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We herein report a bioinspired design of next\u2010generation photosensitizers (PSs) that not only effectively produce ROS but undergo fast metabolism after treatment to overcome undesirable side effects. We constructed a series of \u03b2\u2010pyrrolic ring\u2010opening\n                    <jats:italic>seco<\/jats:italic>\n                    \u2010chlorins, termed beidaphyrin (\n                    <jats:bold>BP<\/jats:bold>\n                    ), beidapholactone (\n                    <jats:bold>BPL<\/jats:bold>\n                    ), and their zinc(II) derivatives (\n                    <jats:bold>ZnBP<\/jats:bold>\n                    and\n                    <jats:bold>ZnBPL<\/jats:bold>\n                    ), featuring intense near\u2010infrared absorption and effective O\n                    <jats:sub>2<\/jats:sub>\n                    photosensitization. Irradiation of\n                    <jats:bold>ZnBPL<\/jats:bold>\n                    led to a non\u2010cytotoxic, metabolizable beidaphodiacetamide (\n                    <jats:bold>ZnBPD<\/jats:bold>\n                    ) via in situ generated O\n                    <jats:sub>2<\/jats:sub>\n                    <jats:sup>.\u2212<\/jats:sup>\n                    but not\n                    <jats:sup>1<\/jats:sup>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    , as revealed by mechanistic studies including time\u2010resolved absorption, kinetics, and isotope labeling. Furthermore, water\u2010soluble\n                    <jats:bold>ZnBPL<\/jats:bold>\n                    showed an effective therapeutic outcome, fast metabolism, and negligible phototoxic reactions.\n                  <\/jats:p>","DOI":"10.1002\/anie.202204330","type":"journal-article","created":{"date-parts":[[2022,4,20]],"date-time":"2022-04-20T23:44:38Z","timestamp":1650498278000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":54,"title":["Bioinspired Design of\n                    <i>seco<\/i>\n                    \u2010Chlorin Photosensitizers to Overcome Phototoxic Effects in Photodynamic Therapy"],"prefix":"10.1002","volume":"61","author":[{"given":"Mengliang","family":"Zhu","sequence":"first","affiliation":[{"name":"Beijing National Laboratory for Molecular Sciences College of Chemistry and Molecular Engineering Peking University  Beijing 100871 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National Laboratory for Molecular Sciences College of Chemistry and Molecular Engineering Peking University  Beijing 100871 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingying","family":"Ning","sequence":"additional","affiliation":[{"name":"Beijing National Laboratory for Molecular Sciences College of Chemistry and Molecular Engineering Peking University  Beijing 100871 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Yu","sequence":"additional","affiliation":[{"name":"Beijing National Laboratory for Molecular Sciences College of Chemistry and Molecular Engineering Peking University  Beijing 100871 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruijing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Beijing National Laboratory for Molecular Sciences College of Chemistry and Molecular Engineering Peking University  Beijing 100871 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Quantum Studies Department of Physics and Applied Optics Beijing Area Major Laboratory Beijing Normal University  Beijing 100875 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing\u2010Wu","family":"Wang","sequence":"additional","affiliation":[{"name":"Beijing National Laboratory for Molecular Sciences College of Chemistry and Molecular Engineering Peking University  Beijing 100871 China"},{"name":"Chemistry and Chemical Engineering Guangdong Laboratory  Shantou 515031 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Song","family":"Gao","sequence":"additional","affiliation":[{"name":"Beijing National Laboratory for Molecular Sciences College of Chemistry and Molecular Engineering Peking University  Beijing 100871 China"},{"name":"Chemistry and Chemical Engineering Guangdong Laboratory  Shantou 515031 China"},{"name":"Spin-X Institute and Guangdong-Hong Kong-Macao Joint Laboratory of Optoelectronic and Magnetic Functional Materials South China University of Technology  Guangzhou 510641 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5731-7354","authenticated-orcid":false,"given":"Jun\u2010Long","family":"Zhang","sequence":"additional","affiliation":[{"name":"Beijing National Laboratory for Molecular Sciences College of Chemistry and Molecular Engineering Peking University  Beijing 100871 China"},{"name":"Chemistry and Chemical Engineering Guangdong Laboratory  Shantou 515031 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These data are provided free of charge by the joint Cambridge Crystallographic Data Centre and Fachinformationszentrum KarlsruheAccess Structures service."},{"key":"e_1_2_7_64_1","doi-asserted-by":"publisher","DOI":"10.1021\/j100373a096"},{"key":"e_1_2_7_65_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.6b12419"},{"key":"e_1_2_7_66_1","doi-asserted-by":"publisher","DOI":"10.1039\/C8SC00259B"},{"key":"e_1_2_7_67_1","doi-asserted-by":"publisher","DOI":"10.1063\/1.1730148"},{"key":"e_1_2_7_68_1","doi-asserted-by":"publisher","DOI":"10.1080\/00268976.2017.1402966"},{"key":"e_1_2_7_69_1","doi-asserted-by":"publisher","DOI":"10.1111\/php.12716"},{"key":"e_1_2_7_70_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201507800"},{"key":"e_1_2_7_70_2","doi-asserted-by":"publisher","DOI":"10.1002\/ange.201507800"},{"key":"e_1_2_7_71_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.7b11036"}],"container-title":["Angewandte Chemie International Edition"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/anie.202204330","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/anie.202204330","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/anie.202204330","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T14:01:20Z","timestamp":1760018480000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/anie.202204330"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,3]]},"references-count":76,"journal-issue":{"issue":"28","published-print":{"date-parts":[[2022,7,11]]}},"alternative-id":["10.1002\/anie.202204330"],"URL":"https:\/\/doi.org\/10.1002\/anie.202204330","archive":["Portico"],"relation":{},"ISSN":["1433-7851","1521-3773"],"issn-type":[{"value":"1433-7851","type":"print"},{"value":"1521-3773","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,3]]},"assertion":[{"value":"2022-03-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-05-03","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e202204330"}}