Synthesis, Characterization, and Molecular Docking Studies of Homoleptic and Heteroleptic Zinc(II), Copper(II), Nickel(II) Complexes of Semicarbazone and Thiosemicarbazone Derivative Ligands for Biological Applications

Abstract

The importance of semicarbazone and thiosemicarbazone organic compounds and their metal complexes as pharmaceutical, medicinal, antibacterial, antioxidant, and antifungal targets has recently become an area of research in both bioinorganic and medicinal chemistry. In this study, the semicarbazone and thiosemicarbazone derivative organic ligands and their metal complexes having a plethora of potentially exciting bioactivities and coordination chemistry were synthesized, characterized and their biological activities were evaluated. Specifically, the Zn(II), Cu(II), and Ni(II) complexes of bidentate ON (L1), Zn(II),and Cu(II)) complexes of SN (L2), and tridentate ONN (L3 and L4) ligands have been prepared. The compounds were characterized with various methods such as 1H-NMR, 13C-NMR, FT-IR, UV-Vis, and mass spectroscopies, conductometer, SEM-EDX, XRD, TGA/DTA techniques. The synthesized ligands and their metal complexes were screened for their antibacterial activity against two Gram-negative (Escherichia coli and Pseudomonas aeruginosa and two Gram- positive (Staphylococcus aureus and Streptococcus pyogenes) bacteria strains using disc diffusion method. The compounds were also evaluated for their antioxidant activity by DPPH assay. On the bases of spectroscopic studies the structure and the molecular formula of the synthesized compounds were proposed. The antimicrobial activity result showed the best activities were achieved by [Zn(L2)2] complex 4 (15.44 ± 0.31 mm) against Pseudomonas aeruginosa), [Cu(L2)2] complex 5 (14.00 ± 0.20 mm) against Streptococcus pyogenes, [Zn(L3)2].2H2O complex 6 (16.22 ± 0.27 mm) against Staphylococcus aureus, [Cu(L3)2].3H2O complex 7 (18.66 ± 0.34 mm) against Staphylococcus aureus bacteria pathogens compared to trimethoprim with a mean inhibition zone of 18.70 ± 0.47 mm to 21.48 ± 0.46 mm diameter. Also, the antioxidant potential result showed that complexes; [Ni(L1)2Cl] (3), [Ni(L3)2].3H2O (8), [Cu(L2)2] (5), [Cu(L3)2].3H2O (7) and [Zn(L2)2] (4) exhibited good antioxidant activity with percentage scavenging potentials of 85.76, 81.43, 78.55, 78.45 and 76.78% at 100 μg/mL respectively compared with standard ascorbic acid 89.74%. The in silico analysis results were also in good agreement with the in vitro experimental results. Thus, this study revealed that the coordination of metal ions with bioactive organic ligands could serve as candidate in metal based drug development for biological applications.