Studies On Design,Synthesis And Applications Of Biothiols-Responsive Fluorescent Probes

In recent years,fluorescent probes are attracting a widespread attention with the benefits of simple operation,high selectivity,good biocompatibility,and real-time tracking visualized imaging in cells,tissues and even in vivo by the confocal imaging technology for the detection of various analytes.Biothiols,such as glutathione(GSH),cysteine(Cys)and homocysteine(Hcy),are an important class of active thiols in organisms,which play crucial roles in maintenance of redox homeostasis inside cellular environment.The alternations in the level of GSH are closely associated with many human diseases states,including liver damage,heart,even cancer and AIDS etc.;Cys could lead to a series of symptoms such as edema,drowsiness and so on;while Hcy was one of the most important health indicators of humans,its excessively high content would reduce immunity,accelerated aging,even cardiovascular and other diseases.However,it’s still a significant challenge for selective and visual distinction between biothiols(e.g.GSH,Cys and Hcy)with similar structures and reactivities.Encouraged by this,in this work,we developed four probes towards Cys or GSH with high selectivity on the basis of predecessors’ research,and then studied their optical properties,recognition mechanism and biological imaging.The main research content is as follows:Firstly,the research progress of fluorescent probes according to the recognition groups in the specific detection of thiols(GSH,Cys or Hcy)was reviewed in detail herein.Secondly,a Cys-responsive fluorescent chemosensors(Ⅱ-1)based on a hemicyanine dye with a long wavelength was synthesized.Investigation showed that the probe displayed rapid response and high selectivity towards Cys over GSH and Hey etc.with a colorimetric and ratiometric change.And it could be applied in visual selective fluorescent bioimaging with dual channel(green and red)towards endogenous and exogenous Cys in living cells.Thirdly,two naphthalimide-based fluorescent probes(Ⅲ-1 and Ⅲ-2)for determining GSH were developed.All could be capable of monitoring GSH with high selectivity and a turn-on fluorescence signal.Interestingly,the oxidation of leaving groups could increase the reaction rate of the probe with GSH according to kinetic tests.Moreover,the sensing behavior showed that they all could selectively respond endogenous and exogenous GSH in living cells.Additionally,both probes could give out a turn-on fluorescence signal upon oxidative stress of sodium hypochlorite.Finally,a ratiometric GSH-responsive probe(Ⅳ-1)was constructed designed via an oxidative strategy based on Ⅲ-1 and III-2.It was capable of efficiently distinguishing GSH from Cys and Hcy with high selectivity and ratiometric change.And bioimaging showed that it could specifically monitor and visualize the endogenous and exogenous GSH in living cells with dual channel(blue and green)imaging.It was worth mentioning that the probe interacted with GSH could also be reduced by excess GSH.Therefore,such oxidation strategy would provide a new idea for the design of thiols sensors.