Synthesis, characterization and antibacterial activity of new Cu(II), Cu(I) and Ag(I) metal complexes with phenoxy-ketimine Schiff base ligands

The growing threat of antimicrobial resistance (AMR) poses a critical challenge to global health, driven by the misuse of existing antibiotics and a stagnant drug development pipeline. In this context, medicinal inorganic chemistry offers a promising platform for designing new therapeutic agents, particularly through metal-based compounds that provide unique chemical properties unattainable with purely organic molecules. Metallo-drugs have demonstrated potential activity in antimicrobial therapy, especially against multidrug-resistant pathogens. Among these, Schiff bases, versatile ligands known for their metal-chelating capabilities, have been widely investigated due to their broad-spectrum biological activities, including antimicrobial and anticancer effects[1]. Notably, Schiff base metal complexes, particularly those incorporating copper(II), exhibit enhanced biological efficacy compared to their free ligands. In this study, two phenoxy-ketimine Schiff base ligands, 2-(1-(benzylimino)ethyl)phenol (HLBSMe) and 2-((benzylimino)(phenyl)methyl)phenol (HLBSPh), were synthesized and used to prepare a series of Cu(II), Cu(I), and Ag(I) complexes, employing the lipophilic PPh3 and the hydrophilic PTA as co-ligands to stabilize the metal in +1 oxidation state[1]. All species were fully characterized both in the solid state and in solution. Interestingly, the single-crystal XRD of [Cu(LBSPh)2] shows a copper(II) ion in a slightly distorted square planar environment (Figure 1). The antimicrobial activity of the complexes as well as of the corresponding free ligands was evaluated against Escherichia coli (Gram-negative) and Staphylococcus aureus (Gram-positive). Several complexes demonstrated significant antimicrobial activity, with some outperforming their parent ligands and approaching the efficacy of the reference antibiotic ciprofloxacin.