Anion Binding of a Cyclopeptide-Derived Molecular Cage in Aqueous Solvent Mixtures.

A molecular cage consisting of two cyclic hexapeptides with an alternating sequence of (2S,4S)-4-aminoproline and 6-aminopicolinic acid subunits, covalently linked via three diglycolic acid subunits, interacts with a variety of inorganic anions in acetonitrile/water. In the respective complexes, the anion resides in a cavity between the two cyclopeptide rings where it interacts with six converging NH groups. The cage binds sulfate anions in acetonitrile/water, 2 : 1 (v/v) with a log K of 6.7, ca. 2.5 orders of magnitude stronger than an analogous bis(cyclopeptide) with only one linker whose sulfate affinity log K amounts to 4.3. The preorganization induced by the three linking units is thus beneficial for sulfate binding. In addition, these linkers cause the dissociation of the sulfate complex to have a substantial Gibbs free energy of activation ΔG of 68.9 kJ mol and they also seem to affect anion selectivity as illustrated by the different effects some anions produce on the H NMR spectra of the triply and singly-linked bis(cyclopeptides). Such anion binding cages represent promising scaffolds to mimic natural anion receptors such as the sulfate-binding protein.