Polyethylene Glycol as String for the Simultaneous Complexation of α-Cyclodextrin and Cucurbit[6]uril

α-Cyclodextrin and cucurbit[6]uril are macrocyclic ligands with nearly identical molecular properties. Both ligands possess nonpolar cavities with similar dimensions. They are able to include nonpolar molecules within their cavities. The main difference between both ligands is their solubility in water. An acceptable solubility for cucurbit[6]uril is only given in the presence of acids or salts. Due to the similarity of both ligands, the formation of mixed polyrotaxanes seems to be possible. The synthesis of statistically threaded α-cyclodextrin and cucurbit[6]uril on polyethylene glycol 2000 is verified using elemental analysis, ¹H-NMR spectroscopy and differential scanning calorimetry. Under the experimental conditions used the number of threaded α-cyclodextrin molecules is higher compared with cucurbit[6]uril. However it is shown that the formation of mixed complexes is possible.     

Polyethylene Glycol as String for the Simultaneous Complexation of α-Cyclodextrin and Cucurbit[6]uril

α-Cyclodextrin and cucurbit[6]uril are macrocyclic ligands with nearly identical molecular properties. Both ligands possess nonpolar cavities with similar dimensions. They are able to include nonpolar molecules within their cavities. The main difference between both ligands is their solubility in water. An acceptable solubility for cucurbit[6]uril is only given in the presence of acids or salts. Due to the similarity of both ligands, the formation of mixed polyrotaxanes seems to be possible. The synthesis of statistically threaded α-cyclodextrin and cucurbit[6]uril on polyethylene glycol 2000 is verified using elemental analysis, ¹H-NMR spectroscopy and differential scanning calorimetry. Under the experimental conditions used the number of threaded α-cyclodextrin molecules is higher compared with cucurbit[6]uril. However it is shown that the formation of mixed complexes is possible.     

Complexation behavior of cucurbit[6]uril with short polypeptides

The binding properties of cucurbit[6]uril towards various peptides have been investigated in acidic aqueous solution. Stability constants and thermodynamic values of the complex formation between following peptides: glycyl-l-alanine, l-leucyl-l-valine, glycyl-l-asparagine, l-leucyl-l-phenylalanine, l-leucyl-l-tryptophan, glycyl-l-histidine, l-glutathione reduced (γ-l-glutamyl-l-cysteinyl-glycine, GSH), and dl-leucyl-glycyl-dl-phenylalanine) with cucurbit[6]uril in aqueous formic acid (50%, v/v) have been calculated from calorimetric titrations. From these results it can be seen that the peptides form exclusion complexes with cucurbit[6]uril. Due to the polar peptide bond they are not included within the hydrophobic cavity of cucurbit[6]uril. The complex formation is favoured by entropic contributions. The release of water molecules from the polar amino groups of the peptides and the carbonyl groups of cucurbituril are responsible.     

Complex Formation of Crown Ethers with the Cucurbit[6]uril–Spermidine and Cucurbit[6]uril–Spermine Complex in Aqueous Solution

Alkyl amines are able to form complexes with either crown ethers or cyclodextrins or cucurbit[6]uril. The same is known for polyamines such as spermidine and spermine. However, the simultaneous formation of such polyamines with crown ethers and cucurbit[6]uril has not been studied. The ability of polyamines such as spermidine and spermine to form mixed complexes with different ligands, e.g. crown ethers and cucurbit[6]uril has been studied in aqueous solution using pH-metric and calorimetric titrations. The thermodynamic data of reaction between crown ethers with spermidine, spermine and their cucurbit[6]uril complexes have been determined. The presence of cucurbit[6]uril on the polyamines has no important influence upon the reaction of these amines with crown ethers. The reactions between polyamines, cucurbit[6]uril and crown ethers are simple examples for the self organization of molecules due to specific interactions. Received in final form: 26 January 2005     

11-Aminoundecanoic acid, Cyclodextrins (α, β) and Cucurbit[n]urils (n = 6, 7) as Building Blocks for Supramolecular Assemblies: A Thermodynamic Study

The formation of 1:1 complexes of α-, β-cyclodextrin, cucurbit[6]uril, and cucurbit[7]uril with 11-aminoundecanoic acid have been studied using calorimetric titrations. The influence of solvent composition (aqueous formic acid) upon the complex stability and the values of the reaction enthalpies and entropies has been studied in the case of α-cyclodextrin (α-CD). With increasing concentration of formic acid the values of the reaction enthalpy decrease and of the reaction entropy increase. All ligands examined form 1:1 complexes with 11-aminoundecanoic acid under the experimental conditions. However, it is also possible to study the formation of 2:1 complexes (ligand:aminocarboxylic acid ratio). Even the formation of mixed 1:1:1 complexes with two different ligands (ligand(1):ligand(2):aminocarboxylic acid ratio) can be measured.     

Cucurbit[5]uril, Decamethylcucurbit[5]uril and Cucurbit[6]uril. Synthesis, Solubility and Amine Complex Formation

A simple way to prepare cucurbit[5]uril is described. The macrocycles of the cucurbituril type are nearly insoluble in water. The solubilities of cucurbit[5]uril, decamethylcucurbit[5]uril and cucurbit[6]uril in hydrochloric acid, formic acid and acetic acid of different concentrations have been investigated. Due to the formation of complexes between cucurbit[n]urils and protons the solubility increases in aqueous acids. The macrocyclic ligands are able to form complexes with several organic compounds. Thus, the complex formation of the cucurbituril macrocycles with different amines has beenstudied by means of calorimetric titrations. The reaction enthalpy gives noevidence of the formation of inclusion or exclusion complexes. ¹H-NMR measurements show that in the case of cucurbit[5]uril and cucurbit[6]uril the organic guest compound is included within the hydrophobic cavity. Decamethylcucurbit[5]uril forms only exclusion complexes with organicamines. This was confirmed by the crystal structure of the decamethylcucurbit[5]uril-1,6-diaminohexane complex.     

瓜环与哌嗪衍生物主客体配合物的研究(英)

本文采用核磁共振技术研究瓜环与哌嗪衍生物主客体配合物的结构特征。¹H核磁共振谱证实八元瓜环能与一些哌嗪衍生物形成稳定的双客体主客体配合物,六元瓜环与一些哌嗪衍生物形成稳定的1∶1主客体配合物。而五、七元瓜环和哌嗪衍生物则未表现出明显地相互作用。形成的自组装主客体配合物得到质谱的进一步证实。     

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.     

Cucurbit[6]uril as Ligand for the Complexation of Diamines, Diazacrown Ethers and Cryptands in Aqueous Formic Acid

The complex formation between cucurbit[6]uril and different diamines, diazacrown ethers, and cryptands has been studied in aqueous formic acid solution. The complex stabilities and the thermodynamic values for the complex formation of diamines are reduced if any further donor atom (e.g., sulfur, oxygen, or nitrogen) is present in the molecules. The inclusion of this polar group inside the cavity of cucurbit[6]uril has a negative effect upon the complex formation. Diazacrown ethers and cryptands do not form inclusive complexes. One nitrogen donor atom interacts with the carbonyl groups at one of the portals.     

Comparative macrocycle binding of the anticancer drug phenanthriplatin by cucurbit[<Emphasis Type="Italic">n</Emphasis>]urils, β-cyclodextrin and <Emphasis Type="Italic">para</Emphasis>-sulfonatocalix[4]arene: a <Superscript>1</Superscript>H NMR and molecular modelling study

The potential anticancer drug phenanthriplatin, [cis-(NH₃)₂(phenanthridine)Cl]⁺, forms supramolecular complexes with cucurbit[n]urils (CB[n], n?=?7 or 8), β-cyclodextrin and para-sulfonatocalix[4]arene (sCX[4]) as determined by ¹H NMR spectroscopy and molecular modeling. The results show that cucurbit[7]uril binds over the long arm of the drug, where hydrophobic effects and two hydrogen bonds stabilise binding. For cucurbit[8]uril, two phenanthriplatin molecules can bind simultaneously within the macrocycle’s cavity. Unfortunately, Na⁺ was able to displace the drug from both CB[7] and CB[8] making the macrocycles unsuitable as delivery vehicles for phenanthriplatin. Drug binding to β-cyclodextrin occurs at the portal of the macrocycle with no part of the phenanthriplatin located within the cavity. Phenanthriplatin binding to sCX[4] occurs in a 2-to-1, macrocycle-to-drug, ratio with the formation of a capsule-like complex where each sCX[4] binds over opposing ends of the drug. The results indicate that para-sulfonatocalix[4]arene is the only suitable macrocycle of the four studied for further research into phenanthriplatin drug delivery.     

Cucurbit[6]uril as Ligand for the Complexation of Diamines, Diazacrown Ethers and Cryptands in Aqueous Formic Acid

The complex formation between cucurbit[6]uril and different diamines, diazacrown ethers, and cryptands has been studied in aqueous formic acid solution. The complex stabilities and the thermodynamic values for the complex formation of diamines are reduced if any further donor atom (e.g., sulfur, oxygen, or nitrogen) is present in the molecules. The inclusion of this polar group inside the cavity of cucurbit[6]uril has a negative effect upon the complex formation. Diazacrown ethers and cryptands do not form inclusive complexes. One nitrogen donor atom interacts with the carbonyl groups at one of the portals.     

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.     

Supramolecular assemblies based on some new methyl-substituted cucurbit[5]urils through hydrogen bonding

Three supramolecular assemblies based on three new partial methyl-substituted cucurbit[5]urils, which are tetramethylcucurbit[5]uril (α,γ-TMeQ[5]), hexamethyl cucurbit[5]uril (α,β,δ-HMeQ[5]), Nonamethylcucurbit[5]uril (NMeQ[5]), were synthesized and structurally characterized by single-crystal X-ray diffractions. For the comparison with these new Q[5]s, crystal structure of an assembly constructing with normal Q[5] and K₂PtCl₆ was also reported. They are (α,γ-TMeQ[5])·15(H₂O) (1), (α,β,δ-HMeQ[5])·2Cl⁻·2(H₃O)⁺·7(H₂O) (2), (NMeQ[5])·14(H₂O) (3), (4). In the corresponding crystal structures, the molecular encapsulates included a water molecule and lidded water molecules at both of the portals were observed. Moreover, these molecular encapsulates are connected through hydrogen bonding and formed supramolecular chains or joined in pair.     

Cucurbit[6]uril pseudorotaxanes: distinctive gas-phase dissociation and reactivity

Cucurbit[6]uril forms a doubly charged complex with 1,4-butanediammonium cation that is observed using electrospray ionization Fourier transform mass spectrometry. Such 1:1 complexes are not observed for the smaller cucurbit[5]uril, which forms a 2:1 ammonium:cucurbituril complex instead. The 1:1 complex with cucurbit[6]uril is difficult to fragment via collisional activation; when it does fragment, both breakup of the cucurbituril cage and loss of the amine are observed. Further, the complex reacts with tert-butylamine via slow adduction. In contrast, nonrotaxane analogues (such as doubly charged 2:1 complexes of either protonated 1,4-butanediamine or protonated ethylenediamine with cucurbit[6]uril) fragment via easy loss of the intact amine upon collisional activation and react with tert-butylamine via rapid displacement of the original amine. On the basis of stoichiometry, fragmentation behavior, and reactivity, we conclude that the doubly charged complex of cucurbit[6]uril with 1,4-butanediammonium is a gas-phase pseudorotaxane.     

七、八元瓜环与二溴化1,n-亚烷基-二-2-甲基吡啶的超分子自组装

合成和表征了4个碳链长度不同二溴化1,n-亚烷基-二-2-甲基吡啶(客体,n=6,8,10,12),利用1H NMR技术、热重分析及紫外吸收光谱法考察了这些客体与七、八元瓜环(主体)的相互作用,以及形成的主客体包结物的结构特征.研究结果表明4个客体与七、八元瓜环形成不同的主客体包合物.七元瓜环可穿梭在线性客体分子上形成类轮烷型或哑铃型主客体包合物;而由于具有较大的空腔,八元瓜环可包容弯曲状的整个客体分子.     

六元瓜环与磺基水杨酸主客体配合物的晶体结构

合成了六元瓜环与磺基水杨酸主客体配合物,并测定了其单晶结构.晶体结构表明六元瓜环包结了3个水分子,磺基水杨酸位于六元瓜环的外侧,且与水分子通过氢键与六元瓜环相连,瓜环之间通过端口的羰基O原子、磺基水杨酸以及水分子间的氢键作用形成一维超分子.     

Sequential formation of a ternary complex among dihexylammonium, cucurbit[6]uril, and cyclodextrin with positive cooperativity

[STRUCTURE: SEE TEXT] A unique ternary 1:1:1 cucurbit[6]uril (CB[6])-cyclodextrin (CD)-dihexylammonium (DHA) complex was designed and noncovalently synthesized in stepwise fashion: first, CB[6] interacts strongly with DHA to form a 1:1 complex; second, addition of CD into the solution of the 1:1 complex leads to the exclusive formation of the 1:1:1 ternary complex. The ternary complex was characterized by various experimental techniques including ITC, NMR, and ESI-MS.     

六元瓜环／1，2-乙二胺的超分子化合物结构及相互作用模式

合成了六元瓜环与链状烷基二胺（1,2-乙二胺）形成的超分子化合物．采用X射线衍射技术测定了其晶体结构,并得到元素分析、热重、红外光谱的佐证,揭示了主客体相互作用的模式．还采用^1HNMR技术研究了溶液中六元瓜环与乙二胺的超分子相互作用．研究表明,在不同的环境下瓜环与客体采取相异的超分子作用模式,晶体结构中显示一个六元瓜环的两个端口通过离子偶极作用以不同的作用模式分别跟两个乙二胺客体分子形成一个三单元组成的超分子作用实体;而在溶液中瓜环与乙二胺的相互作用模式与晶体中的不同．     

Three‐Component Cucurbit[6]uril Framework with 1:2 Host‐Guest Motif and Dimeric Boric Acid

Three‐component framework of cucurbit[6]uril, 3‐(1‐methylimidazolium‐3‐yl)propane‐1‐sulfonate and boric acid has been constructed. The crystal structure reveals 1:2 host‐guest motif of cucurbit[6]uril and 3‐(1‐methyl‐imidazolium‐3‐yl)propane‐1‐sulfonate, demonstrating both cation binding of imidazolium moiety and anion binding of sulfonate moiety for the first time. Incorporation of dimeric boric acid facilitates the formation of metal‐free three‐dimensional framework.     

Improvement of Dispersion and Release Properties of Nifedipine in Suppositories by Complexation with 2-Hydroxypropyl-β-cyclodextrin

Geometries, electronic properties and NMR-shielding of cucurbit[5]uril, decamethylcucurbit[5]uril, cucurbit[6]uril, cucurbit[7]uril, and cucurbit[8]uril are investigated with DFT calculations. All molecules are highly symmetrical with a distinct geometric flexibility. In addition with a characteristic partial charge distribution these findings account for their chemical complex building ability.