Membrane-intercalating conjugated oligoelectrolytes (COEs) are emerging as potential alternatives to conventional, yet increasingly ineffective, antibiotics. Three readily accessible COEs, belonging to an unreported series containing a stilbene core, namely D4, D6, and D8, were designed and synthesized so that the hydrophobicity increases with increasing side-chain length. Decreased aqueous solubility correlates with increased uptake by E. coli. The minimum inhibitory concentration (MIC) of D8 is 4 μg mL against both E. coli and E. faecalis, with an effective uptake of 72 %. In contrast, the MIC value of the shortest COE, D4, is 128 μg mL owing to the low cellular uptake of 3 %. These findings demonstrate the application of rational design to generate efficacious antimicrobial COEs that have potential as low-cost antimicrobial agents.

A novel conjugated oligoelectrolyte (COE) material, named S6, is designed to have a lipid‐bilayer stabilizing topology afforded by an extended oligophenylenevinylene backbone. S6 intercalates biological membranes acting as a hydrophobic support for glycerophospholipid acyl chains. Indeed, Escherichia coli treated with S6 exhibits a twofold improvement in butanol tolerance, a relevant feature to achieve within the general context of modifying microorganisms used in biofuel production. Filamentous growth, a morphological stress response to butanol toxicity in E. coli, is observed in untreated cells after incubation with 0.9% butanol (v/v), but is mitigated by S6 treatment. Real‐time fluorescence imaging using giant unilamellar vesicles reveals the extent to which S6 counters membrane instability. Moreover, S6 also reduces butanol‐induced lipopolysaccharide release from the outer membrane to further maintain cell integrity. These findings highlight a deliberate effort in the molecular design of a chain‐elongated COE to stabilize microbial membranes against environmental challenges.

The design and synthesis of the near‐infrared (NIR)‐II emissive conjugated oligoelectrolyte COE‐BBT are reported. COE‐BBT has a solubility in aqueous media greater than 50 mg mL−1, low toxicity, and a propensity to intercalate lipid bilayers, wherein it exhibits a higher emission quantum yield relative to aqueous media. Addition of COE‐BBT to cells provides two emission channels, at ≈500 and ≈1020 nm, depending on the excitation wavelength, which facilitates in vitro confocal microscopy and in vivo animal imaging. The NIR‐II emission of COE‐BBT is used to track intracranial and subcutaneous tumor progression in mice. Of relevance is that the total NIR‐II intensity increases over time. This phenomenon is attributed to a progressive attenuation of a COE‐BBT self‐quenching effect within the cells due to the expected dye dilution per cell as the tumor proliferates.