{
  "abstract": "Voltage sensitive dyes (VSDs) are versatile and powerful reporters of the membrane potential across cell membranes. Thiazolothiazole (TTz) dyes are a promising new class of VSDs with high photostability and low cytotoxicity. However, the mechanistic basis of their voltage sensitivity is unknown. To address this, we developed a new generation of asymmetrically substituted TTz dyes (asym-TTz). They exhibit strong solvatofluorochromism with large Stokes shifts and exceptionally large changes in dipole moments (23–29 D), representing an 80% increase over those of previously reported TTz VSDs. An asym-TTz derivative, TwistTz-P, bearing a carboxyphenyl acceptor group, shows sustained cellular membrane localization and a voltage sensitivity of ∼10% ΔF/F per 100 mV. Computational analysis of TwistTz-P under varying electric fields revealed a pronounced twist on both sides of the TTz bridging unit in the excited state. The degree of twisting was voltage-dependent, exhibiting an increase upon depolarization, consistent with the experimentally observed fluorescence decrease at an identical voltage. In another asym-TTz dye (FlatTz-P), where a carboxypyrazinyl acceptor group was incorporated, excited-state twisting under varying electric fields was negligible and demonstrated no voltage sensitivity. These observations establish electric field-dependent excited-state twisting as a new voltage sensing mechanism, and, additionally, provide a new strategy for creating highly sensitive VSDs.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Chemistry, University of North Carolina at Charlotte Charlotte NC 28223 USA",
    "Department of Chemistry, The University of Chicago Chicago IL 60637 USA",
    "Neuroscience Institute, The University of Chicago Chicago IL 60637 USA",
    "Institute of Biophysical Dynamics, The University of Chicago Chicago IL 60637 USA",
    "Immunoengineering and Bioengineering Institute, The University of Chicago USA",
    "Department of Chemical and Biomolecular Engineering, University of California, Los Angeles Los Angeles CA 90095 USA"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Pranamita Chakraborti",
      "orcid": "0009-0006-3955-2760"
    },
    {
      "affs": [
        1,
        2,
        3,
        4
      ],
      "name": "Rui Fu"
    },
    {
      "affs": [
        0
      ],
      "name": "Lucia M. Wert"
    },
    {
      "affs": [
        0
      ],
      "name": "Charlie A. L. Darby"
    },
    {
      "affs": [
        0
      ],
      "name": "Joy D. Amuzu"
    },
    {
      "affs": [
        1,
        2,
        3
      ],
      "name": "Daphne Oettinger"
    },
    {
      "affs": [
        5
      ],
      "name": "Aditya Nandy",
      "orcid": "0000-0001-7137-5449"
    },
    {
      "affs": [
        1,
        2,
        3,
        4
      ],
      "name": "Yamuna Krishnan",
      "orcid": "0000-0001-5282-8852"
    },
    {
      "affs": [
        0
      ],
      "name": "Michael G. Walter",
      "orcid": "0000-0002-9724-265X"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/c9w18zmb9xe91.bib",
  "cited_by": 0,
  "doi": "10.1039/d6sc04210d",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13598645/",
  "id": "c9w18zmb9xe91",
  "issns": [
    "2041-6520",
    "2041-6539"
  ],
  "landing_url": "https://doi.org/10.1039/d6sc04210d",
  "language": "en",
  "licence": "CC-BY-3.0",
  "licence_label": "CC BY 3.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/3.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Chemistry"
    ],
    [
      "openalex",
      "1607|Molecular Sensors and Ion Detection"
    ]
  ],
  "openalex": "W7161828230",
  "pdf_url": null,
  "pmcid": "PMC13598645",
  "pmid": "42781324",
  "published": "2026-08-25",
  "publisher": "Royal Society of Chemistry",
  "ris": "https://research.draconitic.com/paper/c9w18zmb9xe91.ris",
  "sources": [
    {
      "first_seen": "2026-11-07T12:23:31Z",
      "native_id": "PMC13598645",
      "source": "pmc",
      "url": "https://doi.org/10.1039/d6sc04210d"
    }
  ],
  "subjects": [
    {
      "field": "chemistry",
      "origin": "openalex:1607|Molecular Sensors and Ion Detection",
      "subfield": "physical"
    }
  ],
  "title": "Electric field-dependent excited-state twisting in donor–acceptor thiazolothiazole dyes establishes a new class of cell membrane voltage sensors",
  "title_text": "Electric field-dependent excited-state twisting in donor–acceptor thiazolothiazole dyes establishes a new class of cell membrane voltage sensors",
  "type": "peer-reviewed",
  "updated_at": "2026-11-08T12:21:00Z",
  "url": "https://research.draconitic.com/paper/c9w18zmb9xe91",
  "venue": "Chemical Science",
  "versions": []
}