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

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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.