We have prepared a crown ether triad containing acylhydrazone units. In solution, the triad can self-assemble linearly to form an organogel. UV light-induced E/Z isomerization of the CN bond of the acylhydrazone unit endows the assembly with photo-sensitivity. The triad was able to insert into the lipid bilayer to form a supramolecular transmembrane channel which showed transport selectivity for NH4+ over K+. The channel exhibited photo-gating properties under microscopic and macroscopic conditions. The transport of the channel could be reversibly switched off and on by irradiation with alternating 320 and 365 nm UV light as supported by the conductance measurements.

Lipid bilayer membranes separate living cells from their environment. Membrane proteins are responsible for the processing of ion and molecular inputs and exports, sensing stimuli and signals across the bilayers, which may operate in a channel or carrier mechanism. Inspired by these wide-ranging functions of membrane proteins, chemists have made great efforts in constructing synthetic mimics in order to understand the transport mechanisms, create materials for separation, and develop therapeutic agents.Since the report of an alkylated cyclodextrin for transporting Cu2+ and Co2+ by Tabushi and co-workers in 1982, chemists have constructed a variety of artificial transmembrane channels by making use of either the multimolecular self-assembly or unimolecular strategy. In the context of the design of unimolecular channels, important advances have been made, including, among others, the tethering of natural gramicidin A or alamethicin and the modification of various macrocycles such as crown ethers, cyclodextrins, calixarenes, and cucurbiturils. Many of these unimolecular channels exhibit high transport ability for metal ions, particularly K+ and Na+.Concerning the development of artificial channels based on macrocyclic frameworks, one straightforward and efficient approach is to introduce discrete chains to reinforce their capability to insert into bilayers. Currently, this approach has found the widest applications in the systems of crown ethers and calixarenes. We envisioned that for macrocycle-based unimolecular channels, control of the arrangement of the appended chains in the upward and/or downward direction would favor the insertion of the molecular systems into bilayers, while the introduction of additional interactions among the chains would further stabilize a tubular conformation. Both factors should be helpful for the formation of new efficient channels.In this Account, we discuss our efforts in designing new unimolecular artificial channels from tubular pillar[n]arenes by extending their lengths with various ester, hydrazide, and short peptide chains. We have utilized well-defined pillar[5]arene and pillar[6]arene as rigid frameworks that allow the appended chains to afford extended tubular structures. We demonstrate that the hydrazide and peptide chains form intramolecular N–H···O═C hydrogen bonds that enhance the tubular conformation of the whole molecule. The new pillar[n]arene derivatives have been successfully applied as unimolecular channels for the selective transport of protons, water, and amino acids and the voltage-gated transport of K+. We also show that aromatic hydrazide helices and macrocycles appended with peptide chains are able to mediate the selective transport of NH4+.

Three shape-persistent aromatic hydrazide macrocycles that bear phenylalanine tripeptide chains have been synthesized. These macrocycles can insert into lipid bilayers to form single-molecular ion channels which exhibit a high NH4+/K+ selectivity.

A new series of hydrogen-bonded helical aromatic hydrazide oligomers and polymer that bear phenylalanine tripeptide chains have been designed and synthesized. It was revealed that the helical structures could insert into lipid bilayers to form unimolecular channels. The longest oligomeric and polymeric helical channels exhibited an NH4+/K+ selectivity that was higher than that of natural gramicidin A, whereas the transport of a short helical channel for Tl+ could achieve an efficiency as high as that of gramicidin A.

Preorganized aryltriazole foldamers 1 and 2 were designed and synthesized. NMR studies and X-ray analysis demonstrate that 1 adopts a crescent conformation driven by a series of continuous hydrogen bonds at the periphery of the foldamer, whereas 2 displays a coil conformation. NMR titrations reveal that the affinities of fully preorganized foldamer 1 for halogen anions are much stronger that those of partially preorganized foldamer 2. Furthermore, it is found that such full preorganization makes 1 an effective transmembrane transporter for the chloride anion across a lipid bilayer.

Peptide-appended pillar[n]arene (n = 5, 6) derivatives have been synthesized. 1H NMR and IR studies revealed that the molecules adopt a tubular conformation in solution and lipid bilayer membranes. Kinetic measurements using the fluorescent labeling method with lipid vesicles revealed that these molecules can efficiently mediate the transport of amino acids across lipid membranes at a very low channel-to-lipid ratio (EC50 = 0.002 mol %). In several cases, chiral selectivity for amino acid enantiomers was achieved, which is one of the key functions of natural amino acid channels.

Pillar[5]arenes with introverted amino groups were produced through aminolysis. X-ray analysis demonstrated that the intramolecular hydrogen bonding induced the amino group toward the inner space of the cavity. The kinetic studies and molecular modelings revealed that the hydrogen bonding also contributed to the acceleration of the aminolysis through stabilizing the intermediate.

Hydrazide-appended pillar[5]arene derivatives have been synthesized. X-ray crystal structure analysis and 1H NMR studies revealed that the molecules adopt unique tubular conformations. Inserting the molecules into the lipid membranes of vesicles leads to the transport of water through the channels produced by single molecules, as supported by dynamic light scattering and cryo-SEM experiments. The channels exhibit the transport activity at a very low channel to lipid ratio (0.027 mol %), and a water permeability of 8.6 × 10–10 cm s–1 is realized. In addition, like natural water channel proteins, the artificial systems also block the transport of protons.

Three pillar[n]arenes (n = 8–10) were synthesized. X-ray analysis demonstrated that, different from early reported small pillar[n]arenes (n = 5, 6), these larger macrocycles gave rise to two cavities. 1H NMR and MS experiments revealed that pillar[9]arene complexed one n-octyltrimethyl ammonium in chloroform, while pillar[10]arene could complex two.

A pillar[5]arene decaamine has been synthesized and revealed to encapsulate linear diacids in neutral, alkaline, and acidic conditions, driven by the hydrophobic and electrostatic interactions, to give rise to pseudo[2]rotaxanes. Ion pair-bonded stoppers can further lock the diacids to generate stable water soluble [2]rotaxanes.

Organic nanotubes have been assembled from pillar[5]arenes 1 and 2. Compound 1 gelates organic solvents through the formation of tubular fibers which are evidenced by TEM and XRD experiments, while 2 assembles into two different channels under the template effect of water wires. In addition, the water wires in the nanotubes of 2 can be under selective proton conductance. The results described herein represent a new strategy for building tubular structures.

A per-hydroxylated pillar[6]arene was prepared. Single-crystal X-ray analysis demonstrated that its molecules are arranged in an up-to-down manner to form infinite channels in the solid state. Its host–guest complexation with a series of bispyridinium salts in solution was further investigated. It was found that the per-hydroxylated pillar[6]arene could form a 1:1 complex with paraquat in acetone with an association constant of 2.2 × 102 M–1. This complex is a [2]pseudorotaxane as shown by its crystal structure, which is the first pillar[6]arene-based host–guest complex crystal structure.

We have prepared a crown ether triad containing acylhydrazone units. In solution, the triad can self-assemble linearly to form an organogel. UV light-induced E/Z isomerization of the CN bond of the acylhydrazone unit endows the assembly with photo-sensitivity. The triad was able to insert into the lipid bilayer to form a supramolecular transmembrane channel which showed transport selectivity for NH4+ over K+. The channel exhibited photo-gating properties under microscopic and macroscopic conditions. The transport of the channel could be reversibly switched off and on by irradiation with alternating 320 and 365 nm UV light as supported by the conductance measurements.

Pillar[5]arenes with introverted amino groups were produced through aminolysis. X-ray analysis demonstrated that the intramolecular hydrogen bonding induced the amino group toward the inner space of the cavity. The kinetic studies and molecular modelings revealed that the hydrogen bonding also contributed to the acceleration of the aminolysis through stabilizing the intermediate.

Three shape-persistent aromatic hydrazide macrocycles that bear phenylalanine tripeptide chains have been synthesized. These macrocycles can insert into lipid bilayers to form single-molecular ion channels which exhibit a high NH4+/K+ selectivity.

Three pillar[n]arenes (n = 8–10) were synthesized. X-ray analysis demonstrated that, different from early reported small pillar[n]arenes (n = 5, 6), these larger macrocycles gave rise to two cavities. 1H NMR and MS experiments revealed that pillar[9]arene complexed one n-octyltrimethyl ammonium in chloroform, while pillar[10]arene could complex two.

A pillar[5]arene decaamine has been synthesized and revealed to encapsulate linear diacids in neutral, alkaline, and acidic conditions, driven by the hydrophobic and electrostatic interactions, to give rise to pseudo[2]rotaxanes. Ion pair-bonded stoppers can further lock the diacids to generate stable water soluble [2]rotaxanes.