细胞器靶向近红外硫醇荧光探针的设计、合成及应用研究

Design and synthesis near-infrared fluorescent probes for biological imaging plays an important role in biological and medical research. This project aims designing and synthesizing near-infrared fluorescent probes of thiols in live cells and model animals. First, we will mix together the near infrared fluorescent dyes and chromene derivatives with a thiol identification site to design and synthesize a series of novel NIR fluorescent probes by adding organelle target groups. Afterwards, it will act as the design platform to regulate the reaction activity and selectivity of thiol by changing the electrical absorption capacity of electron-withdrawing group in the chromene molecule. The nucleophilic attack of thiols to the α,β-unsaturated ketone in chromene moiety would induce the ring-open of chromene and trigger a domino rearrangement reaction to realize the selective identification and sensing of thiols. Furthermore, we expect that these probes would be applicable for monitoring thiols in living cells and organisms and provide new strategies and approaches for biological imaging.

近红外荧光探针的设计合成及应用于生物样品中的荧光分析成像在生物医学研究领域发挥着重要作用。本研究旨在设计合成近红外荧光探针，实现硫醇在活细胞及模式动物中的造影。首先，我们将光学性能优良的近红外荧光染料与具有硫醇识别位点的色烯类分子"熔合"在一起，并向其中引入细胞器靶向基团，设计合成一系列新型近红外硫醇荧光探针。然后，以此探针分子为设计平台，通过改变色烯分子中吸电子基团的吸电能力，来调控色烯分子与硫醇的反应活性和选择性。利用硫醇-色烯“点击”开环，引发分子内发生多米诺重排反应，实现硫醇的选择性识别及传感。并进一步进行细胞及组织的近红外荧光成像，实现活细胞不同区域内硫醇的荧光成像分析。该研究可为生物样品的近红外荧光成像提供新的思路和方法。

本项目致力于近红外硫醇荧光探针的设计与开发，按照项目计划，合成了一系列以色烯类分子为硫醇识别位点的荧光探针，筛选出两种光学性能优良的近红外荧光探针，利用硫醇-色烯“点击”开环，引发分子内发生多米诺重排反应，实现了硫醇的选择性识别及传感，并对活细胞和活体中的荧光成像进行了分析研究。此外，我们对研究内容进行了丰富和拓展，设计合成了一些其他重要的含硫物种硫化氢和亚硫酸氢根的线粒体靶向的近红外荧光探针，探针成功地应用于活细胞内外源性含硫物种的检测，同时，探针还对小鼠和斑马鱼体内的硫醇进行了荧光成像。通过本项目的资助，我们已在J. Am. Chem. Soc., Chem.Sci., Sens. Actuators B: Chem.等刊物发表相关论文7篇；另有3篇研究论文正在整理投稿中。