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.     

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.     

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.     

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.     

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.     

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.     

Effects of cucurbit[7]uril on enzymatic activity

The macrocyclic host cucurbit[7]uril exhibits highly specific inhibitory effects on the activity of proteases, which can be analyzed by a host-substrate complexation model.     

Absolute and relative binding affinity of cucurbit[7]uril towards a series of cationic guests

We determined the relative binding constants (K_rel) for guests 1–19 towards cucurbit[7]uril by ¹H NMR competition experiments in 100 mM Na₃PO₄-buffered D₂O. In these experiments, we use guest 11 as the reference guest because of its strong binding towards CB[7] and its advantageous spectroscopic properties (e.g. slow exchange on NMR timescale and distinct resonances for key protons). To convert the determined K_rel values to absolute binding constants, we performed a direct UV–vis titration of 1 with CB[7] to determine K_a for CB[7]√1. The trends in the determined values of K_rel and K_a are discussed with respect to the importance of the concentration of metal ions in the buffer, the influence of hydroxyl groups located at the portals or inside the CB[7] cavity, geometry of the guest (e.g. regioisomers), the number of guest C atoms and secondary electrostatic interactions.     

Examination of cucurbit[7]uril and its host-guest complexes by diffusion nuclear magnetic resonance

The self-diffusion of cucurbit[7]uril (CB[7]) and its host-guest complexes in D2O has been examined using pulsed gradient spin-echo nuclear magnetic resonance spectroscopy. CB[7] diffuses freely at a concentration of 2 mM with a diffusion coefficient (D) of 3.07 x 10(-10) m(2) s(-1). At saturation (3.7 mM), CB[7] diffuses more slowly (D = 2.82 x 10(-10) m(2) s(-1)) indicating that it partially self-associates. At concentrations between 2 and 200 mM, CsCl has no effect on the diffusion coefficient of CB[7] (1 mM). Conversely, CB[7] (2 mM) significantly affects the diffusion of 133Cs+ (1 mM), decreasing its diffusion coefficient from 1.86 to 0.83 x 10(-9) m(2) s(-1). Similar changes in the rate of diffusion of other alkali earth metal cations are observed upon the addition of CB[7]. The diffusion coefficient of 23Na+ changes from 1.26 to 0.90 x 10(-9) m(2) s(-1) and 7Li+ changes from 3.40 to 3.07 x 10(-9) m(2) s(-1). In most cases, encapsulation of a variety of inorganic and organic guests within CB[7] decreases their rates of diffusion in D2O. For instance, the diffusion coefficient of the dinuclear platinum complex trans-[[PtCl(NH3)2}2mu-dpzm](2+) (where dpzm is 4,4'-dipyrazolylmethane) decreases from 4.88 to 2.95 x 10(-10) m(2) s(-1) upon encapsulation with an equimolar concentration of CB[7].     

Interaction between cucurbit[8]uril and viologen derivatives

The interaction between cucurbit[8]uril (Q[8]) and a series of symmetric viologen derivatives having aliphatic substituents of variable length [N,N′-dialkyl-4,4′-bipyridinium dianions; alkyl = CH₃(CH₂) _n –, n = 0 (MV²⁺), 1 (EV²⁺), 2 (PV²⁺), 3 (BV²⁺), 4 (FV²⁺), 5 (HV²⁺) or 6 (SV²⁺); BPY²⁺ = diprotonated 4,4-bipyridine], determined by ¹H NMR and electronic absorption spectroscopy methods, is described. Some different binding models were observed in this work when compared to the interactions between cucurbit[7]uril (Q[7]) and these guests. The experimental results revealed that the binding site of the guests by Q[8] depended strongly on the length of the aliphatic substituents on the 4,4′-bipyridinium nucleus. While a 1:2 complex was observed for Q[8]-BPY²⁺ under acidic conditions, a 1:1 complex was formed for Q[8]-viologen derivatives with chains shorter than four carbon atoms. However, multiple Q[8] molecules could be threaded on the longer-chain FV²⁺, HV²⁺ or SV²⁺ molecules to form 2:1 and even possibly 3:1 complexes.     

Modes of binding interaction between viologen guests and the cucurbit[7]uril host

[structure: see text] Host-guest interactions between cucurbit[7]uril (CB7) and a series of dialkyl-4,4'-bipyridinium (viologen) dicationic guests were investigated by NMR spectroscopy. CB7 includes the aromatic nucleus of short chain viologens, but the mode of interaction is different with longer chain viologens due to the favorable hydrophobic interactions between the terminal alkyl substituents and the inner cavity of the host. A new pseudorotaxane was designed and synthesized on the basis of viologen-CB7 binding interactions.     

Supramolecular complexation of homocysteine and cysteine with cucurbit[7]uril

Supramolecular complexation of two bio-thiols, homocysteine (Hcys) and cysteine (Cys), by cucurbit[7]uril (CB[7]) has been fully investigated by ¹H NMR spectroscopy, mass spectrometry, isothermal titration calorimetry, and the results were further verified with computational investigations. NMR titration experimental results obviously indicate that the binding stoichiometry of CB[7] to Hcys is 1:1 and to Cys is 1:2 in aqueous solution. The binding constants and thermodynamic parameters associated with the complexation between CB[7] and the bio-thiols were determined by isothermal titration calorimetry. The energy-minimized structures of the supramolecular complexes of CB[7] with Hcys and Cys were determined and provide good agreement with the experimental results. The CB[7] cavity is sufficient to include the two Cys, but is unable to accommodate two Hcys due to steric hindrance. The differing binding abilities of Hcys and Cys in aqueous solution towards CB[7] host may lead to discriminate them.     

A stable cis-stilbene derivative encapsulated in cucurbit[7]uril

cis-Diaminostilbene dihydrochloride encapsulated in cucurbit[7]uril does not spontaneously isomerize to the trans isomer at room temperature as a result of the strong host-guest interactions including strong hydrogen bonds between the two protonated amine termini of the C-shaped guest and the portal oxygen atoms of the host.     

The 1:1 host-guest complexation between cucurbit[7]uril and styryl dye

The photophysical properties of aqueous solution of styryl dye, 4-[(E)-2-(3,4-dimethoxyphenyl)ethenyl]-1-ethylpyridinium perchlorate (dye 1), in the presence of cucurbit[7]uril (CB[7]) was studied by means of fluorescence spectroscopy methods. The production of 1:1 host-guest complexes in the range of CB[7] concentrations up to 16 μM with K = 1.0 × 10(6) M(-1) has been observed, which corresponds to appearance of the isosbestic point at 396 nm in the absorption spectra and a 5-fold increase in fluorescence intensity. The decay of fluorescence was found to fit to double-exponential functions in all cases; the calculated average fluorescence lifetime increases from 145 to 352 ps upon the addition of CB[7]. Rotational relaxation times of dye 1 solutions 119 ± 14 ps without CB[7] and 277 ± 35 ps in the presence of CB[7] have been determined by anisotropy fluorescence method. The comparison of the results of quantum-chemical calculations and experimental data confirms that in the host cavity dye 1 rotates as a whole with CB[7].     

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.     

Supramolecular chemistry of macrocyclic cavitand cucurbit[7]uril with isoleucine

Russian Chemical Bulletin - The l-isoleucine — cucurbit[7]uril system in solution was studied at various concentrations by NMR spectroscopy. The 1H NMR spectra of the L-isoleucine complex...     

Supramolecular assembly of Hoechst-33258 with cucurbit[7]uril macrocycle

Molecular assemblies of potential guest molecules through non-covalent host-guest interactions have found immense use in many applied areas. In this study supramolecular interaction of a biologically important dye Hoechst-33258 (H33258) has been investigated in aqueous solutions at different pHs, in the presence of a macrocyclic host, namely, cucurbit[7]uril (CB7). The pH dependent emission behaviour of H33258 is inherently connected with its protolytic equilibria which allow the dye in different geometrical conformations. This pH dependent structural orientation is greatly affected by the complexation with CB7. The significant structural changes in the monocationic H33258 brought out by CB7 at pH 7 have been documented in the fluorescence emission and lifetime data, which are comparatively less affected in case of the dicationic form, which is prominent in dye solutions at pH 4.5. The strong ion-dipole interactions provided by the carbonyl portals of the CB7 host adequately stabilize the CB7-H33258 complex, both in 1:1 and 2:1 stoichiometries at both the pH conditions. The Job's plot method, fluorescence anisotropy, NMR measurements and geometry optimization calculations confirm the stoichiometric arrangement and are found to be tunable with the addition of metal ions. The non-covalently stabilized assembly brings out large enhancement in the fluorescence emission due to the unique structural orientation attained by H33258, which reduces the non-radiative relaxation pathways. Comparison of the spectral data of the dye at different pH conditions in the absence and presence of CB7 proposes a large upward pK(a) shift due to CB7 encapsulation, thus providing a handy tool to modulate the photophysical characteristics of the guest molecules.