Synthesis and structural characterization of zinc(II) carboxylate complexes with antibacterial and in vivo antibiofilm activities.

Six zinc(II) carboxylate complexes were synthesized under reflux reactions and thoroughly characterized by single crystal X-ray diffraction, Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), and elemental analysis. They adopt to two general formulas: mononuclear [Zn(DPAA)2(H2O)2] (1) and binuclear [Zn₂(DPAA)4(L)2] (2-6), where DPAA = diphenyl acetate anion and L represents an ancillary ligand. L used are pyridine (py, 2), 2-chloropyridine (2-chloro-py, 3), 2-methylpyridine (2-methyl-py, 4), 2-aminopyidine (2-amino-py, 5), and 4,7-diphenyl-1,10-phenthroline (dip-phen, 6). Complex 1 exhibits a distorted octahedral geometry, whereas complexes 2-5 are binuclear with a distorted square pyramidal coordination environment; complex 6 also displays a distorted square pyramidal geometry. Antimicrobial assays against staphylococcus aureus (S. aureus) and other selected strains revealed minimum inhibitory concentrations (MICs) values of 300-1617.6 μM for free ligands and 0.9-1374.5 μM for complexes 1-6. Notably complexes 2, 4 and 5 exhibited stronger in vitro antibiofilm activity and a more pronounced inhibitory effect on extracellular proteins (ECPs) of S. aureus at concentrations of 0.25-15 μg/mL compared to vancomycin and complex 1, 3, and 6.In vivo antibiofilm studies demonstrated that complexes 2, 4, and 5 effectively suppressed dental biofilm formation in a rat model and reduced α-hemolysin secretion, with no observable toxicity toward Wi38 and RAW 264.7 cells. Molecular docking analysis indicated that complexes 2, 4, and 5 engage in diverse binding interactions with biofilm-associated proteins (Baps). Taken together, these findings highlight the therapeutic potential of complexes 2, 4, and 5 in addressing bacterial infections and biofilm-associated challenges.