The cucurbit[n]uril family

In 1981, the macrocyclic methylene-bridged glycoluril hexamer (CB[6]) was dubbed "cucurbituril" by Mock and co-workers because of its resemblance to the most prominent member of the cucurbitaceae family of plants--the pumpkin. In the intervening years, the fundamental binding properties of CB[6]-high affinity, highly selective, and constrictive binding interactions--have been delineated by the pioneering work of the research groups of Mock, Kim, and Buschmann, and has led to their applications in waste-water remediation, as artificial enzymes, and as molecular switches. More recently, the cucurbit[n]uril family has grown to include homologues (CB[5]-CB[10]), derivatives, congeners, and analogues whose sizes span and exceed the range available with the alpha-, beta-, and gamma-cyclodextrins. Their shapes, solubility, and chemical functionality may now be tailored by synthetic chemistry to play a central role in molecular recognition, self-assembly, and nanotechnology. This Review focuses on the synthesis, recognition properties, and applications of these unique macrocycles.     

The cucurbit[n]uril family: prime components for self-sorting systems

We determined the values of Ka for a wide range of host-guest complexes of cucurbit[n]uril (CB[n]), where n = 6-8, using 1H NMR competition experiments referenced to absolute binding constants measured by UV/vis titration. We find that the larger homologues--CB[7] and CB[8]--individually maintain the size, shape, and functional group selectivity that typifies the recognition behavior of CB[6]. The cavity of CB[7] is found to effectively host trimethylsilyl groups. Remarkably, the values of Ka for the interaction of CB[7] with adamantane derivatives 22-24 exceeds 10(12) M(-1)! The high levels of selectivity observed for each CB[n] individually is also observed for the CB[n] family collectively. That is, the selectivities of CB[6], CB[7], and CB[8] toward a common guest can be remarkably large. For example, guests 1, 3, and 11 prefer CB[8] relative to CB[7] by factors greater than 10(7), 10(6), and 3000, respectively. Conversely, guests 23 and 24 prefer CB[7] relative to CB[8] by factors greater than 5100 and 990, respectively. The high levels of selectivity observed individually and collectively for the CB[n] family renders them prime components for the preparation of functional biomimetic self-sorting systems.     

Locating the cyclopentano cousins of the cucurbit[n]uril family

The synthesis of the first family of fully substituted cucurbit[n]uril is discussed, and the structural features of precursor glycolurils are highlighted in their importance to achieving higher homologues. The members of the family, where n = 5-7, have been fully characterized, and increased binding affinities have been identified for dioxane in CyP(6)Q[6] and adamantyl NH(3)(+) in CyP(7)Q[7]. A higher homologue is indicated but not conclusively identified.     

A hemicyanine and cucurbit[n]uril inclusion complex: competitive guest binding of cucurbit[7]uril and cucurbit[8]uril

The interaction between the hemicyanine indole derivative H and the cucubit[n]urils Q[7] and Q[8] has been studied using ¹H NMR and UV spectroscopy as well as by fluorescence experiments. Competitive studies on the inclusion of H by Q[7] and Q[8] have also been conducted, and reveal that on changing the size of the Q[n] cavity, the binding behaviour can be very different.     

Facile synthesis of cucurbit[n]uril derivatives via direct functionalization: expanding utilization of cucurbit[n]uril

A long-standing problem in cucurbituril chemistry is answered through the first direct functionalization of cucurbit[n]uril (CB[n]; n = 5-8)) leading to perhydroxyCB[n] which can be further modified to provide tailored CB[n] derivatives with desired functional groups and good solubility. Anchoring a CB[6] derivative on the surface and its potential application as a sensor are demonstrated. A CB[6] derivative forms nanospheres with possible use in protein and peptide drug delivery.     

Substituted cucurbit[n]uril rings, catenanes and channels

The developments into the synthesis of networked rings, and channels generated in crystalline structures of substituted cucurbit[n]uril with metal ions and organic cations are reviewed. Pertinent chemical features and characteristics are discussed in the context of structural design and supramolecular architecture when utilizing substituted cucurbit[n]uril as building blocks.     

Sequence recognition and self-sorting of a dipeptide by cucurbit[6]uril and cucurbit[7]uril

Cucurbit[7]uril forms very strong complex with zwitterionic dipeptide Phe-Gly with affinity exceeding 10(7) M(-1) and effectively recognizes peptide sequence of Phe-Gly over Gly-Phe as well as Tyr-Gly over Gly-Tyr and Trp-Gly over Gly-Trp with relative affinities of 23 000, 18 000 and 2000, respectively.     

Preparation and recognition property of an acyclic cucurbit[n]uril dimer

Journal of Inclusion Phenomena and Macrocyclic Chemistry - A new acyclic cucurbit[n]uril (CB[n]) dimer is synthesized by copper-catalyzed azide-alkyne cycloaddition or “click” reaction....     

Binding modes of cucurbit[6]uril and cucurbit[7]uril with a series of bis-pyridinium compounds

Binding behaviors of cucurbit[6]uril (CB[6]) and cucurbit[7]uril (CB[7]) with a series of bis-pyridinium compounds N, N’-hexamethylenebis(1-alkyl-4-carbamoyl pyridinium bromide) (HBPB-n) (alkyl chain length, n = 6, 8 and 10) guests were investigated using ¹H-NMR, ESI–MS and single crystal X-ray diffraction methods. The results show that CB[6] and CB[7] can form [2]pseudorotaxanes with HBPB-n easily. When increasing the length of tail alkyl chain, the binding site of CB[6] at guest molecules changed from the tail to the middle part, while CB[7] remained located over the tail chain. As CB[6] and CB[7] were added in HBPB-8 aqueous solution, a [3]pseudorotaxane was formed by the inclusion of the internal middle site in CB[6] and the tail chain in CB[7].     

Inclusion complexation of diquat and paraquat by the hosts cucurbit[7]uril and cucurbit[8]uril

The binding interactions in aqueous solution between the dicationic guest diquat (DQ(2+)) and the cucurbit[7]uril (CB7) and cucurbit[8]uril (CB8) hosts were investigated by (1)H NMR, UV/Vis, and fluorescence spectroscopy; mass spectrometry; single-crystal X-ray diffraction; and electrochemical techniques. The binding data were compared with previously reported results for the related paraquat guest (PQ(2+)). DQ(2+) was found to bind poorly (K=350 m(-1)) inside CB7 and more effectively (K=4.8 x 10(4) m(-1)) inside CB8. One-electron reduction led to increased binding affinity with both hosts (K(r)=1 x 10(4) m(-1) with CB7 and K(r)=6 x 10(5) m(-1) for CB8). While (1)H NMR spectroscopic data revealed that DQ(2+) is not fully included by CB7, the crystal structure of the CB8DQ(2+) complex-obtained from single-crystal X-ray diffraction-clearly establishes its inclusion nature. Overall, both diquat and its one-electron reduced radical cation are bound more effectively by CB8 than by CB7. In contrast to this, paraquat exhibits selectivity for CB7, but its radical cation forms a highly stable dimer inside CB8. These differences highlight the pronounced sensitivity of cucurbit[n]uril hosts to guest features such as charge, charge distribution and shape.     

Cyclodextrin-driven movement of cucurbit[7]uril

The movement of cucurbit[7]uril (CB[7]) driven by alpha-cyclodextrin (alpha-CD) is investigated by various experimental techniques including NMR, ESI-MS, UV-vis, and ITC. CB[7] can form stable pseudorotaxanes with N-methyl-N'-octyl-4,4'-bipyridinium (MVO2+) and N,N'-dioctyl-4,4'-bipyridinium (OV2+) dication in aqueous solution. CB[7] shuttles between the octyl and bipyridinium moieties in MVO2+, but docks at one of the octyl moieties in OV2+. The addition of alpha-CD pushes CB[7] from the octyl moiety of MVO2+ or OV2+ to the bipyridinium moiety. Thermodynamically, the movement of CB[7] is mainly driven by exothermic enthalpy changes coming from the complexation of the octyl moiety of MVO2+ or OV2+ with alpha-CD.     

pH-responsive movement of cucurbit[7]uril in a diblock polypseudorotaxane containing dimethyl beta-cyclodextrin and cucurbit[7]uril

[Structure: see text] A polypseudorotaxane consisting of cucurbit[7]uril (CB[7])/N,N'-(3-phenylenebis(methylene)dipropargylamine (PMPA), [2]pseudorotaxane, and 2,6-O-dimethyl beta-cyclodextrin (DM-beta-CD)/alpha,omega-bisazidopropylene glycol 400 [2]pseudorotaxane was synthesized using the "click" reaction. The polypseudorotaxane structure was maintained in aqueous solution over a wide range of pH values with the DM-beta-CD units contributing to increased solubilization of the polypseudorotaxane without dethreading. The pH-responsive movement of the CB[7] units in the polypseudorotaxane was also observed.     

Acyclic cucurbit[n]uril type receptors: secondary versus tertiary amide arms

ABSTRACT

Two acyclic CB[n]-type hosts (1 and 2) which possess four 2° or 3° amide arms are reported. Host 2 has four 3° amide arms that exist as a mixture of E- and Z-isomers. ¹H NMR was used to qualitatively investigate the binding properties of 1 and 2 which indicates they retain the essential binding features of macrocyclic CB[n] hosts. We measured the K_a values of 1 and 2 toward guests 6–14 by ITC. Neutral hosts 1 and 2 bind less tightly than tetraanionic hosts M1, ACB1, and ACB2. We attribute the lower K_a values to the absence of secondary ion-ion electrostatic interactions for host?guest complexes of 1 and 2. The secondary amide functionality on 1 decreases affinity by the formation of intramolecular NH???O=C H-bonds. Tertiary amide host 2 binds even more weakly than 1 due to backfolding of the amide N-CH₃-groups of 2 into its own cavity.     

Controllable fabrication of a supramolecular polymer incorporating twisted cucurbit[14]uril and cucurbit[8]uril via self-sorting

A linear supramolecular polymer with controllable features based on twisted cucurbit[14]uril (tQ[14]) and cucurbit[8]uril (Q[8]) was firstly fabricated via an effective self-sorting strategy. Herein we designed a monomer, 1?butyl?1′-(naphthalen- 2-ylmethyl)-4,4′-bipyridinium bromide (BNB), that contains bipyridyl, aliphatic butyl and aromatic naphthyl groups, simultaneously. Two host molecules, tQ[14] and Q[8] were employed to develop an effective strategy for constructing a linear supramolecular polymer with controllable features. The alkyl groups on both sides of BNB could insert into the two cavities of tQ[14], the naphthyl part of BNB via π-π stacking in Q[8] cavity, serving as the driving force for supramolecular polymerization. Through self-sorting of the monomer, tQ[14] and Q[8], led to the formation of the linear supramolecular polymer. Depolymerization could be achieved by addition of adamantane hydrochloride (AH) which driven two BNB guest molecules out of the Q[8] cavity. This self-sorting strategy has great potential, not only for designing supramolecular polymer materials with different controllable structures through introduction of multiple functional groups, but also for broadening the application of twisted cucurbit[14]uril in supramolecular chemistry.     

Interaction between cucurbit[6]uril and bispyridinecarboxamide

The interaction between cucurbit[6]uril and N,N′-(m-bispyridinecarboxamide)-1,n-alkane (m = 2, 3, 4; n = 4, 6, 8) has been investigated by ¹H-NMR, ESI-MS and single crystal X-ray diffraction method. The results show that cucurbit[6]uril can form pseudorotaxanes with N,N′-(m-bispyridinecarboxamide)-1,6-hexane (m = 2, 3, 4) easily. When the alkyl chain length increases (n = 8), the binding mode is identical, but the binding ability of the host towards guest decreases. In both two cases cucurbit[6]uril shows no selectivity towards positional isomers. However, in the case of n = 4, the binding mode is different, having relations with positional substitution of the guest. Only N,N′-(m-bispyridinecarboxamide)-1,4-butane (m = 2) can form pseudorotaxane with cucurbit[6]uril, while the other two (m = 3, m = 4) form external complex with cucurbit[6]uril. The possible reason for the difference has been discussed.     

Binding modes of cucurbit[6]uril and cucurbit[7]uril with a tetracationic bis(viologen) guest

Binding behaviors of two cucurbit[n]urils (CB[n]) hosts with the [CH3bpy(CH2)6bpyCH3]4+ (bpy = 4,4'-bipyridinium) guest were investigated by 1H NMR and MALDI-TOF-MS experiments. While the CB[6] and CB[7] form [2]pseudorotaxanes with the host located over the hexamethylene chain of the guest, only the CB[7] forms a [3]pseudorotaxane with both host molecules residing over the bipyridinium groups. The initial CB[7] host vacates the inclusion of the hexamethylene chain as a result of the electrostatic and steric repulsions that would arise in simultaneous binding of adjacent aliphatic and aromatic portions of the guest.     

Acyclic cucurbit[n]uril molecular containers selectively solubilize single-walled carbon nanotubes in water

Making single-walled carbon nanotubes (SWNTs) soluble in water is a challenging first step to use their remarkable electronic and optical properties in a variety of applications. We report that acyclic cucurbit[n]uril molecular containers 1 and 2 selectively solubilize small-diameter and low chiral angle SWNTs. The selectivity is tunable by increasing the concentration of the molecular containers or by adjusting the ionic strength of the solution. Even at a concentration 1000 times lower than typically required for surfactants, the molecular containers render SWNTs soluble in water. Molecular mechanics simulations suggest that these C-shaped acyclic molecules complex the SWNTs such that a large portion of nanotube sidewalls are exposed to the external environment. These "naked" nanotubes fluoresce upon patching the exposed surface with sodium dodecylbenzene sulfonate.     

Recognition of glycine by cucurbit[5]uril and cucurbit[6]uril: A comparative study of exo- and endo-binding

Recognition features of glycine (Gly) with cucurbit[5]uril (Q[5]) and cucurbit[6]uril (Q[6]) both in aqueous solution and solid state were investigated by ¹H NMR spectroscopy and X-ray crystallography. ¹H NMR data indicate that the Gly is located outside of the portals of the Q[5], exhibiting exo binding with the Q[5]. In the case of the Q[6], the Gly shows endo binding or a dual binding mode (endo and exo binding) with the host, which depends on the amount of the host in the aqueous solution. X-ray crystallography clearly display that the Gly forms 2:1 exclusion complex with the Q[5], and 2:1 inclusion complex with the Q[6]. Interestingly, hydrogen bondings between the encapsulated Gly molecules in the Q[6] were observed.     

Cucurbit[n]uril analogues

[structure: see text] Cucurbits come in a variety of sizes, shapes, and colors. We present a building block approach that allows the tailor-made synthesis of CB[5], CB[6], and CB[7] analogues whose sizes, shapes, and colors differ from those of the known CB[n].