Biogenic AgNPs Decorated Cu(II) and Zn(II) Complexes of Imine-Quinoline Ligand: Synthesis, Characterization and Biological Applications

Abstract

Metal complexes have been the subject of extensive research in coordination chemistry since the discovery of metal-based medications. Furthermore, the combination of bioactive compounds with nanomaterial provides the opportunity in drug systems to overcome drug resistance, reduce drug-related side effects and develop new pharmaceutical agents. This dissertation aimed to synthesize and characterize of novel Cu(II) and Zn(II) complexes of imine derivative ligands of quinoline by condensing 7-chloro-2-hydroxyquinoline-3- carbaldehyde and 2,2’-thiodianiline, and decorated synthesized AgNP functionalized the amino acids with the metal complexes. The study evaluated the Cytotoxicity, antibacterial and antitoxic activity of the as-synthesized complexes. Furthermore, the molecular docking properties of these complexes were assessed. The synthesized pristine and silver nanoparticle decorated metal complexes were characterized using spectroscopic (UV-Vis, FTIR, 1H and 13C), microscopic (SEM-EDX and TEM), thermal (TGA/DTA) and diffraction (XRD) techniques. The biological activities of the synthesized ligand and its metal complexes, as well as their AgNP decorated compounds were evaluated in vitro for antibacterial activity against gram-positive (Staphylococcus aureus) and gram-negative (Escherichia coli and Pseudomonas aeruginosa) bacterial strains and for antioxidant activity using DPPH. In vitro anticancer activity against the MCF-7 human breast cancer cell line was examined for Cu(II) complexes. The molar conductivity and chloride test confirmed the non-electrolytic nature of the Cu(II) and Zn(II) complexes, supporting the proposed octahedral geometry. Furthermore, excellent correlation was observed between the experimental absorption peaks and those calculated using TD-DFT, validating the electronic structure predictions. The pXRD diffractogram analysis revealed that the synthesized ligand and its complexes were polycrystalline systems, with average crystallite sizes of nano level 13.28, 31.47, 11.57, 21.19, 16.26, 25.63, 20.67, 20.83, 19.74, 22.68, and 19.25 nm for imine quinoline ligand (L), CuL, and CuL2, ZnL, ZnL2, AgNP, His-AgNP@L, His-AgNP@CuL, His-AgNP@CuL2, His AgNP@ZnL, and His-AgNP@ZnL2 respectively. The TEM micrograph revealed that the morphology of AgNPs had diameters ranging from 5 – 14 nm. The AgNP@CuL showed maximum growth inhibition of 12.00, 10.00, and 11.33 mm at 50 µg/mL with the MIC of 12.5 µg/mL against S. aureus, E. coli, and P. aeruginosa, respectively. Similarly, AgNP@CuL exhibited the highest antioxidant activities against DPPH radicals with a half inhibition concentration (IC50) of 105.9 ±0.978 µg/mL stress. The CuL complex had the highest cytotoxic potency against MCF-7 breast cancer cells, with an IC50 of 43.82±2.351 µg/mL. All the complexes had strong binding affinities according to the molecular docking investigation with L (-11.31 kcal/mol), ZnL (-11.38 kcal/mol), and ZnL2 (-13.51 kcal/mol) against the active sites of S. aureus, and (-7.92, -8.07, and -8.92 kcal/mol, respectively) against E. coli, highlighting the Zn(II) complexes as potent in biological activity. Similarly the synthesized L and Cu(II) complexes (CuL and CuL2) demonstrated significant binding interactions with S. aureus, E. coli, and ERα. CuL showing the strongest binding energy (-13.82 kcal/mol) and inhibition constant (7.5 × 10-5 µM) against S. aureus, while CuL2 exhibited a strong binding energy (- 8.66 kcal/mol) and inhibition constant (0.45 µM) against ERα, scoring their potential as effective inhibitors.