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In this study, we explored the effects of structural rigidity on the antimicrobial activity of QPC structures bearing a two\u2010carbon linker between phosphonium groups, testing against a panel of six bacteria, including multiple strains harboring known disinfectant resistance mechanisms. Using simple alkylation reactions, 21 novel compounds were prepared, although alkene isomerization as well as an alkyne reduction were observed during the respective syntheses. The resulting bisQPC compounds showed strong biological activity, but were hampered by diminished solubility of their iodide salts. One compound (P2P\u201010,10 I) showed single\u2010digit micromolar activity against the entire panel of bacteria. Overall, intriguing biological activity was observed, with less rigid structures displaying better efficacy against Gram\u2010negative strains and more rigid structures demonstrating slightly increased efficacy against <jats:italic>S. aureus<\/jats:italic> strains.<\/jats:p>","DOI":"10.1002\/cmdc.202200224","type":"journal-article","created":{"date-parts":[[2022,5,13]],"date-time":"2022-05-13T10:21:35Z","timestamp":1652437295000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Rigidity\u2010Activity Relationships of bisQPC Scaffolds against Pathogenic Bacteria"],"prefix":"10.1002","volume":"17","author":[{"given":"Aaron C.","family":"Spahr","sequence":"first","affiliation":[{"name":"Department of Chemistry Villanova University  800 E. 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