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.

Conformationally confined three-armed supramolecular folding for boosting near-infrared biological imaging.

Herein, a triphenylamine derivative (TP-3PY) possessing 4-(4-bromophenyl)pyridine (PY) as an electron-accepting group and tris[p-(4-pyridylvinyl)phenyl]amine (TPA) with large two-photon absorption cross-sections as an electron-donating group was obtained, and showed intense absorption in the visible light region (λmax = 509 nm) and weak near-infrared (NIR) fluorescence emission at 750 nm. After complexation with cucurbit[8]uril (CB[8]), TP-3PY showed bright NIR fluorescence emission at 727 nm and phosphorescence emission at 800 nm. When the supramolecular assembly (TP-3PY⊂CB[8]) further interacted with dodecyl-modified sulfonatocalix[4]arene (SC4AD), the fluorescence and phosphorescence emissions were further enhanced at 710 and 734 nm, respectively. However, only the fluorescence emission of TP-3PY was enhanced in the presence of cucurbit[7]uril (CB[7]) and SC4AD. More interestingly, the photoluminescence of TP-3PY⊂CB[8]@SC4AD and TP-3PY⊂CB[7]@SC4AD assemblies could be excited by both visible (510 nm) and NIR light (930 nm). Finally, these ternary supramolecular assemblies with bright NIR light emission were applied to lysosome imaging of tumor cells and real-time biological imaging of mice.

Morpholine-modified permethyl ß-cyclodextrin supramolecular nanoparticles for precise dual-targeted imaging.

Possessing dual-targeted agents toward the lysosome and cancer cells, a ternary supramolecular assembly was constructed by a morpholine-modified permethyl ß-cyclodextrin, sulfonated porphyrin, and folic acid-modified chitosan via multivalent interactions. As compared with free porphyrin, the obtained ternary supramolecular assembly showed promoted photodynamic effect and achieved dual-targeted precise imaging in cancer cells.

An in situ protonation-activated supramolecular self-assembly for selective suppression of tumor growth.

An in situ supramolecular self-assembly in the subcellular organelles could provide a new strategy to treat diseases. Herein, we report a protonation-activated in situ supramolecular self-assembly system in the lysosomes, which could destabilize the lysosome membrane, resulting in the selective suppression of cancer cells. In this system, pyridyl-functionalized tetraphenylethylene (TPE-Py) was protonated in the lysosomes of A549 lung cancer cells to form octahedron-like structures with cucurbit[8]uril (CB[8]), which impaired the integrity of the lysosome membrane, resulting in selective suppression of cancer cells. Moreover, its anticancer efficiency was also systematically evaluated in vivo, triggering the apoptosis of tumor tissues with ignorable effects on normal organs. Overall, the protonation-activated self-assembly in the lysosomes based on the host-guest complexation would provide a method for novel anti-cancer systems.

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.

Supramolecular Dual Polypeptides Induced Tubulin Aggregation for Synergistic Cancer Theranostics.

The advent of macrocycle-based supramolecular chemistry can offer powerful strategies for regulating vital bioactivities in living systems and bring about emerging technology in biomedical science. Herein, we construct a supra-biomacromolecular nanosystem involving microtubules, cell-permeable porphyrins, and antimitotic peptide-decorated permethyl-ß-cyclodextrins for promoting cell apoptosis in a cooperative manner. Through specific polypeptide-tubulin recognition, cyclodextrin moieties are capable of anchoring to the tubulin surface and providing abundant hydrophobic microenvironments to accommodate the photosensitive porphyrins. Consequently, spherical tubulin aggregates are formed, and reactive oxygen species can be efficiently generated via the host-guest complexation. The combined usage of complexation-promoted photodynamic efficacy and tubulin aggregation gives more serious cell apoptosis under light irradiation in vitro and in vivo. To be envisioned, this supramolecularly enhanced photodynamic performance together with controlled aggregation of natural biomacromolecules may be developed as an innovative approach to improve the therapeutic potency against many diseases.

A tunable full-color lanthanide noncovalent polymer based on cucurbituril-mediated supramolecular dimerization.

The construction of lanthanide multicolor luminescent materials with tunable photoluminescence properties has been developed as one of the increasingly significant topics and shown inventive applications in miscellaneous fields. However, fabricating such materials based on synergistically assembly-induced emission rather than simple blending of different fluorescent dyes together still remains a challenge. Herein, we report a europium-based noncovalent polymer with tunable full-color emission, which is constructed from the 2,6-pyridinedicarboxylic acid-bearing bromophenylpyridinium salt. This rationally designed bifunctional component can concurrently serve as a guest molecule and a chelating ligand to associate with cucurbit[8]uril and europium ions, thus leading to the formation of a trichromatic (red-green-blue, RGB) photoluminescent polypseudorotaxane-type noncovalent polymer in aqueous solution. Meanwhile, the full-color emission enclosed within the RGB color triangle could be readily produced by simply tuning the molar ratio of cucurbit[8]uril and europium ions. The lanthanide supramolecular polymer featuring tricolor emission, long lifetime, high photoluminescence efficiency and low cytotoxicity could be further applied in multicolor imaging in a cellular environment. These results provide a new and feasible strategy for the construction of full-color single lanthanide self-assembled nanoconstructs.

Conformationally Confined Emissive Cationic Macrocycle with Photocontrolled Organelle-Specific Translocation.

The optimization of molecular conformation and aggregation modes is of great significance in creation of new luminescent materials for biochemical research and medical diagnostics. Herein, a highly emissive macrocycle (1) is reported, which is constructed by the cyclization reaction of triphenylamine with benzyl bromide and exhibits very distinctive photophysical performance both in aqueous solution and the solid state. Structural analysis reveals that the 1 can form self-interpenetrated complex and emit bright yellow fluorescence in the crystal lattice. The distorted yet symmetrical structure can endow 1 with unique two-photon absorption property upon excitation by near-infrared light. Also, 1 can be utilized as an efficient photosensitizer to produce singlet oxygen (1 O2 ) both in inanimate milieu and under cellular environment. More intriguingly, due to the strong association of 1 with negatively charged biomacromolecules, organelle-specific migration is achieved from lysosome to nucleus during the 1 O2 -induced cell apoptosis process. To be envisaged, this conformationally confined cationic macrocycle with photocontrolled lysosome-to-nucleus translocation may provide a feasible approach for in situ identifying different biospecies and monitoring physiological events at subcellular level.

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.

Cyclodextrin-Activated Porphyrin Photosensitization for Boosting Self-Cleavable Drug Release.

Supramolecular prodrugs that combine the merits of stimuli-responsiveness and targeting ability in a controllable manner have shown appealing prospects in disease diagnostics and therapeutics. Herein, we report that a new theranostic agent with the host-guest-binding-activated photosensitization has been fabricated by a binary supramolecular assembly consisting of the permethyl-ß-cyclodextrin-grafted hyaluronic acid and a combretastatin A-4-appended porphyrin derivative. Illuminated by a red-light source, the production efficiency of singlet oxygen (1O2) pronouncedly increases by ∼60-fold once the porphyrin core is encapsulated by cyclodextrins. Consequently, the cell-selective fluorescence emission is dramatically enhanced, the microtubule-targeted drug is rapidly and completely released, and the 1O2-involved combinational treatment is simultaneously achieved both in vitro and in vivo. To be envisaged, this complexation-boosted light-activatable photosensitizing prodrug delivery system with improved photophysical performance and remarkable phototheranostic outcomes will make a significant contribution to the creation of more advanced stimulus-based biomaterials.

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.

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.

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.

Cyclodextrin-Cross-Linked Hydrogels for Adsorption and Photodegradation of Cationic Dyes in Aqueous Solution.

Possessing three-dimensional porous structures and tunable mechanical strengths, cyclodextrin-containing polymeric hydrogels are one of the most promising water-based adsorbent materials due to their easy availability, simple chemical modification and environmental friendliness. In this work, two kinds of hydrogels were prepared via the copolymerization with acrylic acid and vinyl-derivatized ß-cyclodextrins in water. These two gels have showed good adsorption performance towards cationic dyes through the noncovalent interactions with their anionic backbones and porous network. Meanwhile, pseudo-second-order model was selected to clarify the adsorption kinetics process. Moreover, nano-scaled TiO2 was doped into these resultant cyclodextrins-based hydrogels to achieve efficient degradation of dyes upon light irradiation. The obtained TiO2 -loaded hydrogels could exhibit improved adsorption performance and make the adsorbed dyes photo-degraded with the decolorization rates above 95%. It can be envisioned that such cyclodextrin-based soft materials may find applications in dye clearance and water treatment.

A twin-axial pseudorotaxane for phosphorescence cell imaging.

A twin-axial pseudorotaxane is constructed using a phenylpyridine salt with diethanolamine (DA-PY) and cucurbit[8]uril (CB[8]), and it not only displays phosphorescence in aqueous solution but it can also be used for targeted cell-imaging.

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.

Actin Cytoskeleton-Disrupting and Magnetic Field-Responsive Multivalent Supramolecular Assemblies for Efficient Cancer Therapy.

Actin cytoskeleton disruption is a promising and intriguing anticancer strategy, but their efficiency is frequently compromised by severe side effects of the actin cytoskeleton-disrupting agents. In this study, we constructed the biocompatible actin cytoskeleton-targeting multivalent supramolecular assemblies that specifically target and disrupt the tumor actin cytoskeleton for cancer therapy. The assemblies were composed of ß-cyclodextrin-grafted hyaluronic acid (HACD) and iron oxide magnetic nanoparticles (MNPs) grafted by an actin-binding peptide (ABP) and adamantane (Ada)-modified polylysine. Owing to the multivalent binding between cyclodextrin and Ada, HACD, and peptide-grafted MNPs (MNP-ABP-Ada) could self-assemble to form MNP-ABP-Ada⊂HACD nanofibers in a geomagnetism-dependent manner. Furthermore, the presence of ABP rendered the assemblies to efficiently target the actin cytoskeleton. Interestingly, with the acid of a low-frequency alternating magnetic field (200 Hz), the actin cytoskeleton-targeting nanofibers could induce severe actin disruption, leading to a remarkable cell cycle arrest and drastic cell death of tumor cells both in vitro and in vivo, but showed no obvious toxicity to normal cells. The actin cytoskeleton-targeting/disrupting supramolecular assembly implies an excellent strategy for realizing efficient cancer therapy.