Synthesis of Cationic Biphen[4, 5]arenes as Biofilm Disruptors

Abstract Since bacteria in biofilms are inherently resistant to antibiotics and biofilm‐associated infections pose a serious threat to global public health, new therapeutic agents and schemes are urgently needed to meet clinical requirements. Here two quaternary ammonium‐functionalized biphen[ n ]arenes (WBPn, n =4, 5) were designed and synthesized with excellent anti‐biofilm potency. Not only could they inhibit the assembly of biofilms, but also eradicate intractable mature biofilms formed by Gram‐positive S. aureus and Gram‐negative E. coli bacterial strains. Moreover, they could strongly complex a conventional antibiotic, cefazolin sodium (CFZ) with complex stability constants of (7.41±0.29)×10 4 M −1 for CFZ/WBP4 and (4.98±0.49)×10 3 M −1 for CFZ/WBP5. Combination of CFZ by WBP4 and WBP5 synergistically enhanced biofilm eradication performance in vitro and statistically improved healing efficacy on E. coli ‐infected mice models, providing a novel supramolecular strategy for combating biofilm‐associated infections.