Imidazolium‐Based Main‐Chain Copolymers With Alternating Sequences for Broad‐Spectrum Bactericidal Activity and Eradication of Bacterial Biofilms

Abstract In response to the escalating challenge of bacterial drug resistance, the imperative to counteract planktonic cell proliferation and eliminate entrenched biofilms underscores the necessity for cationic polymeric antibacterials. However, limited efficacy and cytotoxicity challenge their practical use. Here, novel imidazolium‐based main‐chain copolymers with imidazolium (PIm + ) as the cationic component are introduced. By adjusting precursor molecules, hydrophobicity and cationic density of each unit are fine‐tuned, resulting in broad‐spectrum bactericidal activity against clinically relevant pathogens. PIm + 1 stands out for its potent antibacterial performance, with a minimum inhibitory concentration of 32 µg mL −1 against Methicillin‐resistant Staphylococcus aureus (MRSA), and substantial biofilm reduction in Staphylococcus aureus ( S. aureus ) and Escherichia coli ( E. coli ) biofilms. The bactericidal mechanism involves disrupting the outer and cytoplasmic membranes, depolarizing the cytoplasmic membrane, and triggering intracellular reactive oxygen species (ROS) generation. Collectively, this study postulates the potential of imidazolium‐based main‐chain copolymers, systematically tailored in their sequences, to serve as a promising candidate in combatting drug‐resistant bacterial infections.