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

Abstract

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.