Synthesis, Structural\nCharacterization, and Computational\nStudies of Novel Co(II) and Zn(II) Fluoroquinoline Complexes for Antibacterial\nand Antioxidant Activities

Research into heterocyclic\nligands has increased in popularity\ndue to their versatile applications in the biomedical field. Quinoline\nderivatives with their transition metal complexes are popular scaffolding\nmolecules in the ongoing pursuit of newer and more effective bioactive\nmolecules. Subsequently, this work reports on the synthesis and possible\nbiological application of new Zn(II) and Co(II) complexes with a bidentate\nquinoline derivative ligand (H<sub>2</sub><b>L</b>), [(H<sub>2</sub><b>L</b>):(<i>E</i>)-2-(((6-fluoro-2-((2-hydroxyethyl)amino)quinolin-3-yl)methylene)amino)ethanol].\nThe ligand and its metal complexes were structurally characterized\nby spectroscopic methods (<sup>1</sup>H NMR, <sup>13</sup>C NMR, Fourier\ntransform infrared (FTIR), UV–vis, fluorescence, and mass spectroscopy),\nas well as by thermogravimetric and elemental analysis methods. The\nspectroscopic findings were further supported by density functional\ntheory (DFT) and time-dependent (TD)-DFT calculations. The biological\napplication was examined by investigating the inhibitory action of\nthe complexes against bacterial strains using diffusion and agar dilution\nmethods, and their profiles against two Gram-positive and Gram-negative\nbacterial strains were supported by molecular docking analysis. To\nrationalize the <i>in vitro</i> activity and establish the\npossible mechanism of action, the interactions and binding affinity\nof the ligand and complexes were investigated against three different\nbacterial enzymes (Escherichia coli DNA gyrase (PDB ID 6f86), E. coli <i>dihydrofolate</i> reductase B (PDB ID: 7r6g), and Staphylococcus aureus tyrosyl-tRNA synthetase (PDB ID: 1JIJ)) using AutoDock with the standard protocol.\nThe MIC value of 0.20 μg/mL for zinc complex against E. coli and associated binding affinities −7.2\nand −9.9 kcal/mol with <i>DNA</i> gyrase (PDB ID 6f86) and <i>dihydrofolate\nreductase</i> B (PDB ID: 7r6g), as well as the MIC value of 2.4 μg/mL\nfor cobalt(II) complex against Staphylococcus aureus and the associated binding affinity of −10.5 kcal/mol with <i>tyrosyl-tRNA synthetase</i> (PDB ID: 1JIJ), revealed that the complexes’\ninhibitory actions were strong and comparable with those of the standard\ndrug in the experiments. In addition, the ability of the new quinoline-based\ncomplexes to scavenge 1,1-diphenyl-picrylhydrazyl radicals was investigated;\nthe findings suggested that the complexes exhibit potent antioxidant\nactivities, which may be of therapeutic significance.