Effect of Ligand Length on Antibacterial Activity of Ultrasmall Gold Nanoparticles

Three different length ligands (3/6/11-aminopropylthiol hydrochloride (APT/AHT/AUT)) were modified onto the surface of ultrasmall (d < 3 nm) gold nanoparticles (AuNPs) to investigate the ligand length on their antibacterial performance. Compared with the medium-chain AHT-AuNPs, both the short-chain APT-AuNPs and the long-chain AUT-AuNPs exhibited better antibacterial activity against Escherichia coli and Staphylococcus aureus. Antibacterial mechanistic investigations revealed that the adsorption efficiency of AHT-AuNPs on bacterial membranes was significantly lower compared with APT-AuNPs and AUT-AuNPs. This resulted in reduced membrane disruption, decreased ATP depletion, and diminished ROS generation by AHT-AuNPs relative to APT-AuNPs and AUT-AuNPs, ultimately leading to a lower antibacterial efficacy of AHT-AuNPs compared with APT-AuNPs and AUT-AuNPs. This study offers novel insights into the correlation between the structural features of ultrasmall AuNPs and their antibacterial efficacy, serving as a valuable reference for optimizing the ligand chain length in the development of high-performance nanoantibacterial materials.