Peptoid-Based Programmable 2D Nanomaterial Sensor for Selective and Sensitive Detection of H₂S in Live Cells

During the past few decades, a variety of two-dimensional (2D) nanomaterials have been developed through molecular self-assembly. Among them, those assembled from sequence-defined polymers have received particular attention because they enable a programmable display of functional groups, including fluorescent dyes, on their surfaces for applications. On the other hand, due to fluorescence self-quenching, synthesis of 2D nanomaterials exhibiting high fluorescence quantum yields is a significant challenge. Herein, we design and synthesize peptoid-based crystalline 2D nanomembranes (2DNMs) as a biocompatible and programmable sensor for selectively and sensitively detecting H₂S in live cells. This 2DNM sensor is assembled from peptoids covalently attached with H₂S-responsive molecular probes. Compared with its amorphous controls, this crystalline 2DNM sensor exhibits a significantly stronger fluorescence intensity and a higher sensitivity as a result of long-range structural ordering and alignment of H₂S-responsive molecular probes. By sonication-cutting these 2DNM sensors into a colloidal form in an aqueous solution, we further demonstrated the use of colloidal 2DNMs for detecting exogenous and endogenous H₂S inside cells and targeted cell organelles. Because peptoids are biocompatible and peptoid-based 2DNMs are programmable, we expect that this class of 2DNM sensors offer great potential for detecting H₂S in live cells and for investigating H₂S-related diseases.