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

University Of North Carolina Charlotte, Charlotte NC

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Abstract

PROJECT SUMMARY The long-term goal of this project is to understand how highly fluorescent thiazolothiazole molecular sensors are impacted by changing electric fields in cellular membranes. Tracking these changes offers the potential to gain a deep understanding of complex and rapidly changing cellular physiology. 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 continued exploration of unique and highly fluorescent thiazolo[5,4-d] thiazole molecular fluorophores. 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 recently developed a highly improved method to synthetically access asymmetric TTz dyes for cell membrane applications. In addition, we are leveraging new insights into the sensing mechanism of the TTz dyes to design molecular probes with even greater cell membrane potential sensitivity. We will conduct spectroscopic and electrochemical characterizations to understand the role of molecular structure on the cell membrane localization and voltage sensing. We will evaluate the cell membrane voltage sensing performance of the dyes, which will provide important feedback for further tuning of their photophysical properties.