A Cell Trappable Methyl Rhodol‐Based Fluorescent Probe for Hydrogen Sulfide Detection

Hydrogen sulfide is a biologically important molecule and developing chemical tools that enable further investigations into the functions of H2S is essential. Fluorescent turn‐on H2S probes have been developed for use in cellulo and in vivo, but the membrane permeability of these probes can lead to probe leakage and signal attenuation over time. Here we report a cell trappable fluorescent probe for H2S, CT‐MeRhoAz, which is based on a methylrhodolazide scaffold derivatized with an acetoxymethyl ester group. Prior to ester cleavage, the CT‐MeRhoAz probe generates a 2500‐fold turn‐on response to H2S, which is enhanced to a 3000‐fold response for the carboxylic acid form of the probe. Additionally, the probe is highly selective for H2S over other biologically relevant sulfur, oxygen, and nitrogen‐based analytes. Live cell imaging experiments confirmed the biocompatibility of CT‐MeRhoAz and also that it is cell trappable, unlike the parent MeRhoAz scaffold. A bright cell‐trappable fluorescent probe for H2S is reported that is based on a methylrhodol azide scaffold. Reaction with H2S generates a >2500‐fold fluorescence turn‐on and the probe shows excellent selectivity for H2S over other biological thiols.