新型两亲性二芳烯荧光分子的合成及其在细胞成像中的应用

As one of the most promising photoresponsive molecules, diarylethenes have been well-recognized for their excellent photochemical reactivity, thermal stability, fatigue resistance, and potential applications in the fields of functional materials and biochemical analysis. Up to date, most studies on diarylethenes are based on organic solvent systems, resulting in a huge limitation to their applications in biology. In this research proposal, a series of novel amphiphilic diarylethenes will be synthesized according to our novel structural design, which combines a hydrophilic group, diarylethene structural unit, and fluorophore. On the basis of their excellent water solubility and dramatic property changes upon photoirradiation, these molecules will be developed as novel fluorescent probes to realize reversible regulation of the fluorescence of biological systems. The main contents of this proposal include the following research work. 1) Novel amphiphilic PEG- and glycosyl-containing diarylethene core structures will be designed and synthesized. 2) Novel FRET-based amphiphilic diarylethenes will be further constructed by conjugation with various fluorophores with emission wave lengths matching to the absorption maxima of closed-ring form of diarylethene cores. 3) Amphiphilic diarylethene fluorescent probes with low toxicity, high biocompatibility, and multi-addressability will be identified by systematic investigation of their structure-activity relationship, biological screening, and further optimization of the structures, and their applications in bioimaging will also be explored.

二芳基乙烯类化合物是性能最为优越的光致变色体系之一,具有热稳定性好、抗疲劳性强、灵敏度高等优点, 在功能材料和生化分析领域具有广阔的应用前景。迄今，有关二芳烯分子的研究大多局限于有机溶剂体系，这极大地限制了其在生命科学中的应用。本项目采用新的设计思路，拟将亲水基团、二芳烯结构单元和荧光官能团有机结合，合成系列新型两亲性二芳烯荧光分子，利用其良好的水溶性和光致变色前后性质显著改变的特性，构建具有多重调控功能的荧光探针，对染色的生物体荧光进行可逆调控。主要包括：含聚氧乙烯基、糖基等两亲性二芳烯母体分子的设计合成；采用有机合成方法在母体分子中引入多种与其闭环态吸收波长相匹配的荧光官能团，合成系列基于荧光共振能量转移的两亲性二芳烯荧光分子；系统研究目标分子的构效关系，进一步筛选优化，获得具有生物毒性低、生物相容性好和荧光可多重调控等特性的两亲性二芳烯荧光探针分子，并探讨其在细胞荧光成像中的应用。

二芳基乙烯类化合物是性能最为优越的光致变色体系之一,具有热稳定性好、抗疲劳性强、灵敏度高等优点, 在功能材料和生化分析领域具有广阔的应用前景。本项目采用了新的设计思路，将亲水基团、二芳烯结构单元和荧光官能团有机结合，合成系列新型两亲性二芳烯荧光分子。优选部分已经合成的二芳烯化合物作为母体分子，通过分子修饰，在其末端引入功能基团，构建了具有多重调控性能和离子识别性能的二芳烯分子。实现了对二芳烯光致变色性能的多重调控以及对金属离子的传感性能，为该类材料在荧光分子开关和离子传感器中的应用奠定了重要理论和实验基础。首次将二芳烯衍生物引入到活体细胞中，并用于检测活体细胞中的金属离子。通过与金属离子结合前后吸收光谱和荧光光谱的改变，可以快速、选择性地识别环境体系和生物体系中的金属离子。该研究为生化和环境科学领域的快速检测识别技术的发展注入新的生机与活力。