Design,Synthesis,and Application Of Bodipy-Based Fluorescent Probes For Biological Thiols

The most abundant intracellular biothiols,such as cysteine?Cys?,homocysteine?Hcy?and glutathione?GSH?,play many crucial roles in biological systems.The endogenous concentrations of these thiols suggest the functional state of the corresponding enzymes and proteins and their abnormal levels correlate with diseases.Therefore,the detection of these small molecular biothiols compounds in organisms with high selectivity and sensitivity is of great significance in improving understanding of their formation,function and metabolism in biological systems.At the same time,it can promote the early diagnosis,intervention and treatment of its related diseases.Recently,fluorescent probes,together with confocal fluorescence imaging techniques,have been widely applied to multicolor imaging,due to their simultaneous and discriminative monitoring of multiple analytes,or dynamic processes for a specific analyte,compared to conventional analytical methods.Furthermore,fluorescent methods are noninvasive,relatively low cost,highly sensitive,and highly selective.Although a few fluorescent probes have been developed to sense and quantify endogenous and exogenous biothiols,only several fluorescent probes that could differential detect Cys/Hcy/GSH have been reported,owing to their similarities in structure and properties and large differences in their concentrations.Herein,based on the past research of our group and previous report,we rationally design and synthesize BODIPY based fluorescent probes with different structures for selective detection of biothiols.In the second chapter,we were curious about the influence of subtle electronic changes on the aromatic ring at 1-?or 7-?position on the S_NAr-rearrangement cascade reaction and designed three new1,3-dimethyl-5,7-diaryl BODIPY-based probes carrying 4-methoxythiophenol moiety at meso position as a good leaving group with various substitution pattern at para position of 7-aryl?electron-withdrawing trifluoromethyl,BDP-CF₃;neutral substituent hydrogen,BDP-H;electron-donating methoxyl,BDP-OMe?for highly selective detection of intracellular Cys and Hcy.Summary,we designed and synthesized three novel BODIPY-based probes,all of which can be highly selective for Cys/Hcy.In addition,we further studied the influence of different electronegativity substituents?electron-withdrawing trifluoromethyl,BDP-CF₃;hydrogen,BDP-H;electron-donating methoxy,BDP-OMe?on these probes to sensing Cys/Hcy.It can be easily concluded from the test results that the electron withdrawing group on the BDP-CF₃ can accelerate the probe's response to Cys/Hcy.Ultimately,BDP-CF₃ was successfully applied for selective imaging Cys/Hcy in living cells.In the third chapter,based on the second chapter,we designed a novel fluorescent probe with different substituents at 1-,7-and 3-,5-sites based on the parent structure of BODIPY.Subsequently,using2-mercaptothiazole as the recognition group and fluorescence quenching group,BDP-Me was constructed.This probe exhibited high selectivity and sensitivity for Cys,and the detection limits were calculated to be as low as 26 nM.These results demonstrate the excellent perspective for the quantitative fluorescence analysis of these important biothiols in living cells and human serum.Therefore,this probe can serve as an effective tool for studies cellular functions that are related to Cys.