para‐Sulfonatocalix[n]arenes Inhibit Amyloid β‐Peptide Fibrillation and Reduce Amyloid Cytotoxicity

Amyloid β‐peptide (Aβ) fibrillation is a major hallmark of Alzheimer's disease (AD). Inhibition of Aβ fibrillation is thus considered to be an effective strategy for AD prevention and treatment. Here we show that para ‐sulfonatocalix[n ]arenes (SC[n ]A, n =4, 6, 8), a class of amphiphilic calixarene derivatives, can bind to Aβ₄₂ through nonspecific and multipoint hydrophobic interactions. Their binding leads to a pronounced delay in β‐sheet adoption and formation of multiple secondary structures of the peptide, accompanied by changes at the level of the fibrillary architecture. Furthermore, the ζ‐potential value of Aβ₄₂ incubated with SC[6/8]A decreased, which correlated with the reduction of amyloid cytotoxicity. Overall, the SC[n ]A effectively inhibits Aβ₄₂ fibrillation and reduces amyloid cytotoxicity, and SC[8]A showed the best performance among the three macrocycles, possibly owing to its having the strongest interactions with Aβ₄₂.     

Cucurbit[7]uril Inhibits Islet Amyloid Polypeptide Aggregation by Targeting N Terminus Hot Segments and Attenuates Cytotoxicity

Two “hot segments” within an islet amyloid polypeptide are responsible for its self-assembly, which in turn is linked to the decline of β-cells in type 2 diabetes (T2D). A readily available water-soluble, macrocyclic host, cucurbit[7]uril (CB[7]), effectively inhibits islet amyloid polypeptide (IAPP) aggregation through ion–dipole and hydrophobic interactions with different residues of the monomeric peptide in its random-coil conformation. A HSQC NMR study shows that CB[7] likely modulates IAPP self-assembly by interacting with and masking major residues present in the “hot segments” at the N terminus. CB[7] also prevents the formation of toxic oligomers and inhibits seed-catalyzed fibril proliferation. Importantly, CB[7] recovers rat insulinoma cells (RIN-m) from IAPP-assembly associated cytotoxicity.     

Cucurbit[7]uril: Surfactant Host–Guest Complexes in Equilibrium with Micellar Aggregates

In order to compare the formation of host–guest complexes between β‐cyclodextrin (β‐CD) or cucurbit[7]uril (CB7) and cationic surfactants we studied the hydrolysis of 4‐methoxybenzenesulfonyl chloride (MBSC). The selected surfactants allowed the length of the hydrocarbon chain to be varied between 6 and 18 carbon atoms. Contrary to the expected behaviour, the values of the binding constants between CB7 and surfactants are independent of the alkyl chain length of the surfactant. In the case of β‐CD, however, a clear dependence of the binding constant on the hydrophobic character of the surfactant was observed. The values obtained with CB7 are significantly higher than those obtained with β‐CD and these differences are explained to be a consequence of electrostatic interactions of the surfactants with the portals of CB7. It was found that a small percentage of uncomplexed CB7 was in equilibrium with the cationic micelles and this percentage increased on increasing the hydrophobic character of the surfactant.     

Rotaxanes Capped with Host Molecules: Supramolecular Behavior of Adamantylated Bisimidazolium Salts Containing a Biphenyl Centerpiece

Bisimidazolium salts with one central biphenyl binding site and two terminal adamantyl binding sites form water‐soluble binary or ternary aggregates with cucurbit[7]uril (CB7) and β‐cyclodextrin (β‐CD) with rotaxane and pseudorotaxane architectures. The observed arrangements result from cooperation of the supramolecular stopper binding strength and steric barriers against free slippage of the CB7 and β‐CD host molecules over the bisimidazolium guest axle.     

Conditional Copper-Catalyzed Azide–Alkyne Cycloaddition by Catalyst Encapsulation

Supramolecular encapsulation is known to alter chemical properties of guest molecules. We have applied this strategy of molecular encapsulation to temporally control the catalytic activity of a stable copper(I)–carbene catalyst. Encapsulation of the copper(I)–carbene catalyst by the supramolecular host cucurbit[7]uril (CB[7]) resulted in the complete inactivation of a copper-catalyzed alkyne–azide cycloaddition (CuAAC) reaction. The addition of a chemical signal achieved the near instantaneous activation of the catalyst, by releasing the catalyst from the inhibited CB[7] catalyst complex. To broaden the scope of our on-demand CuAAC reaction, we demonstrated the protein labeling of vinculin with the copper(I)–carbene catalyst, to inhibit its activity by encapsulation with CB[7] and to initiate labeling at any moment by adding a specific signal molecule. Ultimately, this strategy allows for temporal control over copper-catalyzed click chemistry, on small molecules as well as protein targets.     

Gold nanoparticles in organic capsules: a supramolecular assembly of gold nanoparticles and cucurbituril

Gold nanoparticles (相似文献   

Determination of Paraquat by Cucurbit[7]uril Sensitized Fluorescence Quenching Method

A method for the determination of paraquat by cucurbit[7]uril (CB[7]) fluorescence quenching was developed. The assay was based on the reaction of the CB[7] with acridine orange. The fluorescence intensity of acridine orange regularly increased with the addition of CB[7]. However, while an appropriate amount of paraquat was added to the CB[7]- acridine orange system, the fluorescence intensity of the system was quenched which was employed to determine paraquat. Under the optimum conditions, a linear range of 3.0–800 nmol L^?1 and a detection limit of 1.61 nmol L^?1 for paraquat were obtained. The simple strategy reported here offers great practical potential for the determination of pesticide residues in agricultural products.     

The cucurbit[n]uril family: prime components for self-sorting systems

We determined the values of Ka for a wide range of host-guest complexes of cucurbit[n]uril (CB[n]), where n = 6-8, using 1H NMR competition experiments referenced to absolute binding constants measured by UV/vis titration. We find that the larger homologues--CB[7] and CB[8]--individually maintain the size, shape, and functional group selectivity that typifies the recognition behavior of CB[6]. The cavity of CB[7] is found to effectively host trimethylsilyl groups. Remarkably, the values of Ka for the interaction of CB[7] with adamantane derivatives 22-24 exceeds 10(12) M(-1)! The high levels of selectivity observed for each CB[n] individually is also observed for the CB[n] family collectively. That is, the selectivities of CB[6], CB[7], and CB[8] toward a common guest can be remarkably large. For example, guests 1, 3, and 11 prefer CB[8] relative to CB[7] by factors greater than 10(7), 10(6), and 3000, respectively. Conversely, guests 23 and 24 prefer CB[7] relative to CB[8] by factors greater than 5100 and 990, respectively. The high levels of selectivity observed individually and collectively for the CB[n] family renders them prime components for the preparation of functional biomimetic self-sorting systems.     

Conditional Copper‐Catalyzed Azide–Alkyne Cycloaddition by Catalyst Encapsulation

Supramolecular encapsulation is known to alter chemical properties of guest molecules. We have applied this strategy of molecular encapsulation to temporally control the catalytic activity of a stable copper(I)–carbene catalyst. Encapsulation of the copper(I)–carbene catalyst by the supramolecular host cucurbit[7]uril (CB[7]) resulted in the complete inactivation of a copper‐catalyzed alkyne–azide cycloaddition (CuAAC) reaction. The addition of a chemical signal achieved the near instantaneous activation of the catalyst, by releasing the catalyst from the inhibited CB[7] catalyst complex. To broaden the scope of our on‐demand CuAAC reaction, we demonstrated the protein labeling of vinculin with the copper(I)–carbene catalyst, to inhibit its activity by encapsulation with CB[7] and to initiate labeling at any moment by adding a specific signal molecule. Ultimately, this strategy allows for temporal control over copper‐catalyzed click chemistry, on small molecules as well as protein targets.     

Radial Hetero[5]catenanes: Peripheral Isomer Sequences of the Interlocked Macrocycles

A pair of radial [5]catenanes, with either an isomeric cyclic ‐AABB‐ or ‐ABAB‐ type sequence of the interlocked β‐cyclodextrin (β‐CD) and cucurbit[6]uril (CB[6]) units, has been efficiently synthesized. Because of a marked difference in the binding strength and interlocking sequence of the peripheral macrocycles, interesting sequence‐dependent properties, characteristic of mechanically bonded macrocycles, were realized. Variable‐temperature ¹H NMR studies showed that the ‐ABAB‐ isomer has a more independent β‐CD dynamic, whereas the β‐CD motions in the ‐AABB‐ isomer are coupled. Dynamics of the pH‐insensitive β‐CD can also be further modulated upon base‐triggered mobilization of the CB[6]. These unique properties of the mechanical bond expressed in a sequence‐specific fashion and the transmission of the control on the macrocycle dynamics from one interlocked component to another, highlight the potential of similar complex hetero[n]catenanes in the design of advanced, multicomponent molecular machines.     

Hexanoate-Cucurbit[7]uril: Highly Soluble with Controlled Release Ability

Current drug delivery systems gain more functions with increased complexity. With the idea of less is more, we synthesized hexanoate-cucurbit[7]uril (CB[7]C₅COONa) with multiple promising features for drug delivery. The hexanoate group integrates multiple functions. It endows CB[7]C₅COONa extremely high solubility of over 600 mg mL⁻¹ and well-defined pH-controlled release ability without sacrificing on the high binding affinity of CB[7] cavity. Based on the pH-controlled release ability, CB[7]C₅COONa can be used for controlling the bioactivity of drug molecules. We anticipate that the strategy of function integration would be useful for the design of simple yet powerful drug delivery systems.     

Restricted Conformational Flexibility of a Triphenylamine Derivative on the Formation of Host–Guest Complexes with Various Macrocyclic Hosts

Herein, we report the host–guest‐type complex formation between the host molecules cucurbit[7]uril (CB[7]), β‐cyclodextrin (β‐CD), and dibenzo[24]crown‐8 ether (DB24C8) and a newly synthesized triphenylamine (TPA) derivative 1 X₃ as the guest component. The host–guest complex formation was studied in detail by using ¹H NMR, 2D NOESY, UV/Vis fluorescence, and time‐resolved emission spectroscopy. The chloride salt of the TPA derivative was used for recognition studies with CB[7] and β‐CD in an aqueous medium. The restricted internal rotation of the guest molecule on complex formation with either of these two host molecules was reflected in the enhancement of the emission quantum yield and the average excited‐state lifetime for the triphenylamine‐based excited states. Studies with DB24C8 as the host molecule were performed in dichloromethane, a medium that maximizes the noncovalent interaction between the host and guest fragments. The Förster resonance energy transfer (FRET) process involving DB24C8 and 1 (PF₆)₃, as the donor and acceptor fragments, respectively, was established by electrochemical, steady‐state emission, and time‐correlated single‐photon counting studies.     

Pyrrole/macrocycle/MOF supramolecular co-assembly for flexible solid state supercapacitors

Supramolecular assemblies constructed through the encapsulation of conductive polymers (CPs) by macrocyclic molecules have attracted increasing interest in the fields of supramolecular chemistry and electrochemistry. In this work, an effective strategy was reported to improve the stability and conductivity of CPs by electrochemically constructing different supramolecular assemblies composed of macrocycles and CPs. Typically, we uploaded zinc-based MOF (ZIF-8) onto carbon nanotube film (CNTF) and further electrically deposited macrocycles and CPs to gain the flexible conductive electrodes. Herein, five different supramolecular macrocycles, including α-cyclodextrin (α-CD), sulfato-β-cyclodextrin (SCD), sulfonatocalix[4]arene (SC[4]), cucurbit[6]uril (CB[6]) and cucurbit[7]uril (CB[7]) were utilized and the electrochemical performances of the assembly electrodes increased in an order of α-CD < SCD < SC[4] < CB[6] < CB[7], significantly improving the areal capacitance up to 1533 mF/cm². This strategy may provide a new way for the application of macrocyclic supramolecules in electrochemical systems.     

Cucurbit[n]uril analogues: synthetic and mechanistic studies

[reaction: see text] The synthesis of cucurbit[n]uril analogues (18, 19, (+/-)-20, 33, 34, 35, 36, and 37) is presented. These CB[5], CB[6], and CB[7] analogues all contain bis(phthalhydrazide) walls that are incorporated into the macrocycle. The tailor-made synthesis of these CB[n] analogues proceeds by the condensation of the appropriate bis(electrophile) (4, 7, or 9) with bis(phthalhydrazide) (17), which delivers the CB[6] and CB[7] analogues in good yield, whereas the CB[5] analogue is formed in low yield. To improve the solubility characteristics of the CB[n] analogues for recognition studies in water or organic solution, the CO2Et groups were transformed to CO2H and CO2(CH2)9CH3 groups. On the basis of the results of product resubmission experiments, we conclude that these macrocycles are kinetic products. To help rationalize the good yields obtained in the CB[6] and CB[7] analogue macrocyclization reactions, we performed mechanistic studies of model methylene bridged glycoluril dimers, which suggest an intramolecular isomerization during CB[n] analogue formation.     

Cucurbit[7]uril moving on side chains of polypseudorotaxanes: Synthesis,characterization, and properties

Novel side chain polypseudorotaxanes with cucurbit[7]uril (CB[7]) threaded onto the side chains are synthesized from a water‐soluble polymer and CB[7] in water by simple stirring at room temperature. CB[7] beads could move from the hexyl groups to the benzyl and a part of viologen units in the side chains of polymer when the molar ratio of CB[7] to the monomer reaches from 1 to 2 as shown by ¹H NMR studies, and it is considered that the hydrophobic and charge‐dipole interactions of CB[7] are the driving forces. The sizes of the polypseudorotaxanes with different molar ratio of CB[7] to 4VBVHeP in aqueous solution increase with increasing the molar ratio of CB[7] to 4VBVHeP as found by DLS and resonance light scattering, while the typical cyclic voltammograms and UV–vis data indicate that CB[7] are not threaded in the viologen units of P4VBVHeP, and the oxidation reduction characteristic of the polymer is remarkably affected by the addition of CB[7]. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

Ultrasensitive Detection of Hepatitis C Virus DNA Subtypes Based on Cucurbituril and Graphene Oxide Nano-composite

Infectious of hepatitis C viruses(HCVs)lead to hepatic fibrosis,cirrhosis even hepatoma.Developing rapid and sensitive diagnostic method for HCV is of great importance.Based on the host-and-guest interaction between cucurbit[7]uril(CB[7])and methylene blue(MB),a CB[7]-graphene nano-composite(CB[7]-N3-GO)is raised for the electrochemical detection of HCV DNA.The method is able to linearly detect the HCV nucleic acid in the range of 0.2—10 nmol/L with detection limit as low as 160.4 pmol/L.The proposed detection strategy is able to discriminate the lb and 6k subtypes of HCV and has a prospective potential in the blood screen for HCV in clinical diagnosis.     

Mechanism of the conversion of inverted CB[6] to CB[6

Inverted cucurbit[n]urils (iCB[n]) form as intermediates during the synthesis of cucurbit[n]urils from glycoluril and formaldehyde in HCl (85 degrees C). Product resubmission experiments establish that the diastereomeric iCB[6] and iCB[7] are kinetic products that are less stable thermodynamically than CB[6] or CB[7] (>2.8 kcal mol(-1)). When iCB[6] or iCB[7] is heated under aqueous acidic conditions, a preference for ring contraction is noted in the formation of CB[5] and CB[6], respectively. Interestingly, under anhydrous acidic conditions ring size is preserved with iCB[6] delivering CB[6] cleanly. To establish the intramolecular nature of the iCB[6] to CB[6] conversion under anhydrous, but not aqueous, acidic conditions we performed crossover experiments involving mixtures of iCB[6] and its (13)C=O labeled isotopomer (13)C(12)-iCB[6]. An unusual diastereomeric CB[6] with a M?bius geometry (13) is proposed as a mechanistic intermediate in the conversion of iCB[6] to CB[6] under anhydrous acidic conditions. The improved mechanistic understanding provided by this study suggests improved routes to CB[n]-type compounds.     

Binding modes of cucurbit[6]uril and cucurbit[7]uril with a series of bis-pyridinium compounds

Binding behaviors of cucurbit[6]uril (CB[6]) and cucurbit[7]uril (CB[7]) with a series of bis-pyridinium compounds N, N’-hexamethylenebis(1-alkyl-4-carbamoyl pyridinium bromide) (HBPB-n) (alkyl chain length, n = 6, 8 and 10) guests were investigated using ¹H-NMR, ESI–MS and single crystal X-ray diffraction methods. The results show that CB[6] and CB[7] can form [2]pseudorotaxanes with HBPB-n easily. When increasing the length of tail alkyl chain, the binding site of CB[6] at guest molecules changed from the tail to the middle part, while CB[7] remained located over the tail chain. As CB[6] and CB[7] were added in HBPB-8 aqueous solution, a [3]pseudorotaxane was formed by the inclusion of the internal middle site in CB[6] and the tail chain in CB[7].     

How Does Solvation Affect the Binding of Hydrophilic Amino Saccharides to Cucurbit[7]uril with Exceptional Anomeric Selectivity?

Cucurbit[7]uril (CB[7]) is known to bind strongly to hydrophilic amino saccharide guests with exceptional α‐anomer selectivities under aqueous conditions. Single‐crystal X‐ray crystallography and computational methods were used to elucidate the reason behind this interesting phenomenon. The crystal structures of protonated galactosamine (GalN) and glucosamine (GluN) complexes confirm the inclusion of α anomers inside CB[7] and disclose the details of the host–guest binding. Whereas computed gas‐phase structures agree with these crystal structures, gas‐phase binding free energies show preferences for the β‐anomer complexes over their α counterparts, in striking contrast to the experimental results under aqueous conditions. However, when the solvation effect is considered, the binding structures drastically change and the preference for the α anomers is recovered. The α anomers also tend to bind more tightly and leave less space in the CB[7] cavity toward inclusion of only one water molecule, whereas loosely bound β anomers leave more space toward accommodating two water molecules, with markedly different hydrogen‐bonding natures. Surprisingly, entropy seems to contribute significantly to both anomeric discrimination and binding. This suggests that of all the driving factors for the strong complexation of the hydrophilic amino saccharide guests, water mediation plays a crucial role in the anomer discrimination.     

Guest Inclusion in Cucurbiturils Studied by ESR and DFT: The Case of Nitroxide Radicals and Spin Adducts of DMPO and MNP

We present an ESR and DFT study of the interaction of cucurbiturils CB[6], CB[7], and CB[8] with di-tert-butyl nitroxide ((CH(3))(3)C)(2)NO (DTBN) and with spin adducts of 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) and 2-methyl-2-nitrosopropane (MNP). The primary goal was to understand the structural parameters that determine the inclusion mechanism in the CBs using DTBN, a nitroxide with great sensitivity to the local environment. In addition, we focused on the interactions with CBs of the spin adducts DMPO/OH and MNP/CH(2)COOH generated in aqueous CH(3)COOH. A range of interactions between DTBN and CBs was identified for pH 3.2, 7, and 10. No complexation of DTBN with CB[6] was deduced in this pH range. The interaction between DTBN and CB[7] is evident at all pH values: "in" and "out" nitroxides, with (14)N hyperfine splitting, a(N), values of 15.5 and 17.1 G, respectively, were detected by ESR. Interaction of DTBN with CB[8] was also detected for all pH values, and the only species had a(N) = 16.4 G, a result that can be rationalized by an "in" nitroxide in a less hydrophobic environment compared to CB[7]. Computational studies indicated that the DTBN complex with CB[7] is thermodynamically favored compared to that in CB[8]; the orientations of the NO group are parallel to the CB[7] plane and perpendicular to the CB[8] plane (pointing toward the annulus). Addition of sodium ions led to the ESR detection of a three-component complex between CB[7], DTBN, and the cations; the ternary complex was not detected for CB[8]. The DMPO/OH spin adduct was stabilized in the presence of CB[7], but the effect on a(N) was negligible, indicating that the N-O group is located outside the CB cavity. Computational studies indicated more favorable energetics of complexation for DMPO/OH in CB[7] compared to DTBN. An increase of a(N) was detected in the presence of CB[7] for the MNP/CH(2)COOH adduct generated in CH(3)COOH, a result that was assigned to the generation of the three-component radical between the spin adduct, sodium cations, and CB[7].