{
  "abstract": "The biological formation of three-membered rings catalyzed by nonheme-iron and 2-oxoglutarate dependent (Fe/2OG) enzymes incurs a thermodynamic cost paid by the four-electron reduction of molecular oxygen. Inspection, however, suggests that this chemistry is closely related to the Fenton reaction, where the central ferryl complex serves as a more reactive surrogate for hydrogen peroxide. While this sacrifices some of the oxidative power of O₂ to heat, sufficient chemical potential is retained to make small-ring cyclization strongly exergonic while also reducing kinetic barriers to reaction. At the same time, mechanistic features must be introduced that raise the relative activation energies for alternative reaction pathways. Current study of Fe/2OG catalyzed small ring cyclization is helping to identify these features including substrate-cofactor disposition, ferric stabilization and active site preorganization among others that likely work together to define reaction channels and thus determine the reaction outcome.",
  "abstract_shown": true,
  "affiliations": [
    "Division of Chemical Biology & Medicinal Chemistry, College of Pharmacy, University of Texas at Austin, Austin, Texas 78712, United States.",
    "Department of Chemistry, North Carolina State University, Raleigh, North Carolina 27607, United States."
  ],
  "article_type": "review article",
  "arxiv": null,
  "author_total": 2,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Mark W Ruszczycky"
    },
    {
      "affs": [
        1
      ],
      "name": "Wei-Chen Chang",
      "orcid": "0000-0002-2341-9846"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/82qvw616embpb.bib",
  "cited_by": 0,
  "doi": "10.1021/acsbiomedchemau.6c00102",
  "fulltext_url": "https://europepmc.org/articles/PMC13692166",
  "id": "82qvw616embpb",
  "issns": [
    "2694-2437"
  ],
  "landing_url": "https://europepmc.org/article/MED/42921253",
  "language": "eng",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1604|Metal-Catalyzed Oxygenation Mechanisms"
    ]
  ],
  "openalex": "W7171458466",
  "pdf_url": "https://europepmc.org/articles/PMC13692166?pdf=render",
  "pmcid": "PMC13692166",
  "pmid": "42921253",
  "published": "2026-07-25",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/82qvw616embpb.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:21:02Z",
      "native_id": "MED:42921253",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42921253"
    }
  ],
  "subjects": [
    {
      "field": "chemistry",
      "origin": "openalex:1604|Metal-Catalyzed Oxygenation Mechanisms",
      "subfield": "inorganic"
    }
  ],
  "title": "Thermodynamic and Mechanistic Aspects of Small-Ring Formation Mediated by Nonheme-Iron and 2‑Oxoglutarate Dependent Enzymes.",
  "title_text": "Thermodynamic and Mechanistic Aspects of Small-Ring Formation Mediated by Nonheme-Iron and 2‑Oxoglutarate Dependent Enzymes.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:21:02Z",
  "url": "https://research.draconitic.com/paper/82qvw616embpb",
  "venue": "ACS bio & med chem Au",
  "versions": []
}