Channel-type molecular structures. Part 4. Transmembrane transport of alkali-metal ions by ‘bouquet’ molecules

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Abstract
This report describes transport experiments with ‘bouquet’ molecules designed to act as artificial ion channels. The ‘bouquets’ are based on a central macrocycle which is either an 18-crown-6 (BM) or a cyclodextrin derivative (BCD) to which are attached polyethylene oxide [poly(oxyethylene)] chains (BM o and BCD o) or polyalkyl chains (BM c and BCD c) tipped with carboxylate endgroups. The ‘bouquets’ were studied in liposomes prepared from egg phosphatidylcholine (egg PC), dipalmitoyl phosphatidylcholine (DPPC) and a mixture of egg PC, stearylamine and cholesterol. Opposing gradients in Li+ and Na+ concentration were created and the transport of alkali-metal ions down their concentration gradients was followed directly by 7Li and 23Na NMR spectroscopy. ‘Bouquets’ were found to cause a one-for-one exchange of Na+ for Li+(antiport). In order to estimate transport rates, the extent of Na+ entry into liposomes was followed as a function of time. All ‘bouquets’ transported ions at similar rates in fluid membranes. Comparison of transport rates in fluid-(egg PC) and gel-state membranes (DPPC) was used to distinguish carrier and channel mechanisms. Control experiments demonstrated that a known carrier (monensin A) gave significantly lower transport rates in gel-state membranes. Two ‘bouquets’, BM c and BCD c, were found to transport Na+ at similar rates in fluid- and gel-state membranes; this suggests that ion passage occurs preferentially by the channel mechanism and not by the carrier mechanism. Variation of transport rate with ‘bouquet’ concentration was probed for BM o and BM c and the rates were found to increase with BM c concentration but not with BM o concentration. Since the transport rate is expected to be proportional to transporter concentration in both the carrier and channel mechanisms, this indicates that BM o uses neither a carrier nor a channel mechanism. The mechanism by which ‘bouquet’ molecules operate and the criteria which may be used to decide whether functioning channels have been created are discussed.