Design,Synthesis And Application Of A Series Of Fluorescence Probes For Sensing Of Sulfur Dioxide Derivatives

Sulfur dioxide?SO₂?has been recognized as a serious environmental pollutant.Excessive intake of SO₂ may cause some respiratory diseases,even lung cancer.Sulfur dioxide mainly exists in the form of SO₃^2-or HSO₃^-in vivo and it can be produced endogenously by cysteine metabolism pathway.SO₂ can regulate cardiovascular and venous relaxation in vivo.However,the specific physiological mechanism of sulfur dioxide derivatives in living system has been not clear.Therefore,it is of great value to develop a method to detect sulfur dioxide derivatives in organism.In addition,the interaction between sulfur dioxide and other related molecules in vivo and the specific physiological relationship have not been studied,such as formaldehyde.From the chemical point of view,formaldehyde can react with sulfur dioxide derivatives,so what about in complex organisms?Will they react with each other in organisms?These problems have not yet been studied.Therefore,it is of great significance to develop a method to detect the interaction between SO₂ and formaldehyde.The fluorescence imaging method combines the fluorescence probe and the micro imaging instrument to realize the detection of the target molecule through the change of the fluorescence signal.This method has many advantages,such as high sensitivity,simple operation,good selectivity,no damage to the sample,real-time in-situ imaging.Therefore,fluorescence imaging is widely used in medicine and environmental science.Based on the literature research,this paper constructs five fluorescent probes for the detection of sulfur dioxide derivatives,which have their own unique properties,and make up for many shortcomings of sulfur dioxide derivatives at present.In the first part,we constructed a two-photon deep-red emission fluorescence probe?CP?for the ratio detection of sulfur dioxide derivatives.The probe combines coumarin with the derivative of pyronin,and uses the benzopyranium salt as the reaction site of sulfur dioxide derivative.The probe has a large conjugated system,which mainly emits red fluorescence.When it interacts with sulfur dioxide derivatives,the conjugated system was interrupted and two-photon coumarin fluorophore is released,so as to realize ratio detection of sulfur dioxide derivatives.In addition,the probe CP can quickly respond to sulfur dioxide derivatives.Before and after the recognition of sulfur dioxide derivatives,the ratio of fluorescence emission displacement and fluorescence intensity changes greatly,and it can detect sulfur dioxide derivatives in living cells.In addition,it can also be used to image sulfur dioxide derivatives in brain tissues and living organism.In the second part,we construct a sulfur dioxide derivative fluorescence probe?TCaP?with high selectivity by adjusting the ability of intramolecular electron-withdrawing.The probe TCaP uses carbazole benzothiazole as the fluorescence platform and benzopyran salt as the reaction site of sulfur dioxide.TCaP mainly shows red emission.After interacting with sulfur dioxide derivatives,it mainly emits blue fluorescence,thus realizing ratio type detection of sulfur dioxide derivatives.TCaP can quickly respond to sulfur dioxide derivatives and is not affected by pH and light.In addition,it has a low detection limit.It is worth noting that TCaP has a high selectivity for sulfur dioxide derivatives,indicating that the selectivity of the probe for sulfur dioxide derivatives can be improved by changing the push-pull electron of the small molecule.The design strategy provides a theoretical basis for the design of high selective fluorescent probes for the recognition of sulfur dioxide derivatives.In the third part,based on the above results and Michael addition reaction characteristics,we carefully designed the first fluorescent probe,CaP,for the reversible detection of sulfur dioxide and formaldehyde.By adjusting the intramolecular electron withdrawing of the probe,the probe not only realizes the high selective recognition of sulfur dioxide,but also realizes the efficient reversibility by formaldehyde.It can recognize sulfur dioxide derivatives quickly,and then be reversible by formaldehyde in a short time.In addition,the probe has good reproducibility and has been successfully used for the real-time reversible detection of exogenous and endogenous sulfur dioxide and formaldehyde.The imaging experiments of zebrafish and mice show that the probe can detect sulfur dioxide and formaldehyde in zebrafish and mice reversibly.We believe that this powerful probe can be used as an effective tool to detect some diseases involving sulfur dioxide and formaldehyde.At the same time,the design strategy of this probe can provide theoretical basis for the detection of other similar molecules.In the fourth part,based on the fluorescence resonance energy transfer?FRET?mechanism,we constructed a reversible fluorescent probe?NP?for the detection of sulfur dioxide and formaldehyde.The probe uses naphthalimide as energy donor and connects it with benzopyran salt by piperazine.Due to the effect of FRET,the probe itself emits red fluorescence of benzopyran salt.After reacting with sulfur dioxide,the FRET process disappears,mainly emitting green fluorescence of naphthalimide.With the addition of formaldehyde,the probe mainly emits red fluorescence.In addition,the probe NP has a high selectivity for sulfur dioxide.It can detect the changes of endogenous and exogenous sulfur dioxide and formaldehyde in cells reversibly,and it is the first time to detect endogenous sulfur dioxide and formaldehyde in living mice.In the fifth part,a reversible fluorescent probe?DP?was constructed to detect sulfur dioxide and formaldehyde in nucleolar region.Based on FRET mechanism,the probe uses danyl chloride as energy donor and benzopyran salt as receptor.After theoretical calculation,the probe can bind to RNA,and it has been successfully used for reversible imaging of sulfur dioxide and formaldehyde in RNA region for the first time.The probe can not only respond to sulfur dioxide and formaldehyde rapidly,but also be successfully used to detect endogenous sulfur dioxide and formaldehyde in living mice.We believe that the probe can be used to explore the physiological diseases which related to sulfur dioxide and formaldehyde in nucleolar region.