Facially amphiphilic skeleton-derived antibacterial crown ether/silver ion complexes.

Abstract

Silver and its derivatives have been widely explored for their antibacterial properties in the treatment of bacterial infections. However, the biological toxicity of silver limits its further development and application. In this study, we designed a facially amphiphilic skeleton incorporating crown ether moieties based on the dendrimer D-CA₆-CE. The high-density crown ether units within this structure enable the chelation of silver ions, forming facially amphiphilic skeleton-derived D-CA₆-CE/Ag⁺ complexes. These results indicate that D-CA₆-CE/Ag⁺ can self-assemble into nano-micelles in aqueous solution. D-CA₆-CE/Ag⁺ exhibited high antibacterial activity against Escherichia coli and Staphylococcus aureus, significantly reducing the minimum inhibitory concentrations (MICs) of Ag⁺ to 6.13 ± 0.19 and 7.33 ± 0.13 μg mL^-1, respectively. This antibacterial efficacy surpassed that of silver sulfadiazine, primarily attributed to the enhanced ability to disturb and destroy bacterial membranes by introducing the amphiphilic structure of the cholic acid units. In addition, D-CA₆-CE/Ag⁺ also exhibited lower hemolysis (approximately four times lower) and reduced cytotoxicity compared to silver sulfadiazine. This was likely due to the micellar structure formed by D-CA₆-CE/Ag⁺, which further decreases the direct contact between Ag⁺ and cells. In summary, the D-CA₆-CE/Ag⁺ complex, with its facially amphiphilic skeletons, exhibited superior antibacterial performance and lower biological toxicity than silver sulfadiazine does. These properties highlight its potential as a promising candidate for the treatment of bacterial infections.