Influence of self-assembly of amphiphilic imidazolium ionic liquids on their host–guest complexes with cucurbit[n]urils

Two symmetric amphiphilic imidazolium ionic liquids having ω-undecenyl chains form supramolecular complexes with CB[7] and CB[8] in water as revealed by ¹H NMR spectroscopy and MALDI-MS. Binding constants in the range 10⁴ to 10⁵ M^?1 were estimated from the conductivity measurements for the 1:1 complexes of these imidazolium ionic liquids with CB[7] and CB[8]. Radical initiated polymerization of these host–guest complexes at concentrations above the critical self-assembly concentration of imidazolium ionic liquids to form liposomes, destroys completely (CB[7]) or partially (CB[8]) the host–guest ionic liquid@CB[n] complex; this behaviour was proved by titration with acridine orange tricyclic dye, of CB[n]s in the colloidal solutions of the liposomes before and after performing dialysis to remove free CB[n]s. Thus, the increase in the fluorescence emission of acridine orange by CB[7] is not observed if the polymerized ionic liquid@CB[7] complex is submitted to dialysis to remove uncomplexed CB[7]. Analogous study by titration of absorbance change of acridine orange solutions caused by CB[8], reveals only a partial destruction of the host–guest complex by self-assembly of amphiphilic ionic liquid above the critical self-assembly concentration. The results obtained have been rationalized considering that the driving force for the formation of supramolecular ionic liquid@CB[n] complexes is a hydrophobic interaction between the apolar alkenyl chain and the cucurbituril interior cavity and that these hydrophobic interactions are disturbed when self-assembly leading to liposomes occurs.     

Benzobis(imidazolium)-cucurbit[8]uril complexes for binding and sensing aromatic compounds in aqueous solution

The utilities of benzobis(imidazolium) salts (BBIs) as stable and fluorescent components of supramolecular assemblies involving the macrocyclic host, cucurbit[8]uril (CB[8]), are described. CB[8] has the unusual ability to bind tightly and selectively to two different guests in aqueous media, typically methyl viologen (MV) as the first guest, followed by an indole, naphthalene, or catechol-containing second guest. Based on similar size, shape, and charge, tetramethyl benzobis(imidazolium) (MBBI) was identified as a potential alternative to MV that would increase the repertoire of guests for cucurbit[8]uril. Isothermal titration calorimetry (ITC) studies showed that MBBI binds to CB[8] in a 1:1 ratio with an equilibrium association constant (K(a)) value of 5.7×10(5) M(-1), and that the resulting MBBI·CB[8] complex binds to a series of aromatic second guests with K(a) values ranging from 10(3) to 10(5) M(-1). These complexation phenomena were supported by mass spectrometry, which confirmed complex formation, and a series of NMR studies that showed the expected upfield perturbation of aromatic peaks and of the MBBI methyl peaks. Surprisingly, the binding behavior of MBBI is strikingly similar to that of MV, and yet MBBI offers a number of substantial advantages for many applications, including intrinsic fluorescence, high chemical stability, and broad synthetic tunability. Indeed, the intense fluorescence emission of the MBBI·CB[8] complex was quenched upon binding to the second guests, thus demonstrating the utility of MBBI as a component for optical sensing. Building on these favorable properties, the MBBI·CB[8] system was successfully applied to the sequence-selective recognition of peptides as well as the controlled disassembly of polymer aggregates in water. These results broaden the available guests for the cucurbit[n]uril family and demonstrate potentially new applications.     

A systems approach to controlling supramolecular architecture and emergent solution properties via host-guest complexation in water

The assembly behavior of aryl/alkyl imidazolium ionic liquid salts in aqueous solution has been investigated. These salts undergo self-assembly into one-dimensional stacks via hydrophobic and π-π interactions upon increasing concentration, which led to a substantial increase in the solution viscosity in water. Addition of the macrocyclic host molecules cucurbit[n]urils (CB[n]) were found to effectively alter the supramolecular assemblies, as evidenced from the dramatic increase (by CB[7]) and decrease (by CB[8]) in solution viscosity and aggregation size in water, on account of the different binding stoichiometries, 1:1 complexation with CB[7] and 2:1 complexation with CB[8]. Furthermore, the aggregate architectures were controllably modified by competitive guests for the CB[n] hosts. This complex supramolecular systems approach has tremendous implications in the fields of molecular sensor design, nonlinear viscosity modification, and controlled release of target molecules from a defined supramolecular scaffold in water.     

Isolated supramolecular [Ru(bpy)3]-viologen-[Ru(bpy)3] complexes with trapped CB[7,8] and photoinduced electron-transfer study in nonaqueous solution

The synthesis of two supramolecular diruthenium complexes, 1 ?CB[7] and 1 ?CB[8] (CB[n]=cucurbit[n]uril), which contain the respective host CB[7] and CB[8], were synthesized and isolated. In the case of host CB[8], the desired supramolecular complex was obtained by utilizing dihydroxynapthalene as a template during the synthesis. The ¹H NMR spectra, electrochemistry, and photochemistry of these supramolecular complexes were performed in nonaqueous solution. The results show that both CB[7,8] hosts mainly bind to the linker part in solution in acetonitrile. This binding also lowers the oxidation potential of the ruthenium metal center and hinders the quenching effect by the viologen moiety. It has also been shown that external methylviologen can be included into 1 ?CB[8]. Analysis with NMR spectroscopy, electrochemistry, and photochemistry clearly shows a viologen radical dimer formation between the bound viologen and free methylviologen, thereby showing that the unique abilities of the CB[8] host can be utilized even in nonaqueous solution.     

Complexation and Fluorescence of Tricyclic Basic Dyes Encapsulated in Cucurbiturils

Tricyclic basic dyes (proflavine, acridine orange, pyronine, pyronine Y, oxonine, thionine and methylene blue) often form one‐to‐one or two‐to‐one complexes with CB[7] and CB[8], respectively. In the case of pyronine Y, the complexes with CB[7] and CB[8] have a one‐to‐one and three‐to‐one stoichiometry, respectively. The binding constants for CB[7] complexes range from 3.07×10⁶ to 1.70×10⁷ m ^?1. In the case of CB[8], the association constant varies between 3.24×10¹³ and 2.50×10¹⁶ m ^?2. Overall, these binding constants are four orders of magnitude higher than those reported for the same dyes in β and γ‐cyclodextrins. Formation of the host–guest complexes leads to an increase in the fluorescence quantum yields in the case of CB[7], while the dimeric or trimeric dye encapsulated in CB[8] are remarkably less fluorescent than the same dye in diluted solutions.     

N,N'-disubstituted methylenediimidazolium salts: a versatile guest for various macrocycles

N,N'-Disubstituted methylenediimidazolium salts allow the formation of flexible inclusion complexes with beta-cyclodextrin, cucurbit[7]uril, tetrapropoxycalix[4]arene, and dibenzo-24-crown-8 ether. Due to the salt nature of the imidazolium guest, the counterion largely determines its solubility in a given solvent. Moreover, by the judicious choice of the imidazolium substituents, inclusion complexes of guest salts were obtained with a variety of macrocyclic hosts, and the binding parameters of the inclusion were determined for each complex.     

Host-guest chemistry and light driven molecular lock of Ru(bpy)(3)-viologen with cucurbit[7-8]urils

Host-guest chemistry and photoinduced electron-transfer processes have been studied in the systems containing Ru(bpy)3 complex covalently linked to viologen as a guest molecule and cucurbit[n]urils (n = 7, 8) as host molecules in aqueous solution. The Ru(bpy)3-viologen complex, [Ru(2,2'-bipyridine)2(4-(4-(1'-methyl-4,4'-bipyridinediium-1-yl)butyl)-4'-methyl-2,2'-bipyridine)]Cl4 (denoted as Ru2+-MV2+, 1) was shown to form stable 1:1 inclusion complexes with cucurbit[7]uril (CB[7]) and cucurbit[8]uril (CB[8]). The binding modes are slightly different with CB[7] and CB[8]. CB[7] preferentially binds to part of the viologen residue in 1 together with the butyl chain, whereas CB[8] preferentially encloses the whole viologen residue. Photoinduced intramolecular electron transfer from the excited-state of the Ru moiety to MV2(+) which is inserted into the cavity of the CBs occurred. Long-lived charge-separated states Ru3(+)-MV(+*) were generated with the lifetimes of 280 ns with CB[7] and 2060 ns with CB[8]. This shows that CBs can slow down the charge recombination within supramolecular systems, and the difference in lifetimes seems to be due to the difference in binding modes. In the presence of a sacrificial electron donor triethanolamine, light-driven formation of a dimer of MV(+*) inside the CB[8] cavity was observed. This "locked" molecular dimer can be "unlocked" by molecular oxygen to give back the original form of the molecular dyad 1 with the MV2(+) moiety inserted in the cavity of CB[8]. The processes could be repeated several times and showed nice reversibility.     

Complexation of ferrocene derivatives by the cucurbit[7]uril host: a comparative study of the cucurbituril and cyclodextrin host families

The formation of inclusion complexes between cucurbit[7]uril (CB[7]) and ferrocene and its derivatives has been investigated. The X-ray crystal structure of the 1:1 inclusion complex between ferrocene and CB[7] revealed that the guest molecule resides in the host cavity with two different orientations. Inclusion of a set of five water-soluble ferrocene derivatives in CB[7] was investigated by 1H NMR spectroscopy and calorimetric and voltammetric techniques. Our data indicate that all neutral and cationic guests form highly stable inclusion complexes with CB[7], with binding constants in the 10(9)-10(10) M(-)(1) and 10(12)-10(13) M(-1) ranges, respectively. However, the anionic ferrocenecarboxylate, the only negatively charged guest among those surveyed, was not bound by CB[7] at all. These results are in sharp contrast to the known binding behavior of the same guests to beta-cyclodextrin (beta-CD), since all the guests form stable inclusion complexes with beta-CD, with binding constants in the range 10(3)-10(4) M(-1). The electrostatic surface potentials of CB[6], CB[7], and CB[8] and their size-equivalent CDs were calculated and compared. The CD portals and cavities exhibit low surface potential values, whereas the regions around the carbonyl oxygens in CBs are significantly negative, which explains the strong affinity of CBs for positively charged guests and also provides a rationalization for the rejection of anionic guests. Taken together, our data suggest that cucurbiturils may form very stable complexes. However, the host-guest interactions are very sensitive to some structural features, such as a negatively charged carboxylate group attached to the ferrocene residue, which may completely disrupt the stability of the complexes.     

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.     

Targeted Polypeptide–Microtubule Aggregation with Cucurbit[8]uril for Enhanced Cell Apoptosis

Tunable protein assemblies not only hold a dominant position in vital biological events but are also a significant theme in supramolecular chemistry. Herein, we demonstrated that the intertubular aggregation of microtubules (MTs) could be efficiently regulated by a synergistic polypeptide–tubulin interaction and host–guest complexation. The benzylimidazolium‐modified antimitotic peptide (BP) could recognize the MTs and concurrently form stable inclusion complexes with avirulent cucurbit[7]uril (CB[7]) and cucurbit[8]uril (CB[8]) in different binding stoichiometries. The self‐assembling morphology of MTs was converted from fibrous to nanoparticulate aggregates via extensive BP?CB[8] cross‐linkage, leading to significant cell apoptosis and tumor ablation in vivo. The targeted (BP?CB[8])@MT ternary assembly provides a facile supramolecular method to enhance the protein–protein interactions, which may be developed as a therapy for degenerative diseases, such as cancer.     

Inclusion of Carboxyl Function Inside of Cucurbiturils and its Use in Molecular Switches

We have prepared organic guest molecules in which two pyridinium rings are connected through an aromatic/aliphatic bridge bearing a carboxyl group. The supramolecular interactions between these guests and macrocyclic hosts cucurbit[7]uril ( CB7 ) and cucurbit[8]uril ( CB8 ) has been studied. We have demonstrated that the binding modes of the complexes depend on the type of central bridge present in the guest molecules and the size of the macrocycle. We have also showed that the binding mode between cucurbiturils and guests with aromatic bridges is pH independent. On the other hand, a guest containing an aliphatic bridge and CB7 formed a pseudorotaxane, which behaved as a pH‐driven molecular switch.     

Electron Density Shift in Imidazolium Derivatives upon Complexation with Cucurbit[6]uril

In this study, we have investigated the supramolecular interaction between series of 1‐alkyl‐3‐methylimidazolium guests with variable alkyl substituent lengths and cucurbit[6]uril (CB6) in the solution and the solid state. Correct interpretation of ¹H NMR spectra was a key issue for determining the binding modes of the complexes in solution. Unusual chemical shifts of some protons in the ¹H NMR spectra were explained by the polarization of the imidazolium aromatic ring upon the complexation with the host. The formation of 1:1 complex between 1‐ethyl‐3‐methylimidazolium and CB6 is in disagreement with previously reported findings describing an inclusion of two guest molecules in the CB6 cavity.     

2:2 Complexes from Diphenylpyridiniums and Cucurbit[8]uril: Encapsulation‐Promoted Dimerization of Electrostatically Repulsing Pyridiniums

Rigid linear compounds G1 and G2 , which contained two 4‐phenylpyridinium (PhPy⁺) units, have been prepared to investigate their binding with cucurbit[8]uril (CB[8]). X‐ray crystallographic structures revealed that in the solid state both compounds were included by CB[8], through antiparallel stacking, to form 2:2 quaternary complexes ( G1 )₂@(CB[8])₂ and ( G2 )₂@(CB[8])₂. For the former complex, CB[8] entrapped G1 by holding two heterodimers of its Py⁺ and benzyl units, which were at opposite ends of the backbone. In contrast, for the first time, the second complex disclosed parallel stacking of two cationic Py⁺ units of G2 in the cavity of CB[8] in the solid state, despite the generation of important electrostatic repulsion. Isothermal titrations in water afforded high apparent association constants of 4.36×10⁶ and 6.43×10⁶ m ^?1 for 1:1 complexes G1 @CB[8] and G2 @CB[8], respectively, and ¹H NMR spectroscopy experiments in D₂O confirmed a similar stacking pattern to that observed in the solid state. A previous study and crystal structures of the 2:1 complexes formed between three new controls, G3–5 , and CB[8] did not display such unusual stacking of the cationic Py⁺ unit; this may be attributed to the multivalency of the two CB[8] encapsulation interactions.     

Photophysical properties of aqueous solutions of a styryl dye in the presence of cucurbit[<Emphasis Type="Italic">n</Emphasis>]uril (<Emphasis Type="Italic">n</Emphasis> = 5, 6, 8)

Photophysical properties of aqueous solutions of the styryl dye 4-[(E)-2-(3,4-dimethoxyphenyl)-1-ethylpyridinium] perchlorate (1) in the presence of cucurbit[n]urils (CB[n]; n = 5, 6, 8) have been studied by fluorescent spectroscopy methods. The fluorescence intensity of a 10^–6 mol L^–1 solution of 1 increases by a factor of 12.6 upon the formation of 1 : 1 inclusion complexes with CB[6] or 1.3 in complexes with CB[8]. Upon the formation of inclusion complexes, the average lifetime of the electronically excited state of 1 increases to about 1 ns for both CB[6] and CB[8]. On the basis of fluorescence anisotropy measurements, the rotational relaxation times were estimated to be 408, 314, and 183 ps for the complexes with CB[6], CB[8], and for unbound 1, respectively. Using the fluorescence titration method developed for the case of poorly soluble cavitands, the binding constant of 1 with CB[6] was determined to be 1.1 × 10⁵ L mol^–1. The addition of CB[5] does not lead to changes in the photophysical properties of a solution of 1, indicating the absence of complexes between CB[5] and 1. It has been found on the basis of the experimental data that the fluorescence rate constant of 1 decreases about twice in the complex with CB[8], but doubles in the complex with CB[6].     

Activation Energies Control the Macroscopic Properties of Physically Cross‐Linked Materials

Here we show the preparation of a series of water‐based physically cross‐linked polymeric materials utilizing cucurbit[8]uril (CB[8]) ternary complexes displaying a range of binding, and therefore cross‐linking, dynamics. We determined that the mechanical strength of these materials is correlated directly with a high energetic barrier for the dissociation of the CB[8] ternary complex cross‐links, whereas facile and rapid self‐healing requires a low energetic barrier to ternary complex association. The versatile CB[8] ternary complex has, therefore, proven to be a powerful asset for improving our understanding of challenging property–structure relationships in supramolecular systems and their associated influence on the bulk behavior of dynamically cross‐linked materials.     

O-atom effect on the dynamic balance between redox-induced viologen derivative radical and its dimer modulated by cucurbit[8]uril

A series of viologen derivatives were synthesised, which can form stable 1:1 inclusion complexes with cucurbit[8]uril (CB[8]) in aqueous solution. The one-electron-reduced viologen radical cations and its dimerisation encapsulated into CB[8] were studied spectroscopically. The monomer–dimer dynamic balance would exist in the molecules containing O-atom, while the molecules without O-atom retain the form of radical monomer in CB[8] cavity. The result demonstrated that the dynamic balance of radical monomer and dimer of these complexes can be modulated by CB[8].     

A study of binding interactions between terpyridine derivatives and cucurbit[10]uril

The binding interactions of a series of 2,2′:6′,2″-terpyridine (TPY) derivatives and their metal complexes with cucurbit[10]uril (CB[10]) were investigated by ¹H NMR, UV/Vis, emission spectroscopy, and ESI mass spectrometry. ¹H NMR titrations revealed CB[10] could encapsulate methylated TPY (MTPY), and the binding ratio between guest MTPY and host was 1:1 and 2:1 via ESI-MS characterization. For the transition metal complexes composed of Fe(II) or Ru(II) or Rh(III) and TPY derivatives, the octahedral TPY?metal?TPY core can be included in the cavity of CB[10]. Three binding modes (1:1, 1:2 and 1:3) have been detected for the binding of the metal?MPTY complexes with CB[10] by ESI-MS.     

Controlling the extent of spin exchange coupling in 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) biradicals via molecular recognition with cucurbit[n]uril hosts

The binding interactions between two paramagnetic cobaltocenium guests and the hosts cucurbit[7]uril (CB7) and cucurbit[8]uril (CB8) were investigated using a combination of electronic absorption, NMR, and electron paramagnetic resonance (EPR) spectroscopies, mass spectrometry, and X-ray crystallography. Guest 1, (4-amido-2,2,6,6-tetramethylpiperidine-1-oxyl)cobaltocenium, forms very stable inclusion complexes with CB7 and CB8. However, CB7 interacts with 1 by including the organometallic cobaltocenium unit, while CB8 engulfs the TEMPO residue. The corresponding equilibrium association constant (K) values are 2.8 ± 0.3 × 10(6) M(-1) for CB7?1 and 2.1 ± 1.0 × 10(8) M(-1) for CB8?1. Biradical guest 2, 1,1'-bis(4-amido-2,2,6,6-tetramethylpiperidine-1-oxyl)cobaltocenium, forms a very stable ternary complex with two CB8 hosts, in which each 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) residue is encircled by a host molecule. The structure of this ternary complex was confirmed in the solid state using single-crystal X-ray diffraction. Binding of the TEMPO side arms by the CB8 hosts gradually decreases the observed level of spin exchange coupling between the two nitroxide groups. In the final 2:1 complex, no spin exchange coupling was observed, but the initial levels of spin exchange coupling could be regenerated in a reversible fashion by adding a competing guest, adamantyltrimethylammonium (AdTMA), to the solution. The binding interactions between 2 and CB7 are similar but the stabilities of the 1:1 and 2:1 complexes are much lower than those of the corresponding CB8 complexes.     

Specific binding effects for cucurbit[8]uril in 2,4,6-triphenylpyrylium-cucurbit[8]uril host-guest complexes: observation of room-temperature phosphorescence and their application in electroluminescence

2,4,6-Triphenylpyrylium (TP(+)) forms host-guest complexes with cucurbiturils (CBs) in acidic aqueous solutions. (1)H NMR spectroscopic data indicates that complexation takes place by encapsulation of the phenyl ring at the four position within CB. Formation of the complex with CB[6] and CB[7] leads to minor shifts in the fluorescence wavelength maximum (lambda(fl)) or quantum yield (Phi(fl)). In sharp contrast, for complexes with CB[8], the emission results in the simultaneous observation of fluorescence (lambda(fl)=480 nm, Phi(fl)=0.05) and room-temperature phosphorescence (lambda(ph)=590 nm, Phi(ph)=0.15). The occurrence of room-temperature phosphorescence can be used to detect the presence of CB[8] visually in solution. Molecular modeling and MM2 molecular mechanics calculations suggest that this effect arises from locking the conformational mobility of the 2- and 6-phenyl rings as a result of CB[8] encapsulation. The remarkably high room-temperature phosphorescence quantum yield of the TP(+)@CB[8] complex has been advantageously applied to develop an electroluminescent cell that contains this host-guest complex. In contrast, analogous cells prepared with TP(+) or TP(+)@CB[7] fail to exhibit electroluminescence.     

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.