Synthetic Receptors Possessing Non-Covalent, Macrocyclic Rings.

In an attempt to provide access to biomimetic ion binders we aimed at molecules that would adopt conformationally restricted arrangements by virtue of non-covalent, intramolecular interactions, and allow extension by suitable ion binding sites. This article introduces four Types of C3-symmetric trispeptides, which satisfy both of these requirements. These trispeptides have been assembled from 1,3,5-tris(aminomethyl)benzene (Type 1), tris(2-aminoethyl)amine (Type 2), and two homologous triscarboxylates (Types 3 and 4) as anchors by symmetric extension with amino acid residues through peptide linkages. Spectral examination, supported by EFF calculations, demonstrates that all these compounds adopt chiral, propellerlike conformations which are stabilized by interstrand H-bonds between amide linkages of different kinds. The stability of these conformations at equilibrium depends on the nature of the anchor, the amino acid residue and the solvent. Their H-bond patterns share common features by consistently generating 15-membered H-bond rings. The differences between the four Types of trispeptides are interpreted in terms of a subtle balance between (i) stabilization through H-bond formation, and (ii) imposed strain and entropy loss through the formation of non-covalent, polycyclic arrangements. The success of this approach in providing biomimetic analogs of siderophores (iron carriers of microbial origin), by extension with catecholate or hydroxamate binding sites, is also indicated.