Development of synthetic membrane transporters for anions

Abstract

The development of low molecular weight anion transporters is an emerging topic in supramolecular chemistry. The major focus of this tutorial review is on synthetic chloride transport systems that operate in vesicle and cell membranes. The transporters alter transmembrane concentration gradients, and thus they have applications as reagents for cell biology research and as potential chemotherapeutic agents. The molecular designs include monomolecular channels, self-assembled channels and mobile carriers. Also discussed are the experimental assays that measure transport rates across model bilayer membranes.

Fig. 1

The use of fluorescent dyes to detect anion transport. (a) Pyranine/HPTS: Transport of X⁻ out of the vesicle is accompanied by cotransport of H⁺ or exchange of OH⁻. Deprotonation of pyranine (pK_a = 7.2) causes an increase in fluorescence when excitation and detection wavelengths are suitably adjusted. (b) Lucigenin: Fluorescence of Lucigenin is quenched by halides (X⁻), but not by oxoanions such as nitrate, sulfate or phosphate (Y⁻). The experiment can detect the cotransport of M⁺X⁻ or exchange of X⁻ and Y⁻. (c) Safranin O: Fluorescence of the lipophilic, cationic dye increases when it associates with a membrane. Anion transport into the vesicle generates a membrane potential difference (i.e. an electric field) that drives the dye into the membrane, thus increasing fluorescence.

Fig. 2

Apparatus for planar lipid bilayer (black lipid membrane, BLM) experiments.

Fig. 3

A patch-clamp experiment, as used in electrophysiology. (a) Pipette approaches cell. (b) Pipette makes contact with cell, surrounding one or more endogenous channels, and gentle suction is applied to the back of the pipette to form a high resistance (GΩ) seal. (c) The patch of membrane is excised from the cell by retracting the pipette so that the properties and regulation of the channel can be studied.

Fig. 4

Gokel et al.'s dimeric peptide-based channel. Reproduced by permission of the Royal Society of Chemistry.

Fig. 5

Matile et al.'s p-octiphenyl β-barrel pores. Octiphenyls are substituted with short peptides that can interdigitate to form β-sheets. Four such units combine to form a pore. Leucine side-chains point outwards into the apolar membrane environment, while the polar side-chains point inwards and line the surface of the pore. Reproduced by permission of the Royal Society of Chemistry.

Fig. 6

Regen's steroid-based ion channel.