Fe(iii) and Ni(ii) imidazole-benzimidazole mixed-ligand complexes: synthesis, structural characterization, molecular docking, DFT studies, and evaluation of antimicrobial and anti-inflammatory activities

Abstract

This work delves into the synthesis, characterization, and bioactivity of new metal complexes of imidazole (IM)-based and benzimidazole (BZ)-based ligands with Fe(III) and Ni(II) ions. Broad characterization techniques, including elemental analysis, IR spectroscopy, magnetic moment measurement, electronic spectral analysis, mass spectrometry, thermal analysis, and DFT calculations, confirmed the successful preparation of the complexes with a 1 : 1 : 1 (M : IM : BZ) stoichiometry. The NiBZI M and FeBZIM complexes possessed octahedral geometry, with one and two water molecules coordinated with Fe(III) and Ni(II), respectively. DFT calculations demonstrated that the reduction of the energy gap and increase in softness for the metal complexes resulted from metal coordination, enhancing the reactivity and biological activity of the complexes. The FeBZIM and NiBZIM complexes exhibited strong antimicrobial activity, with both complexes displaying improved efficacy towards Gram-positive and Gram-negative bacteria compared with their corresponding free ligands. Their activities were comparable to the standard antibiotic chloramphenicol. Furthermore, these complexes exhibited good antifungal activity towards Aspergillus niger and Candida albicans, surpassing that of the free ligands. MIC values also ensured enhanced antimicrobial activity of the metal complexes. Other than these properties, the complexes demonstrated significant anti-inflammatory activity, where the FeBZIM complex exhibited the highest activity, with an IC₅₀ value closer to that of the reference drug. Molecular docking studies on the E. coli FabH–CoA complex (PDB ID: 1HNJ) and human cyclooxygenase-2 (COX-2) (PDB ID: 5IKT) revealed that the FeBZIM complex exhibited the highest binding affinity with the formation of several hydrogen bonds with key amino acid residues, suggesting a favorable antibacterial activity. Overall, the newly synthesized FeBZIM and NiBZIM complexes demonstrated immense potential as novel antimicrobial and anti-inflammatory drugs with enhanced efficacy compared with their free ligands.