Amphiphilic oligocholate macrocycles: self-assembly, transmembrane nanopore formation, and noncovalent tuning

A series of rigid amphiphilic oligocholate macrocycles were synthesized and their pore formation in lipid membrane was studied using hydrophilic molecule leakage assays, fluorescence spectroscopy, and solid-state NMR. The exterior of the macrocycles is hydrophobic and thus fully compatible with lipid membrane, whereas the interior is hydrophilic with inwardly facing amide and hydroxyl groups. These amphiphilic cyclic oligocholates could stack over one another to form a transmembrane nanopore driven by a strong tendency of the water molecules in the internal cavities of the macrocycles to aggregate in a nonpolar environment. To regulate the traffic across the membrane, the nanopore needs to be tunable, preferably through noncovalent interactions. We have taken initial efforts towards this goal and were able to control the pore formation through aromatic and hydrogen-bonding interactions