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.

Carbohydrates are not always as "sticky" as one might expect. Even in organic solvents they are difficult targets for the supramolecular chemist, due to their complex, three-dimensional structures. In their natural environment (water) they are especially elusive, presenting challenges which will occupy synthetic and theoretical chemists for some time to come. The complex of an octaamide supramolecular receptor with beta-D-glucopyranose, which binds through apolar and polar contacts, is shown.

Synthetic anion transporters can facilitate H + transport via deprotonation, or OH À transport via hydrogen bonding to OH À , thus allowing dissipation of transmembrane pH gradients, an undesired side-effect for biomedical applications as Cl À ionophores. To address this limitation, Gale and colleagues have developed two anionophores that show high Cl À > H + /OH À selectivity. Preliminary cellular studies support the biological relevance of the selectivity.

was measured with a physical property measurement system. The electrical resistivity shows the MIT at T c = 154 K on cooling ( Fig. 1) and exhibits large thermal hysteresis behavior indicating a first-order character of the MIT. Ca 1.9 Sr 0.1 RuO 4 crystals for scanning tunneling microscopy (STM), LEED, and HREELS measurements were mounted on the sample plates with conducting silver epoxy, and a small metal post was glued on top. The crystal was cleaved by knocking off the post in ultrahigh vacuum with a base pressure of 1.0 × 10 −10 torr, producing a flat shiny [001] surface that yielded a sharp LEED pattern. The STM images of the freshly cleaved surfaces show large micrometer-sized terraces. Both the LEED pattern and atomically resolved STM images indicate that the surface has a well-ordered lattice structure. All surface steps are integral multiples of~6.4 Å , which is the spacing between two nearest-neighbor RuO6 octahedron layers (Fig. 1) 16. S. Nakatsuji et al., Phys. Rev. Lett. 93, 146401 (2003). 17. Detailed spectral data analysis methods were as follows:The Drude weight is the integrated intensity obtained from the difference between the left and right sides of the quasi-elastic peak through a Lorentzian function. Yann Ferrand, Matthew P. Crump, Anthony P. Davis* Carbohydrate recognition is biologically important but intrinsically challenging, for both nature and host-guest chemists. Saccharides are complex, subtly variable, and camouflaged by hydroxyl groups that hinder discrimination between substrate and water. We have developed a rational strategy for the biomimetic recognition of carbohydrates with all-equatorial stereochemistry (b-glucose, analogs, and homologs) and have now applied it to disaccharides such as cellobiose. Our synthetic receptor showed good affinities, not unlike those of some lectins (carbohydrate-binding proteins). Binding was demonstrated by nuclear magnetic resonance, induced circular dichroism, fluorescence spectroscopy, and calorimetry, all methods giving self-consistent results. Selectivity for the target substrates was exceptional; minor changes to disaccharide structure (for instance, cellobiose to lactose) caused almost complete suppression of complex formation. Carbohydrates are challenging substrates for host-guest chemistry (1-4). They possess extended, complex structures that require large receptor frameworks for full encapsulation. The differences between them are often subtle (e.g., the stereochemistry of a single hydroxyl group), so that meaningful selectivity is hard to achieve. Most particularly they are found in water and, with their arrays of hydroxyl groups, they quite strongly resemble water. The first task of a receptor is to discriminate between solvent and substrate, and in the case of carbohydrates this is clearly nontrivial. There is evidence that even nature finds the problem difficult. Though critical for many biological processes (5-7), protein/carbohydrate binding is remarkably weak (8). For example, lectins, the most common class of natural recepto...

Binding carbohydrates from water is a difficult task, even for the natural carbohydrate-binding proteins known as lectins. The design of synthetic lectin mimics is correspondingly challenging, especially if good selectivities are required. In previous work we showed that success is possible, but only for complex polycyclic architectures that require lengthy and low-yielding syntheses; for example, one glucose-selective system was made in 21 steps and only 0.1% overall yield. Here we report the discovery of a simple monocyclic host that matches the earlier designs, but is far more accessible as it is prepared in just five steps and 23% overall yield. The new synthetic lectin binds glucose with excellent selectivity versus other common monosaccharides (for example, ~50:1 versus galactose) and sufficient affinity for glucose sensing at the concentrations found in blood. It also features a built-in signalling system in the form of strong and guest-dependent fluorescence emission. The effectiveness and simplicity of this molecule suggests the potential for development into a new methodology for practical glucose monitoring.

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Specific molecular recognition is routine for biology, but has proved difficult to achieve in synthetic systems. Carbohydrate substrates are especially challenging, because of their diversity and similarity to water, the biological solvent. Here we report a synthetic receptor for glucose, which is biomimetic in both design and capabilities. The core structure is simple and symmetrical, yet provides a cavity which almost perfectly complements the all-equatorial β-pyranoside substrate. The affinity for glucose, at Ka ~18,000 M-1 , compares well with natural receptor systems. Selectivities also reach biological levels. Most other saccharides are bound ~100 times more weakly, while non-carbohydrate substrates are ignored. Glucose-binding molecules are required for initiatives in diabetes treatment, such as continuous glucose monitoring and glucose-responsive insulin. The performance and tunablity of this system augur well for such applications.

The transport of anions across cell membranes has become an important goal for supramolecular chemistry [1][2][3][4] . It is well-known that cation carriers (cationophores) can serve as antibiotics and toxins 5,6 , and it seems likely that anion carriers might also show useful biological activity. However, suitable anionophores have only recently become available 7-10 , and the nature of their biological effects is still in question. A particular hope is that anionophores might be used to replace the activity of endogenous anion channels which are missing or defective 11,2 . Such deficiencies underlie a number of medical conditions including Best disease, Startle disease, Bartter's syndrome and, most notably, the widespread lifeshortening genetic disease cystic fibrosis (CF) 12,13 .If anionophores are to be used to treat these "channelopathies", it must be shown that they can be delivered to cells in sufficient quantities to produce substantial effects, of the same order of magnitude as endogenous anion channels, and that these quantities are not toxic to the cells. However, while a wide variety of anionophores have been studied in synthetic membranes (principally large unilamellar vesicles, or LUVs), the range of systems subjected to biological investigations is still quite limited. Moreover, from the point of view of CF treatment, the results thus far have been mixed. On the positive side, a few systems have been tested in whole cells, epithelia or (in one case) genetically modified mice 14 , using electrophysiological methods such as patch-clamp and Ussing chamber, and shown to induce anion conduction without obvious toxic effects. These anionophores include synthetic 3 peptides conceptually related to natural anion channels 11,[15][16][17] , as well as the steroid-based system 1 from the authors' laboratory 18 , and other small organic molecules 14,19,20 .Less encouragingly, a number of molecules showing anion transport in LUVs have tested positive for anti-cancer cytotoxicity (potentially valuable, but incompatible with CF treatment) 8,[21][22][23][24][25] . Many of these systems, including the well-studied prodigiosin 2 26 , transport protons as well as anions 8,[21][22][23] . Intracellular acidification can lead to apoptosis 26 , so in these cases proton transport could underlie toxicity. On the other hand, a recent study on calixpyrroles 3 suggested that anion transport as such could be cytotoxic 25 . As the transport activity of 3 was only weak, this raises the concern that powerful anionophores might be highly toxic and thus unsuitable for CF treatment. Thus far the only biological testing of these "1,5-diaxial" systems has been the early study on 1, referred to above 18 . The assay involved the application of 1 to the apical membrane of oriented Madin Darby canine kidney cell (MDCK) epithelia, mounted in an Ussing chamber, and measurement of the resulting electrical current caused by Cl − transport. The methodology is well-established, but not so convenient for screening large numbers of compounds.Mor...