{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T00:12:38Z","timestamp":1785888758855,"version":"3.56.0"},"reference-count":46,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,11,20]],"date-time":"2024-11-20T00:00:00Z","timestamp":1732060800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R35GM119426 to W.M.W."],"award-info":[{"award-number":["R35GM119426 to W.M.W."]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R15AI185860 to K. P. C. M."],"award-info":[{"award-number":["R15AI185860 to K. P. C. M."]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemMedChem"],"published-print":{"date-parts":[[2025,2,16]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Quaternary ammonium compounds (QACs) have been essential for protecting human health for almost a century, functioning as surface disinfectants and sanitizers. With bacterial resistance increasing against commercially available QACs, the development of novel antimicrobials with divergent architectures is essential for effective infection prevention and control. Toward this end, our group has expanded beyond traditional ammonium scaffolds and explored the development of quaternary phosphonium compounds (QPCs). Herein, we report the synthesis and biological investigation of a series of 20 novel multicationic QPCs, bearing multiple short alkyl or aryl chains, also referred to as \u201cbushy\u2010tailed\u201d multiQPCs; these structures were hypothesized to have strong bioactivity while displaying low mammalian toxicity. Select bushy\u2010tailed QPC derivatives with trishexylphosphonium groups displayed single\u2010digit or sub\u2010micromolar activity against all seven bacteria tested, and MIC values of 2\u2010 to 8\u2010fold better than their bushy\u2010tailed QAC counterparts. Importantly, therapeutic indices of these bushy\u2010tailed QPCs were favorable in many cases, and were \u22654 against the entire bacterial panel for <jats:bold>pX\u2010P6*,P6*<\/jats:bold> and <jats:bold>1,8\u2010P6*,P6*<\/jats:bold>, superior to more traditional architectures. This work highlights the promise of a novel set of multicationic phosphonium compounds as novel disinfectants with potent bioactivities and low toxicity.<\/jats:p>","DOI":"10.1002\/cmdc.202400546","type":"journal-article","created":{"date-parts":[[2024,10,24]],"date-time":"2024-10-24T22:34:05Z","timestamp":1729809245000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Bushy\u2010Tailed Multicationic Quaternary Phosphonium Compounds: Potent Amphiphilic Disinfectants with Promising Therapeutic Indices"],"prefix":"10.1002","volume":"20","author":[{"given":"Diana","family":"Rachii","sequence":"first","affiliation":[{"name":"Department of Chemistry Villanova University  Villanova, PA 19085 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elise L.","family":"Bezold","sequence":"additional","affiliation":[{"name":"Department of Chemistry Emory University  Atlanta, GA 30322 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5198-7744","authenticated-orcid":false,"given":"William M.","family":"Wuest","sequence":"additional","affiliation":[{"name":"Department of Chemistry Emory University  Atlanta, GA 30322 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4263-9833","authenticated-orcid":false,"given":"Kevin P. 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