Double-cavity cucurbiturils: synthesis, structures, properties, and applications.

Double-cavity Q[n]s are relatively new members of the Q[n] family and have garnered significant interest due to their distinctive structures and novel properties. While they incorporate n glycoluril units, akin to their single-cavity counterparts, their geometry can best be described as resembling a figure-of-eight or a handcuff, distinguishing them from single-cavity Q[n]s. Despite retaining the core molecular recognition traits of single-cavity Q[n]s, these double-cavity variants introduce fascinating new attributes rooted in their distinct configurations. This overview delves into the synthesis, structural attributes, properties, and intriguing applications of double-cavity Q[n]s. Some of the applications explored include their role in supramolecular polymers, molecular machinery, supra-amphiphiles, sensors, artificial light-harvesting systems, and adsorptive separation materials. Upon concluding this review, we discuss potential challenges and avenues for future development and offer valuable insights for other scholars working in this area with the aim of stimulating further exploration and interest.

A Cucurbit[8]uril-Based Supramolecular Framework Material for Reversible Iodine Capture in the Vapor Phase and Solution.

The safe and efficient management of hazardous radioactive iodine is significant for nuclear waste reprocessing and environmental industries. A novel supramolecular framework compound based on cucurbit[8]uril (Q[8]) and 4-aminopyridine (4-AP) is reported in this paper. In the single crystal structure of Q[8]-(4-AP), two 4-AP molecules interact with the outer surface of Q[8] and the two other 4-AP molecules are encapsulated into the Q[8] cavity to form the self-assembly Q[8]-(4-AP). Iodine adsorption experiments show that the as-prepared Q[8]-(4-AP) not only has a high adsorption capacity (1.74 g· g-1) for iodine vapor but also can remove the iodine in the organic solvent and the aqueous solution with the removal efficiencies of 95% and 91%, respectively. The presence of a large number of hydrogen bonds between the iodine molecule and the absorbent, as seen in the single crystal structure of iodine-loaded Q[8]-(4-AP) (I2@Q[8]-(4-AP)), is thought to be responsible for the exceptional iodine adsorption capacity of the material. In addition, the adsorption-desorption tests reveal that the self-assembly material has no significant loss of iodine capture capacity after five cycles, indicating that it has sufficient reusability.

Treatment of metastatic hormone-sensitive prostate cancer: from doublet therapy to triplet therapy.

For metastatic prostate cancer, androgen deprivation therapy (ADT) is the key strategy to control the disease. However, after 18-24 months of treatment, most patients will progress from metastatic hormone-sensitive prostate cancer (mHSPC) to metastatic castration-resistant prostate cancer (mCRPC) even with ADT. Once patients enter into mCRPC, they face with significant declines in quality of life and a dramatically reduced survival period. Thus, doublet therapy, which combines ADT with new hormone therapy (NHT) or ADT with docetaxel chemotherapy, substitutes ADT alone and has become the "gold standard" for the treatment of mHSPC. In recent years, triplet therapy, which combines ADT with NHT and docetaxel chemotherapy, has also achieved impressive effects in mHSPC. This article provides a comprehensive review of the recent applications of the triplet therapy in the field of mHSPC.

A supramolecular fluorescence sensor array for the differentiation of multiple anions and prediction of iodine in artificial urine using machine learning.

The simultaneous discrimination and detection of multiple anions in an aqueous solution has been a major challenge due to their structural similarity and low charge radii. In this study, we have constructed a supramolecular fluorescence sensor array based on three host-guest complexes to distinguish five anions (F-, Cl-, Br-, I-, and ClO-) in an aqueous solution using anionic-induced fluorescence quenching combined with linear discriminant analysis. Due to the different affinities of the three host-guest complexes for each anion the anion quenching efficiency for each host-guest complex was likewise different, and the five anions were well recognized. The fluorescence sensor array not only distinguished anions at different concentrations (0.5, 10, and 50 µM) with 100% accuracy but also showed good linearity within a certain concentration range. The limit of detection (LOD) was < 0.5 µM. Our interference study showed that the developed sensor array had good anti-interference ability. The practicability of the developed sensor array was also verified by the identification and differentiation of toothpaste brands with different fluoride content and the prediction of the iodine concentration in urine combined with machine learning.

Metal Cation-Doped ns-Cucurbit[10]uril: Adsorption of Para-Phenylenediamine.

The separation of phenylenediamine (PDA) isomers is crucial in the field of chemical manufacturing. Herein, we presented a strategy for the separation of PDA isomers (para-phenylenediamine, p-PDA; meta-phenylenediamine, m-PDA; ortho-phenylenediamine, o-PDA) using four supramolecular framework materials of ns-cucurbit[10]uril (ns-Q[10]), (1) ns-Q[10](Cd), (2) ns-Q[10](Mn), (3) ns-Q[10](Cu), (4) ns-Q[10](Pb). Our findings indicated that these supramolecular framework materials of ns-Q[10] showed remarkable selectivity for para-phenylenediamine (p-PDA) in p-PDA, m-PDA, and o-PDA mixtures, respectively. The variations in selectivity observed in these four single-crystal structures arose from variations in the thermodynamic stabilities and binding modes of the host-guest complexes. Importantly, the supramolecular framework based on ns-Q[10] exhibited selective accommodation of p-PDA over its isomers. This study highlighted the practical application of ns-Q[10] in effectively separating PDA isomers and demonstrated the potential utility of ns-Q[10] in isolating other organic molecules.

Efficient formaldehyde sensor based on PtPd nanoparticles-loaded nafion-modified electrodes.

The noble metal-based electrochemical sensor design for efficient and stable formaldehyde(FA) detection is important ongoing research. In this paper, PtPd/Nafion/GCE is prepared by electrochemical cyclic voltammetry deposition method based on electrodepositing nanostructured platinum (Pt)-palladium (Pd) nanoparticles in Nafion film-coated glassy carbon electrode (GCE). The influence of deposition parameters and chemical composition (atomic ratio of Pt and Pd) on the electrochemical behaviour of PtPd/Nafion/GCE has been investigated. PtPd/Nafion/GCE displays a remarked electrocatalytic activity for the oxidation of FA and exhibits a linear relationship in the range of 10-5000µM, with a detection limit of 3.3µM in 0.1 M H2SO4solution. It is proved that the detection performance of PtPd/Nafion/GCE electrode is valuable for further application with low detection limit, wide linear range, favourable selectivity and high response.

A white-light-emitting sensor array based on cucurbit[8]uril for quantitative detection of multicomponent nitroaniline isomers.

A white-light-emitting supramolecular complex through supramolecular interactions has been assembled; the white luminescent supramolecular complex exhibits two emission spectra. Based on this, a dual-channel white-light array sensor was constructed. The results show that it can quickly identify and detect nitroaniline isomer pollutants (p-nitroaniline, m-nitroaniline, o-nitroaniline). When these three nitroaniline isomers were added to the supramolecular white-light array sensor, the fluorescence intensity of the white-light complex decreased to varying degrees. Linear discriminant analysis (LDA) showed that the supramolecular white-light array sensor could recognize and distinguish three nitroaniline isomers and could classify mixtures containing different concentrations. Factor 1 of the array had a good linear relationship with the concentration of pollutants, and the detection limit (LOD) was as low as 0.7 µM. The method has good reproducibility and stability. In addition, it can also qualitatively detect the nitroaniline isomers in river water and contaminated rice seedling extract. It provides an ideal platform for constructing multiresponse sensors.

Preparation of Decoquinate Solid Dispersion by Hot-Melt Extrusion as an Oral Dosage Form Targeting Liver-Stage Plasmodium Infection.

Liver-stage Plasmodium in humans is an early stage of malarial infection. Decoquinate (DQ) has a potent multistage antimalarial activity. However, it is practically water insoluble. In this study, the hot-melt extrusion (HME) approach was employed to prepare solid dispersions of DQ to improve oral bioavailability. The DQ dispersions were homogeneous in an aqueous suspension that contained most DQ (>90%) in the aqueous phase. Soluplus, a solubilizer, was found compatible with DQ in forming nanoparticle formulations during the HME process. Another excipient HPMC AS-126 was also proven to be suitable for making DQ nanoparticles through HME. Particle size and antimalarial activity of HME DQ suspensions remained almost unchanged after storage at 4°C for over a year. HME DQ was highly effective at inhibiting Plasmodium infection in vitro at both the liver stage and blood stage. HME DQ at 3 mg/kg by oral administration effectively prevented Plasmodium infection in mice inoculated with Plasmodium berghei sporozoites. Orally administered HME DQ at 2,000 mg/kg to mice showed no obvious adverse effects. HME DQ at 20 mg/kg orally administered to rats displayed characteristic distributions of DQ in the blood with most DQ in the blood cells, revealing the permeability of HME DQ into the cells in relation to its antimalarial activity. The DQ dispersions may be further developed as an oral formulation targeting Plasmodium infection at the liver stage.

Cucurbit[10]uril-Based Orthogonal Supramolecular Polymers with Host-Guest and Coordination Interactions and Its Applications in Anion Classification.

A novel orthogonal supramolecular polymer (Q[10]-TPDPB-Lu3+) in a host-guest ratio of 2:1 was successfully constructed utilizing the specificity and excellent cavity matching of Q[10] with the tripyridine derivatives (TPDPB). Significantly, non-covalent interactions between Q[10]'s hydrophobic cavities and Lu3+ were used to induce charge transfer of TPDPB to TPDPB and TPDPB to Lu3+, resulting in the construction of structurally interesting orthogonal assemblies with excellent fluorescence properties. Finally, the Q[10]-TPDPB-Lu3+ assemblies were shown to have good recognition and classification of strong and weak acid anions as well as iodide anions, and the classification was accompanied by a clear fluorescence emission change allowing visual observation.

CdS-Based Catalysts Derived from TMeQ[6]/[CdxCly]n--Based Frameworks for Oxidation Benzylamine.

The anion-induced outer surface interaction of Q[n]s is an important driving force in the construction of Q[n]-based supramolecular frameworks. In this work, a symmetric tetramethyl-substituted cucurbit[6]uril (TMeQ[6]) is selected as the basic structural block. Using the anion-induced outer surface interaction of Q[n]s derived from [CdxCly]n- anions formed by Cd2+ cations in a HCl medium, four different TMeQ[6]-[CdxCly]n--based supramolecular frameworks are constructed. Three of the most common TMeQ[6]-[CdxCly]n--based supramolecular frameworks are selected for further vulcanization, and three different CdS/TMeQ[6]-based framework catalysts with different structures and properties are obtained. The catalytic activities of these three CdS/TMeQ[6]-based framework catalysts are investigated by the coupling photocatalytic reaction of aminobenzyl, and the results showed that the catalytic activities of the three catalysts are all higher than that of pure CdS. Therefore, this work establishes that it is possible to establish a method for synthesizing the Q[n]-based framework-supported catalysts by first synthesizing TMeQ[6]-[CdxCly]n--based supramolecular frameworks and then forming Q[n]-based framework supported catalysts by sulfurization or reduction.

Improved electrochemical properties of polypyrrole with cucurbit[6]uril via supramolecular interactions.

A supramolecular polymer was developed through the encapsulation of polypyrrole by cucurbit[6]uril (PPy@Q[6]), which was employed as the electrode material to improve the capacitor ability of conductive polypyrrole. In the optimized ratio of 2 : 1 (CPPy : CQ[6]), the capacitor properties of the supramolecular material were evaluated, and a high specific capacitance of 414 F g-1 at 10 mV s-1 was obtained, which was 3.1 times higher than that of pure polypyrrole (132 F g-1). A comprehensive analysis suggested that the capacitance performances should be relevant to the component, surface area, and pore volume of the materials. The addition of 0.4 M Fe2(SO4)3 into the electrolyte provided a surprising specific capacitance of 3530 F g-1 on the cucurbituril-encapsulated polypyrrole electrode material, with a high energy density of 707 W h kg-1 at a power density of 32 000 W kg-1 and a current density of 8 A g-1. The 81.6% capacitance retention maintained after 1000 cycles revealed the acceptable cycling capacity of the proposed supramolecular supercapacitor system, which demonstrated good performance even at a low temperature of -20 °C.

Double-Cavity Nor-Seco-Cucurbit[10]uril Enables Efficient and Rapid Separation of Pyridine from Mixtures of Toluene, Benzene, and Pyridine.

Benzene, toluene and pyridine are widely used as essential raw materials in industry and laboratory research, with stringent purity requirements. Herein, we show that solid double-cavity host nor-seco-cucurbit[10]uril (ns-Q[10]) functions as an efficient adsorption separator for pyridine; benzene and toluene can be obtained in >99.9 % purity by this method. Thermal removal of pyridine from ns-Q[10]⋅Py2 allows 10 separation cycles without erosion of performance. The geometry of the ns-Q[10]⋅Py2 ternary complex was established by single-crystal X-ray diffraction methods. The ns-Q[10] cage facilitates the removal of pyridine from toluene and benzene, with >99.9 % purity for the separated compounds.

Multiple Stimuli-Responsive Supramolecular Hydrogels Constructed by Decamethylcucurbit[5]uril-para-phenylenediamine Exclusion Complex.

The hydrogels composed of decamethylcucurbit[5]uril (Me10 Q[5]) and para-phenylenediamine (p-PDA) are first reported herein. They are the first Q[5]-based supramolecular hydrogels, the formation of which is driven by portal exclusion between Me10 Q[5] and p-PDA. The composition, structure, and properties of the Me10 Q[5]/p-PDA-based hydrogels are investigated by various techniques. Since the 1D supramolecular chain forms via portal exclusion between Me10 Q[5] and p-PDA is the key to the formation of the hydrogels, any competitive species, such as metal ions, organic molecules, and amino acids, which can affect the portal exclusion, can change the behavior of the Me10 Q[5]/p-PDA-based hydrogels. Hence, the hydrogels can be used for various applications. Importantly, the results may provide a new research direction for the preparation of Q[n]-based hydrogels via portal exclusion of Q[n]s with guests.

Cucurbit[n]uril-Based Supramolecular Frameworks Assembled through Outer-Surface Interactions.

Porous materials, especially metal-organic frameworks, covalent organic frameworks, and supramolecular organic frameworks, are widely used in heterogeneous catalysis, adsorption, and ion exchange. Cucurbit[n]urils (Q[n]s) suitable building units for porous materials because they possess cavities with neutral electrostatic potential, portal carbonyls with negative electrostatic potential, and outer surfaces with positive electrostatic potential, which may result in the formation of Q[n]-based supramolecular frameworks (QSFs) assembled through the interaction of guests within Q[n]s, the coordination of Q[n]s with metal ions, and outer-surface interaction of Q[n]s (OSIQ). This review summarizes the various QSFs assembled via OSIQs. The QSFs can be classified as being assembled by 1) self-induced OSIQ, 2) anion-induced OSIQ, and 3) aromatic-induced OSIQ. The design and construction of QSFs with novel structures and specific functional properties may establish a new research direction in Q[n] chemistry.

The fluorescence of a mercury probe based on osthol.

The ability of osthol (OST) to recognize mercury ions in aqueous solution was studied using fluorescence, UV-vis spectrophotometry, mass spectrometry, and 1H NMR spectroscopy, and the recognition mechanism is discussed. The results showed that OST and Hg2+ can form a complex with a stoichiometric ratio of 1:1. The binding constant was 1.552 × 105 L∙mol-1, having a highly efficient and specific selectivity for Hg2+. The fluorescence intensity of OST showed a good linear correlation with the Hg2+ concentration (6.0 × 10-5 to 24.0 × 10-5 mol∙L-1, R 2 = 0.9954), and the detection limit of the probe was 5.04 × 10-8 mol∙L-1, which can be used for the determination of Hg2+ traces.

Host-guest interaction and properties of cucurbit[8]uril with chloramphenicol.

The interaction between cucurbit[8]uril (Q[8]) and chloramphenicol (CPE) was investigated using single-crystal X-ray diffraction spectroscopy, isothermal titration calorimetry (ITC) and UV-vis, NMR and IR spectroscopy. The effects of Q[8] on the stability, in vitro release performance and antibacterial activity of CPE were also studied. The results showed that CPE and Q[8] formed a 1:1 inclusion complex (CPE@Q[8]) with an inclusion constant of 5.474 × 105 L/mol. The intervention of Q[8] did not affect the stability of CPE, but obviously reduced the release rate of CPE in artificial gastric and intestinal juice; Q[8] has a slow-release effect on CPE. The antibacterial results showed that the minimum inhibitory concentration (MIC) of CPE and CPE@Q[8] toward Escherichia coli (E. coli) was 1.5 × 10-3 and 1.0 × 10-3 mol/L, respectively, and toward Staphylococcus aureus (S. aureus), the MIC was 2.0 × 10-3 mol/L for both CPE and CPE@Q[8]. Therefore, Q[8] enhanced the inhibitory activity of CPE against E. coli.

Study on the interactions between melamine-cored Schiff bases with cucurbit[n]urils of different sizes and its application in detecting silver ions.

Three different complexes, TMeQ[6]-TBT, Q[7]-TBT, and Q[8]-TBT are constructed by three different cucurbiturils and synthesized by guest melamine-cored Schiff bases (TBT) through outer-surface interaction and host-guest interactions. TBT forms a TMeQ[6]-TBT complex with TMeQ[6] through outer-surface interaction, while Q[7]-TBT and Q[8]-TBT form complexes with Q[7,8] through host-guest interactions. Among them, Q[7]-TBT is selected as a UV detector for the detection of silver ions (Ag+). This work makes full use of the characteristics of each cucurbituril and melamine-cored Schiff base to construct a series of complexes and these are applied to metal detection.

Evidence for the spread of human-derived mutant huntingtin protein in mice and non-human primates.

In recent years, substantial evidence has emerged to suggest that spreading of pathological proteins contributes to disease pathology in numerous neurodegenerative disorders. Work from our laboratory and others have shown that, despite its strictly genetic nature, Huntington's disease (HD) may be another condition in which this mechanism contributes to pathology. In this study, we set out to determine if the mutant huntingtin protein (mHTT) present in post-mortem brain tissue derived from HD patients can induce pathology in mice and/or non-human primates. For this, we performed three distinct sets of experiments where homogenates were injected into the brains of adult a) Wild-type (WT) and b) BACHD mice or c) non-human primates. Neuropathological assessments revealed that, while changes in the endogenous huntingtin were not apparent, mHTT could spread between cellular elements and brain structures. Furthermore, behavioural differences only occurred in the animal model of HD which already overexpressed mHTT. Taken together, our results indicate that mHTT derived from human brains has only a limited capacity to propagate between cells and does not depict prion-like characteristics. This contrasts with recent work demonstrating that other forms of mHTT - such as fibrils of a pathological polyQ length or fibroblasts and induced pluripotent stem cells derived from HD cases - can indeed disseminate disease throughout the brain in a prion-like fashion.

Use of adeno-associated virus-mediated delivery of mutant huntingtin to study the spreading capacity of the protein in mice and non-human primates.

In order to model various aspects of Huntington's disease (HD) pathology, in particular protein spread, we administered adeno-associated virus (AAV) expressing green fluorescent protein (GFP) or GFP coupled to HTT-Exon1 (19Q or 103Q) to the central nervous system of adult wild-type (WT) mice and non-human primates. All animals underwent behavioral testing and post-mortem analyses to determine the long-term consequences of AAV injection. Both mice and non-human primates demonstrated behavioral changes at 2-3 weeks post-surgery. In mice, these changes were absent after 3 months while in non-human primates, they persisted in the majority of tested animals. Post-mortem analysis revealed that spreading of the aggregates was limited, although the virus did spread between synaptically-connected brain regions. Despite circumscribed spreading, the presence of mHTT generated changes in endogenous huntingtin (HTT) levels in both models. Together, these results suggest that viral expression of mHTTExon1 can induce spreading and seeding of HTT in both mice and non-human primates.

A high-sensitive sensor with HEPES-enhanced electrochemiluminescence of benzo[3]uril for Fe3+ and its application in human serum.

An electrochemiluminescence (ECL) sensor based on a benzo[3]uril-modified glassy carbon electrode with sensitized luminescence, with the coexistence of 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES) as the coreactant, was successfully constructed. The sensitization mechanism was proposed by analyzing the results of the control experiments for establishing the relationship of the luminescence effect with the concentration of HEPES. Under the optimized conditions, the fabricated sensor system was applied for the detection of Fe3+ in an aqueous solution with good sensitivity and selectivity. A low detection limit of 0.41 nM was achieved, indicating superior sensor performance over the previous analytical methods. The ECL sensor system was employed for the detection of Fe3+ in human serum samples to produce excellent recoveries ranging from 96.17% to 101.81%.