Stimuli-Responsive Cucurbit[n]uril-Mediated Host-Guest Complexes on Surfaces

Supramolecular functional surfaces are at the heart of many materials and medical applications. Increasing interest can be seen for devising new supramolecular functionalization strategies of surfaces. In this review we place particular emphasis on the use of cucurbit[n]uril-mediated host-guest complexation as surface functionalization strategy. The state of the art of cucurbit[n]uril-mediated host-guest complexes on surfaces is reviewed. Cucurbit[n]urils (CB[n]) are able to form strong host-guest complexes with affinities that span several orders of magnitudes up to the regime of the biotin-streptavidin pair and that can be modulated by applying remote stimuli provided suitably sensitive guests were selected. Strategies to fabricate stimuli-responsive surfaces creates versatile supramolecular systems and several applications of these types of surfaces are outlined.     

Inclusion Complexes of Hymexazol with Three Different Cucurbit[n]uril: Preparation,and Physicochemical and Antifungal Characterization

Host-guest inclusion complexes of hymexazol with three different cucurbit[n]uril, cucurbit[7]uril (Q[7]), hemimethyl-substituted cucurbit[6]uril (HHMeQ[6]), and twisted cucurbit[14]uril (tQ[14]) have been investigated by means of ¹H NMR spectroscopy, quadrupole-time of flight mass spectrometry (Q-TOF), and isothermal titration calorimetry (ITC). ¹H NMR experimental results revealed that hymexazol resides within the respective cavities of the selected Q[n], and mass spectrometric experimental results revealed that it interacts with these three Q[n] through the formation of 1 : 1 inclusion complexes. ITC experimental results indicated moderate binding constants. In vitro assays showed that the complexation of hymexazol by the Q[n] increased its inhibitory effect on the mycelia growth of Botrytis cinerea Pers.     

Recent Progress in Gas Phase Cucurbit[n]uril Chemistry

Cucurbit[n]urils (CB[n]s) are of great significance due to their unique molecular recognition properties and their potential applications in areas such as drug delivery or analytical assays. Gas phase studies, without interference from solvents or counterions, provide fundamental insights into the mechanism of CB[n] complex formation and binding. In this paper, we review the progress in gas phase CB[n] chemistry, mainly based on mass spectrometry, since 2011, including important discoveries in structural studies, mechanistic studies, and gas phase studies related to analytical or clinical applications of CB[n]s. We expect the use of gas phase methods to continue to expand and diversify.     

Cucurbit[n]urils-related Multitopic Supramolecular Components: Design,Properties, and Perspectives

Cucurbit[n]urils (CBns) are an intriguing family of macrocyclic hosts whose chemistry has undergone rapid developments in recent decades. The initial interest in the synthesis, modifications and binding properties has shifted to areas focused on applications in drug storage, delivery, and release, external-stimuli responsive devices, and molecular nano-reactors. Since CBns are fruitfully complemented by cyclodextrins (CDs) in such systems, guest molecules that contain several binding sites are needed. These multitopic guests provide not only a scaffold for holding CBns and CDs together in appropriate arrangements but also allow for manipulation with supramolecular aggregates, e. g., reorganization or release of macrocycles. In this review, we summarize recent studies related to the design of multitopic guests. Binding motifs properties, the role of attractive or repulsive lateral interactions, the competition-compensation effect, and rotaxane versus pseudorotaxane manner are discussed.     

Acyclic Cucurbit[n]uril-type Receptors: Preparation,Molecular Recognition Properties and Biological Applications

This article traces the development of acyclic cucurbit[n]uril-type receptors with a focus on work from the Isaacs group. First, we describe the synthesis of methylene bridged glycoluril dimers capped with aromatic sidewalls which allowed us to probe the interconversion of the S- and C-shaped dimers which is a fundamental step in CB[n] formation. The C-shaped compounds were found to undergo discrete self-assembly (dimerization) in both water and organic solvents which lead us to investigate multicomponent self-sorting systems. We supressed the self-association of 8 by electrostatic repulsion in the putative dimer which allowed expression of its innate molecular recognition properties toward methylene blue and related planar cationic dyes. Longer glycoluril oligomers (trimer-hexamer, acyclic decamer) were prepared by starving the CB[n]-forming reaction of formaldehyde. The longer oligomers (e. g. 15 and 16 ) bind to alkylammonium ions in water ≈100-fold weaker than macrocyclic CB[n] highlighting the high preorganization of the acyclic but polycyclic framework. We prepared a wide variety of acyclic CB[n] compounds (wall variants, solubilizing group variants, linker variants) based on glycoluril trimer and tetramer. In particular, 26 and 27 have been shown to possess a wide variety of chemically and biologically interesting functions. For example, 26 was used to formulate the insoluble drug Albendazole and treat mice bearing SK-OV-3 xenograft tumors. Compound 27 binds tightly to the neuromuscular blocking agents rocuronium, vecuronium, and cisatracurium and acts as an in vivo reversal agent for these compounds in anesthetized rats. Container 27 was also found to modulate the hyperlocomotive effect of rats that had been treated with methamphetamine. Finally, 38 has been used as a cross reactive component of sensor arrays that are capable of classifying and quantifying cancer related nitroamine and a range of over the counter drugs. Overall, the work demonstrates that acyclic CB[n]-type compounds are nicely pre-organized and therefore retain the essential aspects of the recognition properties of macrocyclic CB[n] but allow for more straightforward tailoring of structure and solubility that enables a variety of chemically and biologically important applications.     

Potential Applications of Cucurbit[n]urils Inclusion Complexes in Photodynamic Therapy

Cucurbit[n]urils (CB[n]s) have emerged as potential candidates for drug delivery in several areas due to their strong binding interactions and low toxicity. More recently, their benefits for a type of cancer treatment termed Photodynamic Therapy (PDT) have been recognized. The outcomes of this therapy rely on better drug delivery strategies and improving overall photoactivity of the drugs, which is where CB[n]s could have a strong impact. The effects of these molecular containers on photoactivity are discussed and new interesting work is highlighted.     

Supramolecular Analysis of Monosaccharide Derivatives Using Cucurbit[7]uril and Electrospray Ionization Tandem Mass Spectrometry

Identification of monosaccharide derivatives using an analytical technique is difficult due to their isomeric structures and similar physical properties. Although mass spectrometry (MS) has emerged as a prominent technique for this purpose, a comprehensive MS-based method for analyzing diverse monosaccharide species is yet to be developed. Herein, we employ host-guest chemistry using cucurbit[7]uril (CB[7]) with MS to identify four different monosaccharide derivative species. Tandem MS analysis distinguishes the monosaccharide derivatives based on the unique fragmentation pattern produced when forming gas-phase complexes with CB[7]. The ion mobility studies combined with computational calculations reveal that subtle differences in isomers cause distinct orientations inside CB[7] cavity, resulting in different fragmentation patterns of the isomers. This unique study demonstrates that host-guest chemistry combined with MS can be used for developing effective isomer analysis techniques.     

The Effect of Cucurbit[7]uril on the Antitumor and Immunomodulating Properties of Oxaliplatin and Carboplatin

Cucurbit[7]uril (CB[7]) is a molecular container that may form host–guest complexes with platinum(II) anticancer drugs and modulate their efficacy and safety. In this paper, we report our studies of the effect of CB[7]–oxaliplatin complex and the mixture of CB[7] and carboplatin (1:1) on viability and proliferation of a primary cell culture (peripheral blood mononuclear cells), two tumor cell lines (B16 and K562) and their activity in the animal model of melanoma. At the same time, we studied the impact of platinum (II) drugs with CB[7] on T cells and B cells in vitro. Although the stable CB[7]–carboplatin complex was not formed, the presence of cucurbit[7]uril affected the biological properties of carboplatin. In vivo, CB[7] increased the antitumor effect of carboplatin, but, at the same time, increased its acute toxicity. Compared to free oxaliplatin, its complex with CB[7] shows a greater cytotoxic effect on tumor cell lines B16 and K562, while in vivo, the effects of the free drug and encapsulated drug were comparable. However, in vivo studies also demonstrated that the encapsulation of oxaliplatin in CB[7] lowered the toxicity of the drug.     

对称四甲基六元瓜环与2-戊基苯并咪唑盐酸盐自组装包合物晶体结构

以对称四甲基六元瓜环(TMeQ[6])为主体,2-戊基苯并咪唑盐酸盐(PB)为客体,在水溶液中自组装形成主客体超分子化合物{PB@TMeQ[6]}.Cl.9(H2O),利用X-射线单晶衍射技术对化合物的晶体结构进行了表征。实验结果表明,主客体之间通过多种非共价键作用形成1∶1的主客体包合物,客体的芳环被瓜环包结于空腔内,烷基置于瓜环端口外侧,包合物结构单元之间与共用水分子通过氢键连接成一维超分子链。     

利用八元瓜环Q[8]的荧光增敏作用测定药品中盐酸小檗碱含量

八元瓜环Q[8]对盐酸小檗碱的荧光有较好的增敏作用,用来测定复方黄连素片和盐酸小檗碱片中盐酸小檗碱(C20H18C lNO4)的含量。在电压700V,λex=345.07nm,λem=498.07nm的条件下,测定结果表明:盐酸小檗碱在2×10-8mol/L~1×10-5mol/L之间具有良好的线性关系,加样回收率在97%~103%之间,相对标准偏差(RSD)在1.5%以内。方法适用于盐酸小檗碱含量的测定。     

光度法考察八元瓜环与金橙G、亚甲基蓝的作用

利用紫外可见吸收光谱法考察了八元瓜环与金橙G和亚甲基蓝的相互作用情况。考察了溶液的酸度对作用体系的影响。结果表明,八元瓜环与客体的相互作用随客体及溶液pH的不同而有所改变。在pH=1～12的范围内,八元瓜环与金橙G作用明显,形成稳定的2：1的主客体包结配合物;而八元瓜环与亚甲基蓝（g4）的相互作用则在pH=1～10的范...     

Molecular Recognition of Amino Acids,Peptides, and Proteins by Cucurbit[n]uril Receptors

At the forefront of the endeavor to understand and manipulate living systems is the design and study of receptors that bind with high affinity and selectivity to specific amino acids, peptides, and proteins. Cucurbit[n]urils are among the most promising class of synthetic receptors for these targets due to their high affinities and selectivities in aqueous media and to the unique combination of electrostatic and hydrophobic interactions that govern binding. The fundamental supramolecular chemistry in this area has been explored in depth, and novel, useful applications are beginning to emerge.     

Dynamic supramolecular polymers built from cucurbit[n]urils and viologens

This review article focuses on supramolecular assemblies involving cucurbit[n]uril‐based containers and viologen guests as key building elements. Cucurbit[n]urils (CB[n], n = 5–8,10) are fascinating hosts forming a wide range of inclusion complexes (caviplexes) with 4,4′‐bipyridinium salts, known as viologens, either as discrete 1:1 inclusion compounds with CB[7] or as ternary inclusion compounds involving two hosts or two guests (2:1 with CB[7] and 1:2 or 1:1:1 with CB[8]). This property is currently being actively exploited to design and prepare self‐assembled dynamic stimuli‐responsive supramolecular polymers including gels, vesicles, films and organized arrays of polymeric microspheres or nanoparticles. This review highlights the main benefits of such polymers and gives an overview of the achievements and progress made in this field over the past decades. © 2018 Society of Chemical Industry     

Advanced Functional Materials Constructed from Pillar[n]arenes

Pillar[n]arenes are new generation of supramolecular macrocyclic host, which exhibit excellent host−guest recognition properties. In the last decade, functional materials constructed from pillar[n]arenes have been attracted more and more attention and displayed outstanding characteristics, such as stimuli-responsiveness, self-healing and adaptability. In this mini-review, we provide a survey of the pillar[n]arene-based literatures covering light-harvesting systems, functional hydrogels, and solid materials. It is anticipated that more and more pillar[n]arenes-based advanced materials with multi-functional properties will appear in the near future.     

Chemical Sensors Based on Cucurbit[n]uril Macrocycles

Cucurbit[n]urils (CBn) are glycoluril-based macrocyclic hosts that bind many biologically, medicinally and environmentally relevant analytes with record high affinities in aqueous media. They are therefore prime candidates for the design of chemosensors that are operational in biological fluids, waste and drinking water and have promising potential to be utilized for in vitro and in vivo sensing and imaging applications. Unlike protein-based antibodies, CBn can be prepared in multi kilogram scales, they are chemically robust and they show a desired fast analyte-binding kinetics. Unlike protein-based antibodies, CBn can be prepared in multi kilogram scales, are chemically robust and show a desired fast analyte-binding kinetics Selective analyte detection and differentiation is possible owing to the charge- and size-selective binding characteristics of the CBn members and due to the wide range of cyclic and acyclic CBn derivatives that differ in their analyte binding preference. Because CBn hosts are spectroscopically silent in the visible electromagnetic spectrum, optical signal transduction with CBn based chemosensing ensembles is typically performed by indicator displacement assays (IDA), which are easy to implement and applicable to both aliphatic and aromatic analytes. The extension to array-based sensing with CBn chemosensors is straightforward. Associative binding assays (ABA), which are uniquely available with CB8-based self-assembled receptors offer superior analyte differentiation possibility due to emerging spectral fingerprints in the absorbance, circular dichroism (CD) and emission spectra for the receptor•analyte complexes. Direct signal generation is promising for inherently spectroscopically active analytes, for instance through absorbance, CD, emission and surface enhanced Raman spectroscopy (SERS). Sensitive NMR (¹⁹F, ¹²⁹Xe) techniques, electron spin resonance (ESR), redox, and mass spectrometry are also valuable signal transduction options for specific analytes. CBn based chemosensors were successfully utilized for the monitoring of biophysical processes and enzymatic reactions with label free analytes or substrates in real time. These applications capitalize on the fast equilibration kinetics of CBn-analyte complexes and the bio-compatibility of CBn hosts. The tabulated large body of data extracted from reported CBn-based binding studies is hoped to provide the reader with a valuable starting point for designing practically applicable CBn-based sensors.     

A Fluorescent Unnatural Mannosamine Derivative with Enhanced Emission Upon Complexation with Cucurbit[7]uril

Metabolic incorporation of unnatural functionality on glycans has allowed chemical biologists to observe and affect cellular processes. Recent work has resulted in glycan-fluorophore structures that allow for direct visualization of glycan-mediated processes, shining light on their role in living systems. This work describes the serendipitous discovery of a small chemical reporter-fluorophore. Investigations into the mechanism of fluorescence arising from (trimethylsilyl)methylglycine appended on mannosamine suggest rigidity and restriction of lone pair geometry contribute to the fluorescent behaviour. In fact, in situ cyclization and encapsulation in cucurbit[7]uril enhance fluorescence to levels that can be observed in live cells. While the reported unnatural mannosamine does not traverse the sialic acid biosynthetic pathway, this discovery may lead to small, “turn-on” chemical reporters for incorporation in living systems.     

Application of a novel organic nucleating agent: Cucurbit[6]uril to improve polypropylene injection foaming behavior and their physical properties

In this study, polypropylene (PP) foams were prepared with cucurbit[6]uril (Q[6]) used as a novel nucleating agent through a microcellular injection molding foaming process. The effect of Q[6] content (0.5–2.0 wt %) on the foaming behavior, as well as thermal, rheological and mechanical characterizations of the PP/Q[6] (PQ) samples were performed. According to scanning electron microscopy (SEM) images, the microstructure of foams exhibited a smaller cell size, higher cell density, and more homogeneous distribution of cells at a higher Q[6] content. It was found that the peak temperature of crystallization, the crystallinity and the crystallization rate of PP can be obviously improved by adding a low content of Q[6] (0.25–1.0 wt %), whereas further increasing the content of Q[6] (2.0 wt %) would disfavor the effect. With increasing the Q[6] concentration, the PQ composites had higher complex viscosities at low frequencies and higher modulus than that of PP except the content of 2.0 wt %. Furthermore, the introduction of Q[6] into PP can produce a mild increase in tensile strength, flexural strength and impact strength of PQ foams. This can be due to the well dispersion of Q[6], good compatibility between PP and Q[6], as well as the improvement of the cell morphology. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 134, 44538.     

Terpenes Show Nanomolar Affinity and Selective Binding with Cucurbit[8]uril

Eucalyptol, fenchyl alcohol, and geranylamine were tested for the binding to cucurbit[8]uril. Nanomolar affinities were found, giving rise to a highly selective binding of the terpenes by cucurbit[8]uril when compared to the smaller cucurbit[7]uril. This was rationalized with a better size fit with the larger macrocycle. These notions were supported by the calculation of the packing coefficient and NMR measurements of the free and complexed terpenes. The binding process is mainly enthalpically driven, which is associated with the release of high-energy water.     

微胶囊技术应用于纺织染整研究进展

概述印染行业对水资源的污染和染色工作者围绕清洁生产所做的努力。介绍了目前国内外在微胶囊染料的研究动态、性能特点和使用效果,同时也展现了我们在瓜环与酸性金黄G相互作用的初步研究。     

Nitroxide Radicals with Cucurbit[n]urils and Other Cavitands

The interface of nitroxide radicals with cucurbit[n]urils (CB[n]) is covered in this review. Either used as spin probes, spin labels, or stoppers for paramagnetic rotaxanes, nitroxides offer new opportunities to investigate CB[n] and their inclusion complexes, especially thanks to EPR spectroscopy. On the other hand, CB[n] also offer interesting opportunities to modulate nitroxide properties such as protection or structuring. The multiple back and forth between the two well-established areas where nitroxides bring information about CB[n], and CB[n] modulate nitroxide properties, have enabled to shed some light at this new interesting interface.