Squaratides: A tunable platform for anion binding in peptide inspired macrocycles

Abstract

We report a new class of sequence-defined peptidomimetic macrocycles, termed squaratides, that integrates squaramide units directly into a tunable peptide backbone. These modular receptors exhibit preferential binding of acetate and chloride, with affinity and stoichiometry precisely modulated by sidechain functionality. Comprehensive spectroscopic, crystallographic and density functional theory analyses reveal that conformational preorganisation amplifies recognition, establishing squaratides as a versatile platform for programmable anion binding.