A new cyclic pseudopeptide composed of (L)-proline and 3-aminobenzoic acid subunits as a ditopic receptor for the simultaneous complexation of cations and anions

The synthesis and receptor properties of a cyclic pseudopeptide composed of (L)-proline and the nonnatural amino acid 3-aminobenzoic acid in an alternating sequence are described. The structure of cyclo[(L)Pro-AB](3) was determined in the solid state by X-ray crystallography and in solution by one- and two-dimensional NMR techniques and FT-IR spectroscopy. The cyclic peptide preferentially adopts conformations comparable with the cone conformation of calixarenes. Similar to calixarenes, cyclo[(L)Pro-AB](3) is able to bind cations by cation-pi interactions with its aromatic subunits. In some complexes, the peptide NH groups interact additionally with anions and the cyclic peptide thus behaves as a ditopic receptor. The structure of the ternary complex between cyclo[(L)Pro-AB](3) and N-methylquinuclidinium iodide was determined by X-ray crystallography. Spectroscopic investigations show that this complex has a similar geometry in solution. Stability constants of complexes of the cyclopeptide with various ion pairs have been determined. Crossover experiments show that electrostatic interactions between cation and anion complexed by cyclo[(L)Pro-AB](3) result in cooperative effects of either ion on the complexation of the corresponding counterion. The binding properties of cyclo[(L)Pro-AB](3) are correlated with its conformation in solution. The properties of related cyclic hexapeptides in which one or two (L)-proline subunits are replaced by (L)-glutamic acid are also described. In comparison with cyclo[(L)Pro-AB](3), these peptides possess a reduced cation and anion affinity. Anion complexation is weakened because the amide NH groups at the glutamic acid subunits are involved in strong intramolecular hydrogen bonds and are not available for interactions with other partners. Consequently, the cation complex stabilities also decrease. The amino acid subunits obviously influence the receptor properties of such cyclopeptides by controlling their solution conformation.