{
  "abstract": "Red-light photocatalysis offers opportunities for noninvasive molecular regulation but is challenged by competing pathways that generate cytotoxic reactive oxygen species. Here, we report a protein-controlled photochemical redirection strategy for proximity-activated red-light photocatalytic pharmacology through bioorthogonal deboronative hydroxylation. By integrating a silicon rhodamine (SiR) photocatalyst with a HaloTag scaffold, we establish a protein–photocatalyst hybrid that stabilizes and confines the photoactive open zwitterionic SiR state. Mechanistic studies associate a higher open-state population with preferential Type I photochemical reactivity, supporting superoxide radical anion generation and downstream hydrogen peroxide formation while strongly suppressing singlet oxygen production (ΦΔ = 0.0027). This enables efficient deboronative hydroxylation with yields exceeding 99% and high cellular compatibility. The genetically targetable platform enables proximity-activated pharmacological regulation in living cells. Nuclear-localized release of an HDAC inhibitor increased histone H3 lysine 9 acetylation (H3K9ac) to 2.9 times the control level, compared with 1.9 times the control level following nonlocalized activation under identical conditions, demonstrating that pharmacological outcomes depend on the subcellular site of photocatalytic activation. Photocatalytic activity was also retained through a 1.5 mm tissue barrier under attenuated illumination. These findings establish protein-mediated stabilization and confinement of a photoactive chromophore as a strategy for controlling red-light photochemical reactivity and enabling proximity-activated photocatalytic pharmacology in living systems.",
  "abstract_shown": true,
  "affiliations": [
    "Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences , , 345 Lingling Road , ,",
    "ShanghaiTech University , 100 Haike Road , ,",
    "Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, University of Chinese Academy of Sciences , , ,",
    "School of Chemistry and Material Sciences, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences , 1 Sub-lane Xiangshan , ,"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Ru He"
    },
    {
      "affs": [
        0
      ],
      "name": "Qihang Zhao"
    },
    {
      "affs": [
        2
      ],
      "name": "Zikang Chen"
    },
    {
      "affs": [
        0,
        3
      ],
      "name": "Xiuyu Wang"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Qiaoling Che"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Kaixing Zeng"
    },
    {
      "affs": [
        2
      ],
      "name": "Yi Zeng",
      "orcid": "0000-0003-0694-1795"
    },
    {
      "affs": [
        0
      ],
      "name": "Yixin Zhang"
    },
    {
      "affs": [
        0,
        1,
        3
      ],
      "name": "Yiyun Chen",
      "orcid": "0000-0003-0916-0994"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/d0ta8sgr7z4ea.bib",
  "cited_by": 0,
  "doi": "10.1021/acscentsci.6c01125",
  "fulltext_url": null,
  "id": "d0ta8sgr7z4ea",
  "issns": [
    "2374-7943",
    "2374-7951"
  ],
  "landing_url": "https://pubs.acs.org/acscii/article/doi/10.1021/acscentsci.6c01125/5463487/Protein-Controlled-Photochemical-Redirection",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [],
  "openalex": null,
  "pdf_url": "https://pubs.acs.org/doi/pdf/10.1021/acscentsci.6c01125",
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-04",
  "publisher": "American Chemical Society (ACS)",
  "ris": "https://research.draconitic.com/paper/d0ta8sgr7z4ea.ris",
  "sources": [
    {
      "first_seen": "2026-11-04T12:21:03Z",
      "native_id": "10.1021/acscentsci.6c01125",
      "source": "crossref",
      "url": "https://pubs.acs.org/acscii/article/doi/10.1021/acscentsci.6c01125/5463487/Protein-Controlled-Photochemical-Redirection"
    }
  ],
  "subjects": [
    {
      "field": "chemistry",
      "origin": "issn:2374-7943",
      "subfield": "general"
    }
  ],
  "title": "Protein-Controlled Photochemical Redirection Enables Proximity-Activated Red-Light Photocatalytic Pharmacology",
  "title_text": "Protein-Controlled Photochemical Redirection Enables Proximity-Activated Red-Light Photocatalytic Pharmacology",
  "type": "peer-reviewed",
  "updated_at": "2026-11-06T00:21:08Z",
  "url": "https://research.draconitic.com/paper/d0ta8sgr7z4ea",
  "venue": "ACS Central Science",
  "versions": []
}