Imaging mitochondrial hydrogen sulfide in multicellular spheroids using a near-infrared iridium(III) complex

Abnormal levels of hydrogen sulfide (H₂S) have been linked to multiple diseases, including neurological disorders, cardiovascular diseases, and cancers. Mitochondria play a central role in H₂S metabolism, and dysregulation of H₂S within mitochondria is emerging as a key factor in mitochondrial dysfunction. To explore the role of mitochondrial H₂S in live cells, a near-infrared (NIR) iridium(III) complex-based luminescence probe was constructed for the selective and sensitive detection of endogenous mitochondrial H₂S. Complex 1 exhibits a distinct luminescent response to H₂S. Upon exposure to H₂S, the nitro group in complex 1 is reduced to an amine group for triggering a 1,6-elimination reaction, resulting in luminescence quenching. The probe exhibits high-performance detection with low detection limit of 0.96 μM and exceptional specificity in aqueous buffer. Confocal imaging in living HeLa cells confirmed the probe's ability to detect both exogenous and endogenous H₂S. Additionally, the probe specifically localizes to mitochondria, enabling effective bioimaging of mitochondrial H₂S in multicellular spheroids (MCSs). Notably, this study presents the first luminescence probe for mitochondrial H₂S based on a NIR iridium(III) complex. These findings demonstrate that complex 1 is a promising tool for exploring the biological functions and pathological roles of subcellular H₂S in diseases.