Glutathione-Protected Silver Nanoclusters as Cysteine-Selective Fluorometric and Colorimetric Probe

Abstract

The integration of the unique thiol-Ag chemistry and the specific steric hindrance from the organic layer of fluorescent Ag nanoclusters (AgNCs) was first developed in this work to achieve a simple detection of cysteine (Cys) with high selectivity and sensitivity. The key design is a strongly red-emitting AgNC protected by the interference biothiol, glutathione, or GSH (hereafter referred to as GSH-AgNCs), where both the physicochemical properties (Ag surface chemistry and fluorescence) of the NC core and the physical properties (e.g., steric hindrance) of the organic shell were fully utilized for Cys detection with three major features. First, owing to the specific thiol-Ag interaction, the fluorescent GSH-AgNCs showed superior selectivity for Cys over the other 19 natural amino acids (nonthiol-containing). Second, the GSH protecting layer on the NC surface made possible the differentiation of Cys from GSH (or other large-sized thiol molecules) simply by their size. Third, the ultrasmall size of GSH-AgNCs and the high affinity of the thiol-Ag interaction provided high sensitivity for Cys detection with a detection limit of <3 nM. The assay developed in this study is of interest not only because it provides a simple Cys sensor with high selectivity and sensitivity but also because it exemplifies the utilization of the physical properties of organic ligands on the nanomaterial surface to further improve the sensor performance, which could open a new design strategy for other sensor development.