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.     

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.     

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.     

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.     

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.     

Uptake of Hydrocarbons in Aqueous Solution by Encapsulation in Acyclic Cucurbit[n]uril‐Type Molecular Containers

The ability of two water‐soluble acyclic cucurbit[n]uril (CB[n]) type containers, whose hydrophobic cavity is defined by a glycoluril tetramer backbone and terminal aromatic (benzene, naphthalene) sidewalls, to act as solubilizing agents for hydrocarbons in water is described. ¹H NMR spectroscopy studies and phase‐solubility diagrams establish that the naphthalene‐walled container performs as well as, or better than, CB[7] and CB[8] in promoting the uptake of poorly soluble hydrocarbons into aqueous solution through formation of host–hydrocarbon complexes. The naphthalene‐walled acyclic CB[n] container is able to extract large hydrocarbons from crude oil into aqueous solution.     

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.     

Photoresponsive Hybrid Raspberry‐Like Colloids Based on Cucurbit[8]uril Host–Guest Interactions

Hybrid raspberry‐like colloids (HRCs) were prepared by employing cucurbit[8]uril (CB[8]) as a supramolecular linker to assemble functional polymeric nanoparticles onto a silica core. The formed HRCs are photoresponsive and can be reversibly disassembled upon light irradiation. This facile supramolecular approach provides a platform for the synthesis of colloids with sophisticated structures and properties.     

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.     

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.     

Monoester Copillar[5]arenes: Synthesis,Unusual Self‐Inclusion Behavior,and Molecular Recognition

The self‐inclusion behavior of monoester copillar[5]arenes depends on the position of the ester group, which causes different guest selectivities. Monoester copillar[5]arenes bearing an acetate chain can form stable self‐inclusion complexes in low‐ and high‐concentration solution and exhibit high guest selectivity. However, a monoester copillar[5]arene bearing a butyrate chain can not form a self‐inclusion complex and exhibits low guest selectivity. Thus, a new class of stable self‐inclusion complexes of copillar[5]arenes was explored to improve the selectivity of molecular recognition.     

A Study of the Interaction Between Cucurbit[8]uril and Alkyl‐Substituted 4‐Pyrrolidinopyridinium Salts

The interaction between cucuribit[8]uril (Q[8]) and a series of 4‐pyrrolidinopyridinium salts bearing aliphatic substituents at the pyridinium nitrogen, namely 4‐(C₄H₈N)C₅H₅NRBr, where R=Et (g1), n‐butyl (g2), n‐pentyl (g3), n‐hexyl (g4), n‐octyl (g5), n‐dodecyl (g6), has been studied in aqueous solution by ¹H NMR spectroscopy, electronic absorption spectroscopy, isothermal titration calorimetry and mass spectrometry. Single crystal X‐ray diffraction revealed the structure of the host–guest complexes for g1, g2, g3, and g5. In each case, the Q[8] contains two guest molecules in a centrosymmetric dimer. The orientation of the guest molecule changes as the alkyl chain increases in length. Interestingly, in the solid state, the inclusion complexes identified are different from those observed in solution, and furthermore, in the case of g3, Q[8] exhibits two different interactions with the guest. In solution, the length of the alkyl chain plays a significant role in determining the type of host–guest interaction present.     

Triple Emission from p‐Dimethylaminobenzonitrile–Cucurbit[8]uril Triggers the Elusive Excimer Emission

The intriguing dual‐emission behavior of p‐ dimethylaminobenzonitrile (DMABN) and the identity of the associated excited states is, arguably, the most extensively investigated and also controversially discussed molecule‐ specific phenomenon of modern photochemistry. We have now found a new, third fluorescence band when DMABN is encapsulated within the water‐soluble molecular container cucurbit[8]uril (CB8). It is centered between the previously observed emissions and assigned to the elusive excimer emission from DMABN through 1:2 CB8:DMABN complex formation. Heating of the CB8 ? (DMABN)₂ complex from 0 to 100 °C results in the dissociation of the ternary complex and restoration of the dual‐emission properties of the monomer. Alternatively, monomer emission can be obtained by selecting cucurbit[7]uril (CB7), a host homologue that is too small to accommodate two DMABN molecules, or by introducing ethyl instead of methyl groups at the amino terminus of the aminobenzonitrile guest.