{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T11:51:38Z","timestamp":1781697098344,"version":"3.54.5"},"reference-count":19,"publisher":"Wiley","issue":"20","license":[{"start":{"date-parts":[[2026,4,5]],"date-time":"2026-04-05T00:00:00Z","timestamp":1775347200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,4,5]],"date-time":"2026-04-05T00:00:00Z","timestamp":1775347200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Angew Chem Int Ed"],"published-print":{"date-parts":[[2026,5,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    We previously proposed that cationic oligoimidazolium (OIM) carbon acids kill bacteria via an N\u2010heterocyclic carbene (NHC)\u2010assisted translocation process to reach intracellular targets. Herein, we found that the linkers joining the imidazolium rings in OIM chains profoundly affect the oligomers\u2019 cytosolic uptakes, which correlate with their antibacterial potency. In a hydrophobic environment (DMSO) mimicking a bacterial membrane bilayer, different OIM NHCs were found to be non\u2010transient, and persistent, but with measured half\u2010lives varying from 15.6 to 75.9\u00a0min, depending on the linkers and indicating that increased linker\u2010NHC interaction stabilizes the NHC and leads to increased NHC lifetimes. NHC is more hydrophobic than the precursor imidazolium charge, so that linker\u2010stabilized NHCs with longer lifetimes result in increased observed OIM net hydrophobicity measured via LC\u2010MS retention time. More hydrophobic OIM copolymers persist in membranes rather than translocate to the cytosol, and vice versa. A lead compound\n                    <jats:bold>(15)<\/jats:bold>\n                    shows superior efficacy against extended\u2010spectrum beta\u2010lactamase\n                    <jats:italic>Klebsiella pneumoniae<\/jats:italic>\n                    in a murine thigh infection model. This study establishes linker\u2010stabilized NHC in the membrane as a key handle to tune the antibacterial efficacy of cationic carbon acids, providing insights for rational design of next\u2010generation cationic antimicrobials to tackle multi\u2010drug\u2010resistant bacteria.\n                  <\/jats:p>","DOI":"10.1002\/anie.202517460","type":"journal-article","created":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T03:15:52Z","timestamp":1775445352000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Varying Carbene Persistence in Membrane as a Mechanism for Modulating Antibacterial Carbon Acid Oligomer Killing Efficacy"],"prefix":"10.1002","volume":"65","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-0818-981X","authenticated-orcid":false,"given":"Quang Huy Nhat","family":"Vu","sequence":"first","affiliation":[{"name":"School of Chemical and Biomedical Engineering Nanyang Technological University  Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-1994-3380","authenticated-orcid":false,"given":"Chongyun","family":"Tan","sequence":"additional","affiliation":[{"name":"School of Chemical and Biomedical Engineering Nanyang Technological University  Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mallikharjuna Rao","family":"Lambu","sequence":"additional","affiliation":[{"name":"School of Chemical and Biomedical Engineering Nanyang Technological University  Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Chemical and Biomedical Engineering Nanyang Technological University  Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiow Han","family":"Tan","sequence":"additional","affiliation":[{"name":"School of Chemical and Biomedical Engineering Nanyang Technological University  Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7726-0041","authenticated-orcid":false,"given":"Chong Hui","family":"Koh","sequence":"additional","affiliation":[{"name":"School of Chemical and Biomedical Engineering Nanyang Technological University  Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8148-4216","authenticated-orcid":false,"given":"Panyawut","family":"Tonanon","sequence":"additional","affiliation":[{"name":"School of Chemical and Biomedical Engineering Nanyang Technological University  Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangmin","family":"Wei","sequence":"additional","affiliation":[{"name":"School of Chemical and Biomedical Engineering Nanyang Technological University  Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard D.","family":"Webster","sequence":"additional","affiliation":[{"name":"School of Chemical and Biomedical Engineering Nanyang Technological University  Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3761-7517","authenticated-orcid":false,"given":"Mary B.","family":"Chan\u2010Park","sequence":"additional","affiliation":[{"name":"School of Chemical and Biomedical Engineering Nanyang Technological University  Singapore"},{"name":"Lee Kong Chian School of Medicine Nanyang Technological University  Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,5]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/healthcare11131946"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.2147\/IDR.S173867"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s44222\u2010023\u201000143\u20104"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1039\/D1SC05835E"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010025\u201061724\u2010y"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja039890j"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1128\/aac.00355\u201023"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja0482536"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2011024117"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkad274"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010025\u201064828\u20107"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1128\/jb.186.10.3259\u20103261.2004"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2020.01007"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics9020092"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja00052a028"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.electacta.2015.06.129"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.electacta.2014.11.135"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/celc.201600187"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1128\/aac.44.9.2382\u20102388.2000"}],"container-title":["Angewandte Chemie International Edition"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/anie.202517460","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/anie.202517460","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/anie.202517460","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T10:53:16Z","timestamp":1781693596000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/anie.202517460"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,5]]},"references-count":19,"journal-issue":{"issue":"20","published-print":{"date-parts":[[2026,5,11]]}},"alternative-id":["10.1002\/anie.202517460"],"URL":"https:\/\/doi.org\/10.1002\/anie.202517460","archive":["Portico"],"relation":{},"ISSN":["1433-7851","1521-3773"],"issn-type":[{"value":"1433-7851","type":"print"},{"value":"1521-3773","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,5]]},"assertion":[{"value":"2025-08-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-22","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-05","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e17460"}}