Synthesis and Exploration of Highly Fluorescent Thiazolothiazole Molecular Sensors for Probing Membrane Potential Dynamics

项目摘要： 这个项目的长期目标是了解如何高度荧光和 电荷变化对光稳定性噻唑分子传感器的影响 细胞膜中的场。追踪细胞膜电位的变化 提供了深入了解复杂且快速的 改变细胞生理学。对于绘制协调的 大脑中神经元的活动。荧光、小分子压敏 染料(VSD)对这一领域的影响很大，但仍有很大的需求 开发具有增强长波发射的新型染料用于成像 厚组织，提高了长期成像的光稳定性，并改善了细胞 膜电压灵敏度。在这个项目中，我们提出了综合和 探索一种独特的高荧光的噻唑并[5，4-d]噻唑染料体系。 Ttz染料是下一代成像工具，因为它们表现出很高的 光化学稳定性，易于制备/修改，表现出快速响应时间， 细胞膜定位良好，细胞毒性可忽略不计，对 细胞膜电位。我们将进行光谱和电化学测试 理解各种杂环分子作用的表征 结构对细胞膜的定位和电压传感。我们会 评估染料的电压敏感性性能，这将提供 用于调节光物理性质以增强其细胞的重要反馈 膜电位敏感度。

Project Abstract: The long-term goal of this project is to understand how highly fluorescent and photostable thiazolothiazole molecular sensors are impacted by changing electric fields in cellular membranes. Tracking the changes in cell membrane potential offers the potential to gain a deep understanding of complex and rapidly changing cellular physiology. This is especially true for mapping the coordinated activity of neurons in the brain. Fluorescent, small molecule voltage sensitive dyes (VSDs) have greatly impacted this field, however there is still a great need to develop new dyes with enhanced long wavelength emission for imaging in thick tissues, improved photostability for long-term imaging, and improved cell membrane voltage sensitivity. In this project, we propose the synthesis and exploration of a unique and highly fluorescent thiazolo[5,4-d]thiazole dye system. TTz dyes are the next generation of imaging tools because they exhibit high photochemical stability, are easy to prepare/modify, show fast response times, good cell membrane localization, negligible cytotoxicity, and are sensitive to cellular membrane potential. We will conduct spectroscopic and electrochemical characterizations to understand the role of various heterocyclic molecular structures on the cell membrane localization and voltage sensing. We will evaluate the voltage sensitivity performance of the dyes, which will provide important feedback for tuning the photophysical properties to enhance their cell membrane potential sensitivity.