Novel Pd(II) Rollover Complexes with Antimicrobial and Antibiofilm Activity

Abstract The escalating global crisis of antimicrobial resistance (AMR) urgently demands the development of structurally diverse antimicrobial agents with novel mechanisms of action, including metal-based compounds. Herein, we report the synthesis and characterization of a series of palladium(II) complexes incorporating the 2-(2′-pyridyl)quinoline (pyqui) ligand. In addition to a simple N^N adduct [Pd(pyqui)(OAc)2] (1), rollover cyclometalation allowed the synthesis of less-common rollover-cyclometalated dimers [Pd(pyqui-H)(μ-OAc)]2 (2) and [Pd(pyqui-H)(μ-Cl)]2 (3), and mononuclear rollover derivatives [Pd(pyqui-H)(OAc)(PPh3)] (4) and [Pd(pyqui-H)(Cl)(PPh3)] (5). The new compounds were comprehensively characterized by elemental analysis, FT-IR spectroscopy, and multinuclear (1H, 13C, 31P) NMR spectroscopy, including two-dimensional experiments. Dynamic NMR studies revealed the coexistence of transoid and cisoid isomers in solution for the cyclometalated dimer 2. The antimicrobial and antibiofilm properties of the complexes were evaluated against clinically relevant Gram-positive bacteria (Staphylococcus aureus, Streptococcus pyogenes), Gram-negative bacteria (Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli), and the fungal pathogen Candida albicans, using agar well diffusion, minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and minimum biofilm inhibitory concentration (MBIC) assays. The rollover mononuclear complexes 4 and 5 were the most active compounds, exhibiting broad-spectrum antibacterial activity together with significant antibiofilm effects, particularly against Gram-positive pathogens.