Uncovering the potent antimicrobial activity of squaramide based anionophores - chloride transport and membrane disruption

Antimicrobial resistance (AMR) - often referred to as a silent pandemic, is at present the most serious threat to medicine, and with constantly emerging resistance to novel drugs, combined with the paucity of their development, is likely to worsen. To circumvent this, supramolecular chemists have proposed the applicability of synthetic anion transporters in the fight against AMR. In this article we discuss the synthesis, supramolecular characterisation and biological profiling of six structurally simple squaramide anion transporters. Through a combination of spectroscopic techniques, and cellular assays we have deduced the mode of action of these antimicrobial agents to be as a result of both anion transport and membrane disruption. Furthermore, through the synthesis of two fluorescent analogues we verified this membrane-localised activity using Super-Resolution nanoscopy methods. These compounds represent particularly active antimicrobial anionophores and compliment similar reports showing the applicability of agents such as these in the fight against AMR.