Incorporation of Calix[6]arene macrocycles and pseudorotaxanes in bilayer membranes

There is a growing interest in the study of membrane-active ion transporters and specifically for the transport of anions. The attention of the scientific community is largely due to the great importance of transmembrane ion transport phenomena in many vital processes. For example, it is crucial that precise and different concentrations of Na+ and K+ are ensured between the two sides of a cell membrane. Analogously, cystic fibrosis is caused by a mutation in the CFTR protein that facilitates transmembrane Cl- transport in the epithelial cells lining the lung. In this study we investigated the role of calix[6]arene-based pseudorotaxanes and rotaxanes on transmembrane vehiculation of ions across the bilayer of liposomes composed of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC; diameter 100 nm). The effect of these interlocked systems on the properties of the bilayer and on the membrane permeability towards chloride and 5(6)-carboxyfluorescein are investigated in detail. Tris-N-phenylureidocalix[6]arene inserted in the lipid bilayer of POPC liposomes demonstrates to form a pore able to efficiently transport chloride ions across the membrane and the rate od chloride transport is linearly related to the concentration of guests. It is worth noting that the presence of axle do not disfavor chloride transport. These findings may pave the way to the constuction of new generations of pharmacological systems regulating the transport of Cl-.