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As targeting vectors, chelating molecules called siderophores that are released by bacteria to acquire iron have been investigated for conjugation to antibacterials, leading to the clinically approved drug cefiderocol. The use of small\u2010molecule catalysts for prodrug activation within cells has shown promise in recent years, and here we investigate siderophore\u2010linked ruthenium catalysts for the activation of antibacterial prodrugs within cells. Moxifloxacin\u2010based prodrugs were synthesised, and their catalyst\u2010mediated activation was demonstrated under anaerobic, biologically relevant conditions. In the absence of catalyst, decreased antibacterial activities were observed compared to moxifloxacin versus <jats:italic>Escherichia coli<\/jats:italic> K12 (BW25113). A series of siderophore\u2010linked ruthenium catalysts were investigated for prodrug activation, all of which displayed a combinative antibacterial effect with the prodrug, whereas a representative example displayed little toxicity against mammalian cell lines. By employing complementary bacterial growth assays, conjugates containing siderophore units based on catechol and azotochelin were found to be most promising for intracellular prodrug activation.<\/jats:p>","DOI":"10.1002\/chem.202202536","type":"journal-article","created":{"date-parts":[[2022,11,10]],"date-time":"2022-11-10T11:44:12Z","timestamp":1668080652000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Siderophore\u2010Linked Ruthenium Catalysts for Targeted Allyl Ester Prodrug Activation within Bacterial Cells"],"prefix":"10.1002","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3219-1326","authenticated-orcid":false,"given":"James W.","family":"Southwell","sequence":"first","affiliation":[{"name":"University of York Department of Chemistry  Heslington York YO10 5DD UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reyme","family":"Herman","sequence":"additional","affiliation":[{"name":"University of York Department of Biology  Heslington Wentworth Way YO10 5DD UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3015-6327","authenticated-orcid":false,"given":"Daniel J.","family":"Raines","sequence":"additional","affiliation":[{"name":"University of York Department of Chemistry  Heslington York YO10 5DD UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1380-3833","authenticated-orcid":false,"given":"Justin E.","family":"Clarke","sequence":"additional","affiliation":[{"name":"University of York York Structural Biology Laboratory  Heslington YO10 5DD UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"B\u00f6swald","sequence":"additional","affiliation":[{"name":"University of York Department of Chemistry  Heslington York YO10 5DD UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3284-9266","authenticated-orcid":false,"given":"Thorsten","family":"Dreher","sequence":"additional","affiliation":[{"name":"University of York Department of Chemistry  Heslington York YO10 5DD UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8412-3328","authenticated-orcid":false,"given":"Sophie M.","family":"Gutenthaler","sequence":"additional","affiliation":[{"name":"University of York Department of Chemistry  Heslington York YO10 5DD UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Schubert","sequence":"additional","affiliation":[{"name":"Anorganische Chemie Ruhr-Universit\u00e4t Bochum Universit\u00e4tsstra\u00dfe 150  44801 Bochum Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jana","family":"Seefeldt","sequence":"additional","affiliation":[{"name":"Anorganische Chemie Ruhr-Universit\u00e4t Bochum Universit\u00e4tsstra\u00dfe 150  44801 Bochum Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8111-9959","authenticated-orcid":false,"given":"Nils","family":"Metzler\u2010Nolte","sequence":"additional","affiliation":[{"name":"Anorganische Chemie Ruhr-Universit\u00e4t Bochum Universit\u00e4tsstra\u00dfe 150  44801 Bochum Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gavin H.","family":"Thomas","sequence":"additional","affiliation":[{"name":"University of York Department of Biology  Heslington Wentworth Way YO10 5DD UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3581-2194","authenticated-orcid":false,"given":"Keith S.","family":"Wilson","sequence":"additional","affiliation":[{"name":"University of York York Structural Biology Laboratory  Heslington YO10 5DD UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6214-2459","authenticated-orcid":false,"given":"Anne\u2010Kathrin","family":"Duhme\u2010Klair","sequence":"additional","affiliation":[{"name":"University of York Department of Chemistry  Heslington York YO10 5DD UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,12,21]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.copbio.2017.12.008","volume":"53","author":"Rebelein J. 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