Preparation, Characterization, In Vitro Biological Evaluation, DFT Calculations, and Molecular Docking Investigations of 1H‐Imidazole‐2‐Carboxylic acid and Histidine‐Based Mixed‐Ligand Complexes

Abstract

Mixed‐ligand complexes incorporating 1H‐Imidazole‐2‐Carboxylic acid (IMCA) and Histidine (LHIS) show promise for biomedical and biotechnological applications. This study synthesizes and characterizes FeIMCALHIS, CoIMCALHIS, and NiIMCALHIS coordination compounds using metal chloride salts (FeCl3.6H2O, CoCl2.6H2O, NiCl2.6H2O) in ethanolic solutions. The complexes are characterized by spectroscopic methods (IR, UV‐vis, and mass spectra), elemental analysis, conductivity, magnetic, and thermal analysis. Molar conductivity indicates their non‐electrolytic nature. UV‐vis spectra reveal absorption bands with pathochromic shifts, and electronic spectra show characteristic metal‐ligand transitions, indicating their structural configuration and coordination geometry. 3D geometry optimization shows six‐coordination around Fe(III) and Co(II) in FeIMCALHIS and CoIMCALHIS, and four‐coordination around Ni(II) in NiIMCALHIS. Analysis of the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) suggests decreased electron donation ability upon coordination. Electronic structure parameters (HOMO, LUMO, ionization potential, energy gap, electron affinity, chemical potentials, and electronegativity) provide further insights into stability and reactivity. The metal complexes exhibit enhanced antimicrobial, antioxidant, and anti‐inflammatory activity compared to individual ligands, with FeIMCALHIS showing notable antimicrobial activity. Molecular docking analysis reveals strong binding interactions with target proteins, highlighting their potential therapeutic applications.