Informed Molecular Design of Conjugated Oligoelectrolytes To Increase Cell Affinity and Antimicrobial Activity

Abstract 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 −1 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 −1 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.