Mitochondria-targeting NIR fluorescent probe for rapid, highly sensitive and selective visualization of nitroxyl in live cells, tissues and mice

Nitroxyl (HNO) has been reported to possess unique biological and pharmacological performances, and emerged as a novel therapy for congestive heart failure. Recent studies also suggest that HNO may be produced and involved in important metabolisms in mitochondria. However, due to its high reactivity and short life properties, fast, sensitive and selective observation and monitoring of HNO related dynamic changes in mitochondria still remains a great challenge. Herein, we synthesized a mitochondria-targeting near-infrared (NIR) fluorescent probe (DCMHNO) for rapid detection of HNO with remarkably high sensitivity, selectivity and photostability. DCMHNO shows fast response (about 4 min) towards HNO via 2-(diphenylphosphino)benzoyl group through the Staudinger reaction to boost the bright NIR emission (700 nm) with excellent sensitivity (detection limit of 13 nM), high pH stability and very low interference from other species. DCMHNO can selectively locate in mitochondria and visualize exogenous and endogenous HNO in live HeLa cells with high biocompatibility and photostability. The probe could also monitor the interaction between NO and H2S that gives rise to the generation of HNO in live HeLa cells. In addition, DCMHNO was further utilized in ex vivo NIR imaging of HNO in live mouse liver tissues at the depth of about 50 µm. In vivo imaging of HNO with high signal-to-noise ratio in live mice was also realized by using DCMHNO. These remarkable imaging performances could render NIR DCMNHNO as a useful tool to reveal HNO related dynamic changes in live samples.