Structural, DFT, Molecular Docking and Biological Activity of New Albendazole‐Norfloxacin Mixed‐Ligand Complexes: Promising Metal Complexes for Combating Microbial Resistance and Inflammation

This study presents a comprehensive characterization of the Fe(III) (C1) and Co(II) (C2) complexes that were synthesized from the Albendazole (Alb) and Norfloxacin (Nor) ligands. The complexes exhibit remarkable thermal stability, low water solubility, and a non-electrolytic nature, characteristics that enhance their suitability for diverse applications. Conductivity measurements indicate molar conductivities of 9.85 and 8.59 Ω^-1 cm² mol^-1, confirming their status as neutral molecules. Fourier Transform Infrared (FTIR) spectroscopy reveals significant ligand-metal interactions, marked by shifts in vibrational frequencies that confirm chelation, while Ultraviolet-Visible (UV-Vis) spectroscopy supports the identification of octahedral geometries for both complexes. Magnetic moment assessments align with their electronic configurations, and stoichiometric analysis consistently shows a 1:1:1 ratio, further validated by mass spectrometry. Thermal stability studies highlight anhydrous characteristics and distinct thermal decomposition behaviors, underscoring their structural integrity. Employing Density Functional Theory (DFT) calculations using the B3LYP functional, we evaluate the electronic properties of the ligands and their metal complexes, revealing reduced energy gaps (ΔE) of 2.29 eV for C1 and 2.15 eV for C2, significantly lower than those of the ligands (Alb: 4.61 eV, Nor: 4.17 eV), indicating enhanced reactivity and potential biological activity. Additionally, molecular electrostatic potential (MEP) maps provide insights into charge distributions, suggesting critical regions for interactions with biomolecules. Notably, the results demonstrate that metal coordination significantly enhances antibacterial/anti-fungal activity surpassing both the free ligands and the standard antibiotic Ofloxacin/Fluconazole. Furthermore, the complexes show significant improvement in anti-inflammatory activity by inhibiting protein denaturation more effectively than their ligand counterparts. Molecular docking studies reveal stronger binding affinities and interactions with antimicrobial target proteins 1HNJ and 5IKT, attributed to enhanced hydrophobic interactions and hydrogen bonding. These findings position C1 and C2 as promising candidates for developing effective antimicrobial therapies, highlighting the crucial role of metal ions in enhancing biological reactivity and addressing resistant strains of pathogens.