A light-gated synthetic ion channel

A gated synthetic ion channel with beta-cyclodextrin as the pore and azobenzene as the gate is reported. Irradiation converts a tethered trans-azobenzene to cis-azobenzene which likely transforms the channel from a self-inclusion complex to a dissociated structure. This transformation results in an increase in anion transport and a decrease in cation transport across a phospholipid vesicle membrane.     

Cooperative transport in a potassium ion channel

Our current understanding of ion permeation through the selectivity filter of the KcsA potassium channel is based on the concept of a multi-ion transport mechanism. The details of this concerted movement, however, are not well understood. In the present paper we report on molecular dynamics simulations which provides new insights. It is shown that ion translocation is based on the collective hopping of ions and water molecules which is mediated by the flexible charged carbonyl groups lining the backbone of the pore. In particular, there is strong evidence for pairwise translocations where one ion and one water molecule form a bound state. We suggest a physical explanation of the observed phenomena employing a simple lattice model. It is argued that the water molecules can act as rectifiers during the hopping of ion-water pairs.     

Enhancement of antimicrobial activity by synthetic ion channel synergy

Hydraphile synthetic ion channels were found to enhance the cytotoxicity to E. coli and B. subtilis of erythromycin, kanamycin, rifampicin, and tetracycline when co-administered with the antibiotic at sublethal concentrations of channel.     

Ion transport,ion extraction,and ion binding by synthetic cyclic octapeptide

Cyclic octapeptide, cyclo[Gly-L-Lys(Z)-Sar-L-Pro]₂, (CGLSP2) was synthesized as an ionophore model. Its ion-transport ability through a chloroform membrane was investigated in connection with ion extractability (K_ex) and conformational properties. CGLSP2 transported the picrate salts of Ba²⁺ and Ca²⁺ efficiently. The K_ex sequences were Ba²⁺>Ca²⁺Mg²⁺ and K⁺>Rb⁺>Na⁺, showing good agreement with the selectivity in ion transport. In addition, cation-binding properties of CGLSP2 to alkali and alkaline earth metal ion were investigated in acetonitrile by CD and NMR spectroscopy. Titration curves obtained from CD data revealed three kinds of CGLSP2/cation complexes. The values of 1:1 complex-formation constants (K₁) decreased in the order Ba²⁺>Ca²⁺>Mg²⁺>Li⁺Na⁺K⁺.¹H- and¹³C-NMR data showed that free CGLSP2 exists in at least five different conformational states in acetonitrile. After the addition of equimolar amounts of Ba(ClO₄)₂, these conformations converged into a single C₂-symmetric conformation with all-trans peptide bonds.     

A light-regulated synthetic ion channel constructed by an azobenzene modified hydraphile

A light-regulated synthetic ion channel with hydraphile as the channel architecture and azobenzene as the regulation unit was reported. Photoisomerization changes the transmembrane length of the channel, thus results in regulated ion transport     

Transmembrane anion transport by synthetic systems

This highlight examines recent advances in the development of synthetic membrane transporters for anions, highlighting the underlying principles of transporter design and the promising applications of such transporters to biological systems including potential future treatments for diseases like cystic fibrosis which is caused by dysregulation of chloride transport across epithelial cell membranes.     

A synthetic, chloride-selective channel that alters chloride transport in epithelial cells

An Ussing chamber was used to demonstrate that synthetic amphiphilic anion transporters function as chloride transporters in mammalian airway epithelial cells.     

A parallel finite element simulator for ion transport through three‐dimensional ion channel systems

A parallel finite element simulator, ichannel, is developed for ion transport through three‐dimensional ion channel systems that consist of protein and membrane. The coordinates of heavy atoms of the protein are taken from the Protein Data Bank and the membrane is represented as a slab. The simulator contains two components: a parallel adaptive finite element solver for a set of Poisson–Nernst–Planck (PNP) equations that describe the electrodiffusion process of ion transport, and a mesh generation tool chain for ion channel systems, which is an essential component for the finite element computations. The finite element method has advantages in modeling irregular geometries and complex boundary conditions. We have built a tool chain to get the surface and volume mesh for ion channel systems, which consists of a set of mesh generation tools. The adaptive finite element solver in our simulator is implemented using the parallel adaptive finite element package Parallel Hierarchical Grid (PHG) developed by one of the authors, which provides the capability of doing large scale parallel computations with high parallel efficiency and the flexibility of choosing high order elements to achieve high order accuracy. The simulator is applied to a real transmembrane protein, the gramicidin A (gA) channel protein, to calculate the electrostatic potential, ion concentrations and I – V curve, with which both primitive and transformed PNP equations are studied and their numerical performances are compared. To further validate the method, we also apply the simulator to two other ion channel systems, the voltage dependent anion channel (VDAC) and α‐Hemolysin (α‐HL). The simulation results agree well with Brownian dynamics (BD) simulation results and experimental results. Moreover, because ionic finite size effects can be included in PNP model now, we also perform simulations using a size‐modified PNP (SMPNP) model on VDAC and α‐HL. It is shown that the size effects in SMPNP can effectively lead to reduced current in the channel, and the results are closer to BD simulation results. © 2013 Wiley Periodicals, Inc.     

Potassium ion transport by valinomycin across a Hg-supported lipid bilayer

A biomimetic membrane consisting of a lipid bilayer tethered to a mercury electrode via a hydrophilic spacer was investigated in aqueous KCl by potential-step chronocoulometry and electrochemical impedance spectroscopy, both in the absence and in the presence of the ionophore valinomycin. Impedance spectra, recorded from 1 x 10(-2) to 1 x 10(5) Hz over a potential range of 0.8 V, are satisfactorily fitted to a series of four RC meshes, which are straightforwardly related to the different substructural elements of the biomimetic membrane. The frequency-independent resistances and conductances of both the lipid bilayer and the hydrophilic spacer show a maximum when plotted against the applied potential. This behavior is interpreted on the basis of a general approximate approach that applies the concepts of impedance spectroscopy to a model of the electrified interphase and to the kinetics of potassium ion transport assisted by valinomycin across the lipid bilayer.     

Ligand-gated synthetic ion channels

Supramolecular pi-stack architecture is fundamental in DNA chemistry but absent in biological and synthetic ion channels and pores. Here, a novel rigid-rod pi-stack architecture is introduced to create synthetic ion channels with characteristics that are at the forefront of rational design, that is, ligand gating by a conformational change of the functional supramolecule. Namely, the intercalation of electron-rich aromatics is designed to untwist inactive electron-poor helical pi-stacks without internal space into open barrel-stave ion channels. Conductance experiments in planar lipid bilayers corroborate results from spherical bilayers and molecular modeling: Highly cooperative and highly selective ligand gating produces small, long-lived, weakly anion selective, ohmic ion channels. Structural studies conducted under conditions relevant for function provide experimental support for helix-barrel transition as origin of ligand gating. Control experiments demonstrate that minor structural changes leading to internal decrowding suffice to cleanly annihilate chiral self-organization and function.     

Synthesis and ion conductance behavior of a tetrameric alamethicin ion channel

[structure: see text] A porphyrin-tethered construct, containing four full-length alamethicin monomers, has been synthesized and characterized. The ion conductance data of the assembly in 1 M HCl display long-lived, albeit noisy, channels that appear to be voltage-independent multiples of only one conductance state. The noise in the data is consistent with the molecular modeling studies, which indicate that the side chain of glutamine 7 of alamethicin does not fit well into the narrow pore of a parallel four-helix bundle.     

In vivo cell death mediated by synthetic ion channels

Synthetic ion channel hydraphiles, which are known to infiltrate membranes and disrupt ion homeostasis, were tested as direct injection toxins in live mice as potential schlerotic agents. The study uses a near-IR dye to image and evaluate the success of the approach.     

Recent synthetic transport systems

This critical review covers progress with synthetic transport systems, particularly ion channels and pores, between January 2006 and December 2009 in a comprehensive manner. This is the third part of a series launched in the year 2000, covering a rich collection of structural and functional motifs that should appeal to a broad audience of non-specialists, including to organic, biological, supramolecular and polymer chemists. Impressive breakthroughs have been achieved over the past four years in part because of a fruitful expansion toward new types of interactions, including metal-organic, π-π, aromatic electron donor-acceptor, anion-π or anion-macrodipole interactions as well as dynamic covalent bonds (169 references).     

Cation dependence of chloride ion complexation by open-chained receptor molecules in chloroform solution

Seventeen peptides, most having the sequence GGGPGGG, but differing in the C- and N-terminal ends, have been studied as anion-complexing agents. These relatively simple, open-chained peptide systems interact with both chloride and the associated cation. Changes in the N- and C-terminal side chains appear to make little difference in the efficacy of binding. NMR studies suggest that the primary interactions involve amide NH contacts with the chloride anion, and CD spectral analyses suggest a concomitant conformational change upon binding. Changes in binding constants, which are expected in different solvents, also suggest selective solvent interactions with the unbound host that helps to preorganize the open-chained peptide system. Significant differences are apparent in complexation strengths when the heptapeptide chain is shortened or lengthened or when the relative position of proline within the heptapeptide is varied.     

Cation selective ion channels formed by macrodiolide antibiotic elaiophylin in lipid bilayer membranes

The macrodiolide antibiotic elaiophylin (1) forms stable, long-lasting cation selective ion channels in planar lipid bilayer membranes prepared from soybean phosphatidylcholine. Current of the single ion channel displayed two sublevels corresponding to the two substates of the channel conductance: a slow substate, with about 5 s of mean dwell time in the open state at 40% level of the total amplitude conductance, and a fast substate of higher conductance with dwell times in the open and closed state of about 0.1 s. Amplitude conductances of the single ion channels in 200 mM of LiCl, NaCl, KCl, RbCl and CsCl were 75, 140, 220, 240 and 226 pS, and the conductance was linear function of the electrolyte concentration. Ratios of cation to anion permeabilities of the channel for NaCl and KCl were 8+/-2 and >24, respectively. A molecular model of the channel structure is suggested.     

Cation binding by a crown-capped porphyrin

The crown ether capped metalloporphyrins (6) form complexes with metal cations; complex formation may be detected by fluorescence quenching for (6, M=ZnII or CuII) and paramagnetic guest cations or, in some cases, by FAB mass spectrometry. Complexation with alkyl ammonium cations was also examined using absorption spectrometry.