-crystal XRD analysis. The crystal system and space group of the ligand are monoclinic and P21/c, respectively. Computational studies (DFT and molecular docking) were employed to supplement the experimental findings and predict possible applications of the novel Schiff base. DFT studies indicate that two ligands each coordinate to the metal(II) center in a bidentate manner, resulting in a pseudo-tetrahedral geometry. The Schiff base ligand exhibited tautomerism where the amine-one was more stable than the imine-ol. Molecular docking studies indicate that the Ni(II) complex showed a significant binding affinity and the best binding interaction with the Mycobacterium tuberculosis enoyl acyl carrier protein reductase (ENR) target enzyme. This suggests that binding to these specific proteins might lead to the mechanism of action of the evaluated antibacterial property.