Synthesis and guest exchange reactions of inclusion compounds of cucurbit[8]uril with nickel(II) and copper(II) complexes

Inclusion compounds of the macrocyclic cavitand cucurbit[8]uril (CB[8]) with the nickel(II) complex, {trans-[Ni(en)₂(H₂O)₂]@CB[8]}Cl₂ · 23.5H₂O, the copper(II) complex, {2[Cu(dien)(bipy)(H₂O)]@CB[8]}(ClO₄)₄ · 11H₂O, and the organic molecules, 2(pyCN)@CB[8]} · 16H₂O and {2(bpe)@CB[8]} · 17H₂O, where bipy is 4,4′-bipyridyl, pyCN is 4-cyanopyridine, and bpe is trans-1,2-bis(4-pyridyl)ethylene, were synthesized. The inclusion compounds with organic molecules were synthesized starting from inclusion compounds of cucurbit[8]uril with cyclam and ethylenediamine complexes of copper(II) and nickel(II) by the guest exchange method, which is based on the replacement of one guest with another in the cavity of the cavitand The resulting compounds were characterized by X-ray diffraction, ESR, ¹H NMR, IR, and electronic absorption spectroscopy, and electrospray mass spectrometry. Photochemically induced [2+2]-cycloaddition of two 1,2-bis(4-pyridyl)ethylene molecules included in cucurbit[8]uril was studied. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 25–34, January, 2006.     

Cucurbituril and α- and β-Cyclodextrins as Ligands for the Complexation of Nonionic Surfactants and Polyethyleneglycols in Aqueous Solutions

The complexation of nonionicsurfactants and polyethylene glycols by the ligandscucurbituril, - and -cyclodextrin wasstudied in aqueous solution. All the examined guestmolecules form complexes with these ligands.Calorimetric titrations were performed to determinedirectly the stability constants and reactionenthalpies. The presence of an aromatic part innonionic surfactants leads to more stable complexeswith -cyclodextrin than with the other ligands.If the surfactants contain no benzene group, theinteractions with -cyclodextrin are strongercompared to other ligands. The chain length of thepolyethylene glycols has only an influence upon thevalues of the reaction enthalpy in the case of-cyclodextrin.     

Synthesis of a disulfonated derivative of cucurbit[7]uril and investigations of its ability to solubilise insoluble drugs

Cucurbit[7]uril (CB[7]) is currently being investigated as a solubilising agent for insoluble drugs. We recently found that acyclic CB[n]-type receptors that bear sulfonate solubilising groups are well suited for this application. Herein, we report CB[7] derivative (1) that bears two sulfonate groups on its convex face that we hypothesised would be a superior solubilising excipient for insoluble drugs. Before using 1 for drug solubilisation experiments, we showed that 1 does not self-associate and that it retained its ability to bind to diammonium compounds as common guests for CB[7]-sized cavities. X-ray crystallography shows that 1 maintains the key structural features of CB[7] with only minor ellipsoidal deformations at the equator and carbonyl portals of 1. Unfortunately, the aqueous solubility of 1 (20 mM) is slightly lower than CB[7] (20–30 mM) which limits its potential as a solubilising excipient for insoluble drugs. We created phase-solubility diagrams for the solubilisation of three drugs (camptothecin, albendazole and cinnarizine) with two different containers (1 and CB[7]). CB[7] and 1 exhibit comparable solubilisation abilities (e.g. K_a and maximum solubility) towards camptothecin and albendazole but 1 is an inferior solubilising agent for cinnarizine because of the low solubility exhibited by the 1√cinnarizine complex.     

Molecular dynamics simulation study of the structural features and inclusion capacities of cucurbit[6]uril derivatives in aqueous solutions

Molecular dynamics (MD) simulations were performed for cucurbit[6]uril (CB6) methyl and cyclohexyl derivatives in aqueous solutions. Furthermore, MD simulations have been conducted to study the inclusion complexes between each CB6 derivative with α,ω-pentane diammonium ion (NH₃⁺(CH₂)₅NH₃⁺) to estimate the binding free energies, the complex geometries and the intermolecular forces responsible for complex formation. Results show a complete inclusion of the guest molecule in the cavity of the host for all complexes. Results also indicate that the guest dynamics inside the cavity of the substituted host is similar to that for the unsubstituted host. This demonstrates that the molecular recognition of the host is not affected by the alkyl substitution at the equator. Also, there is an insignificant conformational change of the macrocyclic structure upon inclusion of the guest. Molecular mechanics/Poisson Boltzmann surface area method was used to estimate the binding free energy of each complex. Results indicate that host–guest electrostatic interactions make the largest contribution to the complex binding free energy. Moreover, van der Waals interactions add significantly to the complex stability. The guest molecules show more or less similar binding free energies with the substituted CB6 that exhibits slightly more negative values than unsubstituted CB6 which is proved also by umbrella sampling.     

Oligomeric Cucurbituril Complexes: from Peculiar Assemblies to Emerging Applications

Proteins are an endless source of inspiration. By carefully tuning the amino-acid sequence of proteins, nature made them evolve from primary to quaternary structures, a property specific to protein oligomers and often crucial to accomplish their function. On the other hand, the synthetic macrocycles cucurbiturils (CBs) have shown outstanding recognition properties in water, and a growing number of (host)_n:(guest)_n supramolecular polymers involving CBs have been reported. However, the burgeoning field of discrete (n:n) host:guest oligomers has just started to attract attention. While 2:2 complexes are the major oligomers, 3:3 and up to 6:6 oligomers have been described, some associated with emerging applications, specific to the (n:n) arrangements. Design rules to target (n:n) host:guest oligomers are proposed toward new advanced host:guest systems.     

葫芦脲的研究进展

近几年葫芦脲和其衍生物由于其特殊的结构与性质已引起的密切关注。本文综述了葫芦脲的最新研究进展,包括葫芦脲分子及其衍生物的分子设计与合成,与聚电解质形成主链（准）聚轮烷和侧链（准）聚轮烷,与其他有机客体小分子相互作用形成轮烷和准轮烷,以及葫芦脲分子及其衍生物在囊泡、二维聚合物、色谱固定相、生物体以及药物缓释方面的最新应用。     

Modulation of Excited‐State Proton Transfer of 2‐(2′‐Hydroxyphenyl)benzimidazole in a Macrocyclic Cucurbit[7]uril Host Cavity: Dual Emission Behavior and pKa Shift

The effect of the macrocyclic host, cucurbit[7]uril (CB7), on the photophysical properties of the 2‐(2′‐hydroxyphenyl)benzimidazole (HPBI) dye have been investigated in aqueous solution by using ground‐state absorption and steady‐state and time‐resolved fluorescence measurements. All three prototropic forms of the dye (cationic, neutral, and anionic) form inclusion complexes with CB7, with the largest binding constant found for the cationic form (K≈2.4×10⁶ M ^?1). At pH≈4, the appearance of a blue emission band upon excitation of the HPBI cation in the presence of CB7 indicates that encapsulation into the CB7 cavity retards the deprotonation process of the excited cation, and hence reduces its subsequent conversion to the keto form. Excitation of the neutral form (pH≈8.5), however, leads to an increase in the keto form fluorescence, indicating an enhanced excited‐state intramolecular proton‐transfer process for the encapsulated dye. In both the ground and excited states, the two pK_a values of the HPBI dye show upward shifts in the presence of CB7. The prototropic equilibrium of the CB7‐complexed dye is represented by a six‐state model, and the pH‐dependent changes in the binding constants have been analyzed accordingly. It has been observed that the calculated pK_a values using this six‐state model match well with the values obtained experimentally. The changes in the pK_a values in the presence of CB7 have been corroborated with the modulation of the proton‐transfer process of the dye within the host cavity.     

Supramolecular drug inclusion complex constructed from cucurbit[7]uril and the hepatitis B drug Adefovir

The interaction between cucuribit[7]uril (Q[7]) and Adefovir (ADV) has been studied in aqueous solution by ¹H NMR spectroscopy, electronic absorption spectroscopy, Isothermal Titration Calorimetry and mass spectrometry. The results revealed that an inclusion complex was formed via encapsulation of the purine rings of the guest ADV, while the phosphonomethoxyethyl group was prevented from entering the cavity. ITC data revealed that the formation of this 1:1 inclusion complex is mainly driven by favourable enthalpy changes. Studies investigating the release of ADV from the inclusion complex revealed enhanced rates under acidic conditions, although the rates were slower than observed for the free guest under the same conditions. Thermal stability studies indicated that the included form of ADV was more stable that the free form.     

Molecular recognition properties of acyclic cucurbiturils toward amino acids,peptides, and a protein

The binding of 1 and 2 toward 19 amino acid amides by ¹H NMR and ITC is reported. Hosts 1 and 2 bind to aromatic or hydrophobic residues by cavity inclusion leaving the cationic residues at the C=O portals. K_a values range from 10² to >10⁶ M^?1 with H-Phe-NH₂, H-Trp-NH₂, and H-Tyr-NH₂ displaying sub-micromolar K_d values. Hosts 1 and 2 bind tightly to dicationic H-Lys-NH₂ and H-Arg-NH₂ which are poor guests for CB[7]. Comparison of the affinity of 1 and 2 toward the amino acid amide, N-acetyl-amino-acid amide, and amino acid forms of Phe revealed that the removal of the NH₃⁺ to O=C and SO₃^? electrostatic interactions costs 3.8 kcal/mol whereas the introduction of an unfavourable CO₂^? to O=C and SO₃^? electrostatic interactions costs 2.1 kcal/mol. Hosts 1 and 2 bind to insulin with low micromolar affinity. Acyclic CB[n] display high affinity toward a wider range of N-terminal amino acids residues than CB[n] which suggests a broad range of applications.     

一个强荧光三维超分子有机框架的构建及其对苦味酸的选择性传感

在四苯基甲烷外侧通过C=C双键引入四个N-甲基-4-苯基吡啶盐片段,合成了一个新的全共轭单体T-1.其在水中与2 equiv.的葫芦脲[8]结合,形成了新的高强荧光的超分子有机框架SOF-r-SPP.动态光散射实验表明,在T-1浓度为1.0和0.031 mmol/L时,SOF-r-SPP的流体力学直径分别为68和41 nm.粉末X-射线衍射实验揭示,SOF-r-SPP形成孔径为2.3 nm的三维金刚石型周期性结构.硝基苯衍生物能有效淬灭SOF-r-SPP的荧光.在17个研究的硝基苯类分子中,苦味酸的淬灭效率最高. SOF-r-SPP作为荧光传感器,对苦味酸的检测极限可以达到0.024 mmol/L.