Indole-functionalized naphthalimide: a dual electrochemical and ratiometric fluorescent sensor for detection of hydrogen sulfide

Background: Hydrogen sulfide (H₂S) is a critical reactive sulfur species that serves a vital role in cellular signaling, cardiovascular regulation, and oxidative stress protection. To detect the physiological presence of this small molecule, a new indole-nitronaphthalimide hybrid (INN), wherein the two core units are linked through an acetamide spacer, was synthesized through an imidation reaction between indole-3-acetic acid hydrazide and 4-nitro-1,8-naphthalic anhydride. Results: INN demonstrated sensitivity towards H₂S in electrochemical analysis with a detection limit of 11.04 nM. Electrochemical measurements with INN-coated electrodes in solutions of different pH levels facilitated the elucidation of the underlying redox mechanism. While most fluorescence probes are based on a simple turn-on mode, INN exhibited ratiometric fluorescence sensing of H₂S at physiological pH with a detection threshold of 7.71 mM. The reduction of the nitro group in INN to amino in the presence of H₂S induces a ratiometric change in the fluorescence emission, transitioning from 343 to 547 nm. Live imaging in HEK293T cells confirmed that INN exhibits strong fluorescence in the red channel, highlighting its capability to detect H₂S under physiological conditions. Significance: This small-molecule probe serves as a valuable tool for studying H₂S-mediated biological processes and holds great potential for advancing sulfur chemistry.