含螺环“开-关”结构氟硼二吡咯类荧光染料的构建、可逆荧光“开-关”性能调控及应用

Fluorescent dyes with reversible switching“on-off” fluorescence properties have found wide applications in the design of fluorescent probes and in super-resolution fluorescent imaging areas. Among those, boron dipyrromethene (BODIPY) dyes have found wide applications in chemistry, enviroment and biomedicine areas due to their excellent photophysical properties, including high extinction coefficients, excellent fluorescence quantum yields, good photostability, and relatively long emission wavelengths. In this project, we will develop several new types of BODIPY derived spiro-complexes with reversible ring opening-closing properties, investigate their efficient synthesis, and the new mild efficient methods to regulate the reversible "opening-closing" of the spiro structure and the "off-on" fluorescence properties of these dyes. We will also investigate the effects of the conjugation pathway of the dye, the electronic and steric effects of substituents and the type/position of spiro ring on the reactivity and effeciency of the reversible ring opening-closing transformation reaction and the "off-on" fluorescence properties. Based on the structure-properties relationship investigation, several novel BODIPY spiro probes and super-resolution fluorescent imaging dyes with excellent reversible switching “on-off” fluorescence properties will be developed and their application will be investigated. The success of this project will promote the further applications of BODIPY and related organo-boron complexes in biomedicine areas as fluorescence imaging and probes. It will also provide valuable theoretical support for the further development of new types of switching "on-off" fluorescent dyes.

具有可逆荧光“开-关”效应的荧光染料在高灵敏度荧光探针的构建和超高分辨荧光成像等领域具有重要应用。氟硼二吡咯类染料具有优异的光物理化学性能，且易于修饰衍生，在化学、环境和生命科学等领域中得到广泛应用。本项目旨在1）发展系列含螺杂环”开-关“结构氟硼二吡咯类新型染料骨架，发展其高效合成方法；2）发展温和调控其螺杂环结构“开-关“转换及可逆调控其荧光”开-关“性能的新方法；3）研究染料共轭路径，取代基效应(空间和电子效应)和螺环种类及位点对温和调控染料可逆螺环化反应及可逆荧光“开-关”效应的影响规律，分析构效关系；发展几种在分子离子检测和超高分辨率生物成像领域适用的可逆荧光开关分子。该项目研究将会推动氟硼有机染料在荧光探针和生物医学领域的进一步应用；发展新型具有可逆荧光“开-关”效应的设计新思路和合成新方法也为进一步有效设计具有可逆荧光“开-关”效应的有机染料提供理论支撑。

随着荧光技术的广泛应用以及生命科学的不断发展，荧光成像由于具有非物理接触、良好的时间控制性和以及对生物干扰小等优势，广泛应用于荧光免疫，荧光探针，细胞染色等领域，成为获取蛋白、细胞、乃至活体动物等信息的重要手段。因而对高效的活细胞内特异性或可激活性荧光探针有强烈的需求。氟硼二吡咯类染料具有优异的光物理化学性能，已在化学、环境和生命科学等领域中得到较广泛应用。针对活细胞内特异性荧光标记与超高分辨荧光成像领域亟待解决的问题，项目发展了一系列高效修饰衍生氟硼二吡咯类染料的新方法，合成了一系列2,6 -/3,5 -/4-和8-位含不同吸电子能力基团的氟硼二吡咯类衍生物, 构建了系列含螺杂环”开-关“结构氟硼二吡咯衍生物，研究其随pH变化的荧光“开-关”性能及结构和性能的构效关系，发展了几种性能优异和具有超高分辨率生物成像能力荧光分子探针。迄今为止，本项目培养毕业研究生10名，毕业本科生15名；项目共资助发表SCI收录研究论文53篇，获授权国家发明专利2项。本项目的成果进一步推动了氟硼二吡咯染料在荧光成像等生物医学相关领域的应用。