Exploring the enhanced bioactivity and reactivity of novel Fe (III) and Co (II) complexes incorporating sulfadiazine tetradentate ligand: Structural, DFT, molecular docking, and biological applications.

This current work presented the synthesis, characterization and bio-evaluation of new Fe(III) (FePSD), and Co(II) (CoPSD) complexes based on N-[4-amino-5-cyano-6-(methylthio)pyridin-2-yl]-3-oxobutanamide in pyridine afford N-(4-amino-5-cyano-6-(methylthio) pyridin-2-yl)-3-oxo-2-([4-(pyrimidin-2-ylsulfamoyl) phenyl]hydra- zono) butanamide (PSD). Interestingly, the FePSD and CoPSD complexes exhibit notable stability and solubility in organic solvents, with molar conductivity values of 79.35 Ω− 1 cm2 mol− 1 for FePSD and 8.89 Ω− 1 cm2 mol− 1 for CoPSD, indicating a 1:1 electrolytic nature for FePSD and non-electrolytic behavior for CoPSD. FTIR analysis confirmed metal–ligand interactions, as shifts in key bands were observed, while UV–Vis spectra and magnetic moment measurements supported octahedral geometries for both complexes. DFT calculations provided insights into the electronic structure, revealing that CoPSD has higher reactivity and electrophilicity, while FePSD showed moderate reactivity. Thermal and mass spectral analyses further characterized their stoichiometry and stability. The antibacterial and antifungal activities were evaluated against a range of Gram-positive and Gram- negative bacteria and fungal strains. The FePSD and CoPSD complexes demonstrated significantly enhanced antimicrobial efficacy compared to the parent ligand, as evidenced by larger inhibition zones, higher activity indices, and lower minimum inhibition concentrations (MIC). CoPSD exhibited superior antibacterial and anti- fungal activity compared to FePSD, nearing the effectiveness of standard antibiotics and antifungal drugs. Additionally, the anti-inflammatory potential of these compounds was assessed using the egg albumin dena- turation method. Both FePSD and CoPSD showed remarkable inhibition of protein denaturation, surpassing the parent ligand and even outperforming the standard drug Ibuprofen at higher concentrations. The enhancement in biological activity is attributed to the metal chelation effect, which improves cell membrane permeability and reactive oxygen species (ROS) generation. Molecular docking studies further elucidated the binding interactions of PSD, FePSD, and CoPSD with target proteins, revealing stronger hydrophobic interactions and hydrogen bonding in the metal complexes, correlating with their superior biological activity. These findings highlight the potential of FePSD and CoPSD as promising antimicrobial and anti-inflammatory agents.