Synthesis and Characterization of Octahedral Ni(II) and Cu(II) Complexes With Imidazole‐Based Ligands: Structural, DFT, and Molecular Docking, Enhanced Antimicrobial, and Anti‐Inflammatory Activity

ABSTRACT This study presents the synthesis, characterization, and biological evaluation of novel Ni(II) and Cu(II) metal complexes formed with imidazoleacetic acid (IA) and an imidazole‐based ligand (IM). The novelty of this work lies in the development of these metal–ligand frameworks and their enhanced biological properties, which surpass those of their free ligands. A comprehensive suite of analytical techniques, including elemental analysis, IR spectroscopy, magnetic moment measurements, electronic spectra, mass spectrometry, thermal analysis, and DFT calculations, confirmed the successful formation of the NiIAIM and CuIAIM complexes with a 1:1:1 (M:IA:IM) stoichiometry and octahedral geometry. DFT calculations revealed that metal coordination effectively lowered the energy gap, increasing the complexes softness and reactivity, thereby enhancing their predicted biological activity. Antimicrobial studies demonstrated that both NiIAIM and CuIAIM complexes exhibited superior antibacterial potency against Gram‐positive and Gram‐negative bacteria compared to their free ligands, with activity comparable to the standard antibiotic Chloramphenicol. Furthermore, both complexes showed significant antifungal efficacy against Candida albicans and Aspergillus niger , again outperforming the uncoordinated ligands. Minimum inhibition concentration (MIC) values further validate their potent antimicrobial effects. Additionally, the complexes displayed promising anti‐inflammatory activity, with the CuIAIM complex demonstrating the highest potency, approaching the efficacy of standard drugs based on IC 50 values. Molecular docking studies against DNA gyrase B confirmed the CuIAIM complex as the most potent candidate, showing strong binding affinity through multiple hydrogen bonds with key amino acid residues, highlighting its potential antibacterial mechanism. In conclusion, the synthesized NiIAIM and CuIAIM complexes represent promising new antimicrobial and anti‐inflammatory agents, with significantly enhanced biological activity compared to their free ligands. These findings pave the way for further exploration of metal‐based therapeutics in combating infectious diseases and inflammation.