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    Isomerically Pure Tetramethylrhodamine Voltage Reporters
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    † ‡ § †Department of Chemistry, ‡Department of Molecular & Cell Biology, and §Helen Wills Neuroscience Institute, University of California, Berkeley, California 94720, United States
    *[email protected]
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    Journal of the American Chemical Society

    Cite this: J. Am. Chem. Soc. 2016, 138, 29, 9085–9088
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    https://doi.org/10.1021/jacs.6b05672
    Published July 18, 2016
    Copyright © 2016 American Chemical Society
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    Abstract

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    We present the design, synthesis, and application of a new family of fluorescent voltage indicators based on isomerically pure tetramethylrhodamines. These new Rhodamine Voltage Reporters, or RhoVRs, use photoinduced electron transfer (PeT) as a trigger for voltage sensing, display excitation and emission profiles in the green to orange region of the visible spectrum, demonstrate high sensitivity to membrane potential changes (up to 47% ΔF/F per 100 mV), and employ a tertiary amide derived from sarcosine, which aids in membrane localization and simultaneously simplifies the synthetic route to the voltage sensors. The most sensitive of the RhoVR dyes, RhoVR 1, features a methoxy-substituted diethylaniline donor and phenylenevinylene molecular wire at the 5′-position of the rhodamine aryl ring, exhibits the highest voltage sensitivity to date for red-shifted PeT-based voltage sensors, and is compatible with simultaneous imaging alongside green fluorescent protein-based indicators. The discoveries that sarcosine-based tertiary amides in the context of molecular-wire voltage indicators prevent dye internalization and 5′-substituted voltage indicators exhibit improved voltage sensitivity should be broadly applicable to other types of PeT-based voltage-sensitive fluorophores.

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    The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/jacs.6b05672.

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    Cite this: J. Am. Chem. Soc. 2016, 138, 29, 9085–9088
    Click to copy citationCitation copied!
    https://doi.org/10.1021/jacs.6b05672
    Published July 18, 2016
    Copyright © 2016 American Chemical Society
    Request reuse permissions

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