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Among them, bis\u2010QACs are the most prominent and effective class of biocides. Although mono\u2010QACs still dominate the antiseptic market, their activity against Gram\u2010negative bacteria is largely inferior to bis\u2010QACs. Moreover, the new wave of bacterial resistance during the COVID\u201019 pandemic is threatening the efficiency of popular antiseptics. Therefore, the requirement for novel biocides is urgent. Reported here is a unified and simple two\u2010step synthesis to achieve novel biocide's architectures with aromatic linkers. Thus, a series of 14 bis\u2010QACs have been prepared using an Ullman\u2010type reaction following by N\u2010alkylation. The most prominent compounds showed strong bioactivity against a panel of nineteen microbial pathogens, multi\u2010resistant bacterial ESKAPEE strains, fungi and biofilms, including strains, which acquired resistance during COVID\u201019 in 2021. Moreover, significant improvements in antibiofilm action were observed, where bis\u2010QACs <jats:bold>5\u2009c<\/jats:bold> and <jats:bold>6\u2009a<\/jats:bold> outperformed gold standard pyridinium antiseptic octenidine. These findings will serve as a good basis for further studies of bis\u2010QACs architectures as highly effective biocides.<\/jats:p>","DOI":"10.1002\/cmdc.202400972","type":"journal-article","created":{"date-parts":[[2025,1,16]],"date-time":"2025-01-16T11:40:28Z","timestamp":1737027628000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Expanding the Variety of Pyridinium\u2010Based Bis\u2010QACs with Antimicrobial Properties: Investigation into Linker Structure\u2010Activity Correlation"],"prefix":"10.1002","volume":"20","author":[{"given":"Nikita A.","family":"Frolov","sequence":"first","affiliation":[{"name":"N. D. 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Zelinsky Institute of Organic Chemistry Russian Academy of Sciences  Leninsky prospect 47 119991 Moscow Russia"},{"name":"Mendeleev University of Chemical Technology of Russia, Departments of the Faculty of Natural Sciences and Department of Chemistry and Technology of Biomedical Drugs  Miusskaya square 9 125047 Moscow Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra N.","family":"Tyurina","sequence":"additional","affiliation":[{"name":"Mendeleev University of Chemical Technology of Russia, Departments of the Faculty of Natural Sciences and Department of Chemistry and Technology of Biomedical Drugs  Miusskaya square 9 125047 Moscow Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary A.","family":"Seferyan","sequence":"additional","affiliation":[{"name":"N. D. 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Zelinsky Institute of Organic Chemistry Russian Academy of Sciences  Leninsky prospect 47 119991 Moscow Russia"},{"name":"Federal Budget Institution of Science \u00abState research center for applied microbiology and biotechnology\u00bb  142279 Obolensk, Serpukhov, Moscow Region Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Son","sequence":"additional","affiliation":[{"name":"Federal Budget Institution of Science \u00abState research center for applied microbiology and biotechnology\u00bb  142279 Obolensk, Serpukhov, Moscow Region Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evgeniya A.","family":"Saverina","sequence":"additional","affiliation":[{"name":"N. D. Zelinsky Institute of Organic Chemistry Russian Academy of Sciences  Leninsky prospect 47 119991 Moscow Russia"},{"name":"Federal State Budgetary Educational Institution of Higher Education Tula State University  Prospekt Lenina 92 300012 Tula Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8675-4943","authenticated-orcid":false,"given":"Anatoly N.","family":"Vereshchagin","sequence":"additional","affiliation":[{"name":"N. D. 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