Weak Interaction-Tailored Catalytic Interface of Ultrasmall Gold Nanoclusters as Enzyme Mimics for Enhanced Colorimetric Biosensing

Gold nanoclusters (AuNCs) represent an emerging type of engineered nanomaterials with intrinsic enzymatic activity for both chemical and biological applications, but the catalytic activity of most reported AuNCs remains rather limited. Herein, we report a new, efficient strategy of promoting the peroxidase-mimic activity of AuNCs by tailoring their catalytic interfaces via small molecule-mediated weak interactions. Inspired by the presence of imidazole structures in many biocatalytic centers, we screened a series of imidazole-containing small molecules to evaluate their impact on the enzymatic activity of AuNCs. Through monitoring the absorbance change of 3,3',5,5'-tetramethylbenzidine, 1-methyl-2-imidazolecarboxaldehyde (MCA) was identified to possess the most significant effect on enhancing the peroxidase-mimic activity of glutathione-stabilized AuNCs (GSH-AuNCs) among all the examined molecules. Interestingly, the enhancement effect of MCA on the catalytic activity of these AuNCs was found to be highly reversible and can be switched on/off by simply adding MCA/dialysis treatment. Molecular dynamics simulations and further experimental analysis confirmed that these MCA molecules were adsorbed on the surface of GSH-AuNCs through weak non-covalent interactions. The underlying mechanism analysis suggested that the presence of MCA can efficiently promote the production of center dot OH in the GSH-AuNC system. As a proof of example, we then demonstrated that the presence of MCA can greatly increase the bioanalytical performance of AuNC-based peroxidase mimics, as evidenced by a 65-fold lower LOD for glucose detection of AuNCs@MCA than that using AuNCs only. Finally, the present system has been successfully applied for sensing the blood glucose level of both healthy people and diabetics with promising results.

Automated summary

Through tailored catalytic interfaces via small molecule-mediated weak interactions, the peroxidase-mimic activity of gold nanoclusters (AuNCs) can be significantly enhanced. The small molecule 1-methyl-2-imidazolecarboxaldehyde (MCA) was found to have the most significant effect on enhancing the catalytic activity of glutathione-stabilized AuNCs among all the molecules tested. The presence of MCA promotes the production of center dot OH in the GSH-AuNC system, leading to improved bioanalytical performance of AuNC-based peroxidase mimics.