ORCID

Abstract

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.

Keywords

anion transport, antimicrobial resistance, chemical biology, squaramides, supramolecular chemistry

Publication Date

2026-03-13

Publication Title

ChemBioChem

Volume

27

Issue

5

ISSN

1439-4227

Deposit Date

2026-09-25

Funding

L. E. B. thanks the Irish Research Council (IRC) for a Government of Ireland Postgraduate Scholarship (GOIPG/2020/78), and RCSI (Prof. Donal O’Shea, Department of Chemistry) for access to the Super Resolution Imaging Consortium. R. B. P. E. and K. K. acknowledge funding from Science Foundation Ireland (SFI) (Grant no. 12/RC/2275/P2), which is cofunded under the European Regional Development Fund. SFI is also acknowledged for funding of the NMR facility (12/RI/2346/SOF) through the Research Infrastructure Programme. Dr. Massimiliano Garre is thanked for his insight regarding STED analysis of microbial samples. This study was supported by Science Foundation Ireland (12/RC/2275/P2, 12/RI/2346/SOF, 18/RI/5723), Irish Research Council for Science, Engineering and Technology (GOIPG/2020/78). L. E. B. thanks the Irish Research Council (IRC) for a Government of Ireland Postgraduate Scholarship (GOIPG/2020/78), and RCSI (Prof. Donal O’Shea, Department of Chemistry) for access to the Super Resolution Imaging Consortium. R. B. P. E. and K. K. acknowledge funding from Science Foundation Ireland (SFI) (Grant no. 12/RC/2275/P2), which is cofunded under the European Regional Development Fund. SFI is also acknowledged for funding of the NMR facility (12/RI/2346/SOF) through the Research Infrastructure Programme. Dr. Massimiliano Garre is thanked for his insight regarding STED analysis of microbial samples. This study was supported by Science Foundation Ireland (12/RC/2275/P2, 12/RI/2346/SOF, 18/RI/5723), Irish Research Council for Science, Engineering and Technology (GOIPG/2020/78).

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