基于BODIPY染料的生物活性巯基小分子长波长荧光探针的合成及检测

The current proposal is going to design and synthesis Cys, Hcy, GSH, H2S responsive long wavelength visible-NIR "off-on" fluorescent probes based on the platforms of long wavelength BODIPY and NIR Aza-BODIPY fluorophores with appropriate thiol-recognizing functionalities, to overcome the drawbacks of reported fluorescent probes for thiols in sensitivity, selectivity, and detection limit etc. Novel thiol responsive BODIPY NIR fluorescent probes containing constrained pyrroles/constrained pyrroles with extended conjugation, as well as probes with dual thiol responsive systems will be studied. The imaging of thiols in vitro and in vivo, the differentiation of Cys/Hcy in plasma will be carried out as well.

本项目针对已有巯基小分子荧光探针在灵敏度、选择性、检测极限等方面存在的不足，基于长波长可见BODIPY和近红外Aza-BODIPY荧光染料平台，选择适当的巯基识别体系，设计、合成Cys，Hcy，GSH，H2S响应的长波长可见-近红外"关-开"型荧光探针。尝试基于全新并环吡咯及共轭延伸并环吡咯的BODIPY巯基识别近红外荧光探针，探索双巯基识别体系，改善巯基识别荧光探针的选择性，实现细胞及活体内巯基检测的成像研究及血浆中的Cys/Hcy区分检测。

本项目自获国家自然科学基金资助以来，已按计划开展了相关研究，围绕常见巯基识别荧光探针普遍存在的问题，集中在BODIPY和氮杂-BODIPY体系设计了分别针对硫化氢及含巯基氨基酸（Cys，Hcy，GSH）的各种荧光探针，设计、合成了多种Cys，Hcy，GSH，H2S响应的关-开型荧光探针，拓展选择性巯基识别方法，实现细胞及活体内硫醇检测的成像研究；拓展Aza-BODIPY染料的应用，重点解决了：1）荧光探针的水溶性修饰；2）亚细胞器靶向；3）选择性、响应速度等关键问题。围绕关键组分吡咯的制备开展了创新方法研究，成功实现了多种新结构分子的制备。.已发表26篇研究论文，尚有约10篇论文在投稿或组织之中。此外，约3-4篇专利在起草中，预计将于2018年度申请。