同时检测生物活性小分子H2Sn和HNO的荧光探针构建及生物成像研究

生物活性小分子H2Sn和HNO在传导氧化还原信号、调节神经系统等方面具有重要作用；且两者的分子信号通路相互关联。现已报道的分别检测H2Sn、HNO的荧光探针不能准确反映生物体中两者之间的相互关系和作用，而同时检测的荧光探针尚未见报道，亟需开展这方面的研究。.本项目构建基于荧光物质氟硼二吡咯（BODIPY）同时识别H2Sn和HNO的荧光探针，研究将其用于细胞和帕金森症、阿尔兹海默症疾病模型小鼠脑部H2Sn与HNO的成像检测。作为一类光学性能和生物相容性优异的荧光分子，BODIPY的2, 6-位和3, 5-位容易通过化学修饰分别引入与H2Sn、HNO发生特异性化学反应的识别基团，识别后BODIPY产生强度和波长变化的不同荧光信号，实现H2Sn和HNO的可区分性同时检测。该研究从分子水平准确阐明H2Sn和HNO的产生、相互关系、生理作用及信号转导机制，有十分重要的生物学意义。

Hydrogen polysulfides (H2Sn) and nitroxyl (HNO) are very important small molecules with biological activity. They play crucial roles in many physiological processes such as redox signal transduction and regulating the nervous system. Recent years have witnessed the development of a variety of fluorescent probes for in vivo detection of H2Sn or HNO individually. To unravel the complicated interrelationship and cellular cross-talk between H2Sn and HNO, the development of single-molecule as fluorescent probe that can selectively respond to both H2Sn and HNO simultaneously with different fluorescent signals is highly desirable..In this project, we deem to develop BODIPY-based fluorescent probe that can function as a detector for both H2Sn and HNO in living cells as well as disease model mice of Parkinson's disease and Alzheimer's disease. BODIPY has excellent optical properties and good bio-compatibility. Its fluorescence property can be tuned by introducing different substituent group at the 2, 6- or 3, 5- sites. Based on the specific chemical reaction of the target analytes of H2Sn and HNO with their recognition groups anchored on the probe, the probe can respond to both H2Sn and HNO with different signals, thus achieving the selective sensing of H2Sn and HNO in complicate environment of living cells. We anticipate that this study will help to elucidate the generation, correlation and signal transduction mechanism of H2Sn and HNO at the molecular level more accurately, and therefore have potential significance in biological study.