Ball-milling synthesis technique for Cu(II)-Schiff base complexes with variable anions; characterization, potentiometric study and in-vitro assay confirmed by in-silico method

Abstract The condensation reaction of 3-oxo-N-(pyridine-2-yl)butanamide and 4-chlorobenzo hydrazide yields a new Schiff base ligand which was characterized to be a mixture of tautomer forms. Two new Cu(II) complexes were prepared from chloride or acetate salt and then characterized to recognize the effect of conjugated anion nature on the chemical formulae of complexes. IR, UV-Vis, ESR, EDX, SEM, TEM and XRD were used to analyze the two complexes. Two discriminating modes were appeared, mono-basic bidentate within square-planer geometry and di-basic tridentate within octahedral geometry. Hamiltonian factors and field vector obtained from ESR spectra, assert on octahedral and square-planer geometries. The two complexes appeared nano-crystalline with different morphology and their particle-sizes were in nanometer range. In order to determine the ionization constants for the ligand and stability constants of the complex in solution, potentiometric studies were performed. Molecular modeling was executed by advanced programs to confirm some aspects. Important parameters and maps were obtained and promising biological efficiency of the ligand, is strongly expected. Properties of molecular surface contact inside crystal packing, were evaluated by Crystal Explorer program. Oxygen and hydrogen atoms play a good role in contact efficiency between crystal molecules. Antimicrobial, antioxidant and antitumor efficiency of all compounds were examined and the ligand achieved excellent superiority. In-silico assay was carried out by MOE-docking approach for confirmation and comparison with in-vitro results. Two tautomer forms of Schiff base ligand exhibited excellent inhibition towards 1cca and 2h80 co-crystal proteins. The high conformity and credibility of in-silico and in-vitro results may be concluded