{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T20:44:57Z","timestamp":1791924297948,"version":"4.3.4"},"reference-count":27,"publisher":"American Chemical Society (ACS)","issue":"40","license":[{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007465","name":"Universitetet i Troms?","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007465","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,13]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Antibiotic resistance is a major global health challenge, with the rapid spread of metallo-\u03b2-lactamase (MBL)-expressing bacteria presenting a serious clinical threat. In this study, we synthesized and investigated a series of novel cephalosporin conjugates envisioned to release MBL inhibitors upon MBL-mediated hydrolysis. The designed compounds consist of a cephalosporin core linked to trifluoromethylated aliphatic thiol-based MBL inhibitors. Conjugates releasing aliphatic thiols upon hydrolysis by the New Delhi Metallo-\u03b2-lactamase-1 (NDM-1) were identified, confirming that fluorination improves the leaving group properties of some aliphatic thiols compared to a nonfluorinated control. However, when comparing with a conjugate containing an aromatic thiol, fluorinated aliphatic thiol release appeared slower and mechanistically more complex, thus incompletely resolved. The conjugates exhibited potent inhibitory activity against several subclass B1 MBLs. In addition, the utility of 19F NMR as an alternative method for hydrolysis monitoring was exemplified. The findings highlight the potential, but also some unsolved challenges, of altering the leaving group ability of aliphatic thiol-based inhibitors to exploit the catalytic activity of NDM-1 for the selective release of inhibitors in MBL-producing bacteria.<\/jats:p>","DOI":"10.1021\/acsomega.6c07917","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T20:02:15Z","timestamp":1790798535000},"page":"61913-61920","source":"Crossref","is-referenced-by-count":0,"title":["Fluorinated Aliphatic\nThiols in the Design of Cephalosporin\nConjugates for Metallo-\u03b2-Lactamase Inhibition"],"prefix":"10.1021","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-0854-6715","authenticated-orcid":true,"given":"Alexandra","family":"Kondratieva","sequence":"first","affiliation":[{"name":"UiT The Arctic University of Norway , , ,","place":["Troms\u00f8, Norway, NO-9037"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip","family":"Rainsford","sequence":"additional","affiliation":[{"name":"UiT The Arctic University of Norway , , ,","place":["Troms\u00f8, Norway, NO-9037"]},{"name":"University of Copenhagen , , ,","place":["Copenhagen, Denmark, 2200"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Perwez","family":"Bakht","sequence":"additional","affiliation":[{"name":"Indian Institute of Technology , , , ,","place":["Roorkee, Uttarakhand, India, 247667"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7965-8176","authenticated-orcid":true,"given":"Ranjana","family":"Pathania","sequence":"additional","affiliation":[{"name":"Indian Institute of Technology , , , ,","place":["Roorkee, Uttarakhand, India, 247667"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3481-200X","authenticated-orcid":true,"given":"Annette","family":"Bayer","sequence":"additional","affiliation":[{"name":"UiT The Arctic University of Norway , , ,","place":["Troms\u00f8, Norway, NO-9037"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,9,30]]},"reference":[{"key":"2026101315084350100_cit1","doi-asserted-by":"publisher","first-page":"1623","DOI":"10.1039\/D1MD00200G","article-title":"\u03b2-Lactam Antibiotic Targets and Resistance Mechanisms:\nfrom Covalent Inhibitors to Substrates","volume":"12","author":"Mora-Ochomogo","year":"2021","journal-title":"RSC\nMed. 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Pat."},{"key":"2026101315084350100_cit5","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1111\/j.1749-6632.2012.06796.x","article-title":"Metallo-\u03b2-Lactamase\nStructure and Function","volume":"1277","author":"Palzkill","year":"2013","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"2026101315084350100_cit6","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1038\/s41579-019-0159-8","article-title":"Interplay Between\n\u03b2-Lactamases and New \u03b2-Lactamase\nInhibitors","volume":"17","author":"Bush","year":"2019","journal-title":"Nat. Rev. Microbiol."},{"key":"2026101315084350100_cit7","doi-asserted-by":"publisher","first-page":"1427","DOI":"10.1111\/cbdd.13526","article-title":"Approaches for the Discovery of Metallo-\u03b2-Lactamase Inhibitors:\nA Review","volume":"94","author":"Shi","year":"2019","journal-title":"Chem. Biol. Drug Des."},{"key":"2026101315084350100_cit8","doi-asserted-by":"publisher","first-page":"2282","DOI":"10.1039\/b802311e","article-title":"Structural Basis for the Broad-Spectrum Inhibition\nof Metallo-\u03b2-Lactamases by Thiols","volume":"6","author":"Lienard","year":"2008","journal-title":"Org.\nBiomol. Chem."},{"key":"2026101315084350100_cit9","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/B978-0-443-18611-0.00036-X","article-title":"Chapter\n14 - Thiols as a Privileged Scaffold Against Metallo-\u03b2-Lactamases","volume-title":"Privileged Scaffolds in Drug\nDiscovery","author":"Chen","year":"2023"},{"key":"2026101315084350100_cit10","doi-asserted-by":"publisher","first-page":"711","DOI":"10.1021\/acsinfecdis.7b00094","article-title":"Thiol-Containing Metallo-\u03b2-Lactamase Inhibitors\nResensitize Resistant Gram-Negative Bacteria to Meropenem","volume":"3","author":"Tehrani","year":"2017","journal-title":"ACS Infect. 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Fluor.\nChem."},{"key":"2026101315084350100_cit27","doi-asserted-by":"publisher","first-page":"8578","DOI":"10.1021\/bi050302j","article-title":"Inhibitors\nof Metallo-\u03b2-Lactamase Generated from \u03b2-Lactam Antibiotics","volume":"44","author":"Badarau","year":"2005","journal-title":"Biochemistry"}],"container-title":["ACS Omega"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acsomega.6c07917","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/acsodf\/article-pdf\/11\/40\/61913\/68717199\/acsomega.6c07917.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/acsodf\/article-pdf\/11\/40\/61913\/68717199\/acsomega.6c07917.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T19:50:15Z","timestamp":1791921015000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/acsodf\/article\/11\/40\/61913\/5442746\/Fluorinated-Aliphatic-Thiols-in-the-Design-of"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,30]]},"references-count":27,"journal-issue":{"issue":"40","published-online":{"date-parts":[[2026,9,30]]},"published-print":{"date-parts":[[2026,10,13]]}},"URL":"https:\/\/doi.org\/10.1021\/acsomega.6c07917","relation":{},"ISSN":["2470-1343"],"issn-type":[{"value":"2470-1343","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,30]]}}}