Antimicrobial resistance is regarded as one of the foremost public health risks of the 21st century, highlighting the need for new antimicrobial agents and chemical tools to interrogate their biological activity. Artificial transmembrane anion transporters have emerged as promising supramolecular scaffolds in this context, having demonstrated membrane activity in mammalian systems and showing growing potential in antimicrobial research. Here, we report a series of heterocycle-fused squaramide anionophores capable of binding and transporting chloride. Several members of this series display measurable antimicrobial activity, alongside evidence of intracellular chloride modulation in bacterial cells. Taken together, these findings indicate that membrane localisation and anion transport are important contributing factors to the observed antimicrobial effects, and support further investigation of squaramide-based anionophores as membrane-active chemical biology tools.
Brennan et al. (Sun,) studied this question.