Atomically Precise Trehalose-Capped Au25 Nanoclusters: Synthesis and Tunable Antimicrobial Activity

Abstract

The ability to synthesize well-defined and atomically precise nanoclusters is important both in advancing fundamental understanding of structure–property relationships of nanomaterials and for materials, energy, and biomedical applications. Nonetheless, incorporating bioactive ligands into the nanoclusters poses a significant challenge, mostly due to complex metallophilic interactions and incompatibility with typical synthetic conditions. In this work, we developed a straightforward method for the synthesis of an atomically precise gold nanocluster capped with a carbohydrate ligand, trehalose, Au₂₅Tre₁₈, in one step and in 55% yield. The formation of the nanocluster was enabled by using a mild reducing agent, t-butylamine borane, in a biphasic condition. The structure was confirmed by high-resolution mass spectrometry, optical absorption spectroscopy, and nuclear magnetic resonance (NMR) spectroscopy. 2D DOSY NMR gave a diffusion coefficient of 1.9 × 10⁻¹⁰ m²s⁻¹ and the hydrodynamic diameter of 1.6 nm for Au₂₅Tre₁₈. The CD spectrum of Au₂₅Tre₁₈ indicated chirality, having features differing from other chiral Au₂₅ nanoclusters. The aqueous solution of Au₂₅Tre₁₈ was stable and showed no degradation during a heating and cooling cycle from room temperature to 80°C. In a thiourea (TU)-triggered release assay, Au₂₅Tre₁₈ exhibited enhanced antimicrobial activity against Mycobacterium smegmatis, showing a minimal inhibitory concentration (MIC) four times lower than that of Au₂₅ nanocluster capped with glutathione, Au₂₅SG₁₈. Treating the bacteria at 1 × MIC of Au₂₅Tre₁₈/TU resulted in complete eradication of bacteria, whereas bacteria treated with Au₂₅SG₁₈/TU at the same concentration continued to grow.