Sequential Formation of Heteroternary Cucurbit[10]uril (CB[10]) Complexes

The globular and monocationic guest molecule trimethyl-azaphosphatrane ( AZAP , a protonated Verkade superbase) was shown to form a host:guest 1 : 1 complex with the cucurbit[10]uril (CB[10]) macrocycle in water. Molecular dynamics calculations showed that CB[10] adopts an 8-shape with AZAP occupying the majority of the internal space, CB[10] contracting around AZAP and leaving a significant part of the cavity unoccupied. This residual space was used to co-include planar and monocationic co-guest ( CG ) molecules, affording heteroternary CB[10]⋅ AZAP ⋅ CG complexes potentially opening new perspectives in supramolecular chemistry.     

Selective Release of Doxorubicin from Cucurbit[8]uril Stabilized Gold Supra-Pyramid Host at pH of Small Intestine

Gold supra-pyramid structures were obtained by the addition of acidic solution of cucurbit[8]uril (CB[8]) to an aqueous solution of citrate stabilized gold nanoparticles (AuNP). The reaction resulted in the precipitation of supra-pyramid from the solution after just 1 min of shaking. Microscopic images confirmed formation of the supra-pyramid. The stepwise structural transformation towards the supra-pyramid was examined with variable concentrations of CB[8] to AuNP solution. Anionic counter parts of these acids (Br⁻, NO₃⁻, SO₄²⁻ and Cl⁻) controlled the size of the synthesized supra-pyramids. These supra-pyramid hosts showed uptake of three anticancer drugs: oral drugs etoposide, prednisolone and intravenous drug doxorubicin. Releases of drugs from these hosts were emulated at acidic stomach pH, basic small intestinal pH and in the presence of human serum albumin (HSA). The specific release of doxorubicin was confirmed at small intestinal pH 7.4. Poor release of drugs in presence of CB[8] specific guest 1-adamantanamine confirmed the role of the supra-pyramid as the exclusive host. The release of doxorubicin from the supra-pyramid at pH 7.4 was confirmed by fluorescence microscopic imaging with prostate cancer DU-145 cell line.     

In Vitro and In Vivo Sequestration of Methamphetamine by a Sulfated Acyclic CB[n]-Type Receptor

We report the synthesis of two new acyclic sulfated acyclic CB[n]-type receptors ( TriM0 and Me₄TetM0 ) and investigations of their binding properties toward a panel of drugs of abuse ( 1 – 13 ) by a combination of ¹H NMR spectroscopy and isothermal titration calorimetry. TetM0 is the most potent receptor with K_a≥10⁶ M⁻¹ toward methamphetamine, fentanyl, MDMA and mephedrone. TetM0 is not cytotoxic toward HepG2 and HEK 293 cells below 100 μM according to MTS metabolic and adenylate kinase release assays and is well tolerated in vivo when dosed at 46 mg kg⁻¹. TetM0 does not inhibit the hERG ion channel and is not mutagenic based on the Ames fluctuation test. Finally, in vivo efficacy studies show that the hyperlocomotion of mice treated with methamphetamine can be greatly reduced by treatment with TetM0 up to 5 minutes later. TetM0 has potential as a broad spectrum in vivo sequestrant for drugs of abuse.     

Rotaxanes Capped with Host Molecules: Supramolecular Behavior of Adamantylated Bisimidazolium Salts Containing a Biphenyl Centerpiece

Bisimidazolium salts with one central biphenyl binding site and two terminal adamantyl binding sites form water‐soluble binary or ternary aggregates with cucurbit[7]uril (CB7) and β‐cyclodextrin (β‐CD) with rotaxane and pseudorotaxane architectures. The observed arrangements result from cooperation of the supramolecular stopper binding strength and steric barriers against free slippage of the CB7 and β‐CD host molecules over the bisimidazolium guest axle.     

Cucurbit[6]uril dimer induces supramolecular polymerisation of a cationic polyethylene glycol derivative

Recently, we reported the synthesis of two new dimeric cucurbit[6]uril compounds (1 and 2). Herein, we describe the ability of compound 1 to undergo supramolecular polymerisation when combined with polyethylene glycol (PEG) derived divalent guests 3_MW (MW = 300, 1000, 3350, 10,000). Interestingly, we find that the shorter PEG-derived guests 3₃₀₀, 3₁₀₀₀ and 3₃₃₅₀ lead to low degrees of oligomerisation based on the diffusion coefficients obtained by diffusion-ordered spectroscopy measurements. In contrast, when 1 was combined with the longest PEG-derived guest 3_10,000, we observed the formation of a supramolecular polymer with a degree of oligomerisation of at least 36. We observe that the supramolecular polymer 1_n·(3_10,000)n undergoes a slow decrease in its degree of oligomerisation to 22 over the course of 14 days controlled by the slow dissociation rate constant of the hexanediammonium unit of 3_10,000 from the CB[6]-sized cavity of 1.     

Cucurbituril Based Luminescent Materials in Aqueous Media and Solid State

Cucurbit[n]urils, the pumpkin shaped macrocyclic host molecules possessing a hydrophobic cavity and two identical carbonyl portals, have drawn a lot of attention in recent years due to their high-affinity yet dynamic molecular recognition properties in water. The reversible and stimuli-responsive nature of their host-guest complexes imparts “smart” features leading to materials with intriguing optical, mechanical and morphological properties. In this review, we focus on the design of cucurbituril based luminescent materials in aqueous media as well in solid or film state. The design principles of fluorescent complexes, small assemblies as well as supramolecular polymers along with their stimuli-responsive properties and applications in diverse areas such as optoelectronic devices, light harvesting, anti-counterfeiting and information technology, cell imaging, etc are highlighted with selected examples from recent literature. We also discuss examples of room temperature phosphorescent materials derived from purely organic luminogens in the presence of cucurbiturils.     

Supramolecular Polymerization Promoted and Controlled through Self‐Sorting

A new method in which supramolecular polymerization is promoted and controlled through self‐sorting is reported. The bifunctional monomer containing p‐phenylene and naphthalene moieties was prepared. Supramolecular polymerization is promoted by selective recognition between the p‐phenylene group and cucurbit[7]uril (CB[7]), and 2:1 complexation of the naphthalene groups with cucurbit[8]uril (CB[8]). The process can be controlled by tuning the CB[7] content. This development will enrich the field of supramolecular polymers with important advances towards the realization of molecular‐weight and structural control.     

Synthesis of a symmetrical octamethyl-substituted cucurbituril with a dimethyl-substituted glycoluril dimer

A symmetrical octamethyl-substituted cucurbituril has been synthesized in a controlled manner by using a dimer of dimethyl-substituted glycoluril, which was in turn synthesized under formaldehyde-deficient conditions. The dimer of dimethyl-substituted glycoluril and the symmetrical octamethyl-substituted cucurbituril have been characterized by NMR spectrometry, ESI mass spectrometry and single-crystal X-ray diffraction analysis. The structure of the dimer of dimethyl-substituted glycoluril is notable because it constitutes a useful new building block that could permit the formation of such cucurbit[n]urils with substituents in certain positions or with limited numbers of methine groups on their backbones.