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.     

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.     

Modulating the Nucleated Self‐Assembly of Tri‐β3‐Peptides Using Cucurbit[n]urils

The modulation of the hierarchical nucleated self‐assembly of tri‐β³‐peptides has been studied. β³‐Tyrosine provided a handle to control the assembly process through host‐guest interactions with CB[7] and CB[8]. By varying the cavity size from CB[7] to CB[8] distinct phases of assembling tri‐β³‐peptides were arrested. Given the limited size of the CB[7] cavity, only one aromatic β³‐tyrosine can be simultaneously hosted and, hence, CB[7] was primarily acting as an inhibitor of self‐assembly. In strong contrast, the larger CB[8] can form a ternary complex with two aromatic amino acids and hence CB[8] was acting primarily as cross‐linker of multiple fibers and promoting the formation of larger aggregates. General insights on modulating supramolecular assembly can lead to new ways to introduce functionality in supramolecular polymers.     

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...     

Highly Enhanced Fluorescence of Supramolecular Polymers Based on a Cyanostilbene Derivative and Cucurbit[8]uril in Aqueous Solution

Supramolecular polymers (SPs) have received great attention because of their potential for various practical applications. As part of our search for SPs that are highly fluorescent in aqueous media, we designed a system based on a cucurbit[8]uril (CB[8]) host and a newly designed cyanostilbene guest. Fluorescence quantum yields of ≈0 % in the disassembled monomer state and 91 % in the CB[8]‐induced SP state were obtained. The intriguing photophysical properties of the SP are elucidated through detailed experimental and computational analysis, paving the way towards a fascinating class of water‐soluble fluorescent SPs.     

Surface‐Bound Cucurbit[8]uril Catenanes on Magnetic Nanoparticles Exhibiting Molecular Recognition

We demonstrate the preparation of surface‐bound cucurbit[8]uril (CB[8]) catenanes on silica nanoparticles (NPs), where CB[8] was employed as a tethered supramolecular “handcuff” to selectively capture target guest molecules. In this catenane, CB[8] was threaded onto a methyl viologen (MV²⁺) axle and immobilized onto silica NPs. The formation of CB[8] catenanes on NPs were confirmed by UV/Vis titration experiments and lithographic characterization, demonstrating a high density of CB[8] on the silica NPs surface, 0.56 nm^?2. This CB[8] catenane system exhibits specific molecular recognition towards certain aromatic molecules such as perylene bis(diimide), naphthol and aromatic amino acids, and thus it can act as a nanoscale molecular receptor for target guests. Furthermore, we also demonstrate its use as an efficient and recyclable nano‐platform for peptide separation. By embedding magnetic NPs inside silica NPs, separation could be achieved by simply applying an external magnetic field. Moreover, the peptides captured by the catenanes could be released by reversible single‐electron reduction of MV²⁺. The entire process demonstrated high recoverability.     

Supramolecular Recognition of Amino Acids by Twisted Cucurbit[14]uril

Binding interactions between twisted cucurbit[14]uril (tQ[14]) and twenty standard amino acids (AAs) have been investigated by NMR spectroscopy and isothermal titration calorimetry (ITC) in aqueous HCl solutions and in DMSO. The results showed that tQ[14] displays clear binding affinity for AAs with a positively charged side chain or containing an aromatic ring, but weaker binding affinity for AAs with hydrophobic or polar side chains, with the binding mode depending on the type of side chain present in the AAs.     

Acid‐Labile Acyclic Cucurbit[n]uril Molecular Containers for Controlled Release

Stimuli‐responsive molecular containers are of great importance for controlled drug delivery and other biomedical applications. A new type of acid labile acyclic cucurbit[n ]uril (CB[n ]) molecular containers is presented that can degrade and release the encapsulated cargo at accelerated rates under mildly acidic conditions (pH 5.5–6.5). These containers retain the excellent recognition properties of CB[n ]‐type hosts. A cell culture study demonstrated that the cellular uptake of cargos could be fine‐tuned by complexation with different containers. The release and cell uptake of cargo dye was promoted by acidic pH.     

Cucurbit[7]uril⋅Guest Pair with an Attomolar Dissociation Constant

Host?guest complexes between cucurbit[7] (CB[7]) or CB[8] and diamantane diammonium ion guests 3 or 6 were studied by ¹H NMR spectroscopy and X‐ray crystallography. ¹H NMR competition experiments revealed that CB[7]? 6 is among the tightest monovalent non‐covalent complexes ever reported in water with K_a=7.2×10¹⁷ M ^?1 in pure D₂O and 1.9×10¹⁵ M ^?1 in D₂O buffered with NaO₂CCD₃ (50 mM ). The crystal structure of CB[7]? 6 allowed us to identify some of the structural features responsible for the ultratight binding, including the distance between the NMe₃⁺ groups of 6 (7.78 Å), which allows it to establish 14 optimal ion‐dipole interactions with CB[7], the complementarity of the convex van der Waals surface contours of 6 with the corresponding concave surfaces of CB[7], desolvation of the C?O portals within the CB[7]? 6 complex, and the co‐linearity of the C₇ axis of CB[7] with the N⁺???N⁺ line in 6 . This work further blurs the lines of distinction between natural and synthetic receptors.     

Stimuli‐Responsive Cucurbit[7]uril‐Mediated BSA Nanoassembly for Uptake and Release of Doxorubicin

We report the construction of a non‐toxic nanoassembly of bovine serum albumin (BSA) protein and the cucurbit[7]uril macrocycle as well as its stimuli‐responsive breakage with adamantylamine or pH, which restores the protein structure and recognition properties. The assembly showed efficient loading and controlled release of a standard drug, doxorubicin (DOX), and the same was validated in live cells. The cell viability studies documented that the DOX‐loaded assembly mask the cytotoxicity of DOX and the toxicity can be revived at the target on demand, triggering its therapeutic activation. This is found to be more effective in the cancer cells. In addition, such host‐assisted protein assemblies are also highly promising for stabilizing/protecting the native protein structure, a viable approach to prevent/inhibit protein misfolding and aggregation.     

Dynamic Interfacial Adhesion through Cucurbit[n]uril Molecular Recognition

Supramolecular building blocks, such as cucurbit[n]uril (CB[n])‐based host–guest complexes, have been extensively studied at the nano‐ and microscale as adhesion promoters. Herein, we exploit a new class of CB[n]‐threaded highly branched polyrotaxanes (HBP‐CB[n]) as aqueous adhesives to macroscopically bond two wet surfaces, including biological tissue, through the formation of CB[8] heteroternary complexes. The dynamic nature of these complexes gives rise to adhesion with remarkable toughness, displaying recovery and reversible adhesion upon mechanical failure at the interface. Incorporation of functional guests, such as azobenzene moieties, allows for stimuli‐activated on‐demand adhesion/de‐adhesion. Macroscopic interfacial adhesion through dynamic host–guest molecular recognition represents an innovative strategy for designing the next generation of functional interfaces, biomedical devices, tissue adhesives, and wound dressings.     

High Affinity Recognition of a Selected Amino Acid Epitope within a Protein by Cucurbit[8]uril Complexation

Supramolecular interactions between the host cucurbit[8]uril (CB[8]) and amino acids have been widely interrogated, but recognition of specific motifs within a protein domain have never been reported. A phage display approach was herein used to select motifs with the highest binding affinity for the heteroternary complex with methyl viologen and CB[8] (MV?CB[8]) within a vast pool of cyclic peptide sequences. From the selected motifs, an epitope consisting of three amino acid was extrapolated and incorporated into a solvent‐exposed loop of a protein domain; the protein exhibited micromolar binding affinity for the MV?CB[8] complex, matching that of the cyclic peptide. By achieving selective CB[8]‐mediated conjugation of a small molecule to a recombinant protein scaffold we pave the way to biomedical applications of this simple ternary system.     

Applications of Pillar[n]arene‐Based Supramolecular Assemblies

Macrocycles are an important player in supramolecular chemistry. In 2008, a new class of macrocycles, “pillar[n]arenes”, were first discovered. Research efforts in the area of pillar[n]arenes have elucidated key properties, such as their shape, reaction mechanism, host–guest properties, and their versatile functionality, which has contributed to the development of pillar[n]arene chemistry and their applications to various fields. This Minireview describes how pillar[n]arene‐based supramolecular assemblies can be applied to supramolecular gel formation, reactions, light‐harvesting systems, drug‐delivery systems, biochemical applications, separation and storage materials, and surface chemistry.     

Investigation of Host–Guest Compounds of Cucurbit[n=5–8]uril with Some Ortho Aminopyridines and Bispyridine

Host–guest complexes of cucurbit[n=5–8]uril and some examples of ortho substituted pyridines or aminopyridines were examined by ¹H NMR spectroscopy. Portal binding of two ortho aminopyridine free bases, by cucurbit[5]uril, was observed in ¹H NMR spectra. Combined cavity and portal binding in cucurbit[6]uril were observed for both the free base 2-aminomethylpyridine, ampy, the HCl salt, ampy·1HCl, and the salt of 2,2′-bispyridine, bpy·1HCl. Two novel complexes were formed with cucurbit[6]uril. The free base ampyas a dual occupant, formed a 2:1 complex, and bpy·1HCl formed a stable asymmetric 1:1 complex. Only portal binding of 2,6-bisaminomethylpyridine and its salts was observed for cucurbit[6]uril. Fast exchange of the free base and pyridineammonium salts was observed for cucurbit[7-8]uril.This revised version was published online in July 2005 with a corrected issue number.     

A Nexus between Theory and Experiment: Non‐Empirical Quantum Mechanical Computational Methodology Applied to Cucurbit[n]uril⋅Guest Binding Interactions

A training set of eleven X‐ray structures determined for biomimetic complexes between cucurbit[n]uril (CB[7 or 8]) hosts and adamantane‐/diamantane ammonium/aminium guests were studied with DFT‐D3 quantum mechanical computational methods to afford ΔG_calcd binding energies. A novel feature of this work is that the fidelity of the BLYP‐D3/def2‐TZVPP choice of DFT functional was proven by comparison with more accurate methods. For the first time, the CB[n] ? guest complex binding energy subcomponents [for example, ΔE_dispersion, ΔE_{electrostatic}, ΔG_solvation, binding entropy (?TΔS), and induced fit E_{deformation(host)}, E_{deformation(guest)}] were calculated. Only a few weeks of computation time per complex were required by using this protocol. The deformation (stiffness) and solvation properties (with emphasis on cavity desolvation) of cucurbit[n]uril (n=5, 6, 7, 8) isolated host molecules were also explored by means of the DFT‐D3 method. A high ρ²=0.84 correlation coefficient between ΔG_exptl and ΔG_calcd was achieved without any scaling of the calculated terms (at 298 K). This linear dependence was utilized for ΔG_calcd predictions of new complexes. The nature of binding, including the role of high energy water molecules, was also studied. The utility of introduction of tethered [‐(CH₂)_nNH₃]⁺ amino loops attached to N,N‐dimethyl‐adamantane‐1‐amine and N,N,N′,N′‐tetramethyl diamantane‐4,9‐diamine skeletons (both from an experimental and a theoretical perspective) is presented here as a promising tool for the achievement of new ultra‐high binding guests to CB[7] hosts. Predictions of not yet measured equilibrium constants are presented herein.     

Supramolecular Crystal Networks Constructed from Cucurbit[8]uril with Two Naphthyl Groups

Naphthyl groups are widely used as building blocks for the self-assembly of supramolecular crystal networks. Host–guest complexation of cucurbit[8]uril (Q[8]) with two guests NapA and Nap1 in both aqueous solution and solid state has been fully investigated. Experimental data indicated that double guests resided within the cavity of Q[8], generating highly stable homoternary complexes NapA₂@Q[8] and Nap1₂@Q[8]. Meanwhile, the strong hydrogen-bonding and π···π interaction play critical roles in the formation of 1D supramolecular chain, as well as 2D and 3D networks in solid state.