Hydraphile channels: Structural and fluorescent probes of position and function in a phospholipid bilayer

Three novel tris(macrocycle)s having fluorescent residues at their distal termini have been prepared and studied. The compounds are of the form R[N18N]C-12[N18N]C-12[N18N]R in which R is 2-(3-indolyl)ethyl (1), 2-(3-(N-methylindolyl))ethyl (2), and dansyl (3). Compounds 2 and 3 were found to transport Naf at rates similar to those of other tris(macrocyclic)s but 1 was not an ionophore in the bilayer as assessed by Na-23 NMR analysis. The latter failure may be due to a hydrogen-bond blockade leading to a globular conformation adopted by the hydraphile. The fluorescence maximum of 3 was determined in a variety of solvents and in a phospholipid bilayer. The polarity experienced by the dansyl group in the bilayer was intermediate between that observed in methanol and ethanol. Fluorescence depth quenching using doxyl-substituted lipids showed that the dansyl headgroups of 3 were 14 Angstrom from the bilayer's midplane or separated by about 28 Angstrom. Fluorescence energy transfer between 2 acid 3 showed that these two hydraphiles were not appreciably aggregated in the bilayer.