Triazole‐Tailored Guanosine Dinucleosides as Biomimetic Ion Channels to Modulate Transmembrane Potential

A “click” ion channel platform has been established by employing a clickable guanosine azide or alkyne with covalent spacers. The resulting guanosine derivatives modulated the traffic of ions across the phospholipid bilayer, exhibiting a variation in conductance spanning three orders of magnitude (pS to nS). Förster resonance energy transfer studies of the dansyl fluorophore with the membrane binding fluorophore Nile red revealed that the dansyl fluorophore is deeply embedded in the phospholipid bilayer. Complementary cytosine can inhibit the conductance of the supramolecular guanosine channels in the phospholipid bilayers.     

Structure‐Driven Selection of Adaptive Transmembrane Na+ Carriers or K+ Channels

Self‐assembled alkyl‐ureido‐benzo‐15‐crown‐5‐ethers are selective ionophores for K⁺ cations, which are preferred to Na⁺ cations. The transport mechanism is determined by the optimal coordination rather than classical dimensional compatibility between the crown ether hole and the cation diameter. Herein, we demonstrate that systematic changes of the structure lead to unexpected modifications in the cation‐transport activity and suffice to produce adaptive selection. We show that the main contribution to performance arises from optimal constraints on the conformational freedom, which are determined by the binding macrocycles, the nature of the hydrogen‐bonding groups, and the hydrophobic tails. Simple changes to the flexible 15‐crown‐5‐ether lead to selective carriers for Na⁺. Hydrophobic stabilization of the channels through mutual interactions between lipids and variable hydrophobic tails appears to be an important cause of increased activity. Oppositely, restricted translocation is achieved when constrained hydrogen‐bonded macrocyclic relays are less dynamic in a pore superstructure.     

Oligonorbornenes with Hammock‐Like Crown Ether Pendants as Artificial Transmembrane Ion Channel

Trimeric oligonorbornenes with hammock‐like crown ether pendants 3b and 3c were selectively synthesized by cascade metathetical cyclopolymerization upon treatment with the first generation Grubbs catalyst. These crown‐ether‐containing oligonorbornenes are impregnated in egg yolk phosphatidylcholine (EYPC) liposome as an artificial ion channel. The efficiency of the sodium ion transport properties has been examined. Oligomer 3c having a polar hydroxy end group exhibits the highest transport efficiency, which is comparable with the best efficiencies reported in literature. The orientation of the crown ether moieties in these oligomers may be critical for the ion transport properties.     

Voltage‐Driven Reversible Insertion into and Leaving from a Lipid Bilayer: Tuning Transmembrane Transport of Artificial Channels

Three new artificial transmembrane channel molecules have been designed and synthesized by attaching positively charged Arg‐incorporated tripeptide chains to pillar[5]arene. Fluorescent and patch‐clamp experiments revealed that voltage can drive the molecules to insert into and leave from a lipid bilayer and thus switch on and off the transport of K⁺ ions. One of the molecules was found to display antimicrobial activity toward Bacillus subtilis with half maximal inhibitory concentration (IC₅₀) of 10 μM which is comparable to that of natural channel‐forming peptide alamethicin.     

Metal–Organic Framework Membrane Nanopores as Biomimetic Photoresponsive Ion Channels and Photodriven Ion Pumps

Biological ion channels and ion pumps with sub‐nanometer sizes modulate ion transport in response to external stimuli. Realizing such functions with sub‐nanometer solid‐state nanopores has been an important topic with wide practical applications. Herein, we demonstrate a biomimetic photoresponsive ion channel and photodriven ion pump using a porphyrin‐based metal–organic framework membrane with pore sizes comparable to hydrated ions. We show that the molecular‐size pores enable precise and robust optoelectronic ion transport modulation in a broad range of concentrations, unparalleled with conventional solid‐state nanopores. Upon decoration with platinum nanoparticles to form a Schottky barrier photodiode, photovoltage across the membrane is generated with “uphill” ion transport from low concentration to high concentration. These results may spark applications in energy conversion, ion sieving, and artificial photosynthesis.     

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.     

Synthesis of Triazole‐Linked Amino Acid‐Aryl C‐Glycoside Hybrids via Click Chemistry as Novel PTP1B Inhibitors

Triazolyl phenylalanine and tyrosine‐aryl C‐glycoside hybrids were readily synthesized via microwave‐assisted Cu(I)‐catalyzed azide‐alkyne 1,3‐dipolar cycloaddition in high yields. Successive enzymatic assay identified the synthesized glycoconjugates as novel PTP1B inhibitors with low micromole‐ranged inhibitory activity and at least several‐fold selectivity over other homologous PTPs tested. In addition, the benzyl groups on glucosyl moiety were found crucial toward PTP1B inhibition.     

IrIII and RuII Complexes Containing Triazole‐Pyridine Ligands: Luminescence Enhancement upon Substitution with β‐Cyclodextrin

Novel 2‐(1‐substituted‐1H‐1,2,3‐triazol‐4‐yl)pyridine (pytl) ligands have been prepared by “click chemistry” and used in the preparation of heteroleptic complexes of Ru and Ir with bipyridine (bpy) and phenylpyridine (ppy) ligands, respectively, resulting in [Ru(bpy)₂(pytl‐R)]Cl₂ and [Ir(ppy)₂(pytl‐R)]Cl (R=methyl, adamantane (ada), β‐cyclodextrin (βCD)). The two diastereoisomers of the Ir complex with the appended β‐cyclodextrin, [Ir(ppy)₂(pytl‐βCD)]Cl, were separated. The [Ru(bpy)₂(pytl‐R)]Cl₂ (R=Me, ada or βCD) complexes have lower lifetimes and quantum yields than other polypyridine complexes. In contrast, the cyclometalated Ir complexes display rather long lifetimes and very high emission quantum yields. The emission quantum yield and lifetime (Φ=0.23, τ=1000 ns) of [Ir(ppy)₂(pytl‐ada)]Cl are surprisingly enhanced in [Ir(ppy)₂(pytl‐βCD)]Cl (Φ=0.54, τ=2800 ns). This behavior is unprecedented for a metal complex and is most likely due to its increased rigidity and protection from water molecules as well as from dioxygen quenching, because of the hydrophobic cavity of the βCD covalently attached to pytl. The emissive excited state is localized on these cyclometalating ligands, as underlined by the shift to the blue (450 nm) upon substitution with two electron‐withdrawing fluorine substituents on the phenyl unit. The significant differences between the quantum yields of the two separate diastereoisomers of [Ir(ppy)₂(pytl‐βCD)]Cl (0.49 vs. 0.70) are attributed to different interactions of the chiral cyclodextrin substituent with the Δ and Λ isomers of the metal complex.     

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.     

Engineering Fast Ion Conduction and Selective Cation Channels for a High‐Rate and High‐Voltage Hybrid Aqueous Battery

The rechargeable aqueous metal‐ion battery (RAMB) has attracted considerable attention due to its safety, low costs, and environmental friendliness. Yet the poor‐performance electrode materials lead to a low feasibility of practical application. A hybrid aqueous battery (HAB) built from electrode materials with selective cation channels could increase the electrode applicability and thus enlarge the application of RAMB. Herein, we construct a high‐voltage K–Na HAB based on K₂FeFe(CN)₆ cathode and carbon‐coated NaTi₂(PO₄)₃ (NTP/C) anode. Due to the unique cation selectivity of both materials and ultrafast ion conduction of NTP/C, the hybrid battery delivers a high capacity of 160 mAh g^?1 at a 0.5 C rate. Considerable capacity retention of 94.3 % is also obtained after 1000 cycles at even 60 C rate. Meanwhile, high energy density of 69.6 Wh kg^?1 based on the total mass of active electrode materials is obtained, which is comparable and even superior to that of the lead acid, Ni/Cd, and Ni/MH batteries.     

Click Chemistry Route to the Synthesis of Unusual Amino Acids,Peptides, Triazole‐Fused Heterocycles and Pseudodisaccharides

Conjugation of different molecular species using copper(I)‐catalyzed click reaction between azides and terminal alkynes is among the best available methods to prepare multifunctional compounds. The effectiveness of this method has provided wider acceptance to the concept of click chemistry, which is now widely employed to synthesize densely functionalized organic molecules. This article summarizes the contributions from our group in the development of new methods for the synthesis of functional molecules using copper(I)‐catalyzed click reactions. We have developed very efficient methods for the synthesis of peptides and amino acids conjugated with carbohydrates, thymidine and ferrocene. We have also developed an efficient strategy to synthesize triazole‐fused heterocycles from primary amines, amino alochols and diols. Finally, an interesting method for the synthesis of pseudodisaccharides linked through triazoles, starting from carbohydrate‐derived donor‐acceptor cyclopropanes is discussed.     

New Polyalkynyl Dendrons and Dendrimers: “Click” Chemistry with Azidomethylferrocene and Specific Anion and Cation Electrochemical Sensing Properties of the 1,2,3‐Triazole‐Containing Dendrimers

Dendrimers for ion sensing : The synthesis and use of new tris‐alkynyl dendrons are reported. So‐called “click” reactions of the dendrimers described with azidomethylferrocene give 27‐ferrocenyl, 81‐ferrocenyl, and 243‐ferrocenyl dendrimers. Electrochemical recognition of oxo‐anions and Pd²⁺ cations has been compared using the three polyferrocenyl dendrimers.