Quantitative Monitoring and Visualization of Hydrogen Sulfide In Vivo Using a Luminescent Probe Based on a Ruthenium(II) Complex

Development of novel bioanalytical methods for monitoring of H 2 S is key toward understanding the physiological and pathological functions of this gasotransmitter in live organisms. A ruthenium(II)‐complex‐based luminescence probe, Ru‐MDB (MDB: 4’‐methyl‐[2,2’‐bipyridine]‐4‐yl)methyl 2‐((2,4‐dinitrophenyl)thio)benzoate), was developed by introducing a new H 2 S responsive masking moiety to a red‐emitting Ru II luminophore. Cleavage of this masking group by a H 2 S‐triggered reaction leads to a luminescence “off–on” response. The long‐lived emissions of Ru‐MDB and its reaction product with H 2 S allowed quantitative detection of H 2 S in autofluorescence‐rich human sera and adult zebrafish organs using the time‐gated luminescence mode. Ru‐MDB exhibits red emission, a large Stokes shift, high specificity and sensitivity for H 2 S detection, and low cytotoxicity, which enables imaging and flow cytometry analysis of lysosomal H 2 S generation in live inflamed cells under drug stimulation. Monitoring of H 2 S in live Daphnia magna , zebrafish embryos, adult zebrafish, and mice, was conducted by in vivo imaging using Ru‐MDB as a probe.