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Tuning the Baird aromatic triplet-state energy of cyclooctatetraene to maximize the self-healing mechanism in organic fluorophores

Pati, Avik K. (author)
Weill Cornell Med, Dept Physiol & Biophys, New York, NY 10065 USA.;St Jude Childrens Res Hosp, Dept Struct Biol, Memphis, TN 38105 USA.
El Bakouri, Ouissam (author)
Uppsala universitet,Syntetisk molekylär kemi
Jockusch, Steffen (author)
Columbia Univ, Dept Chem, New York, NY 10027 USA.
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Zhou, Zhou (author)
Weill Cornell Med, Dept Physiol & Biophys, New York, NY 10065 USA.
Altman, Roger B. (author)
Weill Cornell Med, Dept Physiol & Biophys, New York, NY 10065 USA.;St Jude Childrens Res Hosp, Dept Struct Biol, Memphis, TN 38105 USA.
Fitzgerald, Gabriel A. (author)
Weill Cornell Med, Dept Physiol & Biophys, New York, NY 10065 USA.
Asher, Wesley B. (author)
Columbia Univ, Dept Psychiat, New York, NY 10032 USA.;Columbia Univ, Dept Pharmacol, New York, NY 10032 USA.;New York State Psychiat Inst & Hosp, Div Mol Therapeut, New York, NY 10032 USA.
Terry, Daniel S. (author)
Weill Cornell Med, Dept Physiol & Biophys, New York, NY 10065 USA.;St Jude Childrens Res Hosp, Dept Struct Biol, Memphis, TN 38105 USA.
Borgia, Alessandro (author)
St Jude Childrens Res Hosp, Dept Struct Biol, Memphis, TN 38105 USA.
Holsey, Michael D. (author)
Columbia Univ, Dept Psychiat, New York, NY 10032 USA.;Columbia Univ, Dept Pharmacol, New York, NY 10032 USA.
Batchelder, Jake E. (author)
Weill Cornell Med, Dept Physiol & Biophys, New York, NY 10065 USA.;St Jude Childrens Res Hosp, Dept Struct Biol, Memphis, TN 38105 USA.
Abeywickrama, Chathura (author)
St Jude Childrens Res Hosp, Dept Struct Biol, Memphis, TN 38105 USA.
Huddle, Brandt (author)
Weill Cornell Med, Dept Physiol & Biophys, New York, NY 10065 USA.
Rufa, Dominic (author)
Weill Cornell Med, Dept Physiol & Biophys, New York, NY 10065 USA.
Javitch, Jonathan A. (author)
Columbia Univ, Dept Psychiat, New York, NY 10032 USA.;Columbia Univ, Dept Pharmacol, New York, NY 10032 USA.;New York State Psychiat Inst & Hosp, Div Mol Therapeut, New York, NY 10032 USA.
Ottosson, Henrik (author)
Uppsala universitet,Syntetisk molekylär kemi
Blanchard, Scott C. (author)
Weill Cornell Med, Dept Physiol & Biophys, New York, NY 10065 USA.;St Jude Childrens Res Hosp, Dept Struct Biol, Memphis, TN 38105 USA.
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Weill Cornell Med, Dept Physiol & Biophys, New York, NY 10065 USA;St Jude Childrens Res Hosp, Dept Struct Biol, Memphis, TN 38105 USA. Syntetisk molekylär kemi (creator_code:org_t)
2020-09-10
2020
English.
In: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences (PNAS). - 0027-8424 .- 1091-6490. ; 117:39, s. 24305-24315
  • Journal article (peer-reviewed)
Abstract Subject headings
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  • Bright, photostable, and nontoxic fluorescent contrast agents are critical for biological imaging. "Self-healing" dyes, in which triplet states are intramolecularly quenched, enable fluorescence imaging by increasing fluorophore brightness and longevity, while simultaneously reducing the generation of reactive oxygen species that promote phototoxicity. Here, we systematically examine the self-healing mechanism in cyanine-class organic fluorophores spanning the visible spectrum. We show that the Baird aromatic triplet-state energy of cyclooctatetraene can be physically altered to achieve order of magnitude enhancements in fluorophore brightness and signal-to-noise ratio in both the presence and absence of oxygen. We leverage these advances to achieve direct measurements of large-scale conformational dynamics within single molecules at submillisecond resolution using wide-field illumination and camera-based detection methods. These findings demonstrate the capacity to image functionally relevant conformational processes in biological systems in the kilohertz regime at physiological oxygen concentrations and shed important light on the multivariate parameters critical to self-healing organic fluorophore design.

Subject headings

NATURVETENSKAP  -- Kemi -- Analytisk kemi (hsv//swe)
NATURAL SCIENCES  -- Chemical Sciences -- Analytical Chemistry (hsv//eng)

Keyword

self-healing fluorophore
photostability
Baird aromaticity
cyclooctatetraene
single-molecule imaging

Publication and Content Type

ref (subject category)
art (subject category)

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