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

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.