Exploration of Novel Nickel(II) and Copper(II)–Levofloxacin Mixed‐Ligand Complexes: Structural Study, DFT Insights, Molecular Docking, and In Vitro Bioactivity Assessment

ABSTRACT In this study, we combined NiCl 2 and CuCl 2 with levofloxacin (LEV) in the presence of 2,6‐di(1 H ‐pyrazol‐1‐yl)pyridine (DPP) to generate two novel NiLEVDPP and CuLEVDPP mixed‐ligand complexes. Evaluating their antibacterial, antifungal, anti‐inflammatory, and antioxidant properties was the goal. Numerous analytical methods, such as elemental analysis, molar conductivity, electronic spectroscopy, infrared spectroscopy, mass spectrometry, magnetic susceptibility measurements, and thermogravimetric analysis, were used to confirm the chelation process and determine the structures of these complexes. The findings demonstrated that the carbonyl and carboxylic oxygen atoms in LEV and the –C=N– nitrogen of DPP's pyridine and pyrazole rings facilitate coordination between LEV and the metal ions. The octahedral geometries of the Ni(II) (NiLEVDPP) and Cu(II) (CuLEVDPP) complexes were proposed and confirmed by density functional theory (DFT) calculations. In addition, metrics including energy gaps, chemical hardness, softness, chemical potential, and electrophilicity index were studied. Frontier molecular orbitals (HOMO and LUMO) and molecular electrostatic potential (MEP) were also investigated. The synthesized compounds showed remarkable efficiency when tested in vitro against a variety of harmful bacteria and fungi for their antibacterial activities. Additionally, the anti‐inflammatory effects were studied, and the antioxidant activity was evaluated using the DPPH test. The results showed that these novel complexes outperformed the free ligands in terms of antibacterial, antioxidant, and anti‐inflammatory effects. Molecular docking experiments further supported the in vitro results by demonstrating the strong binding affinity and activity of the Ni(II) (NiLEVDPP) and Cu(II) (CuLEVDPP) complexes towards the target receptors 1HNJ, 5IJT, and 5IKT.