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This is particularly relevant in kidney disease, where NT concentration in blood is considerably high. Therefore, NT is a crucial biomarker of renal damage, although it has been underestimated in clinical diagnosis due to the lack of an appropriate sensing method. Herein we report the first fluorescent supramolecular sensor for such a relevant compound: Fluorescence by rotational restriction of tetraphenylethenes (TPE) in a covalent cage is selectively quenched in human blood serum by 3\u2010nitrotyrosine (NT) that binds to the cage with high affinity, allowing a limit of detection within the reported physiological concentrations of NT in chronic kidney disease.<\/jats:p>","DOI":"10.1002\/anie.202205403","type":"journal-article","created":{"date-parts":[[2022,5,5]],"date-time":"2022-05-05T11:33:25Z","timestamp":1651750405000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":59,"title":["A Fluorescent Cage for Supramolecular Sensing of 3\u2010Nitrotyrosine in Human Blood Serum"],"prefix":"10.1002","volume":"61","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5719-1491","authenticated-orcid":false,"given":"Lidia A.","family":"P\u00e9rez\u2010M\u00e1rquez","sequence":"first","affiliation":[{"name":"Instituto de Productos Naturales y Agrobiolog\u00eda (IPNA-CSIC)  Avda. Astrof\u00edsico Fco. S\u00e1nchez 3 38206 La Laguna Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3708-0684","authenticated-orcid":false,"given":"Marcelle D.","family":"Perretti","sequence":"additional","affiliation":[{"name":"Instituto de Productos Naturales y Agrobiolog\u00eda (IPNA-CSIC)  Avda. Astrof\u00edsico Fco. S\u00e1nchez 3 38206 La Laguna Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0699-3894","authenticated-orcid":false,"given":"Ra\u00fal","family":"Garc\u00eda\u2010Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"GIR MIOMeT-IU Cinquima-Qu\u00edmica Inorg\u00e1nica Facultad de Ciencias Campus Miguel Delibes Universidad de Valladolid  47011 Valladolid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8008-1696","authenticated-orcid":false,"given":"Fernando","family":"Lahoz","sequence":"additional","affiliation":[{"name":"Departamento de F\u00edsica, IUdEA Universidad de La Laguna  38200 San Crist\u00f3bal de La Laguna Tenerife Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7078-300X","authenticated-orcid":false,"given":"Romen","family":"Carrillo","sequence":"additional","affiliation":[{"name":"Instituto de Productos Naturales y Agrobiolog\u00eda (IPNA-CSIC)  Avda. Astrof\u00edsico Fco. S\u00e1nchez 3 38206 La Laguna Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,5,23]]},"reference":[{"key":"e_1_2_7_1_1","first-page":"3","volume-title":"Advances in Experimental Medicine and Biology, Vol.\u20051165","author":"Lv J.-C.","year":"2019"},{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201510136"},{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/ange.201510136"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.9b12071"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1159\/000469669"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00134-017-4691-6"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0891-5849(96)00401-7"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.289.13.1675"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2000.00046.x"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2012.09.005"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2013.520"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0891-5849(98)00184-1"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijms.15463"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1097\/00024382-200208000-00004"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M501773200"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneph.2009.155"},{"key":"e_1_2_7_16_1","first-page":"F561","volume":"272","author":"Kone B. 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These results could be consistent with a photoinduced electron transfer in which after light irradiation an excited electron of cage\u2005Bis transferred to the LUMO of the quencher (NT). Further investigations will be carried out in the future such as experimental determination of the redox potential as well as computational calculation of the frontier orbitals of the cage and NT."},{"key":"e_1_2_7_64_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrev.7b00568"},{"key":"e_1_2_7_65_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.joc.8b02677"},{"key":"e_1_2_7_66_1","unstructured":"See the Supporting Information."},{"key":"e_1_2_7_67_1","unstructured":"Due to the low quality of the crystals the single-crystal X-ray data was of poor quality and therefore the structure is not presented here. More details can be obtained from the authors on request and in the Supporting Information."},{"key":"e_1_2_7_68_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.6b07087"},{"key":"e_1_2_7_69_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-0-387-46312-4"},{"key":"e_1_2_7_70_1","doi-asserted-by":"publisher","DOI":"10.1021\/ac062160k"},{"key":"e_1_2_7_71_1","doi-asserted-by":"publisher","DOI":"10.1039\/D0CS00495B"},{"key":"e_1_2_7_72_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201310958"},{"key":"e_1_2_7_72_2","doi-asserted-by":"publisher","DOI":"10.1002\/ange.201310958"},{"key":"e_1_2_7_73_1","unstructured":"Actually a much lower association constant was measured for cage\u2005Band TNT in pure organic solvent (ethyl acetate). See the Supporting Information."},{"key":"e_1_2_7_74_1","unstructured":"Unfortunately NMR titrations or ITC experiments were not helpful due to the low solubility of cage\u2005Bin aqueous media: Only the low concentrations employed in the fluorescence and UV experiments allowed a successful evaluation."},{"key":"e_1_2_7_75_1","doi-asserted-by":"publisher","DOI":"10.1039\/C0CS00062K"},{"key":"e_1_2_7_76_1","doi-asserted-by":"publisher","DOI":"10.1039\/D1CS00422K"},{"key":"e_1_2_7_77_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0123652"},{"key":"e_1_2_7_78_1","unstructured":"International conference on harmonisation of technical requirements for registration of pharmaceuticals for human use Q2(r1): validation of analytical procedures: text and methodology (2005) (https:\/\/database.ich.org\/sites\/default\/files\/Q2(R1)%20Guideline.pdf)."},{"key":"e_1_2_7_79_1","unstructured":"We also calculated LoD based on the measurement of the analytical background response analyzing an appropriate number of blank samples and calculating the standard deviation of these responses. The value obtained for LoD is almost identical (see Supporting Information)."},{"key":"e_1_2_7_80_1","unstructured":"Tyrosine nitration represents one of the most important oxidative protein post-translational modifications in many organisms and it is the most relevant footprint of peroxynitrite in biological systems although other nitrated compound can be formed such as nitro-tryptophan but in way lesser amounts. See Ref.\u2005[47]."},{"key":"e_1_2_7_81_1","unstructured":"Due to the dilution the LoD in pure serum would be 5\u2005times higher which would correspond to renal failure patients with septic shock. See Ref.\u2005[6]."}],"container-title":["Angewandte Chemie International Edition"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/anie.202205403","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/anie.202205403","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/anie.202205403","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T14:03:26Z","timestamp":1760018606000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/anie.202205403"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,23]]},"references-count":92,"journal-issue":{"issue":"28","published-print":{"date-parts":[[2022,7,11]]}},"alternative-id":["10.1002\/anie.202205403"],"URL":"https:\/\/doi.org\/10.1002\/anie.202205403","archive":["Portico"],"relation":{},"ISSN":["1433-7851","1521-3773"],"issn-type":[{"value":"1433-7851","type":"print"},{"value":"1521-3773","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,23]]},"assertion":[{"value":"2022-04-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-05-23","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e202205403"}}