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The lead channel,\n                    <jats:bold>2<\/jats:bold>\n                    , shows outstanding proton transport activity (EC\n                    <jats:sub>50<\/jats:sub>\n                    \u00a0=\u00a013.1\u201314.7\u00a0nM) and high selectivity (H\n                    <jats:sup>+<\/jats:sup>\n                    \/Cl\n                    <jats:sup>\u2212<\/jats:sup>\n                    \u00a0=\u00a0249.7; H\n                    <jats:sup>+<\/jats:sup>\n                    \/Na\n                    <jats:sup>+<\/jats:sup>\n                    \u00a0=\u00a023.9; H\n                    <jats:sup>+<\/jats:sup>\n                    \/K\n                    <jats:sup>+<\/jats:sup>\n                    \u00a0=\u00a045.0), forming transmembrane channels without compromising membrane integrity or facilitating the transport of competing ions. By exploiting the unique acidic tumor microenvironment,\n                    <jats:bold>2<\/jats:bold>\n                    mediates proton influx to acidify the intracellular environment of cancer cells, inducing cell death via ferroptosis. This is evidenced by the downregulation of AKR1B1 and GPX4, corresponding increases in reactive oxygen species (ROS) and malondialdehyde (MDA) levels, and lipid remodeling. Accordingly,\n                    <jats:bold>2<\/jats:bold>\n                    exhibits potent cytotoxicity across multiple cancer cell lines (IC\n                    <jats:sub>50<\/jats:sub>\n                    &lt; 10 \u00b5M) and significantly suppresses tumor growth in vivo without observable systemic toxicity. This work establishes the first artificial proton channel (APC) that induces ferroptosis via channel\u2010mediated intracellular acidification, offering a membrane\u2010targeted anticancer strategy with low propensity for drug resistance.\n                  <\/jats:p>","DOI":"10.1002\/anie.8040741","type":"journal-article","created":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T09:49:09Z","timestamp":1792144149000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Selective Cancer Cell Killing via a Fluorofoldamer\u2010Based Proton Channel That Triggers Ferroptosis"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1656-628X","authenticated-orcid":false,"given":"Zhao\u2010Xi","family":"Zhou","sequence":"first","affiliation":[{"name":"Fujian Provincial Key Laboratory of Molecular Synthesis and Functional Discovery College of Chemistry Fuzhou University  Fuzhou Fujian 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Provincial Key Laboratory of Molecular Synthesis and Functional Discovery College of Chemistry Fuzhou University  Fuzhou Fujian China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9852-2661","authenticated-orcid":false,"given":"Maolin","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Pancreatic Surgery Fuzhou University Affiliated Provincial Hospital  Fuzhou Fujian China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"LiXian","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology School of Pharmacy Fujian Medical University  Fuzhou Fujian China"},{"name":"Fujian Key Laboratory of Natural Medicine Pharmacology Fujian Medical University  Fuzhou Fujian 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