{
  "abstract": "We present a computationally-guided workflow for designing dual turn-on and ratiometric Raman sensors. The workflow has been used to rationally design activity-based alkyne tagged Raman, ABATaR , sensors that overcome the inherently low Raman sensitivity via strategic placement of electron-donating and electron-withdrawing groups. An ABATaR sensing scaffold designed via the workflow afforded ~ 9000 times higher Raman scattering cross-section than the dimethylsulfoxide C-H stretching-mode. The sensitivity of the scaffold was compared to that of 5-ethynyl-2'-deoxyuridine ( EdU ) to determine Raman intensity versus EdU , RIE, a parameter used to benchmark Raman probes. An RIE value of 170 was obtained which is one of the highest amongst previously reported monoyne and diyne-based Raman probes. The sensitive ABATaR -scaffold was developed into a dual turn-on and ratiometric Fe 2+ -sensor that was applied to distinctly quantify endogenous cellular labile Fe 2+ ion levels. In a key result, live-cell, temporal imaging with the Fe 2+ - ABATaR sensor revealed that intracellular labile Fe 2+ levels progressively increase with ferroptosis while the total Fe-level remains constant. To demonstrate the generalizability of the design workflow, we synthesized an orthogonal ABATaR -sensor for H 2 O 2 . The H 2 O 2 -sensor was applied together with the Fe 2+ -sensor along with inherent Raman peaks for cytochromes to enable simultaneous, multiplexed spontaneous Raman imaging of three distinct ferroptosis hallmarks—labile Fe 2+ , H 2 O 2 , and redox-sensitive cytochrome Raman signals—in living cells. Importantly, the ability to pre-design orthogonal ratiometric Raman sensors and simultaneously track three regulators of ferroptosis via discrete non-overlapping Raman peaks highlights the tremendous potential of Raman sensors toward attaining live cell multiplexed imaging and quantification.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Chemical Sciences",
    "Tata Institute of Fundamental Research",
    "Department of Applied Physics",
    "University of Osaka",
    "Institute for Open and Transdisciplinary Research Initiatives"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Sujit K Das"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Heqi Xi"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Saurabh Kumar"
    },
    {
      "affs": [
        2,
        3,
        4
      ],
      "name": "Katsumasa Fujita"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Ankona Datta",
      "orcid": "0000-0003-0821-6044"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/b21n3xwpdfjcf.bib",
  "cited_by": 0,
  "doi": "10.26434/chemrxiv.15010169/v1",
  "fulltext_url": null,
  "id": "b21n3xwpdfjcf",
  "issns": [],
  "landing_url": "https://chemrxiv.org/doi/full/10.26434/chemrxiv.15010169/v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1607|Molecular Sensors and Ion Detection"
    ]
  ],
  "openalex": "W7221105602",
  "pdf_url": "https://chemrxiv.org/doi/pdf/10.26434/chemrxiv.15010169/v1",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-09",
  "publisher": "American Chemical Society (ACS)",
  "ris": "https://research.draconitic.com/paper/b21n3xwpdfjcf.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:22Z",
      "native_id": "10.26434/chemrxiv.15010169",
      "source": "chemrxiv",
      "url": "https://chemrxiv.org/doi/full/10.26434/chemrxiv.15010169/v1"
    }
  ],
  "subjects": [
    {
      "field": "chemistry",
      "origin": "openalex:1607|Molecular Sensors and Ion Detection",
      "subfield": "physical"
    }
  ],
  "title": "High-Sensitivity, Dual Ratiometric and Turn-on ABATaRs for Multiplexed Temporal Imaging of Ferroptosis Hallmarks in Living Cells",
  "title_text": "High-Sensitivity, Dual Ratiometric and Turn-on ABATaRs for Multiplexed Temporal Imaging of Ferroptosis Hallmarks in Living Cells",
  "type": "preprint",
  "updated_at": "2026-10-30T12:17:22Z",
  "url": "https://research.draconitic.com/paper/b21n3xwpdfjcf",
  "venue": "ChemRxiv",
  "versions": []
}