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.     

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.     

Biomimetic Nanocones that Enable High Ion Permselectivity

Artificial counterparts of conical‐shaped transmembrane protein channels are of interest in biomedical sciences for biomolecule detection and selective ion permeation based on ionic size and/or charge differences. However, industrial‐scale applications such as seawater desalination, separation of mono‐ from divalent cations, and treatment of highly‐saline industrial waste effluents are still big challenges for such biomimetic channels. A simple monomer seeding experimental approach is used to grow ionically conductive biomimetic charged nanocone pores at the surface of an acid‐functionalized membrane. These readily scalable nanocone membranes enable ultra‐fast cation permeation (Na⁺=8.4× vs. Mg²⁺=1.4×) and high ion charge selectivity (Na⁺/Mg²⁺=6×) compared to the commercial state‐of‐the‐art permselective membrane (CSO, Selemion, Japan) owing to negligible surface resistance and positively charged conical pore walls.     

Cation Transport across Bulk Liquid Organic Membranes with Oligomers of (R)-3-Hydroxybutanoic Acid

Several oligomeric derivatives 1–5 of (R)-3-hydroxybutanoic acid and a cyclic trimer of (R)-3-hydroxypentanoic acid ( 6 ) were used as ionophores to transport potassium picrate across a bulk liquid CH₂Cl₂ membrane. Using the cyclic trimer 1 and an oligomer mixture of (R)-3-hydroxybutanoic acid, 5 (ca. 28-mer), for the transport experiments, the alkali-metal ions from Li⁺ to Cs⁺ and the alkaline-earth-metal ions from Mg²⁺ to Ba²⁺ were also shown to be transported through the organic phase. Although a pronounced enhancement of the transport rates was observed in the presence of 3-hydroxyalkanoate oligomers, no special selectivity for one ion was detected. The ionophore properties of the investigated oligomers and oligolides derived from 3-hydroxybutanoic acid are compatible with the alleged role of oligo(3-hydroxybutanoate) (c-PHB; ca. 120-mer) as component of ion channels through cell membranes.     

Polystyrene Sulfonate Threaded through a Metal–Organic Framework Membrane for Fast and Selective Lithium‐Ion Separation

Extraction of lithium ions from salt‐lake brines is very important to produce lithium compounds. Herein, we report a new approach to construct polystyrene sulfonate (PSS) threaded HKUST‐1 metal–organic framework (MOF) membranes through an in situ confinement conversion process. The resulting membrane PSS@HKUST‐1‐6.7, with unique anchored three‐dimensional sulfonate networks, shows a very high Li⁺ conductivity of 5.53×10^?4 S cm^?1 at 25 °C, 1.89×10^?3 S cm^?1 at 70 °C, and Li⁺ flux of 6.75 mol m^?2 h^?1, which are five orders higher than that of the pristine HKUST‐1 membrane. Attributed to the different size sieving effects and the affinity differences of the Li⁺, Na⁺, K⁺, and Mg²⁺ ions to the sulfonate groups, the PSS@HKUST‐1‐6.7 membrane exhibits ideal selectivities of 78, 99, and 10296 for Li⁺/Na⁺, Li⁺/K⁺, Li⁺/Mg²⁺ and real binary ion selectivities of 35, 67, and 1815, respectively, the highest ever reported among ionic conductors and Li⁺ extraction membranes.     

Hydration of the H<Superscript>+</Superscript>, Li<Superscript>+</Superscript>, Na<Superscript>+</Superscript>, and Cs<Superscript>+</Superscript> ions in MF-4SK perfluorinated sulfonic acid cation-exchange membranes modified with inorganic dopants

The hydration, state, and mobility of protons and Li⁺, Na⁺, and Cs⁺ ions in MF-4SK perfluorinated sulfonic acid cation-exchange membranes doped with silicon dioxide and phosphotungstic acid have been investigated by NMR and impedance spectroscopy. The dopants increase the moisture content of the membrane and change the system of pores and channels in which ion transport takes place. At low humidities, the dopant particles are involved in ion transport. The greatest effect is observed for the membranes doped with both SiO₂ and phosphotungstic acid. The water molecules sorbed by dopant particles as a material participate in the hydration of alkali metal cations in the membrane.     

Improving the Electrochemical Performance of the Li4Ti5O12 Electrode in a Rechargeable Magnesium Battery by Lithium–Magnesium Co‐Intercalation

Rechargeable magnesium batteries have attracted recent research attention because of abundant raw materials and their relatively low‐price and high‐safety characteristics. However, the sluggish kinetics of the intercalated Mg²⁺ ions in the electrode materials originates from the high polarizing ability of the Mg²⁺ ion and hinders its electrochemical properties. Here we report a facile approach to improve the electrochemical energy storage capability of the Li₄Ti₅O₁₂ electrode in a Mg battery system by the synergy between Mg²⁺ and Li⁺ ions. By tuning the hybrid electrolyte of Mg²⁺ and Li⁺ ions, both the reversible capacity and the kinetic properties of large Li₄Ti₅O₁₂ nanoparticles attain remarkable improvement.     

Water transference through nickel hydroxide precipitate membrane

The transference of water that results from ion migration through the nickel hydroxide precipitate membrane was studied in chloride, perchlorate, nitrate, and sulphate solutions to estimate the transference number of water and the co-ion transport. In the systems of univalent anions, the moles of water transported per mole of electrons in 0.1 N solutions is almost identical to the hydration number of each anion. This water flow decreases gradually as the concentration of external solution increases, because of increase in the co-ion (cation) transport with increasing concentration of the solution. In the system of sulphate solutions the co-ion transport is remarkable, the transport number of Na⁺ ions being 0.03 in 0.01 N, 0.27 in 0.10 N, and 0.50 in 0.5 N Na₂SO₄ solution. This large co-ion transport in Na₂SO₄ solution is attributed to the partical replacement of hydroxyl groups on the membrane by SO^2?₄ ions, which then acts as a negative fixed charge. The order of the selectivity for co-ion transport is K⁺ > Na⁺ > Li⁺ > Ni²⁺ ? Mg²⁺ in sulphate solutions and also in chloride solutions, although the transport number of the cations is much smaller in chloride solution than in sulphate solution.     

Selective Ion Exchange in Supramolecular Channels in the Crystalline State

Artificial ion channels are of increasing interest because of potential applications in biomimetics, for example, for realizing selective ion permeability through the transport and/or exchange of selected ions. However, selective ion transport and/or exchange in the crystalline state is rare, and to the best of our knowledge, such a process has not been successfully combined with changes in the physical properties of a material. Herein, by soaking single crystals of Li₂([18]crown‐6)₃[Ni(dmit)₂]₂(H₂O)₄ ( 1 ) in an aqueous solution containing K⁺, we succeeded in complete ion exchange of the Li⁺ ions in 1 with K⁺ ions in the solution, while maintaining the crystalline state of the material. This ion exchange with K⁺ was selectively conducted even in mixed solutions containing K⁺ as well as Na⁺/Li⁺. Furthermore, remarkable changes in the physical properties of 1 resulted from the ion exchange. Our finding enables not only the realization of selective ion permeability but also the development of highly sensitive biosensors and futuristic ion exchange agents, for example.     

Reactions of poly(ethylene glycol) cations with iodide and perfluorocarbon anions

Multiply charged poly(ethylene glycol) ions of the form (M+nNa) ⁿ⁺ derived from electrospray ionization have been subjected to reactions with negative ions in the quadrupole ion trap. Mixtures of multiply charged positive ions ranging in average mass from about 2000 to about 14,000 Da were observed to react with perfluorocarbon anions by either proton transfer or fluoride transfer. Iodide anions reacted with the same positive ions by attachment. In no case was fragmentation of the polymer ion observed. In all cases, the multiply charged positive ion charge states could be readily reduced to +1, thereby eliminating the charge state overlap observed in the normal electrospray mass spectrum. With all three reaction mechanisms, however, the +1 product ions were comprised of mixtures of products with varying numbers of sodium ions, and in the case of iodide attachment and fluoride transfer, varying numbers of halogen anions. These reactions shift the mass distributions to higher masses and broaden the distributions. The extents to which these effects occur are functions of the magnitudes of the initial charges and the width of the initial charge state distributions. Care must be taken in deriving information about the polymer molecular weight distribution from the singly charged product ions arising from these ion/ion reactions. The cluster ions containing iodide were shown to be intermediates in sodium ion transfer. Dissociation of the adduct ions can therefore lead to a +1 product ion population that is comprised predominantly of M+Na⁺ ions. However, a strategy based on the dissociation of the iodide cluster ions is limited by difficulties in dissociating high mass-to-charge ions in the quadrupole ion trap.     

Structural determination of oxofatty acids by charge-remote fragmentations

A strategy is described to locate the carbonyl position in oxofatty acids by utilizing charge-remote fragmentations of various molecular ions that are desorbed by fast atom bombardment (FAB). Oxofatty acids were cationized with alkali metal ions (Li⁺, Na⁺, K⁺, Rb⁺, and Cs⁺) to form [M+2Met?H]⁺ or alkaline earth metal ions (Mg²⁺, Ca²⁺, Sr²⁺ or Ba²⁺) to form [M+Met?H]⁺ in the gas phase. The cationized acids undergo charge-remote fragmentations upon high-energy activation, giving a product-ion pattern that has a gap corresponding to the oxo position and bordered by two high-intensity peaks. One of the peaks corresponds to an ion that is formed by the cleavage of the C-C bond β to the oxo position and proximal to the charge (β ion), whereas the other is formed from the cleavage of the C-C bond γ to the oxo position and distal to the charge (γ′ ion). The oxo position is easily determined by identifying the gap and the β and γ′ ions. Furthermore, there are two competing patterns of fragments in a CAD spectrum of an oxofatty acid or ester [M+Li]⁺ ion. These arise because Li⁺ attaches to either the oxo or the carboxylic end, as was confirmed by ab initio molecular orbital calculations. The results demonstrate that control of the fragmentation can be guided by an understanding of metal-ion affinities. Collisional activation of the anionic carboxylates gives results that are similar to those for positive ions, showing that the process is not related to the charge status. Collisional activation of [M+H]⁺ ions does not give structural information because the charge migrates, leading to charge-mediated fragmentations.     

Bimetallic cluster cations ejected from a liquid metal ion source: Li-Na and Li-Mg

Cluster ions of alloys (Li-Na, Li-Mg) have been produced by a liquid metal ion source (LMIS), and analyzed by mass spectrometry. For the Li-Na system, bimetallic clusters with various compositions were formed, and dominant bimetallic species were Na₂Li⁺, NaLi⁺, NaLi ₂ ⁺ and NaLi ₈ ⁺ with this sequence of ion intensity. These clusters are systems containing 2 or 8 valence electrons except for NaLi⁺. For the Li-Mg, observed bimetallic clusters were limited to only three species (MgLi⁺, MgLi ₂ ⁺ and Mg₂Li⁺), but unexpectedly small multiply charged homonuclear clusters, Mg ₂ ²⁺ and Mg ₃ ²⁺ , were observed.     

Charge Neutralization Drives the Shape Reconfiguration of DNA Nanotubes

Reconfiguration of membrane protein channels for gated transport is highly regulated under physiological conditions. However, a mechanistic understanding of such channels remains challenging owing to the difficulty in probing subtle gating‐associated structural changes. Herein, we show that charge neutralization can drive the shape reconfiguration of a biomimetic 6‐helix bundle DNA nanotube (6HB). Specifically, 6HB adopts a compact state when its charge is neutralized by Mg²⁺; whereas Na⁺ switches it to the expanded state, as revealed by MD simulations, small‐angle X‐ray scattering (SAXS), and FRET characterization. Furthermore, partial neutralization of the DNA backbone charges by chemical modification renders 6HB compact and insensitive to ions, suggesting an interplay between electrostatic and hydrophobic forces in the channels. This system provides a platform for understanding the structure–function relationship of biological channels and designing rules for the shape control of DNA nanostructures in biomedical applications.     

A Bioinspired Free-Standing 2D Crown-Ether-Based Polyimine Membrane for Selective Proton Transport

Biological proton channels play important roles in the delicate metabolism process, and have led to great interest in mimicking selective proton transport. Herein, we designed a bioinspired proton transport membrane by incorporating flexible 14-crown-4 (14C4) units into rigid frameworks of polyimine films by an interfacial Schiff base reaction. The Young's modulus of the membrane reaches about 8.2 GPa. The 14C4 units could grab water, thereby forming hydrogen bond-water networks and acting as jumping sites to lower the energy barrier of proton transport. The molecular chains present a vertical orientation to the membrane, and the ions travel between the quasi-planar molecular sheets. Furthermore, the 14C4 moieties could bond alkali ions through host–guest interactions. Thus, the ion conductance follows H⁺≫K⁺>Na⁺>Li⁺, and an ultrahigh selectivity of H⁺/Li⁺ (ca. 215) is obtained. This study provides an effective avenue for developing ion-selective membranes by embedding macrocycle motifs with inherent cavities.     

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.     

Napthaquinone derived ionophores: interaction with biologically important metal ions (Li+, Na+, K+, Mg2+ and Ca2+)

The synthetic model systems based on the study of supramolecular compounds are proficient in mimicking the biological processes so as to get the insight of their processes. In this perspective, a series of naphthaquinone derived redox switchable ionophores namely D₁ (2,3,5,6,8,9,11,12-octahydronaphtho [2,3b] [1,4,7,10,13] pentaoxacyclo octadecine-14,19-dione) and D₂ (2,3,5,6,8,9-hexahydronaphtho[2,3-b] [1,4,7,10] tetraoxacyclododecine-11,16-dione) have been synthesized and interacted with Li⁺, Na⁺, K⁺, Ca²⁺, Mg²⁺ cations. The isolated solid state soft materials obtained after interaction were characterized by melting point, TLC, ¹H NMR spectroscopy and CHN estimation. The extraction, transport potential and stability constant determination of these ionophores towards cations helped in investigating their binding strength in solution. The selective extraction of Na⁺ and Li⁺ by D₁ and D₂ correspondingly proves them an efficient compound for the manufacturing of chemosensor. Whereas efficient transport of Mg²⁺ by both the ionophores especially by D₁ may assist in developing biomodels for understanding its transport through membrane in living system. The selectivity of these ionophores towards metal ions can be modulated by molecular tailoring.     

Highly Selective Artificial Potassium Ion Channels Constructed from Pore‐Containing Helical Oligomers

Potassium ion channels specifically transport K⁺ ions over Na⁺ ions across a cell membrane. A queue of four binding sites in the K⁺ channel pore plays significant roles during highly selective conduction. A kind of aromatic helical oligomer was synthesized that can selectively bind K⁺ over Na⁺. By aromatic stacking of helical oligomers, a type of artificial K⁺ channels with contiguous K⁺ binding sites was constructed. Such artificial channels exhibited exceptionally high K⁺/Na⁺ selectivity ratios during transmembrane ion conduction.     

Stabilization of Th ions into mixed-valence thorium fluoride

The unusual oxidation state +3 of the thorium has been stabilized into a lithium containing non-stoichiometric mixed-valence (III/IV) thorium fluorinated phase with formula Li_2+xTh₁₂F₅₀ (0<x<1.8). This phase is closely related to the Li_5.5Ce₁₂F₅₀ one, the structure of which has been determined from the combined single-crystal X-ray diffraction and high resolution synchrotron powder diffraction. In these phases, the Li⁺ ions can be divided into two groups and are located either in locked positions or in open channels of the three dimensional framework. The amount of Li⁺ ions in open channels can be variable, so that the afore mentioned single phase may be considered as an insertion compound. The Li⁺ insertion is accompanied by the simultaneous reduction of a part of the Th⁴⁺ ions, resulting in a mixed-valence III/IV thorium fluoride. The electrochemical insertion of Li⁺ ions into the open channels of the host matrix has been carried out at 60 °C, using an alkylcarbonate PC-LiClO₄ 1 M electrolyte. The Li⁺ and Th³⁺ contents, both in the starting composition and the Li⁺ inserted ones, were investigated by high resolution solid state ⁷Li NMR and EPR, respectively.     

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.