Aromatic pentaamide macrocycles bind anions with high affinity for transport across biomembranes.

The convergent positioning of functional groups in biomacromolecules leads to good binding, catalytic and transport capabilities. Synthetic frameworks capable of convergently locking functional groups with minimized conformational uncertainty-leading to similar properties-are highly desirable but rare. Here we report C5-symmetric aromatic pentaamide macrocycles synthesized in one pot from the corresponding monomers. Their crystal structures reveal a star-shaped, fully constrained backbone that causes ten alternating NH/CH hydrogen-bond donors and five large amide dipoles to orient towards the centre of the macrocycle. With a highly electropositive cavity in a high-energy unbound state, the macrocycles bind anions in a 1:1 stoichiometry in solution, with high affinity for halides and very high affinity for oxoanions. We demonstrate that such macrocycles are able to transport anions across lipid bilayers with a high chloride selectivity and restore the depleted airway surface liquid of cystic fibrosis airway cell cultures.

Oligo(5-amino-N-acylanthranilic acids): Amide Bond Formation without Coupling Reagent and Folding upon Binding Anions.

Oligomers of 5-amino-N-acylanthranilic acid, previously unknown aromatic oligoamides that cannot be obtained with known amide coupling methods, are synthesized based on a new, highly efficient amide-bond formation strategy that takes advantage of the ring-opening of benzoxazinone derivatives. These oligoamides offer multiple backbone NH groups as H-bond donors which, in the presence of iodide or chloride ion, are convergently arranged and H-bonded, which enforces a folded, crescent conformation. These aromatic oligoamides provide a versatile platform based on which anion-dependent foldamers, or anion binders with tunable affinity and specificity, are being constructed.