Polyhydrazide‐Based Organic Nanotubes as Efficient and Selective Artificial Iodide Channels

Reported herein is a series of pore‐containing polymeric nanotubes based on a hydrogen‐bonded hydrazide backbone. Nanotubes of suitable lengths, possessing a hollow cavity of about a 6.5 Å diameter, mediate highly efficient transport of diverse types of anions, rather than cations, across lipid membranes. The reported polymer channel, having an average molecular weight of 18.2 kDa and 3.6 nm in helical height, exhibits the highest anion‐transport activities for iodide (EC₅₀=0.042 μm or 0.028 mol % relative to lipid), whcih is transported 10 times more efficiently than chlorides (EC₅₀=0.47 μm ). Notably, even in cholesterol‐rich environment, iodide transport activity remains high with an EC₅₀ of 0.37 μm . Molecular dynamics simulation studies confirm that the channel is highly selective for anions and that such anion selectivity arises from a positive electrostatic potential of the central lumen rendered by the interior‐pointing methyl groups.     

Specific Binding of a d‐RNA G‐Quadruplex Structure with an l‐RNA Aptamer

G‐quadruplex (G4) structures are of general importance in chemistry and biology, such as in biosensing, gene regulation, and cancers. Although a large repertoire of G4‐binding tools has been developed, no aptamer has been developed to interact with G4. Moreover, the G4 selectivity of current toolkits is very limited. Herein, we report the first l ‐RNA aptamer that targets a d ‐RNA G‐quadruplex (rG4). Using TERRA rG4 as an example, our results reveal that this l ‐RNA aptamer, Ap3‐7, folds into a unique secondary structure, exhibits high G4 selectivity and effectively interferes with TERRA‐rG4–RHAU53 binding. Our approach and findings open a new door in further developing G4‐specific tools for diverse applications.     

Optically Active Hexaazamacrocycles: Protonation Behavior and Chiral‐Anion Recognition

The protonation features of two optically active 22‐membered hexaazamacrocycles possessing one ( L1 ) or two ( L2 ) (R,R)‐cyclohexane‐1,2‐diamine moieties have been studied by means of potentiometric ¹H‐ and ¹³C‐NMR techniques. This study allows the determination of the basicity constants and the stepwise protonation sites. The presence of the cyclohexane decreases the protonation ability, and this effect can be explained in terms of conformational and electrostatic factors. Binding of different chiral dicarboxylates has been studied by potentiometry. Macrocycle L2 presents higher anion‐complexation equilibrium constants than L1 . The stability of the diastereoisomeric complexes depends on the pH, and the structures of the macrocycles and anions. Receptor L1 ⋅6 H⁺ shows moderate D ‐selectivity towards tartrate anion, whereas L2 ⋅6 H⁺ exhibits a good preference for N‐Ac‐D ‐aspartate. Both protonated L1 and L2 form strong complexes with N‐Ac‐glutamate, and the stoichiometry of the complex depends on the degree of protonation and the absolute configuration of the anion. For this last anion, both azamacrocycles exhibit a clear D ‐preference.     

An Artificial Single Molecular Channel Showing High Chloride Transport Selectivity and pH-Responsive Conductance

Inspired by the unique structure and function of the natural chloride channel (ClC) selectivity filter, we present herein the design of a ClC-type single channel molecule. This channel displays high ion transport activity with half-maximal effective concentration, EC₅₀, of 0.10 μM, or 0.075 mol % (channel molecule to lipid ratio), as determined by fluorescent analysis using lucigenin-encapsulated vesicles. Planar bilayer lipid membrane conductance measurements indicated an excellent Cl⁻/K⁺ selectivity with a permeability ratio P /P up to 12.31, which is comparable with the chloride selectivity of natural ClC proteins. Moreover, high anion/anion selectivity (P /P =66.21) and pH-dependent conductance and ion selectivity of the channel molecule were revealed. The ClC-like transport behavior is contributed by the cooperation of hydrogen bonding and anion–π interactions in the central macrocyclic skeleton, and by the existence of pH-responsive terminal phenylalanine residues.     

Photosensory Functions of Channelrhodopsins in Native Algal Cells†

Photomotility responses in flagellate alga are mediated by two types of sensory rhodopsins (A and B). Upon photoexcitation they trigger a cascade of transmembrane currents which provide sensory transduction of light stimuli. Both types of algal sensory rhodopsins demonstrate light‐gated ion channel activities when heterologously expressed in animal cells, and therefore they have been given the alternative names channelrhodopsin 1 and 2. In recent publications their channel activity has been assumed to initiate the transduction chain in the native algal cells. Here we present data showing that: (1) the modes of action of both types of sensory rhodopsins are different in native cells such as Chlamydomonas reinhardtii than in heterologous expression systems, and also differ between the two types of rhodopsins; (2) the primary function of Type B sensory rhodopsin (channelrhodopsin‐2) is biochemical activation of secondary Ca²⁺‐channels with evidence for amplification and a diffusible messenger, sufficient for mediating phototaxis and photophobic responses; (3) Type A sensory rhodopsin (channelrhodopsin‐1) mediates avoidance responses by direct channel activity under high light intensities and exhibits low‐efficiency amplification. These dual functions of algal sensory rhodopsins enable the highly sophisticated photobehavior of algal cells.     

Polyhydrazide-Based Organic Nanotubes as Efficient and Selective Artificial Iodide Channels

Reported herein is a series of pore-containing polymeric nanotubes based on a hydrogen-bonded hydrazide backbone. Nanotubes of suitable lengths, possessing a hollow cavity of about a 6.5 Å diameter, mediate highly efficient transport of diverse types of anions, rather than cations, across lipid membranes. The reported polymer channel, having an average molecular weight of 18.2 kDa and 3.6 nm in helical height, exhibits the highest anion-transport activities for iodide (EC₅₀=0.042 μm or 0.028 mol % relative to lipid), whcih is transported 10 times more efficiently than chlorides (EC₅₀=0.47 μm ). Notably, even in cholesterol-rich environment, iodide transport activity remains high with an EC₅₀ of 0.37 μm . Molecular dynamics simulation studies confirm that the channel is highly selective for anions and that such anion selectivity arises from a positive electrostatic potential of the central lumen rendered by the interior-pointing methyl groups.     

Tight and Selective Caging of Chloride Ions by a Pseudopeptidic Host

The selective molecular recognition of chloride versus similar anions is a continuous challenge in supramolecular chemistry. We have designed and prepared a simple pseudopeptidic cage ( 1 a ) that defines a cavity suitable for the tight encapsulation of chloride. The interaction of the protonated form of 1 a with different inorganic anions was studied in solution by ¹H NMR spectroscopy and ESI‐MS, and in the solid state by X‐ray diffraction. The solution binding data showed that the association constants of 1 a to chloride are more than two orders of magnitude higher than to any other tested inorganic anion. Remarkably, 1 a displayed a high selectivity for chloride over other closely related halides such as bromide (selectivity=111), iodide (selectivity=719), and fluoride (selectivity >1000). Binding experiments (¹H NMR spectroscopy and ESI‐MS) suggested that 1 a has a high‐affinity (inner) binding site and an additional low‐affinity (external) binding site. The supramolecular complexes with F^?, Cl^?, and Br^? have been also characterized by the X‐ray diffraction of the corresponding [ 1 a? nHX] crystalline salts. The structural data show that the chloride anion is tightly encapsulated within the host, in a binding site defined by a very symmetric array of electrostatic H‐bonds. For the fluoride salt, the size of the cage cavity is too large and is occupied by a water molecule, which fits inside the cage efficiently competing with F^?. In the case of the bigger bromide, the mismatch of the anion inside the cage caused a geometrical distortion of the host and thus a large energetic penalty for the interaction. This minimalistic pseudopeptidic host represents a unique example of the construction of a simple well‐defined binding pocket that allows the highly selective molecular recognition of a challenging substrate.     

A Porphyrin‐Based Porous rtl Metal–Organic Framework as an Efficient Catalyst for the Cycloaddition of CO2 to Epoxides

A porous rtl metal–organic framework (MOF) [Mn₅L(H₂O)₆?(DMA)₂]?5DMA?4C₂H₅OH ( 1? Mn) (H₁₀L=5,10,15,20‐tetra(4‐(3,5‐dicarboxylphenoxy)phenyl)porphyrin; DMA=N,N′‐dimethylacetamide) was synthesized by employing a new porphyrin‐based octacarboxylic acid ligand. 1? Mn exhibits high Mn^II density in the porous framework, providing it great Lewis‐acid heterogeneous catalytic capability for the cycloaddition of CO₂ with epoxides. Strikingly, 1? Mn features excellent catalytic activity to the cycloaddition of CO₂ to epoxides, with a remarkable initial turnover frequency 400 per mole of catalyst per hour at 20 atm. As‐synthesized 1? Mn also exhibits size selectivity to different epoxide substrates on account of their steric hindrance. The high catalytic activity, size selectivity, and stability toward the epoxides on catalytic cycloaddition of CO₂ make 1? Mn a promising heterogeneous catalyst for fixation and utilization of CO₂.     

A Tetrameric Cage with D2h Symmetry through Alkyne Metathesis

Shape‐persistent covalent organic polyhedrons (COPs) with ethynylene linkers are usually prepared through kinetically controlled cross‐coupling reactions. The high‐yielding synthesis of ethynylene‐linked rigid tetrameric cages via one‐step alkyne metathesis from readily accessible triyne precursors is presented. The tetrameric cage contains two macrocyclic panels and exhibits D_2h symmetry. The assembly of such a COP is a thermodynamically controlled process, which involves the initial formation of macrocycles as key intermediates followed by the connection of two macrocycles with ethynylene linkages. With a large internal cavity, the cage exhibits a high binding selectivity toward C₇₀ (K=3.9×10³ L mol^?1) over C₆₀ (no noticeable binding).     

Conformational Re‐engineering of Porphyrins as Receptors with Switchable N−H⋅⋅⋅X‐Type Binding Modes

The selectivity and functional variability of porphyrin cofactors are typically based on substrate binding of metalloporphyrins wherein the pyrrole nitrogen units only serve to chelate the metal ions. Yet, using the porphyrin inner core system for other functions is possible through conformational engineering. As a first step towards porphyrin “enzyme‐like” active centers, a structural and spectroscopic study of substrate binding to the inner core porphyrin system shows that a highly saddle‐distorted porphyrin with peripheral amino receptor groups ( 1 , 2,3,7,8,12,13,17,18‐octaethyl‐5,10,15,20‐tetrakis(2‐aminophenyl)porphyrin) coordinates analytes in a switchable manner dependent on the acidity of the solution. The supramolecular ensemble exhibits exceptionally high affinity to and selectivity for the pyrophosphate anion (2.26±0.021)×10⁹ m ^?1. ¹H NMR spectroscopic studies provided insight into the likely mode of binding and the characterization of atropisomers, all four of which were also studied by X‐ray crystallography.     

A Hydrophobic Metal–Organic Framework Based on Cubane‐Type [Co4(μ3‐F)3(μ3‐SO4)]3+ Clusters for Gas Storage and Adsorption Selectivity of Benzene over Cyclohexane

Hydrophobic metal‐organic frameworks (MOFs) not only have high water stability, but also exhibit high adsorption capacity towards organic molecules, in particular hydrocarbons. Herein we report a rare metal fluoride organic framework MFOF‐1 with high hydrophobicity, which is constructed from unprecedented fluoride‐ and sulfate‐bridged cubane‐type tetranuclear cobalt clusters. MFOF‐1 consists of three types of polyhedral cages with face‐sharing configurations, and possesses a novel (3,9)‐connected 3D+3D→3D self‐interpenetrating array or the rare pyr topology. MFOF‐1 shows high thermal stability and high stability in water and even acid/base aqueous solutions, and exhibits rather high H₂ and CO₂ storage capacities at ambient pressure. Remarkably, MFOF‐1 shows little adsorption of water but considerably high uptakes of methanol, n‐hexane, cyclohexane, and benzene, and exhibits a certain degree of adsorption selectivity of benzene over cyclohexane.     

A Highly Selective and Sensitive Barium(II)‐Selective PVC Membrane Based on Dimethyl 1‐Acetyl‐8‐oxo‐2,8‐dihydro‐ 1H‐pyra‐zolo[5,1‐a]isoindole‐2,3‐dicarboxylate

A poly(vinyl chloride)‐based membrane of dimethyl 1‐acetyl‐8‐oxo‐2,8‐dihydro‐1H‐pyra‐zolo[5,1‐a]isoindole‐2,3‐dicarboxylate as a neutral carrier with sodium tetraphenylborate (NaTPB) as an anion excluder and 2‐nitrophenyl octyl ether (NPOE) as plasticizer was prepared and investigated as a Ba(II)‐selective electrode. The electrode exhibits a Nernstian slope of 29.7±0.4 mV per decade over a wide concentration range (1.0×10^?6 to 1.0×10^?1 M) with a detection limit of 7.6×10^?7 M between pH 3.0 and 11.0. The response time of the sensor is about 10 s and it can be used over a period of 2 months without any divergence in potential. The proposed membrane sensor revealed good selectivity for Ba(II) over a wide variety of other metal ions. It was successfully used in direct determination of barium ions in industrial wastewater samples.     

Silica‐Bound 3‐{2‐[Poly(ethylene Glycol)]ethyl}‐Substituted 1‐Methyl‐1H‐imidazol‐3‐ium Bromide: A Recoverable Phase‐Transfer Catalyst for Smooth and Regioselective Conversion of Oxiranes to β‐Hydroxynitriles in Water

A series of β‐hydroxynitriles were efficiently synthesized from the regioselective ring opening of oxiranes by cyanide anion in the presence of silica‐bound 3‐{2‐[poly(ethylene glycol)]ethyl}‐substituted 1‐methyl‐1H‐imidazol‐3‐ium bromide (SiO₂? PEG? ImBr) as a novel recoverable phase‐transfer catalyst in H₂O (Scheme 1 and Table 2). The workup procedure was straightforward, and the catalyst could be reused over four times with almost no loss of catalytic activity and selectivity.     

Specific Binding of a d-RNA G-Quadruplex Structure with an l-RNA Aptamer

G-quadruplex (G4) structures are of general importance in chemistry and biology, such as in biosensing, gene regulation, and cancers. Although a large repertoire of G4-binding tools has been developed, no aptamer has been developed to interact with G4. Moreover, the G4 selectivity of current toolkits is very limited. Herein, we report the first l -RNA aptamer that targets a d -RNA G-quadruplex (rG4). Using TERRA rG4 as an example, our results reveal that this l -RNA aptamer, Ap3-7, folds into a unique secondary structure, exhibits high G4 selectivity and effectively interferes with TERRA-rG4–RHAU53 binding. Our approach and findings open a new door in further developing G4-specific tools for diverse applications.     

Monomer sequencing and microstructural analysis on polymers of dimethyl norbornene dicarboxylate and 7‐oxanorbornene dicarboxylic derivatives employing ruthenium catalysts by ring‐opening metathesis polymerization

The physiochemical properties, comonomer sequencing, and regiospecificity of the linkages between monomeric units within homo/copolymers based on 5,6‐di‐substituted norbornene and 7‐oxanorbornene type monomers by ring‐opening metathesis polymerization are reported and correlated to their primary and secondary structural elements. In general, first‐generation Grubbs‐ I1 ruthenium catalyst generates polymers with high trans content that exhibits an extended secondary structure with exo,exo substituents, whereas second‐generation Grubbs‐ I2 catalyst produces polymers with high cis content that forms tight turns, resulting in a compact structure. Furthermore, I2 ‐produced polymers exhibit a high level of alternating cis–trans double bonds along their polymeric backbone. In stark contrast, both first‐ and second‐generation Grubbs catalysts display complete reversal in cis/trans selectivity when an oxygen atom is in position‐7 of the norbornene‐ring along with mono‐endo‐substitution in position‐5 or 6, and hence highlighting the importance of stereoelectronic complexation by the catalyst with the next incoming monomer for cis/trans selectivity. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014 , 52, 2477–2501     

Phenacyl–Thiophene and Quinone Semiconductors Designed for Solution Processability and Air‐Stability in High Mobility n‐Channel Field‐Effect Transistors

Electron‐transporting organic semiconductors (n‐channel) for field‐effect transistors (FETs) that are processable in common organic solvents or exhibit air‐stable operation are rare. This investigation addresses both these challenges through rational molecular design and computational predictions of n‐channel FET air‐stability. A series of seven phenacyl–thiophene‐based materials are reported incorporating systematic variations in molecular structure and reduction potential. These compounds are as follows: 5,5′′′‐bis(perfluorophenylcarbonyl)‐2,2′:5′,‐ 2′′:5′′,2′′′‐quaterthiophene ( 1 ), 5,5′′′‐bis(phenacyl)‐2,2′:5′,2′′: 5′′,2′′′‐quaterthiophene ( 2 ), poly[5,5′′′‐(perfluorophenac‐2‐yl)‐4′,4′′‐dioctyl‐2,2′:5′,2′′:5′′,2′′′‐quaterthiophene) ( 3 ), 5,5′′′‐bis(perfluorophenacyl)‐4,4′′′‐dioctyl‐2,2′:5′,2′′:5′′,2′′′‐quaterthiophene ( 4 ), 2,7‐bis((5‐perfluorophenacyl)thiophen‐2‐yl)‐9,10‐phenanthrenequinone ( 5 ), 2,7‐bis[(5‐phenacyl)thiophen‐2‐yl]‐9,10‐phenanthrenequinone ( 6 ), and 2,7‐bis(thiophen‐2‐yl)‐9,10‐phenanthrenequinone, ( 7 ). Optical and electrochemical data reveal that phenacyl functionalization significantly depresses the LUMO energies, and introduction of the quinone fragment results in even greater LUMO stabilization. FET measurements reveal that the films of materials 1 , 3 , 5 , and 6 exhibit n‐channel activity. Notably, oligomer 1 exhibits one of the highest μ_e (up to ≈0.3 cm² V^?1 s^?1) values reported to date for a solution‐cast organic semiconductor; one of the first n‐channel polymers, 3 , exhibits μ_e≈10^?6 cm² V^?1 s^?1 in spin‐cast films (μ_e=0.02 cm² V^?1 s^?1 for drop‐cast 1 : 3 blend films); and rare air‐stable n‐channel material 5 exhibits n‐channel FET operation with μ_e=0.015 cm² V^?1 s^?1, while maintaining a large I_on:off=10⁶ for a period greater than one year in air. The crystal structures of 1 and 2 reveal close herringbone interplanar π‐stacking distances (3.50 and 3.43 Å, respectively), whereas the structure of the model quinone compound, 7 , exhibits 3.48 Å cofacial π‐stacking in a slipped, donor‐acceptor motif.     

Aza‐Bambusurils En Route to Anion Transporters

Previous calculations of anion binding with various bambusuril analogs predicted that the replacement of oxygen by nitrogen atoms to produce semiaza‐bambus[6]urils would award these new cavitands with multiple anion binding properties. This study validates the hypothesis by efficient synthesis, crystallography, thermogravimetric analysis and calorimetry. These unique host molecules are easily accessible from the corresponding semithio‐bambusurils in a one‐pot reaction, which converts a single anion receptor into a potential anion channel. Solid‐state structures exhibit simultaneous accommodation of three anions, linearly positioned within the cavity along the main symmetry axis. The ability to hold anions at a short distance of about 4 Å is reminiscent of natural chloride channels in E. coli, which exhibit similar distances between their adjacent anion binding sites. The calculated transition‐state energy for double‐anion movement through the channel suggests that although these host–guest complexes are thermodynamically stable they enjoy high kinetic flexibility to render them efficient anion channels.     

1H‐Detected Solid‐State NMR Studies of Water‐Inaccessible Proteins In Vitro and In Situ

¹H detection can significantly improve solid‐state NMR spectral sensitivity and thereby allows studying more complex proteins. However, the common prerequisite for ¹H detection is the introduction of exchangeable protons in otherwise deuterated proteins, which has thus far significantly hampered studies of partly water‐inaccessible proteins, such as membrane proteins. Herein, we present an approach that enables high‐resolution ¹H‐detected solid‐state NMR (ssNMR) studies of water‐inaccessible proteins, and that even works in highly complex environments such as cellular surfaces. In particular, the method was applied to study the K⁺ channel KcsA in liposomes and in situ in native bacterial cell membranes. We used our data for a dynamic analysis, and we show that the selectivity filter, which is responsible for ion conduction and highly conserved in K⁺ channels, undergoes pronounced molecular motion. We expect this approach to open new avenues for biomolecular ssNMR.     

A solution‐processible poly(p‐phenylene vinylene) without alkyl substitution: Introducing the cis‐vinylene segments in polymer chain for improved solubility,blue emission,and high efficiency

A soluble all‐aromatic poly(2,5‐diphenyl‐1,4‐phenylenevinylene) (2,5‐DP‐PPV) is synthesized by utilizing aromatic phosphonium and aldehyde monomers through Wittig reaction. The H¹ NMR and FTIR measurements indicate that over 50% content of cis‐vinylene units exist in polymer backbone. The diphenyl‐substituted benzaldehyde monomer plays an important role to enhance cis‐products (Z‐selectivity) in Wittig reactions. The twisted cis‐segments in polymer backbone reduce the interchain interactions and enhance the solubility of such all‐aromatic PPV derivative in common organic solvents. 2,5‐DP‐PPV exhibits good solubility in common organic solvents, such as tetrahydrofuran and chloroform. The polymer film exhibits a blue light emission (λ_max = 485 nm) and a very high photoluminescence efficiency of 78%. The cis‐trans photo isomerization of this polymer in solution and the impact on the optical properties are also investigated. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 5242–5250, 2008