Silver(I) complexes containing bioactive salicylic acid derivatives: Synthesis, characterization, antibacterial activity, and their underlying mechanism

Abstract

Recognizing that silver-metallodrugs are a potential source of novel anti-infective therapeutic agents, this work adopts the complexation of biologically active salicylic acid derivatives with inherently antibacterial silver(I) ions as a strategy for developing new antibacterial agents. The synthesized silver(I) complexes were characterized by elemental analysis, spectroscopy, and X-ray diffraction analysis. The crystallographic results indicate that the silver(I) ion in complexes [Ag(imH)₂](SalH) (1) and [Ag(imH)₂](DiSalH)·H₂O (2) only coordinates with the imidazole nitrogen atom, while the 4-aminosalicylic acid in complex [Ag(imH)₂(AmSalH)]·H₂O (3) additionally coordinate with the silver(I) ion through the amino nitrogen atom. Salicylic acid molecules play an important role in the construction of the three-dimensional network structure through weak interactions. In addition, thermogravimetric analysis, stability, and silver(I) ion release experiments indicate that these complexes have good stability and slow ion release rates. Cell toxicity and antibacterial tests were conducted on selected cell lines and microorganisms using complexes 1–3, and compared with silver(I) salts, organic ligands, and antibiotic. All complexes exhibit better biocompatibility and certain anti-tumor selectivity than silver(I) salts. From the perspective of microbial toxicity, complexes 1–3 all have significant inhibitory effects on three bacteria strains, with complex 1 having the strongest antibacterial activity, exhibiting 4–6 times higher activity against certain strains than AgNO₃ and chloramphenicol. Mechanism studies have shown that cell wall perforation and imbalance of intracellular ROS levels may be possible reasons for silver(I) complexes induced bacterial cell death. The biofilm removal experiment further proves the potential use of silver(I) complexes 1–3 in the treatment of bacterial infections.