Anion−Macrodipole Interactions: Self-Assembling Oligourea/Amide Macrocycles as Anion Transporters that Respond to Membrane Polarization

Abstract

Macrocyclic urea/amide hybrids are introduced as functional, anion-selective membrane transporters in lipid bilayer membranes. Six derivatives with varying side chains (aliphatic and aromatic) and conformations (parallel and antiparallel carbonyl dipoles) are investigated by fluorescence methods, among which the more active aromatic derivatives were selected for an in-depth study. Strong response of transport activity toward anion exchange and weak response toward cation exchange establish anion selectivity for all macrocycles. "Antiparallel" macrocycles that self-assemble into "antiparallel" nanotubes without macrodipole exhibit Hofmeister selectivity. Parallel macrocycles that self-assemble into parallel nanotubes with strong macrodipole are capable of overcoming the dehydration penalty of the Hofmeister bias. Both systems show additional chloride selectivity. The activity of antiparallel and parallel nanotubes in binary mixtures of bromide/perchlorate and chloride/thiocyanate is over- and underadditive, respectively (positive and negative AMFE). The activity of antiparallel nanotubes decreases rapidly with increasing membrane polarization, whereas parallel nanotubes are inactivated at high and activated by membrane potentials at low concentration. Hill coefficients of parallel nanotubes decrease significantly with membrane polarization, whereas those of antiparallel nanotubes increase slightly. The overall unusual characteristics of parallel nanotubes call for a new transport mechanism, where macrodipole-potential interactions account for voltage sensitivity and anion-macrodipole interactions account for anion selectivity.