Symmetry-Breaking and Symmetry-Retaining Morphological Evolution of the Single Crystals of Cyclodextrin Metal-Organic Frameworks.

The morphological symmetry-retaining and symmetry-breaking of single crystals of the γ-cyclodextrin metal-organic framework have been achieved via introducing lower symmetric ß-cyclodextrins and α-cyclodextrins, respectively. ß-cyclodextrins led to a morphological evolution with retained symmetry from cubic to rhombic dodecahedra, while α-cyclodextrins resulted in the original cubic crystal missing a vertex angle presenting symmetry-breaking behavior. The crystal structures of rhombic dodecahedra and angle-deficient crystals were confirmed through X-ray crystallography, and the mechanisms underlying the morphological transformation evolution were further analyzed. Our work not only provides a rare case realizing two different paths of morphological evolution in one system, but also encourages future efforts towards the evolution of artificial crystal systems in a natural way.

Polymerization Based on Modified ß-Cyclodextrin Achieves Efficient Phosphorescence Energy Transfer for Anti-Counterfeiting.

Supramolecular polymerization can not only activate guest phosphorescence, but also promote phosphorescence Förster resonance energy transfer and induce effective delayed fluorescence. Herein, the solid supramolecular assemblies of ternary copolymers based on acrylamide, modified ß-cyclodextrin (CD), and carbazole (CZ) are reported. After doping with polyvinyl alcohol (PVA) and dyes, a NIR luminescence supramolecular composite with a lifetime of 1.07 s, an energy transfer efficiency of up to 97.4% is achieved through tandem phosphorescence energy transfer. The ternary copolymers can realize macrocyclic enrichment of dyes in comparison to CZ and acrylamide copolymers without CD, which can facilitate energy transfer between triplet and singlet with a high donor-acceptor ratio. Additionally, the flexible polymeric films exhibit regulable lifetime, tunable luminescence color, and repeatable switchable afterglow by adjusting the excitation wavelength, donor-acceptor ratio, and wet/dry stimuli. The luminescence materials are successfully applied to information encryption and anti-counterfeiting.

Boosting the Kinetics and Stability of Zn Anodes in Aqueous Electrolytes with Supramolecular Cyclodextrin Additives.

The hydrophobic internal cavity and hydrophilic external surface of cyclodextrins (CDs) render promising electrochemical applications. Here, we report a comparative and mechanistic study on the use of CD molecules (α-, ß-, and γ-CD) as electrolyte additives for rechargeable Zn batteries. The addition of α-CD in aqueous ZnSO4 solution reduces nucleation overpotential and activation energy of Zn plating and suppresses H2 generation. Computational, spectroscopic, and electrochemical studies reveal that α-CD preferentially adsorbs in parallel on the Zn surface via secondary hydroxyl groups, suppressing water-induced side reactions of hydrogen evolution and hydroxide sulfate formation. Additionally, the hydrophilic exterior surface of α-CD with intense electron density simultaneously facilitates Zn2+ deposition and alleviates Zn dendrite formation. A formulated 3 M ZnSO4 + 10 mM α-CD electrolyte enables homogenous Zn plating/stripping (average Coulombic efficiency ∼ 99.90%) at 1 mA cm-2 in Zn|Cu cells and a considerable capacity retention of 84.20% after 800 cycles in Zn|V2O5 full batteries. This study provides insight into the use of supramolecular macrocycles to modulate and enhance the interface stability and kinetics of metallic anodes for aqueous battery chemistry.

Cyclodextrin-Confined Supramolecular Lanthanide Photoswitch.

The utilization of azobenzene-based photoisomerization cannot only control the morphology of supramolecular assemblies, but can also regulate many biological processes. However, the design of azobenzene-involved nanoconstructs with switchable photoluminescence remains challenging because of the light-quenching ability of azobenzene. Herein, an azobenzene-derived multicomponent nanosystem is reported and its function as a supramolecular lanthanide photoswitch is explored. The metal chelation between lanthanide ions (Ln3+  = Eu3+ and Tb3+ ) and 2,6-pyridinedicarboxylic acid is utilized as the light-emitting center but its inherent fluorescence emission is completely suppressed via the disordered motion of the adjoining azophenyl unit. Interestingly, the hydrophobic cavity of α-cyclodextrin can provide a confined microenvironment to immobilize the molecular conformation of trans-azobenzene, thus leading to the recovery of characteristic lanthanide luminescence both in aqueous solution and the hydrogel state. Also, the luminescence can be reversibly turned off when the cis-azobenzene is expelled from the cavity of α-cyclodextrin upon alternating light irradiation. This mutual cooperation arising from host-guest complexation and metal-ligand coordination confers the desired photoswitchable luminescence abilities on the commonly used azobenzenes, which may hold great promise in the creation of more advanced light-responsive smart materials.

Induced Near-Infrared Emission and Controlled Photooxidation based on Sulfonated Crown Ether in Water.

Regulation of physio-chemical properties and reaction activities via noncovalent methodology has become one of increasingly significant topics in supramolecular chemistry and showed inventive applications in miscellaneous fields. Herein, we demonstrate that sulfonated crown ether can form very stable host-guest complexes with a series of push-pull-type photosensitizers, eventually leading to the dramatic fluorescence enhancement in visible and near-infrared regions. Meanwhile, severe suppression in singlet oxygen (1 O2 ) production is found, mainly due to the higher energy barriers between the excited single and triple states upon host-guest complexation. Moreover, such complexation-induced tuneable 1 O2 generation systems has been utilized in adjusting the photochemical oxidation reactions of polycyclic aromatic hydrocarbons (anthracene) and sulfides ((methylthio)benzene) in water. This supramolecularly controlled photooxidation based on the selective molecular binding of crown ether with photosensitizers may provide a feasible and applicable strategy for monitoring and modulating many photocatalysis processes in aqueous phase.

Enhanced molecular binding affinity toward aromatic dications by anthracene-derived crown ethers in water.

The pursuit of high molecular binding affinity using conventional crown ethers in water remains a challenging task in the field of supramolecular chemistry and may hold great promise in the creation of advanced biocompatible nanoconstructs. In this work, the molecular binding strength toward a series of structurally relevant cationic guests has been greatly enhanced by tetrasulfonated 1,5-dianthracenyl-42-crown-10 and as investigated by means of 1H NMR, UV-vis, and fluorescence spectroscopy, the host-guest association constants can reach up to 108 M-1 order of magnitude in aqueous solution. X-ray crystal diffraction analysis further demonstrates that the aromatic dication can be tightly encapsulated in the ring of anthracene-derived crown ether via multiple π-stacking and electrostatic interactions. Meanwhile, the obtained association constants are remarkably higher than the ones in the cases of the known benzene- and naphthalene-derived sulfonated crown ethers, substantiating that the appropriate extension of π-conjugation in the molecular skeleton of crown ether is a feasible method in attaining a highly affiliative host-guest complex. Taken together, our results indicate that the anthracene-based sulfonated crown ether can be developed as a new family of water-soluble macrocyclic receptors in the fabrication of functional nanoarchitectures.

Dual-responsive drug release and fluorescence imaging based on disulfide-pillar[4]arene aggregate in cancer cells.

The construction of multistimuli-responsive nanoaggregate has become one of the increasingly significant research topics in supramolecular chemistry. We herein reported the pH- and glutathione dual-responsive supramolecular assemblies fabricated by the disulfide-containing pillar[4]arene and tetraphenylethylene derivatives possessing different alkyl chains in length. Morphological characterization experiments showed the binary supramolecular assemblies formed well-defined nanoparticles, which could facilitate their endocytosis in cells. More remarkably, due to the compact nanostructures and the existence of acidifiable carboxyl group and bioreducible disulfide linkage in pillar[4]arene, the obtained nanoaggregates presented high drug-loading efficiency and sustained drug release behaviors, as well as the targeted fluorescence imaging ability in cancer cells. Thus, it can be envisioned that such microenvironment-adaptable supramolecular nanoassemblies featuring dual stimuli-responsiveness and fluorescence-imaging abilities may be developed as more appealing nanosystems for the therapy of refractory disease.

Photooxidation-Driven Purely Organic Room-Temperature Phosphorescent Lysosome-Targeted Imaging.

The construction of host-guest-binding-induced phosphorescent supramolecular assemblies has become one of increasingly significant topics in biomaterial research. Herein, we demonstrate that the cucurbit[8]uril host can induce the anthracene-conjugated bromophenylpyridinium guest to form a linear supramolecular assembly, thus facilitating the enhancement of red fluorescence emission by the host-stabilized charge-transfer interactions. When the anthryl group is photo-oxidized to anthraquinone, the obtained linear nanoconstructs can be readily converted into the homoternary inclusion complex, accompanied by the emergence of strong green phosphorescence in aqueous solution. More intriguingly, dual organelle-targeted imaging abilities have been also distinctively achieved in nuclei and lysosomes after undergoing photochemical reaction upon UV irradiation. This photooxidation-driven purely organic room-temperature phosphorescence provides a convenient and feasible strategy for supramolecular organelle identification to track specific biospecies and physiological events in the living cells.

Cucurbituril-Based Biomacromolecular Assemblies.

The construction of controlled biomacromolecular assemblies has become a thriving area of supramolecular chemistry. In this context, cucurbiturils (CBs), a class of macrocyclic receptors having robust skeletons, hydrophobic cavities, and carbonyl-laced portals, have been drawn into the limelight because of their advantageous molecular recognition characteristics with a variety of biomacromolecules, including peptides, nucleic acids, and proteins. In this minireview, we focus on the impressive advances in CB-based biomacromolecular assemblies, such as in biosensors and assays, the regulation of biochemical reactions, and the treatment of serious diseases. CB-promoted subcellular bioimaging has also been demonstrated in different organelles. The case studies presented herein demonstrate the numerous applications, from fundamental research to translational applications, of diverse CB-based supra/biomacromolecular architectures.

Alkyl-Substituted Cucurbit[6]uril Bridged ß-Cyclodextrin Dimer Mediated Intramolecular FRET Behavior.

A novel triazolyl bridged cucurbituril (CB)-cyclodextrin (CD) dimer was synthesized via click reaction of monopropargyl modified octamethylcucurbit[6]uril and mono-6-azido-ß-cyclodextrin. Moreover, it could form stable supramolecular inclusion complexes possessing efficient fluorescence resonance energy transfer, which benefited from the fact that CD and CB can bind amantadine- and pyridinium-containing fluorophores simultaneously. The supramolecular inclusion complex behaviors were investigated by NMR spectroscopy, UV-vis absorption, and fluorescence spectroscopy.

Targeted Polypeptide-Microtubule Aggregation with Cucurbit[8]uril for Enhanced Cell Apoptosis.

Tunable protein assemblies not only hold a dominant position in vital biological events but are also a significant theme in supramolecular chemistry. Herein, we demonstrated that the intertubular aggregation of microtubules (MTs) could be efficiently regulated by a synergistic polypeptide-tubulin interaction and host-guest complexation. The benzylimidazolium-modified antimitotic peptide (BP) could recognize the MTs and concurrently form stable inclusion complexes with avirulent cucurbit[7]uril (CB[7]) and cucurbit[8]uril (CB[8]) in different binding stoichiometries. The self-assembling morphology of MTs was converted from fibrous to nanoparticulate aggregates via extensive BP⊂CB[8] cross-linkage, leading to significant cell apoptosis and tumor ablation in vivo. The targeted (BP⊂CB[8])@MT ternary assembly provides a facile supramolecular method to enhance the protein-protein interactions, which may be developed as a therapy for degenerative diseases, such as cancer.

Photo-Controlled Reversible Microtubule Assembly Mediated by Paclitaxel-Modified Cyclodextrin.

The design and construction of multi-stimuli-responsive supramolecular nanoassemblies that can mimic and regulate the fundamental biological processes have become a focus of interest in supramolecular chemistry. In this work, a perfect combination has been achieved between naturally occurring microtubules and artificially macrocyclic receptors. The self-assembling morphology of microtubules can be photo-tuned by the host-guest interaction of paclitaxel-modified ß-cyclodextrin (PTX-CD) and photochromic arylazopyrazole (PTX-AAP). Moreover, the supramolecularly aggregated microtubules in a cellular environment can induce a pronounced cell morphological change and cell death. This supramolecular approach based on the secondary PTX-AAP⊂PTX-CD complexation provides us a facile method to reversibly control the intertubular aggregation behaviors of microtubules, which may bring new perspectives in the treatment of diseases related to improper protein aggregation.

Dual Visible Light-Triggered Photoswitch of a Diarylethene Supramolecular Assembly with Cucurbit[8]uril.

Research on photochromic molecules switched by visible light is of particular interest for their application in bioimaging and stimuli-responsive materials. Here, a photoswitchable supramolecular assembly comprised of monocharged bispyridinium-modified diarylethenes (DAEs) and cucurbit[8]uril (CB[8]) has been constructed, which exhibits reversible photochromic behaviour with visible light in both directions. The transformation of CB[8] not only prompts the DAEs to form charge-transfer complexes, but also restricts its intramolecular rotation to enhance fluorescence emission. In this CB[8]-containing supramolecular system, the π-conjugation is extended and its absorption is bathochromically shifted for visible light-driven cyclization of DAEs. Meanwhile, the fluorescence of the supramolecular assembly can also be reversibly modulated by visible light. These findings may furnish a new strategy for the development of visible light-driven fluorescent biomaterials and molecular machines.

Camptothecin-Polysaccharide Co-assembly and Its Controlled Release.

ß-Cyclodextrin modified camptothecin (CPT-CD) was synthesized through esterification reaction and "click chemistry" to greatly improve the solubility of CPT in aqueous solution, and then, a supramolecular nanoparticle was constructed by strong noncovalent interaction between ß-cyclodextrin and adamantane and amphiphilic interaction by simply mixing CPT-CD and adamantane modified hyaluronic acid (HA-ADA) together. The obtained nanoparticle had a hydrophilic HA shell, which could target and recognize HA receptors overexpressed on the surface of cancer cells, and a hydrophobic CPT core, which could protect CPT from hydrolyzation. The results of cytotoxicity experiments showed that the nanoparticle we have designed in this work exhibited similar anticancer activities to, but with much lower side effects than, the commercial chemotherapeutic drug CPT in vitro. We believe that this work might provide a strategy for improving the treatment performance of CPT in laboratory and clinical settings.

Efficacy of Whole-Lung Lavage in Treatment of Pulmonary Alveolar Proteinosis.

The aim of the study was to investigate the therapeutic effect of whole-lung lavage (WLL) for pulmonary alveolar proteinosis (PAP). The cohort studies that investigated the therapeutic effect of WLL for PAP were selected strictly on the basis of the inclusion and exclusion criteria. The statistical analysis was performed using STATA statistical software (version 12.0; Stata Corporation, College Station, TX). Twelve studies were included in this meta-analysis. Totally, 206 PAP patients who received WLL were recruited in the 12 studies. We compared the differences in blood gas analysis and lung function before and after the treatment in this meta-analysis. The results indicated that there were statistical differences in the levels of diffusing capacity for carbon monoxide, forced expiratory volume in 1 second, forced vital capacity, and arterial partial pressure of oxygen after the treatment of WLL for patients with PAP, whereas there were no evident differences in the levels of arterial partial pressure of carbon dioxide and arterial oxygen saturation. In conclusion, WLL can evidently improve the diffusing capacity for carbon monoxide, forced expiratory volume in 1 second, forced vital capacity, and arterial partial pressure of oxygen of patients with PAP, thus WLL may be an important treatment of PAP.

Tunable Nanosupramolecular Aggregates Mediated by Host-Guest Complexation.

Nanosupramolecular assemblies with controlled topological features have inventive applications in fundamental studies and material manufacturing. Herein, a variety of morphologically interesting aggregates have been constructed using the supramolecular modulation with bipyridinium-modified diphenylalanine derivative (BP-FF). Benefiting from the high binding affinity of bipyridinium group with four different macrocyclic receptors, namely cucurbit[7]uril, cucurbit[8]uril, pillar[5]arene, and tetrasulfonated crown ether, we have succeeded in tuning the topological aggregates of BP-FF from fine nanofibers to nanorods, octahedron-like nanostructure, helical nanowires, and rectangular nanosheets without any tedious chemical modification. This supramolecular approach may provide us a powerful method to construct well-defined nanostructures with different morphologies that can be conveniently controlled by facile host-guest interactions.

Photolysis of an amphiphilic assembly by calixarene-induced aggregation.

Photosensitizers generally show great tendency for self-aggregation in aqueous media, leading to quenched fluorescence and lower photosensitizing ability. Herein, we report that amphiphilic anthracene is highly photoreactive after aggregation induced by p-sulfonatocalix[4]arene in water. The formation of a host-guest supramolecular assembly and the photolysis of the anthryl core are identified by UV-vis and NMR spectroscopy, dynamic light scattering, and transmission electron microscopy. Additionally, the assembly exhibited efficient photolysis with visible light in the presence of exogenous photosensitizers. This approach could be extended to various photoresponsive self-assemblies and applications in phototherapy and the design of photodegradable materials.

Selective binding affinity between quaternary ammonium cations and water-soluble calix[4]resorcinarene.

An amphiphilic calix[4]resorcinarene bearing four hydrophilic sulfonate sites at the upper rim and four hydrophobic n-pentyl chains at the lower rim (SR4A5) was synthesized by sulfonation of tetramethoxyresorcinarene. The molecular binding behaviors of SR4A5 with different types of organic cations, i.e., singly and doubly charged aliphatic ammonium salts and singly and doubly charged π-aromatic ammonium salts, were comprehensively investigated by means of (1)H NMR, fluorescence, and UV/vis spectroscopic titration experiments. The competitive binding titrations demonstrate that, superior to the reported p-sulfonatocalix[4]arene systems, the stability constants upon association with SR4A5 can reach up to 10(6) M(-1) order of magnitude in water, ultimately leading to better binding affinity and molecular selectivity toward dicationic guests. Significantly, UV/vis spectroscopic experiments further revealed that the specific binding behaviors of SR4A5 with bispyridinium guests can be attributed to the charge transfer interaction between electron-rich and electron-deficient aromatics upon host-guest complexation. These obtained results provide an effective strategy to realize the highly selective molecular recognition process with multiply charged macrocyclic receptors and will definitely promote the development of the field of water-soluble resorcinarene-based supramolecular assemblies.

A supramolecular tubular nanoreactor.

The extremely strong noncovalent complexation between the rigid host of phthalocyanine-bridged ß-cyclodextrins and the amphiphilic guest carboxylated porphyrin is employed to construct a hollow tubular structure as a supramolecular nanoreactor. A representative coupling reaction occurs in the hydrophobic interlayers of the tubular walls in pure water at room temperature, leading to an enhancement of ten times higher reaction rate without any adverse effect on catalytic activity and conversion.