NATURALLY occurring membrane channels and pores are formed from a large family of diverse proteins, peptides and organic secon-dary metabolites whose vital biological functions include control of ion flow, signal transduction, molecular transport and produc-tion of cellular toxins. But despite the availability of a large amount of biochemical information about these molecules1, the design and synthesis of artificial systems that can mimic the bio-logical function of natural compounds remains a formidable task2–12. Here we present a simple strategy for the design of artifi-cial membrane ion channels based on a self-assembled cylindrical β-sheet peptide architecture13. Our systems—essentially stacks of peptide rings—display good channel-mediated ion-transport activ-ity with rates exceeding 107 ions s−1, rivalling the performance of many naturally occurring counterparts. Such molecular assemblies should find use in the design of novel cytotoxic agents, membrane transport vehicles and drug-delivery systems.

Artificial transmembrane ion channels from self-assembling peptide nanotubes

MUCH attention has been focused recently on the design and fabrication of large-scale molecular structures1. Carbon nanotubes formed by an arc-discharge method2,3 have attracted particular attention. These tubes range from about 1 to 30 nanometres in diameter and a micrometre or so in length. To construct smaller tubes, direct chemical synthesis may be a more convenient approach. The cyclic oligomers of glucose known as cyclodextrins (CDs) would seem to be ideal candidates for the components of a molecular tube: they contain cylindrical cavities about 0.7 nm deep, with diameters of 0.45 nm, 0.7 nm and 0.85 nm for α-CD, β-CD and γ-CD respectively4. Lehn has recently reported the use of 'bouquet molecules' built from β-CD with long side chains as artificial ion channels5. We have previously prepared rotaxane super-molecules in which CDs are threaded on a polymer chain, and we6 and others7,8, have reported polyrotaxanes with many threaded CDs. Here we report the crosslinking of adjacent CD units in apolyrotaxane to create a molecular tube. By removing the bulky ends of the polymer thread, the tube can be unthreaded and can act as a host for reversible binding of small molecules.

Synthesis of a tubular polymer from threaded cyclodextrins

Although water is often hailed as the lubricant of life, a detailed understanding of its role in many chemical and biological processes still eludes us. In many natural systems, water is confined in an environment where its free movement is restricted and its three-dimensional hydrogen-bonded network is disrupted. Very recently, several groups applied ultrafast laser spectroscopy to study the dynamics of the constrained water molecules. It is observed that the dynamic behavior of the confined water molecules is markedly different from that of the ordinary water molecules. The most striking result is the bimodal response of confined water, with one bulk water-like subpicosecond component and a much slower component in a time scale of hundreds or thousands of picoseconds. This slow second component constitutes 10−30% of the total response and is crucial in the understanding of the role of water in complex chemical and biological processes. The origin of the slow component has been a subject of intense recen...

Slow dynamics of constrained water in complex geometries

Molecular Photoionic AND Logic Gates with Bright Fluorescence and “Off−On” Digital Action

The synthesis, chemistry, and properties of curved-surface, polynuclear aromatics would be of great interest even if buckminsterfullerene had never been discovered. The presence of both convex and concave surfaces provides the potential for exceptional stereo-selectivities, as well as attractive opportunities for some very interesting metal complexation. However, the fullerenes have been discovered, and there can be no denying that this relationship adds an additional level of excitement to what is already an intriguing new class of aromatic compounds. 46 refs., 3 figs., 1 tab.

Buckybowls: Polynuclear Aromatic Hydrocarbons Related to the Buckminsterfullerene Surface

Towards Artificial Ion Channels: Transport of Alkali Metal Ions across Liposomal Membranes by “Bouquet” Molecules

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 (BMo and BCDo) or polyalkyl chains (BMc and BCDc) 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’, BMc and BCDc, 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 BMo and BMc and the rates were found to increase with BMc concentration but not with BMo concentration. Since the transport rate is expected to be proportional to transporter concentration in both the carrier and channel mechanisms, this indicates that BMo 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.

Marko J. Pregel

Papers

Towards Artificial Ion Channels: Transport of Alkali Metal Ions across Liposomal Membranes by “Bouquet” Molecules

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

Auf dem Weg zu künstlichen Ionenkanälen: Transport von Alkalimetall‐Ionen durch Liposomenmembranen über Bukettmoleküle