Design,Synthesis And Performance Of A Series Of Fluorescence Probes For Sensing Carbon Monoxide

Carbon monoxide（CO）is a colorless and odorless gas,and has higher affinity to hemoglobin than oxygen（O₂）,which causes hemoglobin to lose its ability and function to carry oxygen easily.When the concentration of CO is too high in the environment,it competes with the oxygen in the blood for hemoglobin,which reduces the concentration of oxygen in the blood,causing asphyxiation and even death.Recent studies have shown that CO can be produced internally during the degradation of heme by heme oxygenase.It is an important multi-functional signal molecule and plays an important role in maintaining the normal operation of life.However,the abnormal concentration of endogenous CO is closely related to the occurrence and deterioration of various diseases,including inflammatory diseases,lung diseases,cardiovascular diseases and even cancer.Therefore,non-invasive real-time monitoring of the concentration of CO in organisms is very important for the prevention of related diseases.Among the numerous detection methods,fluorescent probe stands out due to its advantages of non-invasive,specificity,high sensitivity,real-time response.At present,a series of CO fluorescent probes have been developed.However,there are still some urgent problems in the detection process.Based on the current research status,three fluorescent probes are reasonably designed and synthesized for the specific detection.And their spectral properties and bioimaging applications are also studied.The specific content includes the following aspects:（Ⅰ）Due to the absence of fluorescent probe which could precisely detect CO in endoplasmic reticulum,we reasonably designed and synthesized the first novel CO fluorescent probe（Na-CM-ER）with endoplasmic reticulum targeting characteristics.The classic dye naphthalimide in Na-CM-ER was selected as the fluorescence platform.Under the trigger of CO,Na-CM-ER constructed intramolecular charge transfer（ICT）mechanism by reducing nitro group to amino group（Na-ER-NH）.Na-CM-ER showed excellent response speed,selectivity,photostability and fluorescence response ratio in vitro.In addition,Na-CM-ER was successfully used to monitor CO in endoplasmic reticulum of living cells in situ.（Ⅱ）Ratiometric fluorescent probe can effectively avoid the background interference,is a very appealing design strategy.Many ratiometric CO probes have been reported,however,mose exhibit（<600 nm）after reacting with CO.This means that probes with short emission wavelengths may be susceptible to autofluorescence,which is disadvantageous to biological imaging,particularly in vivo imaging.Therefore,it is urgent to develop ratiometric CO fluorescent probes working at long wavelengths.The ratiometric CO fluorescent probe（Hcy-CO）was designed and synthesized based on Tsui-Trost reaction.The probe exhibits ideal response speed（<10 s）,long emssion（>600 nm）,high signal-to-noise ratio,high selectivity towards CO.Biological imaging experiments results show that Hcy-CO has succeeded in detecting exogenous and endogenous CO in living cells.Importantly,it has ability for imaging CO in living zebrafish.Overall,Hcy-CO could be a useful molecular tool for imaging CO with long-wavelength emission in vitro and in vivo.（Ⅲ）Aiming at the lack of fluorescent probes for detecting mitochondrial SO₂precisely in cancer cells,we have reasonably designed and synthesized a biotin-guided and mitochondria-targeting SO₂fluorescent probe（NS）.Naphthalimide and hemicyanine were combined to construct a fluorescence platform for NS.Under the trigger of SO₂,NS exhibited ratiometric fluorescence signal response.Probe NS has advantages of fast response,high sensitivity and good selectivity to SO₂.At the same time,the results of biological imaging experiments indicated that the probe NS has excellent specific property of cancer cell and mitochondria,and has ability to monitor SO₂in mitochondria of cancer cells.In addition,probe NS has succeeded in visualizing SO₂in living zebrafish.