Pyridine/Oxadiazole‐Based Helical Foldamer Ion Channels with Exceptionally High K+/Na+ Selectivity

Protein channels are characterized by high transport selectivity, which is essential for maintaining cellular function. Efforts to reproduce such high selectivity over the past four decades have not been very successful. We report a novel series of aromatic foldamer‐based polymeric channels where the backbone is stabilized by differential electrostatic repulsions among heteroatoms helically arrayed along the helical backbone. Nanotubes averaging 2.3 and 2.7 nm in length mediate highly efficient transport of K⁺ ions as a consequence of hydrophilic electron‐rich hollow cavities that are 3 Å in diameter. Exceptionally high K⁺ and Na⁺ selectivity values of 16.3 and 12.6, respectively, are achieved.     

Synthesis and ionophore properties of a series of new tetrapyrazolic macrocycles

The synthesis of several macrocycles containing two bipyrazolic subunits, with different cavity sizes and with donor-group-bearing side arms attached, is reported. Their alkali cation binding ability has been studied from two aspects : extraction and transport through an artificial liquid membrane. Macrocycles described here show a high selectivity towards Li⁺ and Na⁺ cations; furthermore one of them is remarkably well adapted to extract selectively and to transport efficiently the lithium cation in competitive conditions.     

Cation transport at 25°c from binary Na+Mn+, Cs+Mn+ and Sr2+Mn+ nitrate mixtures in a H2OCHCl3H2O liquid membrane system containing a series of macrocyclic carriers

Cation fluxes from binary mixtures of either Na⁺, Cs⁺ or Sr²⁺ with other alkali metal cations, alkaline earth metal cations, and Pb²⁺ through a H₂OCHCl³H₂O bulk liquid membrane system containing one of several macrocyclic carriers have been determined Nitrate salts were used in all cases. The most selective transport of Na⁺ over all other cations studied was found with the carrier cryptand [2.2.1]. Selective transport of Na⁺ relative to Li⁺, Cs⁺ and the alkaline earth cations was found with cryptand [2.2.2B] and cryptand [2.2.2D]. The ligands 21-crown-7 and dibenzo-24-crown-8 showed selective transport of Cs⁺ over the second cation in all cases. Several macrocycles showed selectivity for Sr²⁺ over the second cation with the macrocycle 1,10-diaza-18-crown-6 showing the highest selectivity for this cation of all ligands studied. Relative fluxes from binary cation mixtures are rationalized in terms of macrocycle cavity size, donor atom type and ring substituents.     

864 — Electrochemistry of asymmetric membranes

The ion transport behaviour of neutral carriers (ionophores) in asymmetric membrane environments has been investigated. Composite solvent-polymeric membranes consisting of two segments of different polarity exhibit two different selectivities, depending on the orientation of the membrane and on the direction of ion transport, respectively. From zero-current membrane potentials and electrodialytic ion transport numbers, the permeability selectivity Ca²⁺ > Na⁺ is found when the ions enter the polar membrane side, and the selectivity Na⁺ > Ca²⁺ for the non-polar entry. The asymmetry effects expected for ionophores in bilayer membranes are also discussed.     

Artificial K+ Channels Formed by Pillararene‐Cyclodextrin Hybrid Molecules: Tuning Cation Selectivity and Generating Membrane Potential

A class of artificial K⁺ channels formed by pillararene‐cyclodextrin hybrid molecules have been designed and synthesized. These channels efficiently inserted into lipid bilayers and displayed high selectivity for K⁺ over Na⁺ in fluorescence and electrophysiological experiments. The cation transport selectivity of the artificial channels is tunable by varying the length of the linkers between pillararene and cyclodexrin. The shortest channel showed specific transmembrane transport preference for K⁺ over all alkali metal ions (selective sequence: K⁺ > Cs⁺ > Rb⁺ > Na⁺ > Li⁺), and is rarely observed for artificial K⁺ channels. The high selectivity of this artificial channel for K⁺ over Na⁺ ensures specific transmembrane translocation of K⁺, and generated stable membrane potential across lipid bilayers.     

Highly Selective Transmembrane Transport of Exogenous Lithium Ions through Rationally Designed Supramolecular Channels

Lithium ions have been applied in the clinic in the treatment of psychiatric disorders. In this work, we report artificial supramolecular lithium channels composed of pore-containing small aromatic molecules. By adjusting the lumen size and coordination numbers, we found that one of the supramolecular channels developed shows unprecedented transmembrane transport of exogenous lithium ions with a Li⁺/Na⁺ selectivity ratio of 23.0, which is in the same level of that of natural Na⁺ channels. Furthermore, four coordination sites inside channels are found to be the basic requirement for ion transport function. Importantly, this artificial lithium channel displays very low transport of physiological Na⁺, K⁺, Mg²⁺, and Ca²⁺ ions. This highly selective Li⁺ channel may become an important tool for studying the physiological role of intracellular lithium ions, especially in the treatment of psychiatric disorders.     

Studies of inorganic precipitate membrane. Part XXX. Membrane selectivity from electrical potential and conductivity measurements

Bi-ionic and multi-ionic potentials across parchment-supported mercuric sulfide membrane with various combinations of 1:1 electrlytes at different concentrations were measured. Membrane conductivity in contact with a single electrolyte was experimentally determined to evaluate selectivity of the membrane with the predetermined values of intramembrane mobility ratio. The selectivity sequence of the membrane was K⁺>Na⁺>Li⁺, which on the basis of the Eisenman–Sherry model of membrane selectivity, points toward the weak field strength of the charge groups attached to the membrane matrix. The permeability ratio of ions within the membrane was also evaluated by use of the equation based on the macroscopic linear laws of nonequilibrium thermodynamics derived by Sandblom and Eisenman. Three different methods of various integrated forms of the Nernst-Plank flux equation were used to derive the potentiometric selectivity constant K_ij^pot of the membrane. These values were close to one another.     

Highly active artificial potassium channels having record-high K+/Na+ selectivity of 20.1

Replicating extraordinarily high membrane transport selectivity of protein channels in artificial channel is a challenging task. In this work, we demonstrate that a strategic application of steric code-based social self-sorting offers a novel means to enhance ion transport selectivities of artificial ion channels, alongside with boosted ion transport activities. More specifically, two types of mutually compatible sterically bulky groups (benzo-crown ether and tert-butyl group) were appended onto a monopeptide-based scaffold, which can order the bulky groups onto the same side of a one-dimensionally aligned H-bonded structure. Strong steric repulsions among the same type of bulky groups (either benzo-crown ethers or tert-butyl groups), which are forced into proximity by H-bonds, favor the formation of hetero-oligomeric ensembles that carry an alternative arrangement of sterically compatible benzo-crown ethers and tert-butyl groups, rather than homo-oligomeric ensembles containing a single type of either benzo-crown ethers or tert-butyl groups. Coupled with side chain tuning, this social self-sorting strategy delivers highly active hetero-oligomeric K⁺-selective ion channel (5F12‧BF12)_n, displaying the highest K⁺/Na⁺ selectivity of 20.1 among artificial potassium channels and an excellent EC₅₀ value of 0.50 μmol/L (0.62 mol% relative to lipids) in terms of single channel concentration     

Active transport of Na + and K + through animal cell membranes

The transport of Na⁺ out of the cell and K⁺ into the cell against a concentration gradient is catalyzed by a (Na⁺ + K⁺)-activated ATPase. The way in which the cations pass through the cell membrane has not yet been elucidated. Studies on the ATP hydrolysis revealed a Na⁺-dependent phosphorylation of the enzyme protein; the conformation of the enzyme also appears to change. The energy required for transport of the cations against their concentration gradients is probably provided by K⁺-dependent hydrolysis of the enzyme-bound phosphate. The enzyme can synthesize ATP from inorganic phosphate and ADP on reversal of the cation concentration gradient. By keeping the enzyme in a particular conformation, the cardiac glycoside ouabain specifically inhibits the Na⁺ pump.     

Squalyl Crown Ether Self‐Assembled Conjugates: An Example of Highly Selective Artificial K+ Channels

The natural KcsA K⁺ channel, one of the best‐characterized biological pore structures, conducts K⁺ cations at high rates while excluding Na⁺ cations. The KcsA K⁺ channel is of primordial inspiration for the design of artificial channels. Important progress in improving conduction activity and K⁺/Na⁺ selectivity has been achieved with artificial ion‐channel systems. However, simple artificial systems exhibiting K⁺/Na⁺ selectivity and mimicking the biofunctions of the KcsA K⁺ channel are unknown. Herein, an artificial ion channel formed by H‐bonded stacks of squalyl crown ethers, in which K⁺ conduction is highly preferred to Na⁺ conduction, is reported. The K⁺‐channel behavior is interpreted as arising from discreet stacks of dimers resulting in the formation of oligomeric channels, in which transport of cations occurs through macrocycles mixed with dimeric carriers undergoing dynamic exchange within the bilayer membrane. The present highly K⁺‐selective macrocyclic channel can be regarded as a biomimetic alternative to the KcsA channel.     

Synthesis,characterisation and transport properties of layered conducting electroactive polypyrrole membranes

A novel method for producing asymmetric membranes based on conducting polymers is described. Two layers of different polypyrrole films (PPy–p-toluene sulphonate and PPy–dodecyl sulphate) were electrodeposited onto an electrode to form a sandwich or layer structure. The films produced could be removed from the electrode and had sufficiently good mechanical properties to be used as free-standing membranes in simple transport experiments. Using electrochemically induced transport utilising technology described previously it was shown that a highly asymmetric membrane had been formed with a ratio of up to 35:1 in terms of the flux in one direction compared with another. This was for the transport of simple salts such as KCl and NaCl. In mixtures of these salts it was still possible to derive some reasonable selectivity between cations with selectivity of K⁺ over Na⁺ in ratios up to 4.5:1.     

Transport of Na+, K+ ions in a bubbling pseudo-emulsion liquid membrane system with p-tert-butylcalixarenes as carriers

The liquid membrane transport of Na⁺ ions by p-tert-butylcalix[6]arene and that of K⁺ ions by p-tert-butylcalix[8]arene were investigated by means of a bubbling pseudo-emulsion liquid membrane system. This system represents a proton-coupled transport with a flow of protons in the opposite direction. The driving force for the transport is the pH gradient between the source and receiving phases. When the pH difference between the two phases is sufficient, the carriers calix[6]arene(or calix[8]arene) can successfully transport Na⁺ (or K⁺) ions from the source phase with a lower Na⁺ (or K⁺) concentration into the receiving phase with a higher Na⁺ (or K⁺) concentration, like a Na⁺ (or K⁺) ion pump.     

The effect of carbonyl carbon atom replacement in acetone molecule (ACN) by sulfur atom (DMSO): Part II. Thermodynamic functions of complex formation of crown ethers with Na<Superscript>+</Superscript> in mixed solvents

The thermodynamic functions of complex formation of benzo-15-crown-5 ether (B15C5) and sodium cation (Na⁺) in acetone–water mixtures at 298.15 K have been calculated. The equilibrium constants of B15C5/Na⁺ complex formation have been determined by conductivity measurements. The enthalpic effect of complex formation has been measured by the calorimetric method. The complexes are enthalpy-stabilized but entropy-destabilized in acetone–water mixtures. The effects of hydrophobic hydration, preferential solvation of B15C5 by a molecule of water and acetone, respectively and the solvation of Na⁺ on the complex formation processes have been discussed. The calculated thermodynamic functions of B15C5/Na⁺ complex formation and the effect of benzene ring on the complex formation have been compared with analogous data obtained in dimethylsulfoxide–water mixtures. The effect of carbonyl atom replacement in acetone molecule by sulphur atom (DMSO molecule) on the thermodynamic functions of complex formation has been analysed.     

Selective separation of alkali metal cations by bulk chloroform membranes containing lipophilic crown ether phosphonic acid monoethyl esters

A series of crown ether phosphonic acid monoethyl esters with crown ether ring size variation from 12-crown-4 to 24-crown-8 is used in bulk chloroform membranes to separate alkali metal cations from mixtures. Selective proton-coupled transport of alkali metal cations from weakly alkaline aqueous phases is achieved. With individual ionizable crown ether carriers, transport selectivity for Li⁺, Na⁺, K⁺, and Rb⁺-Cs⁺ is achieved. A closely related lipophilic phosphonic acid monoethyl ester derivative with a cyclohexyl unit in place of the crown ether exhibits transport selectivity for Li⁺. However, the corresponding phosphonic acid diethyl ester is devoid of transport activity. Effects of structural variation within the carrier upon the selectivity and efficiency of competitive alkali metal cation transport are assessed.     

The Crystal Structure of a Potassium Channel— A New Era in the Chemistry of Biological Signaling

The similarity to crown ethers is apparent when the arrangement of the oxygen atoms of the carbonyl groups of the protein backbone in the structure of the potassium channel (see schematic drawing of a section of the structure) found in the bacterium Streptomyces lividans is considered. This particular part of the channel pore acts as the selectivity filter, with the permeability of the channel for K⁺ being as much as 10 000 times greater than for the Na⁺ ion. In fact, in this area of the structure two K⁺ ions are located, a feature that enables high flux through the channel.     

Sulfur-Containing Foldamer-Based Artificial Lithium Channels

Unlike many other biologically relevant ions (Na⁺, K⁺, Ca²⁺, Cl⁻, etc) and protons, whose cellular concentrations are closely regulated by highly selective channel proteins, Li⁺ ion is unusual in that its concentration is well tolerated over many orders of magnitude and that no lithium-specific channel proteins have so far been identified. While one naturally evolved primary pathway for Li⁺ ions to traverse across the cell membrane is through sodium channels by competing with Na⁺ ions, highly sought-after artificial lithium-transporting channels remain a major challenge to develop. Here we show that sulfur-containing organic nanotubes derived from intramolecularly H-bonded helically folded aromatic foldamers of 3.6 Å in hollow cavity diameter could facilitate highly selective and efficient transmembrane transport of Li⁺ ions, with high transport selectivity factors of 15.3 and 19.9 over Na⁺ and K⁺ ions, respectively.     

Bis(crown ether)s as Na+-K+ ATPase model in a liquid membrane

A new type of bis(crown ether)s containing 15-crown-5 and monoaza-18-crown-6 actively transported Na⁺ and K⁺ in opposite directions across a dichloromethane membrane by pH control. The effect of the structure of the ion carriers on their transport abilities was examined. A key point for the molecular design of the carriers is how to give them complexing ability toward Na⁺ under acidic conditions. A proper choice of the transport conditions was found to be essential for the success of the double uphill transport.This paper is dedicated to the memory of the late Dr C. J. Pedersen.     

Properties and Applications of Cryptand‐22 Surfactant for Ion Transport and Ion Extraction

A non‐ionic cryptand‐22 surfactant consisting of a macrocyclic cryptand‐22 polar head and a long paraffinic chain (C₁₀H₂₁‐Cryptand‐22) was synthesized and characterized. The critical micellar concentration (CMC) of the cryptand surfactant in ROH/H₂O mixed solvent was determined by the pyrene fluorescence probe method. In general, the cmc of the cryptand surfactant increased upon decreasing the polarity of the surfactant solution. The cryptand surfactant also can behave as a pseudo cationic surfactant by protonation of cryptand‐22 or complexation with metal ions. Effects of protonation and metal ions on the cmc of the cryptand surfactant were investigated. A preliminary application of the cryptand surfactant as an ion‐transport carrier for metal ions, e.g., Li⁺, Na⁺, K⁺ and Sr²⁺, through an organic liquid‐membrane was studied. The transport ability of the cryptand surfactant for these metal ions was in the order: K⁺ ≥ Na⁺ < Li⁺ < Sr²⁺. A comparison of the ion‐transport ability of the cryptand surfactant with other macrocyclic polyethers, e.g., dibenzo‐18‐crown‐6, 18‐crown‐6 and benzo‐15‐crown‐5, was studied and discussed. Among these macrocyclic polyethers, the cryptand surfactant was the best ion‐transport carrier for Na⁺, Li⁺ and Sr²⁺ ions. Furthermore, a foam extraction system using the cryptand surfactant to extract the cupric ion was also investigated.     

Design and synthesis of a novel bis-crown ether carrier molecule mimic of (Na+,K+)-ATPase

A new bis-crown ether carrier molecule 3b with an ammonium tall was synthesized to mimic some of the properties of (Na⁺,K⁺)-ATPase activity. At low pH, the ammonium salt shows stabilization by intramolecular hydrogen bonding with the 18-crown-6 portion of the molecule and the compound has some selectivity for the transport of Na⁺ over K⁺ ions. As the pH is increased, the Na⁺ and K⁺ ion-binding ability changes and in the free amino form, the host molecule carries both Na⁺ and K⁺ ions at comparable rates.     

Selective Transport of Cesium and Strontium Ions Through Polymer Inclusion Membranes Containing Calixarenes as Carriers

Abstract

Cs⁺ and Sr²⁺ are selectively removed over Na⁺ from acidic aqueous solutions with high Na⁺ concentrations by using membranes designed to selectively transport one of the two cations. To this end, calix[4]arene derivatives were used as carriers in polymer inclusion membranes (PIMs). The synthesis and characterization of new calix[4]arene derivatives (a bisamide (2) and three bisesters (3, 5 and 6)) used for the separation of Sr²⁺ are described. Another bisester (4) was employed for the same separation. In addition, a calix[4]arene-crown-6 (7) was incorporated into the membrane for Cs⁺ extraction. The concentration of each membrane component (polymer, carrier and counter-ion) was optimized and the permeability coefficients (P, m sec^?1) of Cs⁺, Sr²⁺ and Na⁺ were determined. A synergistic effect between the calixarenes and dinonylnaphtalenesulfonic acid, used as counterion, (DNNS, 8) was observed. High selectivity of Cs⁺ over Na⁺ and of Sr²⁺ over Na⁺ were obtained with compounds 7 and 3, respectively. The best P for Sr²⁺ was obtained with compound 4. A long-term experiment was carried out to demonstrate the durability of PIMs. PIMs are compared to classical supported liquid membranes.