Construction Of Novel Hydrogen Sulfide Fluorescent Probes And Their Application In Biological Detection

In recent years,fluorescence imaging has been widely applied in environmental detection,biosensing,disease diagnosis and other fields due to its outstanding advantages such as high sensitivity,real-time detection,high temporal and spatial resolution and non-invasive in situ.Hydrogen sulfide（H2S）is a vital gas signaling molecule in living systems and is involved in a variety of physiological processes including neurotransmitter transmission,cell proliferation and apoptosis,angiogenesis,glycolysis and maintenance of oxidative stress homeostasis.In addition,there is increasing evidence that abnormal expression of H2 S is closely associated with various diseases such as Alzheimer’s disease,hyperlipidemia,hypertension,liver cirrhosis and cancer.In this context,three novel fluorescent probes were constructed in this paper to detect H2 S and applied in imaging studies of various diseases.1.First,a near-infrared hydrogen sulfide fluorescent probe（IX-H₂S）based on isophorone-cyclohexene xanthene was designed and synthesized.The probe IX-H2 S utilizes 2,4-dinitrophenyl（DNP）ether moiety as a fluorescence quencher and a specific recognition receptor for H2 S,showing excellent selectivity.The probe also displayed excellent sensitivity,fast response capability and a large Stokes shift（186nm）.Importantly,the probe was successfully applied not only to the fluorescence detection of exogenous and endogenous H2 S in living cells,but also for in situ imaging of H2 S in tumor-bearing mice,which is expected to provide important information for early cancer diagnosis.2.Encouraged by the excellent performance of the probe in the previous chapter,a fluorescent probe with better performance（DCP-H2S）was synthesized by improving the probe structure for real-time imaging of H2 S in tumor mice.The probe DCP-H2 S not only has a long emission wavelength（770 nm）and a large Stokes shift（200 nm）,but also exhibits a low detection limit and a high fluorescence increase fold for H2 S,which is more favorable for high-contrast fluorescence imaging.In addition,the probe DCP-H2 S not only realized the detection of H2 S levels in 293 T,Caco-2 and CT-26 cells,but also realized the visualization of exogenous H2 S in normal mice and endogenous H₂ S in tumor mice,which has the potential to be an effective tool for early-stage cancer diagnosis.3.Based on the study of H₂S-related diseases,a novel near-infrared fluorescent probe（TX-H2S）was constructed for the detection of H2 S in a model mice of alcoholic fatty liver disease（AFLD）.The probe TX-H2 S not only possesses the advantages of near-infrared emission wavelength（715 nm）and large Stokes shift（125 nm）at the same time,but also shows high specificity,high sensitivity and fast response for H2 S detection.In addition,due to the dual signal quenching mechanism of ICT and PET,the probe exhibits extremely low background fluorescence and was successfully applied to fluorescence image H2 S in live cells as well as AFLD mice,promising to be a reliable tool for monitoring the level fluctuation of H₂ S in alcoholic fatty liver.