Stimuli-responsive mechanically interlocked molecules constructed from cucurbit[n]uril homologues and derivatives.

Cucurbit[n]uril supramolecular chemistry has developed rapidly since 2001 when different cucurbit[n]uril homologues (Q[n]) were successfully separated in pure form. The combination of Q[n] cavity size and various types of external stimuli has given birth to numerous types of Q[n]-based mechanically interlocked molecules (MIMs), including (pseudo)rotaxanes, catenanes, dendrimers and poly(pseudo)rotaxanes. In this review article, the important advances in the field of Q[n]-based MIMs over the past two decades are highlighted. This review also describes examples of heterowheel (pseudo)rotaxanes and poly(pseudo)rotaxanes involving Q[n]s, and reflects on the opportunities and challenges of constructing Q[n]-based stimuli-responsive MIMs.

You are what you eat: nutrient and water relations between mistletoes and hosts.

Mistletoes play important roles in biogeochemical cycles. Although many studies have compared nutrient concentrations between mistletoes and their hosts, no general patterns have been found and the nutrient uptake mechanisms in mistletoes have not been fully resolved. To address the water and nutrient relations in mistletoes compared with their hosts, we measured 11 nutrient elements, two isotope ratios and two leaf morphological traits for 11 mistletoe and 104 host species from four sites across a large environmental gradient in southwest China. Mistletoes had significantly higher phosphorus, potassium, and boron concentrations, nitrogen isotope ratio, and lower carbon isotope ratio (δ13 C) indicative of lower water-use efficiency than hosts, but other elements were similar to those in hosts. Sites explained most of the variation in the multidimensional trait space. With increasing host nitrogen concentration, both mistletoe δ13 C and the difference between mistletoe and host δ13 C increased, providing evidence to support the 'nitrogen parasitism hypothesis'. Host nutrient concentrations were the best predictors for that of the mistletoe nutrient elements in most cases. Our results highlight the important roles of environmental conditions and host nutrient status in determining mistletoe nutrient pools, which together explain their trophic interactions with hosts in subtropical and tropical ecosystems.

Mirror image stimulation could reverse social-isolation-induced aggressiveness in the high-level subsocial lactating spider.

Conspecific aggressiveness often increases after social isolation for species that are not entirely solitary, and this increased aggression could also be reversed after resocialization. However, literature on this aggression plasticity refers to either permanently social or low-level subsocial species in invertebrates. Examinations of conspecific aggressiveness reversibility in high-level subsocial invertebrates, in which offspring cohabitate with parents for a certain period of time after sexual maturation, would enhance the understanding of the role of conspecific-aggression plasticity in social evolution. Here, using the lactating spider Toxeus magnus, which exhibits extremely high-level subsociality, we assessed three questions. (1) Is its conspecific aggression affected by social living and/or kinship? The results indicated that conspecific aggression increased after social isolation, while kinship did not affect aggressiveness. (2) Could the social-isolation-induced higher aggression be reversed after resocialization? The results showed that the increased aggression of the spiders could be reversed 3 days after resocialization. (3) What is the proximate mechanism that caused the aggression reversibility by resocialization? A simulated resocialization experiment in which single spider was provided with mirrors demonstrated that the visual cues of conspecifics alone could reverse the aggression after 6 days. These results indicate that the high-level subsocial invertebrate showed aggressiveness reversibility without chemical cues. This is more similar to permanently social species rather than to low-level subsocial species, and visual cues could be vital to induce aggression change. These results suggest that conspecific-aggression reversibility might play a key role in social evolution and may functionally enhance species' adaptiveness under variable conditions.

A light-responsive molecular switch based on cucurbit[7]uril and 1,1'-bis(benzyl)-4-[2-(4-pyridyl)-vinyl]-pyridinium dibromide displaying white light emission.

By using 1H NMR, ESI-MS and UV spectra, a novel light-responsive molecular switch constructed using 1,1'-bis(benzyl)-4-[2-(4-pyridyl)-vinyl]-pyridinium (12+) and cucurbit[7]uril (Q[7]) is demonstrated. The E- to Z-isomerization of the double bond in 12+ results in the transition of the switching states from the 1 : 2 complex E-12+@Q[7]2 to the stable 1 : 1 complex Z-12+@Q[7]. In particular, both the 1 : 2 complex and the 1 : 1 complex can emit cold white fluorescence under UV light.

An inclusion complex of cucurbit[7]uril with benzimidazolyl benzyl viologen exhibits fluorescence and photochromic properties.

In order to investigate the photochromic mechanism of photochromic materials based on supramolecular host-guest systems, we designed and synthesized a unique viologen derivative (benzimidazolyl benzyl viologen, guest 1·Cl3), which does not contain oxygen atoms. The binding interaction of guest 13+ with host cucurbit[7]uril (Q[7]) was investigated by various techniques. The obtained supramolecular host-guest complex 13+@Q[7] exhibits interesting fluorescence emission and reversible photochromism. The ESR and XPS experimental data suggest that the photochromic process of the complex 13+@Q[7] comes from the electron transfer from the carbonyl O atoms of the host Q[7] to the bipyridinium N atoms of the guest 13+.

[Preparation and Evaluation of Intranasal in situ Gel of Bupleuri Radix Volatile Oil and Baicalin].

OBJECTIVE: To prepare and evaluate a new formulation of thermosensitive and ion-sensitive in situ gel for nasal administration, using the volatile oil of Bupleuri radix and baicalin, the effective component extracted from Scutellariae radix . METHODS: Formulation of in situ nasal gel of Bupleuri radix volatile oil and baicalin was prepared by using poloxamer 407 and deacetylated gellan gum as the gel base, 10% pharmasolve and 2% polysorbate 80 as the solubilizer, and 0.8% triethanolamine as the pH regulator. The physical appearance, phase transition temperature, and baicalin release performance of the prepared gel were examined. The pharmacodynamic evaluation was done with the rat fever model developed with dry yeast and the mouse auricle swelling inflammation model. RESULTS: The phase transition temperature of the gel was optimized to be 36 ℃. The release of baicalin from the gel showed obvious features of sustained release, which accorded well the zero-order kinetics equation. The results of experiments with the rat dry yeast fever model and the mouse xylene auricle swelling inflammation model showed that the gel had significant antipyretic and anti-inflammatory effects that were significantly better than those of the groups treated with the blank gel base and the Bupleuri radix and Scutellariae radix granule. Results from the cilia toxicity test showed that the gel did not have obvious toxic effect on toad palate mucosal cilia. CONCLUSION: The in situ nasal gel of Bupleuri radix volatile oil and baicalin prepared in the study had a rapid onset time, high efficiency, and prolonged release of active ingredients, thus showing promises for further applicational development.

Symmetrical-Tetramethyl-Cucurbit[6]uril-Driven Movement of Cucurbit[7]uril Gives Rise to Heterowheel [4]Pseudorotaxanes.

Two novel heterowheel [4]pseudorotaxanes consisting of cucurbit[7]uril (Q[7]) and symmetrical-tetramethyl-cucurbit[6]uril (TMeQ[6]) were constructed via the multirecognition mechanism, in which Q[7] can rotate freely around the horizontal axis, while TMeQ[6] cannot. In the construction process, due to strong repulsive forces between carbonyl portals of two neighboring wheels, the dethreading and movement of the wheels along the axle was observed. The dissociation of the [4]pseudorotaxanes was also discussed.

Selective Recovery and Detection of Gold with Cucurbit[n]urils (n = 5-7).

Environmentally benign methods for gold recovery and detection are highly desirable for a sustainable future. Herein, we demonstrate a selective recovery and detection strategy of gold with cucurbit[n]urils (Q[n = 5-7]) by means of outer-surface interactions. Tetrachloroaurate anion ([AuCl4]-) is able to be rapidly precipitated with Q[n] in forms of supramolecular adducts. X-ray crystallography of four Q[n = 5-7]·[AuCl4]- complexes reveal that strong outer-surface interactions between Q[n = 5-7] and [AuCl4]- are the major driving force for the formation of Q[n = 5-7]·[AuCl4]- complexes. Impressively, each Q[6] macrocycle is surrounded by 12 [AuCl4]- anions. Each of these 12 [AuCl4]- anions is connected to four adjacent [AuCl4]- anions, leading to the formation of a three-dimensional supramolecular framework with tubular channels. In addition, we found an interesting inclusion complex [Au(OH2)4]3+⊂Q[7] in the Q[7]·[AuCl4]- complex, which is the first example of hydrated metal cation encapsulated inside the cavity of Q[n]. Spectroscopic data suggest that Q[n = 5-7] possess a high affinity and selectivity for [AuCl4]- even in the presence of other transition-metal ions. Q[n] modified electrodes are found to be an effective material for the detection of trace gold in dilute solutions.

Effectiveness of high-intensity interval training on glycemic control and cardiorespiratory fitness in patients with type 2 diabetes: a systematic review and meta-analysis.

AIMS: The aim of this systematic review and meta-analysis was to quantify the effect of high-intensity interval training (HIIT) on glycemic control and cardiorespiratory fitness compared with moderate-intensity training (MICT) and no training at all in patients with type 2 diabetes (T2D). METHODS: Relevant articles were sourced from PubMed, Embase, the Web of Science, EBSCO, and the Cochrane Library. Randomized-controlled trials were included based upon the following criteria: participants were clinically diagnosed with T2D, outcomes that included glycemic control (e.g., hemoglobin A1c); body composition (e.g., body weight); cardiorespiratory fitness (e.g., VO2peak) are measured at baseline and post-intervention and compared with either a MICT or control group. RESULTS: Thirteen trials involving 345 patients were finally identified. HIIT elicited a significant reduction in BMI, body fat, HbA1c, fasting insulin, and VO2peak in patients with type 2 diabetes. Regarding changes in the body composition of patients, HIIT showed a great improvement in body weight (mean difference: - 1.22 kg, 95% confidence interval [CI] - 2.23 to - 0.18, P = 0.02) and body mass index (mean difference: - 0.40 kg/m2, 95% CI - 0.78 to - 0.02, P = 0.04) than MICT did. Similar results were also found with respect to HbA1c (mean difference: - 0.37, 95% CI - 0.55 to - 0.19, P < 0.0001); relative VO2peak (mean difference: 3.37 ml/kg/min, 95% CI 1.88 to 4.87, P < 0.0001); absolute VO2peak (mean difference: 0.37 L/min, 95% CI 0.28 to 0.45, P < 0.00001). CONCLUSIONS: HIIT may induce more positive effects in cardiopulmonary fitness than MICT in T2D patients.

Norditerpenoids and Dinorditerpenoids from the Seeds of Podocarpus nagi as Cytotoxic Agents and Autophagy Inducers.

Nine new norditerpenoids and dinorditerpenoids, 2-oxonagilactone A (1), 7ß-hydroxynagilactone D (2), nagilactones K and L (3 and 4), 3ß-hydroxynagilactone L (5), 2ß-hydroxynagilactone L (6), 3-epi-15-hydroxynagilactone D (7), 1α-chloro-2ß,3ß,15-trihydroxynagilactone L (8), and 15-hydroxynagilactone L (9), were isolated from the seeds of Podocarpus nagi, along with eight known analogues. The structures of the new compounds were established based on detailed NMR and HRESIMS analysis, as well as from their ECD spectra. The absolute configuration of the known compound 1-deoxy-2α-hydroxynagilactone A (16) was confirmed by single-crystal X-ray diffraction. All of the isolates were tested for their cytotoxic activities against cancer cells. The results indicated that compounds 4 and 6, as well as several known compounds, displayed cytotoxicity against A2780 and HEY cancer cells. Among the new compounds, 2ß-hydroxynagilactone L (6) showed IC50 values of less than 2.5 µM against the two cell lines used. Furthermore, compound 6 induced autophagic flux in A2780 cells, as evidenced by an enhanced expression level of the autophagy marker phosphatidylethanolamine-modified microtubule-associated protein light-chain 3 (LC3-II) and increased mRFP-GFP-LC3 puncta. Also, compound 6 activated the c-Jun N-terminal kinase (JNK) pathway, while pretreatment with the JNK inhibitor SP600125 decreased compound 6-induced autophagy.

Phytochemical profiling in single plant cell by high performance liquid chromatography-mass spectrometry.

Phytochemicals are essential secondary plant metabolites which play important roles in the areas of plant biochemistry, pharmacy and medical science because of their significant bioactivities. Conventional analysis of phytochemicals in plants needs a complex combination of different extraction and separation steps. Here a simple and universal method for profiling phytochemicals in a single plant cell was demonstrated based on high performance liquid chromatography-mass spectrometry. Single purple and colorless cell samples (about 15 µm in size) found in the outer layer of a young stem of Forsythia suspensa, just inside the cuticles were collected and transferred by glass micropipettes from cell monolayers. At least 30 peaks were separated and detected, and 24 of these peaks were identified. Apart from several common plant metabolites in high abundance, like polysaccharides and amino acids, 9 phytochemicals that have special bioactivities in this plant and in medical treatment were successfully detected. Phytochemical differences between these two kinds of cells were also distinguished which was applied to investigate the heterogeneity of cells from different parts of plants and the dependency of important plant bioprocesses on phytochemical changes.

Host-guest complexation of di-cyclohexanocucurbit[6]uril and hexa-cyclohexanocucurbit[6]uril with alkyldiammonium ions: a comparative study.

The host-guest complexation of symmetrical di-cyclohexanocucurbit[6]uril (Cy2Q[6]) and hexa-cyclohexanocucurbit[6]uril (Cy6Q[6]) with a series of alkyldiammonium ions (H(3+)N(CH(2))nNH(3+), n = 2-8) has been studied both in solution and in the gas phase. (1)H NMR data indicate that all alkyldiammonium ions have inclusion interactions with both hosts except for the ethanediammonium ion. In addition, if the alkyl chain of the alkyldiammonium ion is longer than n = 5 methylene groups, compressed conformation may occur, which depends on the cavity shape of the hosts and the length of the alkyl chain. Isothermal titration calorimetry (ITC) studies point out that the host-guest complexations of both hosts with the latter five alkyldiammonium ions are enthalpically driven. The comparison of the thermodynamic data reveals that the enthalpies of the van der Waals interactions contribute more to the host-guest complexation enthalpy than the ion-dipole interactions. The enthalpic gain arises from the van der Waals interactions and the reduction of entropy upon the host-guest complexation is strongly affected by the cavity shape of the host. Gas phase structures of long alkyldiammonium guests within both hosts are completely different from those in aqueous solution.

The Binding Interactions between Cyclohexanocucurbit[6]uril and Alkyl Viologens Give Rise to a Range of Diverse Structures in the Solid and the Solution Phases.

The binding interactions between the cyclohexanocucurbit[6]uril (Cy6CB6) host and a series of dialkyl-4,4'-bipyridinium (viologen) dicationic guests were investigated in the solution phase, using (1)H NMR spectroscopy, and in the solid phase, using X-ray diffraction methods. In D2O solution, methyl viologen (MV(2+)) and ethyl viologen (EV(2+)) form 1:1 complexes in which the bipyridinium aromatic nucleus is partially included inside the Cy6CB6 cavity. Propyl viologen (PV(2+)), butyl viologen (BV(2+)), pentyl viologen (FV(2+)), and heptyl viologen (HV(2+)) form 2:1 complexes with Cy6CB6, in which each of the viologen aliphatic chains is included by a host molecule. In the solid state, EV(2+) forms a polypseudorotaxane via pseudorotaxane interdigitation of Cy6CB6 hosts. The PV(2+) guest forms a dumbbell-shaped structure with a Cy6CB6 host residing over each of the terminal propyl groups of the guest. In contrast to this, the BV(2+) guest and Cy6CB6 form a different polypseudorotaxane structure in which dumbbell-shaped structures, formed by two host molecules interacting with a single guest, are interconnected through metal-host coordination.

Mixed behavior of p-phenylenediaminium guest binding with the inverted cucurbit[6]uril host.

The binding interaction between inverted cucurbit[6]uril (iQ[6]) and p-phenylenediaminium both in the solid state and in aqueous solution has been investigated by X-ray crystallography, (1)H NMR spectroscopy and isothermal titration calorimetry (ITC). The experimental results suggest that the binding interaction between iQ[6] and p-phenylenediaminium may generate two different types of complexes in the solid state: one is an inclusion structure and the other is a sandwich structure. In aqueous solution, the iQ[6] host has an ability to accommodate the p-phenylenediaminium guest and in-out guest exchange is fast on the NMR time scale. ITC data indicate that the complexation of iQ[6] with p-phenylenediaminium is entropy driven.

Encapsulation of haloalkane 1-(3-chlorophenyl)-4-(3-chloropropyl)-piperazinium in symmetrical α,α',δ,δ'-tetramethyl-cucurbit[6]uril.

Complexation of haloalkane 1-(3-chlorophenyl)-4-(3-chloropropyl)-piperazinium (PZ(+)) dihydrochloride with symmetrical α,α',δ,δ'-tetramethyl-cucurbit[6]uril (TMeQ[6]) has been investigated using NMR spectroscopy, MALDI-TOF mass spectrometry, isothermal titration calorimetry (ITC), and X-ray crystallography. Our data indicate that the chloropropyl group of PZ(+) resides within the cavity of TMeQ[6] in both aqueous solution and the solid state, generating a highly stable inclusion complex PZ(+)@TMeQ[6]. In aqueous solution, the formation of the inclusion complex PZ(+)@TMeQ[6] benefits from the ion-dipole interactions between the guest PZ(+) and the host TMeQ[6]. While in the solid state, hydrogen-bonding interactions also play an important role in stabilizing the inclusion complex PZ(+)@TMeQ[6].

Double-layer poly(vinyl alcohol)-coated capillary for highly sensitive and stable capillary electrophoresis and capillary electrophoresis with mass spectrometry glycan analysis.

Glycosylation plays an important role in protein conformations and functions as well as many biological activities. Capillary electrophoresis combined with various detection methods provided remarkable developments for high-sensitivity glycan profiling. The coating of the capillary is needed for highly polar molecules from complex biosamples. A poly(vinyl alcohol)-coated capillary is commonly utilized in the capillary electrophoresis separation of saccharides sample due to the high-hydrophilicity properties. A modified facile coating workflow was carried out to acquire a novel multiple-layer poly(vinyl alcohol)-coated capillary for highly sensitive and stable analysis of glycans. The migration time fluctuation was used as index in the optimization of layers and a double layer was finally chosen, considering both the effects and simplicity in fabrication. With migration time relative standard deviation less than 1% and theoretical plates kept stable during 100 consecutive separations, the method was presented to be suitable for the analysis of glycosylation with wide linear dynamic range and good reproducibility. The glycan profiling of enzymatically released N-glycans from human serum was obtained by the presented capillary electrophoresis method combined with mass spectrometry detection with acceptable results.

Differential detection of Rhizoma coptidis by capillary electrophoresis electrospray ionization mass spectrometry with a nanospray interface.

A lab prototype CE-nanospray-MS platform with a high sensitivity porous sprayer was successfully applied in differential identification of Rhizoma coptidis in this paper. To obtain a stable and reliable nanospray, detailed optimizations about emitter geometry, buffer composition, emitter position, and spray voltage, as well as emitter cleanliness were discussed. Results showed that the reproducibility and sensitivity for separations of alkaloid standards were satisfactory using CE-nanospray-MS, which were also compared to ultra-HPLC (UHPLC)-MS. Their signal responds were at the same order of magnitude (intensities: 0.8 - 1.5 × 10(8) vs. 3.8 - 6.2 × 10(8) ), even though a 2 nL injection for CE was 2500-fold lower than UHPLC (5 µL injection). The absolute LOD results of CE-MS showed a remarkable superiority (18-24 fg), equal to 1000-fold lower than that of UHPLC-MS. Principal component analysis (PCA) of adulterated R. coptidis showed that this protocol had the ability to profile and qualify complex herb medicines, which also created a great potential for evaluation and qualification of rare and valuable Chinese medicines in future.

Extended and contorted conformations of alkanediammonium ions in symmetrical α,α',δ,δ'-tetramethylcucurbit[6]uril cavity.

Binding interactions between symmetrical α,α',δ,δ'-tetramethylcucurbit[6]uril (TMeQ[6]) and a series of alkyldiammonium ions in aqueous solution and in the solid state were investigated by (1)H NMR spectroscopy, MALDI-TOF mass spectrometry, X-ray crystallography, and isothermal titration calorimetry (ITC). Their (1)H NMR spectra reveal that the actual binding behaviors vary depending upon the alkyl chain length. Their single-crystal X-ray diffraction analyses indicate the guest 1,2-ethanediammonium is located outside of the TMeQ[6] portal, while the other four alkyldiammonium guests can be accommodated in the TMeQ[6] cavity, forming 1:1 inclusion complexes. Most importantly, the long-chain alkyldiammoniums (1,8-octanediammonium and 1,10-decanediammonium) take a contorted conformation when bound within the TMeQ[6] cavity. Additionally, ITC experiments show that the complexation of the alkyldiammonium guests with TMeQ[6] is mainly enthalpy driven, which benefits from ion-dipole interactions.

Analysis of endogenous nucleotides by single cell capillary electrophoresis-mass spectrometry.

Analytical technologies that enable investigations at the single cell level facilitate a range of studies; here a lab-fabricated capillary electrophoresis-electrospray ionization-mass spectrometry (CE-ESI-MS) platform was used to analyze anionic metabolites from individual Aplysia californica neurons. The system employs a customized coaxial sheath-flow nanospray interface connected to a separation capillary, with the sheath liquid and separation buffer optimized to ensure a stable spray. The method provided good repeatability of separation and reliable detection sensitivity for 16 mono-, di- and triphosphate nucleosides. For a range of anionic analytes, including cyclic adenosine monophosphate (cAMP), adenosine diphosphate (ADP) and adenosine triphosphate (ATP), the detection limits were in the low nanomolar range (<22 nM). A large Aplysia R2 neuron was used to demonstrate the ability of CE-ESI-MS to quantitatively characterize anionic metabolites within individual cells, with 15 nucleotides and derivatives detected. Following the method validation process, we probed smaller, 60 µm diameter Aplysia sensory neurons where sample stacking was used as a simple on-line analyte preconcentration approach. The calculated energy balance ([ATP] + 0.5 × [ADP])/([AMP] + [ADP] + [ATP]) of these cells was comparable with the value obtained from bulk samples.