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However, the high activity of these molecules often comes at the cost of elevated toxicity against eukaryotic organisms. In this study, a series of cationic ionenes with varying molecular weights to assess the influence of polymer chain length on ionene activity is investigated. To enhance polymer antimicrobial activity and limit toxicity a PEG side chain is introduced into the repeating unit. The resulting molecules consistently exhibited high activity against three model organisms: <jats:italic>E. coli<\/jats:italic>, <jats:italic>S. aureus<\/jats:italic> and <jats:italic>C. albicans<\/jats:italic>. The incorporation of side PEG chain improves antifungal properties and biocompatibility, regardless of molecular weight. The most important finding of this work is that the reduction of polymer molecular mass led to increased antifungal activity and reduced cytotoxicity against HMF and MRC\u20105 cell lines simultaneously. As a result, the best\u2010performing molecules reported herein displayed minimal inhibitory concentrations (MIC) as low as 2 and 0.0625\u00a0\u00b5g\u00a0mL<jats:sup>1<\/jats:sup> for <jats:italic>C. albicans<\/jats:italic> and <jats:italic>C. tropicalis<\/jats:italic> respectively, demonstrating exceptional selectivity. It is plausible that some of described herein molecules can serve as potential lead candidates for new antifungal drugs.<\/jats:p>","DOI":"10.1002\/mabi.202400032","type":"journal-article","created":{"date-parts":[[2024,7,17]],"date-time":"2024-07-17T19:19:49Z","timestamp":1721243989000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Unlocking the Potential: PEGylation and Molecular Weight Reduction of Ionenes for Enhanced Antifungal Activity and Biocompatibility"],"prefix":"10.1002","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5178-2434","authenticated-orcid":false,"given":"Jan M.","family":"Kurzyna","sequence":"first","affiliation":[{"name":"Faculty of Chemistry Warsaw University of Technology  Noakowskiego 3 Warsaw 00\u2013664 Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8902-1761","authenticated-orcid":false,"given":"Rafa\u0142 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