An iridium(III) complex-based luminogenic probe for high-throughput screening of hydrogen sulfide donors in living cells

The scarcity of suitable high-throughput screening technology for hydrogen sulfide (H2S) donors has hampered the discovery of H2S donors. In this study, a long-lived cyclometalated iridium complex was rationally designed as a mitochondria-targeted H2S probe to monitor the real-time dynamic change of H2S. By using the time-resolved emission spectroscopy (TRES) technique, an anti-interference high-throughput screening system was developed to monitor H2S in living cells with decreased false negative results. As a proof-of-concept, three natural products were identified as potential H2S donors from a natural product library using the developed TRES probe. Notably, the discovery of allicin and diallyl trisulfide demonstrated the feasibility of this screening platform, while garlic-derived allyl methyl sulfide was explored as a H2S donor candidate. The results were further validated by a commercial assay. We anticipate this high-throughput platform could facilitate the discovery of H2S donors by discriminating the endogenous interfering fluorescence from biological systems. H2S donors in living cells are essential for modulating H2S levels and have been proposed to be relevant for managing hepatic disorders, but conventional platforms to screen for H2S donors are plagued by interference by endogenous background fluorescence signals. Here, the authors develop a luminogenic probe—based on an Ir(III) complex with a 1,10-phenanthroline-5,6-dione moiety—capable of selective response to mitochondrial H2S, and set up an anti-interference high-throughput screening system capable of distinguishing target signals from complex background autofluorescence in living cells.