Zhan-Ting Li

Single-molecular artificial transmembrane water channels.

Hydrazide-appended pillar[5]arene derivatives have been synthesized. X-ray crystal structure analysis and (1)H 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.

Selective Artificial Transmembrane Channels for Protons by Formation of Water Wires

Lined up water molecules: Artificial transmembrane channels from pillar[5]arene monomeric and dimeric derivatives have been prepared. Single-channel conductance measurements and isotope effect experiments under acidic conditions showed selective proton transport through the channels, which were mediated by water wires formed in the pillar[5]arene backbones (see picture).

Peptide Mimics by Linear Arylamides: A Structural and Functional Diversity Test

Hydrogen-bonded oligoamide foldamers represent a large family of peptide mimics. Pioneered by Gellman and Seebach (Appella , J. Am. Chem. Soc. 1996, 118, 13071- 13072; Seebach , Helv. Chim. Acta 1996, 79, 913- 941), aliphatic amino acid-based mimic structures have been extensively studied. Results of these studies have found many useful applications in areas including chemical biology and drug design. This Account describes our efforts in creating arylamide-based foldamers whose compact conformations are stabilized by hydrogen bonding. The aim of our study was to test whether this class of mimic structures is sufficiently rigid to lead to new interesting functions. It was envisioned that, if our approach was workable, it might be developed into a new family of useful soft frameworks for studies toward molecular recognition, self-assembly, and materials science. Three classes of mimic structures, that is, folded or helical, zigzag, and straight oligomers, have been constructed by simply changing the positions of the substituents at the benzene rings in the backbones. Both amide and hydrazide units have been employed to construct the frameworks. In most cases, O...H-N hydrogen bonding was chosen to stabilize the compact conformations. Notably, for the first time the F...H-N hydrogen-bonding pattern has been used to tune the size of the cavity. To test their usefulness, these frameworks have been extensively modified and functionalized. (1)H NMR, UV-vis, fluorescence, circular dichroism, and X-ray diffraction techniques have all been employed to establish the compact structures and their interactions with guest molecules. The properties or functions of the mimic structures have been studied in seven aspects. (1) Acyclic molecular receptors: The amide foldamers can bind amine cations, while the hydrazide foldamers can complex saccharides. (2) Acceleration of anisole hydrolysis: Several folded oligomers are able to bind alkali metal cations and consequently promote the hydrolysis of the nitro-substituted anisole by alkali hydroxides. (3) Facilitation of macrocyclization: The straight and zigzag backbones can be readily functionalized, from which two classes of macrocycles have been prepared. (4) Homoduplex assembly: Zigzag oligomers that are appended with amide units at one side can form stable homoduplexes through the cooperative self-binding of the amide units. (5) Assembly of molecular tweezers: Discrete binding moieties are introduced at the ends of the oligomers, which can bind structurally matched guests. (6) Assembly of nano networks: F...H-N hydrogen-bonded foldamers can stack with fullerenes; thus a mixture of fullerenes with a trifoldamer generates honeycomb-styled nanoarchitectures. (7) Assembly of dynamic [2]catenanes: A preorganized porphyrin tweezer has been synthesized, from which dynamic three-component [2]catenanes have been assembled in high yields. Our results demonstrate that hydrogen-bonding-driven arylamide oligomers are a class of structurally unique mimic structures. The folded oligomers themselves can be used as synthetic receptors for binding different guest molecules, while incorporation of different segments into one system can produce many desired shapes. In addition, all of the rigid frameworks can be readily functionalized at specific sites. We believe that our results have helped to open the door for some new chemistry in molecular recognition, self-assembly, and other related areas.

Vesicles and organogels from foldamers: a solvent-modulated self-assembling process.

Nonamphiphilic, hydrogen-bonded hydrazide foldamers appended with four or six long flexible chains were revealed to spontaneously assemble to form vesicles in methanol and organogels in aliphatic hydrocarbons. SEM, AFM, TEM, DLS, and fluorescence microscopy were all used to identify the structures of the vesicles. It was proposed that intermolecular pi stacking of the folded frameworks and hydrogen bonding of the amide units in the appended chains induced the molecules to produce cylindrical aggregates. In polar methanol, these aggregates packed together to generate one-layered vesicles owing to hydrophobically induced entanglement of the peripheral chains, while in nonpolar hydrocarbons, the peripheral chains entwined across stacked cylinders to form three-dimensional networks and thus immobilize the liquid molecules.

Chiral Selective Transmembrane Transport of Amino Acids through Artificial Channels

Peptide-appended pillar[n]arene (n = 5, 6) derivatives have been synthesized. (1)H 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 (EC(50) = 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.

Tubular Unimolecular Transmembrane Channels: Construction Strategy and Transport Activities

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 Cu(2+) and Co(2+) 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(+).

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.

Three-dimensional periodic supramolecular organic framework ion sponge in water and microcrystals

Self-assembly has emerged as a powerful approach to generating complex supramolecular architectures. Despite there being many crystalline frameworks reported in the solid state, the construction of highly soluble periodic supramolecular networks in a three-dimensional space is still a challenge. Here we demonstrate that the encapsulation motif, which involves the dimerization of two aromatic units within cucurbit[8]uril, can be used to direct the co-assembly of a tetratopic molecular block and cucurbit[8]uril into a periodic three-dimensional supramolecular organic framework in water. The periodicity of the supramolecular organic framework is supported by solution-phase small-angle X-ray-scattering and diffraction experiments. Upon evaporating the solvent, the periodicity of the framework is maintained in porous microcrystals. As a supramolecular ‘ion sponge’, the framework can absorb different kinds of anionic guests, including drugs, in both water and microcrystals, and drugs absorbed in microcrystals can be released to water with selectivity.

Hydrogen-bonded aryl amide macrocycles: synthesis, single-crystal structures, and stacking interactions with fullerenes and coronene.

Six hydrogen-bonded shape-persistent aryl amide macrocycles have been prepared by using one-step and (for some) step-by-step approaches. From the one-step reactions, 3 + 3, 2 + 2, or even 1 + 1 macrocycles were obtained in modest to good yields. The reaction selectivity was highly dependent on the structures of the precursors. The X-ray structural analysis of two methoxyl-bearing macrocycles revealed intramolecular hydrogen bonding and weak intermolecular stacking interaction; no column-styled stacking structures were observed. The 1H (DOSY) NMR, UV-vis, and fluorescent experiments indicated that the new rigidified macrocycles complex fullerenes or coronene in chloroform through intermolecular pi-stacking interaction. The association constants of the corresponding 1:1 complexes have been determined if the stacking was able to cause important fluorescent quenching of the macrocycles or coronene.

The Organic Flatland—Recent Advances in Synthetic 2D Organic Layers

Ultrathin, 2D organic layers of sub-ten nanometer thicknesses and high aspect ratios have received a great deal of attention for their graphene-like topological features and emerging properties. Rational synthetic strategies have led to the realization of periodic 2D layers with unprecedented structural precision. Herein, recent progress on the synthesis of 2D organic layers, including methods based on both non-covalent and covalent interactions, is summarized, and potential applications are highlighted. Such 2D organic nanostructures have a brilliant future as prospective multifunctional materials, showing great promise as platforms for engineering novel optoelectronic, interfacial, and bioactive properties.