Polysaccharide-based supramolecular drug delivery systems mediated via host-guest interactions of cucurbiturils

With excellent biocompatibility and biodegradability,natural polysaccharides and their derivative s have exhibited great potential in constructing drug delivery ve hicles for tissue engineering and therapeutics.Cucurbit[n]uril(CB [n])-mediated reversible crosslinking of polysaccharides possess intrinsic stimuliresponsiveness towards competitive guests and have been extensively investigated to fabricate various particles and hydrogels for multiple stimuli-re sponsive drug release by incorpo ration with other stimuli including photo,redox,and enzyme.Through host-guest interactions between CB[6] and aliphatic diamines,functional tags covalently connected with CB[6] can be readily anchored into polysaccharidebased hydrogels,realizing multiple functionalization.The rheological prope rty and drug release profile of polysaccharide-based supramolecular hydrogels can be facilely tuned through CB [8]-mediated dyna mic homo or hetero crosslinking of polysaccharides and/or other polymers.In this review,we introduce and summarize recent progress regarding polysaccharide-based supramolecular drug delivery systems mediated via host-guest interactions of CB[6] and CB[8],covering both bulk hydrogels and particular systems.At the end,possible utilization of CB[7]-based host-guest interactions in constructing polysaccharide-based drug delivery systems and future perspectives of this research direction are also discussed.     

Cucurbit[6]uril-based supramolecular frameworks assembled via the outer surface interaction of cucurbit[n]urils

Curcurbit[n]uril(Q[n])-based supramolecular frameworks(QSFs) constructed from the outer surface interaction of Q[n]s(OSIQ) have the characteristic of simplicity,diversity and modulability.Their simplicity is reflected in their simple composition and preparation methods used for QSFs.The diversity of supramolecular organic frameworks(SOFs) is reflected in the synthesis methods and structural characteristics of the as-obtained QSFs,as well as the variety of structural directing agents and basic building blocks used to prepare QSFs.The modulability is reflected by the controllable channel size in the QSFs,which can be adjusted using different sizes of Q[n]s.In this work,the first re ported cucurbituril Q[6]was selected as the basic building block and three Q[6]-based su p ramolecular frameworks were obtained from aqueous HCl solutions in the presence of [CdCl₄]^2-respectively.The OSIQs are the main driving forces for the formation of these frameworks.This study shows the diversity of the QSFs.     

Cucurbit[n]uril-calix[n]arene-based supramolecular frameworks assembled using the outer surface interactions of cucurbit[n]urils

Based on the crystal structures of two cucurbit[6]uril/calix[n]arene-based supramolecular frameworks reported by Long and co-workers,we further investigated the interactions of cucurbit[6]uril with 4-sulfocalix[4]arene and 4-sulfocalix[6]arene using ¹H NMR spectroscopy and isothermal titration calorimetry(ITC),respectively.Moreover,solid fluorescent materials were prepared via the adsorption of fluorescent dyes by these porous supramolecular frameworks,which exhibit a selective response to certain volatile organic compounds.     

瓜环基金属纳米催化剂的电化学研究进展（英文）

金属纳米材料在电催化应用中展示出良好的性能,但是它们依旧面临着稳定性差和调控策略有限的问题。引入第二组分是一种有效的策略,能够很好的改善其催化活性与稳定性。在这篇综述中,我们概述了结合金属纳米材料和瓜环（CB[n]）用于电催化应用。瓜环是一系列的具有刚性结构、高稳定性、与金属配位的官能团的大环,它们适合稳定金属纳米材料并对其进行调控。本文讨论按照瓜环的功能分类,包含瓜环作为保护剂、瓜环基的超分子自组装体以及瓜环作为前驱体制备氮掺杂多孔碳。多种金属纳米催化剂,包括金属纳米颗粒（Pt,Ir,Pd,Ru,Au）、金属单原子（Fe,Co,Ni）以及过渡金属碳化物（TMCs）成功与瓜环或瓜环衍生的碳材料复合,这些复合材料在许多电催化反应中展示出优异的性能和稳定性,反应包括了氧还原反应（ORR）、析氧反应（OER）、析氢反应（HER）、二氧化碳还原反应（CO2RR）、甲烷氧化反应（MOR）、乙醇氧化反应（EOR）。其中,一些金属-瓜环复合物可进一步作为双功能催化剂用于全水解和燃料电池中。瓜环基的纳米催化剂具有媲美商用催化剂的性能,甚至其稳定性可优于商用催化剂。实验分析以及密度泛函理论（DFT）计算...     

pH- and H2O2-sensitive drug delivery system based on sodium xanthate: Dual-responsive supramolecular vesicles from one functional group

Nano-drug delivery systems with multiple stimulus-responsive capabilities have superior response performance and efficient drug release. Nevertheless, it is sophisticated to construct multiple stimulus-responsive systems where the two or more functional groups need to be introduced simultaneously. Xanthate, one functional group with pH and H₂O₂ stimulus responsiveness, has significant potential applications for building dual-responsive drug delivery system. Herein, we present a novel dual stimuli-responsive supramolecular drug delivery system by using sodium xanthate derivative (SXD) as guest molecule and quaternary ammonium capped pillar[5]arene (QAP5) as host molecule through host-guest interaction on the basis of electrostatic interaction. The amphiphile QAP5?SXD could self-assemble into vesicles to efficiently load the anti-cancer drug DOX. The experimental results showed that QAP5?SXD nanoparticles could achieve efficient drug delivery and controlled release in the tumor microenvironment. Cytotoxicity experiments proved that DOX@QAP5?SXD nanoparticles could significantly improve the anticancer efficiency of free DOX on cancer cells. The present study provides an efficient strategy to develop supramolecular nanocarriers with dual-responsiveness in one functional group for controlled drug release.     

葫芦脲的研究进展

葫芦脲(CB[n])及其衍生物是由n个苷脲单元连接成的穴状分子,因其结构特殊,受到广泛的关注与研究。本文综述了CB[n]的性质、合成以及近年来CB[n]在分子开关、催化剂、药物载体等方面的研究进展。     

Water-soluble supramolecular polymers constructed by macrocycle-based host-guest interactions

Water soluble supramolecular polymers are especially important due to their superior biocompatibility and environmental adaptation, which determined they have wide applications in various areas, such as drug delivery, self-healing, shape memory. On the other hand, macrocyclic compounds are the most used building blocks in the preparation of supramolecular polymers. Macrocycle-based supramolecular polymers, which introduce the host-guest interaction in the system, endow these polymers with interesting and smart physicalchemical properties. In this review, we summarized recent studies about supramolecular polymers in aqueous solution based on macrocyclic compounds.     

Cucurbituril-modulated supramolecular assemblies: from cyclic oligomers to linear polymers

Employing bis(p-sulfonatocalix[4]arenes) (bisSC4A) and N',N'hexamethylenebis(1-methyl-4,4'-bipyridinium) (HBV(4+)) as monomer building blocks, the assembly morphologies can be modulated by cucurbit[n]uril (CB[n]) (n = 7, 8), achieving the interesting topological conversion from cyclic oligomers to linear polymers. The binary supramolecular assembly fabricated by HBV(4+) and bisSC4A units, forms an oligomeric structure, which was characterized by NMR spectroscopy, atomic force microscopy (AFM), transmission electron microscopy (TEM), dynamic light scattering (DLS), isothermal titration calorimetry (ITC), and gel permeation chromatography (GPC) experiments. The ternary supramolecular polymer participated by CB[8] is constructed on the basis of host-guest interactions by bisSC4A and the [2]pseudorotaxane HBV(4+)@CB[8], which is characterized by means of AFM, DLS, NMR spectroscopy, thermogravimetric analysis (TGA), UV/Vis spectroscopy, and elemental analysis. CB[n] plays vital roles in rigidifying the conformation of HBV(4+), and reinforcing the host-guest inclusion of bisSC4A with HBV(4+), which prompts the formation of a linear polymer. Moreover, the CB[8]-participated ternary assembly could disassemble into the molecular loop HBV(2+)@CB[8] and free bisSC4A after reduction of HBV(4+) to HBV(2+), whereas the CB[7]-based assembly remained unchanged after the reduction. CB[8] not only controlled the topological conversion of the supramolecular assemblies, but also improved the redox-responsive assembly/disassembly property practically.     

Recent development of pillar[n]arene-based amphiphiles

Pillar[n]arene-based amphiphiles,mainly including amphiphilic pillar[n]arenes and supra-amphiphilic pillar[n]arenes,have obtained considerable interests in recent years due to their fascinating chemical structures,various self-assembly behaviors,and widely applications.Thanks to the pillar-like frameworks and the rich host-guest recognitions of the cavities,these amphiphiles can be easily controlled to form dimensional and morphologic assemblies for multiple applications.Compared with traditional linear covalent amphiphiles,the introduction of host-guest recognitions facilitated the preparation and controllability of these supramolecular amphiphilic systems.Moreover,the host-guest recognitions endow the assemblies from pillar[n]arene-based amphiphiles with stimuli-responsive functions.In this mini-review,we summarized the chemical structures,self-assembly features,and the applications of pillar[n]arene-based amphiphiles.However,several research topics of pillar[n]arenebased amphiphiles can be further developed in the future,such as larger cavity amphiphilic pillar[n]arenes,co-assembly with 2 D materials and utilization of the host-guest interactions.     

A theoretical study of protonated OCnOH ions, n=3–8

Since ion-neutral reactions are a major component of the processes driving interstellar chemistry, most reaction network include protonated species. Besides, these ions are able to initiate chemical processes that would not occur with their neutral parents. In this contribution we report a systematic study of the protonated adducts of the OC_nO series (n=3–8) using the B3LYP level of theory. The structures of all possible O-protonated and C-protonated isomers of [OC_nOH⁺] have been determined together with their rotational constants, vibrational frequencies and intensities. Although it appears that these ions belong to two different series, odd-n and even-n, it is found that protonation occurs at the carbons second to the terminal oxygens for all n. The most stable structure is found to be the singlet ion whatever the singlet or triplet spin state of the parent species. However, due to the lack of efficient spin–orbit coupling, only the odd series [OC_nOH⁺] with n=3,5,7 should be formed on the singlet ground state surface. Analysis of the infrared intensities shows that the spectra are dominated by only one or two very strong bands (CC stretching) that carry most of the overall intensity in the 2200–2350 cm⁻¹ region.     

Cucurbit[10]uril-based chemistry

With the biggest cavity in the cucurbit[n]urils (CB[n]s) family, CB[10] has shown its unique molecular recognition properties. This review gives a brief summary of the research progresses in the CB[10]-based chemistry, involving its purification and applications in fields such as molecular recognition and molecular assembly.     

Aptamer-based self-assembled supramolecular vesicles for pH-responsive targeted drug delivery

Supramolecular vesicles have received great attention in biomedical application due to their inherent features, including simple synthesis and tunable amphiphilicity of the building blocks. Despite tremendous research efforts, developing supramolecular vesicles with targeted recognition and controlled release remains a major challenge. Herein, we constructed a novel aptamer-based self-assembled supramolecular vesicle by host-guest complexation of pyrene, viologen lipid, and cucurbit[8]urils for pH-responsive and targeted drug delivery. The proposed supramolecular vesicles are easy to be assembled and offer simple drug loading. Based on confocal fluorescence microscopy and cytotoxicity experiments, the drug-loaded supramolecular vesicles were shown to possess highly efficient internalization and apparent cytotoxic effect on target cancer cells, but not control cells. Furthermore, through simple aptamer or drug substitution, supramolecular vesicles can be applied to a variety of target cell lines and drugs, making it widely applicable. Taking advantage of the easy preparation, good stability, rapid pH response, and cell targeting ability, the aptamer-based self-assembled supramolecular vesicles hold great promise in controlled-release biomedical applications and targeted cancer therapy.     

葫芦[n]脲超分子水凝胶的研究进展

超分子化学的发展一直是众多研究者所关注的一大热点,葫芦[n]脲作为第四代大环主体分子,拓宽了超分子化学领域的发展。水凝胶是一种具有可拉伸性、生物相容性、环境响应性等多种优异性能的软材料。人们充分利用葫芦[n]脲优异的分子识别能力和配位能力,研究出了一系列具有特殊功能的超分子水凝胶材料。本文在结合葫芦[n]脲特点的基础上,着重论述了葫芦[n]脲水凝胶在(刺激响应性、粘附性、自愈合性)功能性材料、(药物传递、伤口敷料、仿生)生物医学材料、超分子发光材料等领域的研究前沿和动态,并且对葫芦[n]脲水凝胶的主要设计思路进行了讨论。最后,针对当前存在的问题以及未来可能的发展方向对葫芦[n]脲水凝胶的研究前景作出了展望。     

Probing the stability of multicomponent self-assembled architectures based on cucurbit[8]uril in the gas phase

Aqueous supramolecular chemistry and highly controlled self-assembly of multi-component architectures are novel tools for investigating and answering questions with different biological implications. Among other self-assembly motifs the barrel-shaped host molecule cucurbit[8]uril (CB[8]) is of particular interest due to its capability of incorporating two guest molecules simultaneously in its hydrophobic cavity. This allows for its use as a supramolecular linking unit to conjugate two different entities such as polymers, peptides, and proteins as well as conjugation of various species to surfaces, colloids and nanoparticles. This study aims to improve our understanding of CB[8] ternary complex formation and stability. A series of CB[8] architectures of different size and chemistry have been analyzed in the gas phase to obtain information about their stability in the absence of solvent effects. While hydrophobic effects and solvation energies play a crucial role for host-guest affinities in solution, gas phase stabilities are determined by the guest's ability to form hydrogen bonding and electrostatic interactions. Increasing the size of the second guest resulted in an increase of gas phase stability, likely due to additional non-covalent interactions.     

Switchable peptide-equipped protein/cucurbit[7]uril supramolecular assembly for targeted drug delivery

ABSTRACT

Herein, we develop a switchable peptide-equipped protein/cucurbit[7]uril (CB[7]) supramolecular assembly as novel targeted drug vector. Specifically, bovine serum albumin (BSA) is used to interact with CB[7], serving as the core of drug vector. Then, a peptide shield layer is formed on the surface of BSA/CB[7], yielding peptide-equipped supramolecular assembly (Pep@BSA@CB[7]). The equipped peptide shield layer is composed of switchable peptide probes consisting of a polycationic cell-penetrating peptide (CPP) motif, a polyanionic motif and a linking motif, and therefore provides a variety of desirable properties. First, the CPP motif displays excellent cell penetration ability and can facilitate internalisation of the drug vector. Secondly, the polyanionic motif performs intramolecular electrostatic interaction with CPP motif and thereby can reduce non-targeted delivery towards normal cells. Thirdly, the linking motif can be specifically cleaved by matrix metalloproteinases 2 that is up-regulated in tumour microenvironment, thus enabling precise cancer-targeting. As a consequent, Pep@BSA@CB[7] can serve as a promising drug vector that exhibits superior targeting ability and high uptake efficiency towards cancer cells, which may be of great potential in cancer-targeted treatment.     

Supramolecular interaction of cucurbit[n]urils and coptisine by spectrofluorimetry and its analytical application

The supramolecular interaction of a homologous series of cucurbit[n]uril (CB[n], n = 5, 6, 7, 8) hosts and coptisine (COP) was studied by spectrofluorimetry. All of the CB[n]s were found to react with COP to form 1:1 host-guest stable complexes and the fluorescence intensity of the complexes was greatly enhanced. The apparent association constants of the complexes were 1.44 × 10⁴, 1.28 × 10⁴, 1.86 × 10⁴ and 1.26 × 10⁴ L mol⁻¹ for CB[5], CB[6], CB[7] and CB[8], respectively. In addition, CB[5] and CB[7] exhibited a higher fluorescence signal than CB[6] and CB[8]. The fluorescence intensity of the complex with CB[7] was enhanced 70-fold compared to that of the studied drug itself. Based on the significant enhancement of fluorescence intensity of supramolecular complex, a simple, rapid, highly sensitive, and selective spectrofluorimetric method was developed for the determination of COP in aqueous solution in the presence of CB[7]. At the optimum reaction conditions, a linear relationship was obtained in the range from 0.05 to 1700 ng mL⁻¹ with a detection limit of 0.012 ng mL⁻¹. The proposed method was successfully applied for the determination of the drug in urine and serum samples.     

Probing the kinetics in supramolecular chemistry and molecular assembly by microfluidic-NMR spectroscopy

Microfluidic-NMR spectroscopy has been extended to study the kinetics in supramolecular chemistry and molecular assembly. Kinetics of a multicomponent host-guest supramolecular system containing viologen derivatives, β-cyclodextrins and cucurbit [7]urils are studied by a PMMA based microfluidic chip combined with a dedicated transmission line probe for NMR detection. By combining microfluidic technology with NMR spectroscopy, the amount of material required for a full kinetic study could be minimized. This is crucial in supramolecular chemistry, which often involves highly sophisticated and synthetically costly building blocks. The small size of the microfluidic structure is crucial in bringing the time scale for kinetic monitoring down to seconds. At the same time, the transmission line NMR probe provides sufficient sensitivity to work at low (2 mM) concentrations.     

Cucurbit[n]urils for Supramolecular Catalysis

The control over chemical reactivity and selectivity are always pursued. Using non-covalent interactions to achieve efficient and selective catalysis is an essential goal of supramolecular catalysis. Supramolecular catalysis based on cucurbit[n]urils (CB[n]s) possesses distinct characteristics for the unique structure of CB[n]s. CB[n]s are a family of pumpkin-shaped host molecules with various molecular sizes, rigid structures, electronegative portals and wealthy host-guest chemistry. Herein, we summarize the three major mechanisms of CB[n]s based supramolecular catalysis. Owing to the structural properties of CB[n]s, CB[n]s can serve as nanoreactors and steric hindrance to modulate the reactivity of substrates. They can also catalyze the reactions by modulating the reactivity of ionized intermediates. Recent progresses on the CB[n]s based supramolecular catalysis are introduced in this Minireview and the future development in this field is discussed. It is anticipated that this review provides insights into the mechanism of CB[n]s based supramolecular catalysis and may help scientists find new opportunities in this field.     

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[8]uril (CB[8])‐Based Supramolecular Switches

The use of cucurbit[8]uril as a molecular host has emerged in the chemical literature as a reliable strategy for the creation of dynamic chemical systems, owing to its ability to form homo‐ and heteroternary complexes in aqueous media with appropriate molecular switches as guests. In this manner, CB[8]‐based supramolecular switches can be designed in a predictable and modular fashion, through the selection of appropriate guests able to condition the redox, photochemical, or pH‐triggered behavior of tailored multicomponent systems. Furthermore, CB[8] allows the implementation of dual/triple and linear/orthogonal stimuli‐dependent properties into these molecular devices by a careful selection of the guests. This versatility in their design gives these supramolecular switches great potential for the rational development of new materials, in which their function is not only determined by the custom‐made stimuli‐responsiveness, but also by the transient aggregation/disaggregation of homo‐ or heteromeric building blocks.