Uril Molecules Research Articles

Thixotropic Hydrogels Based on Laponite® and Cucurbituril for Delivery of Lipophilic Drug Molecules.

Nowadays the use of hydrogels for biomedical purposes is increasing because of their interesting features that allow the development of targeted drug delivery systems. Herein, hydrogel based on Laponite® (Lap) clay mineral as gelator and cucurbit[6]uril (CB[6]) molecules were synthetized for the delivery of flufenamic acid (FFA) for potential topical application. Firstly, the interaction between CB[6] and FFA was assessed by UV-vis spectroscopic measurements and molecular modeling calculations. Then, the obtained complex was used as filler for Lap hydrogel (Lap/CB[6]/FFA). The properties of the hydrogel in terms of viscosity and, self-repair abilities were investigated; its morphology was imaged by scanning electron and polarized optical microscopies. Furthermore, the changes in the hydrodynamic radii and in the colloidal stability of CB[6]/Lap mixture were investigated in terms of translational diffusion from dynamic light scattering and ζ-potential measurements. Finally, the kinetic in vitro release of FFA, from Lap/CB[6]/FFA hydrogel, was studied in a medium mimicking the pH of skin and the obtained results were discussed both by an experimental point of view and by molecular modeling calculations.

Investigation of Copper-64-Based Host-Guest Chemistry Pretargeted Positron Emission Tomography.

Pretargeting is a technique that uses macromolecules as targeting agents for nuclear imaging and therapy with the goal of reducing the radiation toxicity to healthy tissues often associated with directly radiolabeled macromolecules. In pretargeting, a macromolecule is radiolabeled in vivo at the target site using a radiolabeled small molecule (radioligand) that interacts with the macromolecule with high specificity. We report an investigation of host-guest chemistry-driven pretargeting using copper-64 radiolabeled ferrocene (Fc; guest) compounds and a cucurbit[7]uril (CB7; host) molecule functionalized carcinoembryonic antigen targeting hT84.66-M5A monoclonal antibody (CB7-M5A). Two novel ferrocene-based radioligands ([64Cu]Cu-NOTA-PEG3-Fc and [64Cu]Cu-NOTA-PEG7-Fc) were prepared, and their in vitro stability, pharmacokinetic in vivo profile in healthy mice, and pretargeting performance in a subcutaneous BxPC3 human pancreatic cancer cell xenograft mouse model were compared. The antibody dosing was optimized using a zirconium-89 radiolabeled M5A antibody ([89Zr]Zr-DFO-M5A) in a BxPC3 xenograft model, and the dosimetry of [89Zr]Zr-DFO-M5A and the pretargeting approach were compared. Finally, the effects of varying lag times up to 9 days between CB7-M5A and radioligand injection were investigated. In vivo pretargeting studies with both ferrocene radioligands resulted in specific tumor uptake (p = 0.0006 and p = 0.003) and also showed that the host-guest-based pretargeting approach excels with extended lag times up to 9 days with good tumor localization, suggesting that host-guest pretargeting may be suitable for use without clearing agents which have complicated clinical application of this technique. To our knowledge, the reported lag time of 9 days is the longest investigated lag time in any reported pretargeting studies.

Synthesis and crystal structure of new coordination polymers based on sodium aqua complexes and macrocyclic cavitand cucurbit[6]uril

The crystals of the compounds [Na4(H2O)14CB[6]](bdc)2 · 13H2O (1) and [Na6(H2O)19CB[6]]-(bdc)3 ·15H2O (2) were obtained by heating an aqueous solution of sodium terephthalate (Na2bdc) and cucurbit[6]uril (CB[6]). According to the single-crystal X-ray diffraction data, the sodium aqua complexes and cucurbit[6]uril molecules form chains (in structure 1) and layered metal-organic frameworks (in structure 2). The structures of the sodium aqua complexes [Na3(H2O)10]3+ in 1 and [Na6(H2O)19]3+ in 2 have been previously unknown. When submitted to ultraviolet radiation, crystals of 1 and 2 exhibit luminescence with an emission maximum at 428 and 434 nm, respectively.

Observing Host-Guest Interactions at Molecular Interfaces by Monitoring the Electrochemical Current.

Macrocyclic cucurbit[n]uril (CB[n]) molecules have triggered renewed interest because of their outstanding capabilities as host molecules to selectively interact with a wide range of small guest molecules. Here, CB[7]-based host–guest interactions were investigated for a guest-modified nanoelectrode by monitoring the electrochemical current. A ferrocene (Fc)-terminated molecule immobilized on a gold nanoelectrode (GNE) showed suitable affinity with CB[7] when the effective exposing area of the GNE was between 5.3 and 12 μm2 and the bias applied on the GNE was −500 mV. Monitoring the dynamics of nanoparticles (NPs) on a nanoelectrode provides new insights into the host–guest interactions at molecular interfaces.

Zinc and Cobalt Aqua Complexes with Cucurbit[6]uril: Syntheses and Crystal Structures

Supramolecular complexes [Zn(H2O)4(C36H36N24O12)](NO3)2 · 6.5H2O (I), [Zn(H2O)4-(C36H36N24O12)](NO3)2 · 7H2O (II), and [Co(H2O)4(C36H36N24O12)](NO3)2 · 7H2O (III) are synthesized by the slow (for I and III) and fast (for II) cooling (after reflux) of aqueous solutions of a mixture of salts of the corresponding metals and cucurbit[6]uril. According to the X-ray diffraction data (СIF files CCDC nos. 1862494 (I), 1862495 (II), and 1862496 (III)), the supramolecular complexes are the first examples of the direct coordination of the zinc and cobalt atoms to the cucurbit[6]uril molecule. Compounds I–III are characterized by X-ray diffraction analysis, thermogravimetry, IR spectroscopy, and elemental analysis.

Piperine Encapsulation within Cucurbit[n]uril (n=6,7): A Combined Experimental and Density Functional Study

AbstractThe formation of host‐guest between piperine and cucurbit[n]uril (n=6,7) molecules were studied using experimental and density functional theory (DFT) calculations. The host‐guest complexation was monitored using UV‐Visible and isothermal calorimetric (ITC) methods. The obtained Jobs plot indicate the formation of 1:1 complex. ITC analysis shows a moderate binding of the guest to the host molecules. The enthalpy of binding and the free energy of formation were negative indicating the facile formation of inclusion complex at room temperature. DFT studies confirm the formation of stable inclusion complexes. In stable inclusion complex of piperine with cucurbit[6]uril, the aromatic moiety was found to be inside the cucurbituril cavity, while in the cucurbit[7]uril inclusion complex, the piperidine moiety was inside the cavity, which was further confirmed by time dependent‐DFT study. The global reactivity descriptors analysis, indicate the formation of piperine inclusion complex with cucurbit[7]uril, could prevent the isomerization reaction of piperine. Atoms‐in‐molecules analysis shows the presence of extra inter and intramolecular bond critical points in the piperine inclusion complex with cucurbit[7]uril, which accounts for its extra stability. The computed intermolecular bond parameters confirm the existence of a non‐covalent with partial electrostatic interactions between the guest and host molecules. Energy decomposition analysis, suggest the Pauli repulsion to be higher for the cucurbit[6]uril inclusion complex, while the dispersion plays a major role in stabilizing the cucurbit[7]uril inclusion complex, which was further corroborated by noncovalent index analysis.

Uranyl Complexes as Scaffolding or Spacers for Cucurbit[6]uril Molecules in Homo‐ and Heterometallic Species, Including a Uranyl–Lanthanide Complex

The reaction of uranyl nitrate with cucurbit[6]uril (CB6) and carboxylic or sulfonic ligands under hydrothermal conditions and in the presence of additional metal cations (KI or CeIII) or cosolvents provided four complexes, which were crystallographically characterized. The compound [(UO2)2K2(CB6)(adc)2(NO3)2(H2O)2]·5H2O (1), where H2adc is 1,3‐adamantanedicarboxylic acid, crystallizes in the form of a central K2(CB6)2+ column surrounded by two one‐dimensional (1D) polymeric UO2(adc)(NO3)– chains attached to the column by nitrate bridges, with a perfect match of the repeat lengths in the two subunits. The longer 1,3‐adamantanediacetic acid (H2adac) gives the complex [(UO2)2(adac)2(HCOOH)2]·CB6·6H2O (2), in which the 1D uranyl‐containing polymer and columns of CB6 molecules form a layered arrangement held by weak CH···O hydrogen bonds. The complex formed with the dipotassium salt of methanedisulfonic acid (K2mds), [(UO2)2K2(CB6)(mds)2(OH)2(H2O)8]·4H2O (3), is a 1D polymer, in which K2(CB6)2+ units are connected to one another by doubly hydroxide‐bridged uranyl dimers in which the disulfonates are terminal, chelating ligands; connection between the two subunits is solely through potassium oxo‐bonding to uranyl. The complex [(UO2)2Ce2(CB6)(C2O4)3(NO3)4(H2O)6]·2H2O (4) is a 1D polymer containing bridging oxalate ligands formed in situ, in which CB6 is coordinated to the lanthanide cations only; one nitrate ligand and one water ligand, hydrogen‐bonded to each other, are included in the CB6 cavity, with the possible occurrence of interactions between nitrate oxygen atoms and ureido carbon atoms.

Host-guest interaction of 3-hydroxyflavone and 7-hydroxyflavone with cucurbit [7]uril: A spectroscopic and calorimetric approach

The modulation of photophysical behaviour of small organic molecules in the presence of macrocycles is one of the most interesting areas of research. In this work we reported the interaction of two biologically active molecules 3-hydroxyflavone and 7-hydroxyflavone with macrocyclic host cucurbit [7]uril in aqueous medium. To investigate the change of photophysical properties of these two flavones, we have used steady state absorption, fluorescence, time resolved fluorescence emission spectroscopy and isothermal titration calorimetric technique. It is observed that on complexation with cucurbit [7]uril, the excited state proton transfer processes in both flavones have been facilitated. Isothermal titration calorimetric method was used in order to investigate the involvement of thermodynamic parameters in complexation between flavone with cucurbit [7]uril. The changes in thermodynamic properties due to the complexation of the flavones molecules with cucurbit [7]urils help to understand about the governing parameters involved in this complexation. The inclusion of flavone molecules inside the cavity of cucurbit [7]uril molecules was studied theoretically to decipher the molecular orientation of flavones in the presence of cucurbit [7]uril. The structure of HOMO and LUMO of the complexes between cucurbit [7]uril with flavones was reported. This study will be helpful to get the knowledge about the modulation of photophysical properties of the flavones molecules on addition of macrocyclic host cucurbit [7]uril. This study will be helpful for the use of cucurbit [7]uril as a potential drug delivery system.

Smart supramolecular sensing with cucurbit[n]urils: probing hydrogen bonding with SERS.

Rigid gap nano-aggregates of Au nanoparticles formed using cucurbit[n]uril (CB[n]) molecules are used to investigate the competitive binding of ethanol and methanol in an aqueous environment. We show it is possible to detect as little as 0.1% methanol in water and a ten times higher affinity to methanol over ethanol, making this a useful technology for quality control in alcohol production. We demonstrate strong interaction effects in the SERS peaks, which we demonstrate are likely from the hydrogen bonding of water complexes in the vicinity of the CB[n]s.

Halloysite nanotubes loaded with peppermint essential oil as filler for functional biopolymer film

The purpose of this paper is to show how a functional bionanocomposite film with both antioxidant and antimicrobial activities was successfully prepared by the filling of a pectin matrix with modified Halloysite nanotubes (HNT) containing the essential peppermint oil (PO). Firstly, HNT surfaces were functionalized with cucurbit[6]uril (CB[6]) molecules with the aim to enhance the affinity of the nanofiller towards PO, which was estimated by means of HPLC experiments. The HNT/CB[6] hybrid was characterized by several methods (thermogravimetry, FT-IR spectroscopy and scanning electron microscopy) highlighting the influence of the supramolecular interactions on the composition, thermal behavior and morphology of the filler. Then, a pectin+HNT/CB[6] biofilm was prepared by the use of the casting method under specific experimental conditions in order to favor the entrapment of the volatile PO into the nanocomposite structure. Water contact angle measurements, thermogravimetry and tensile tests evidenced the effects of the modified filler on the thermo-mechanical and wettability properties of pectin, which were correlated to the microscopic structure of the biocomposite film. In addition, PO release in food simulant solvent was investigated at different temperatures (4 and 25°C), whereas the antioxidant activity of the nanocomposite film was estimated using the DPPH method. Finally, we studied the in vitro antibacterial activity of the biofilm against Escherichia coli (Gram-negative) and Staphylococcus aureus (Gram-positive), which were isolated by beef and cow milk, respectively. These experiments were carried out at specific temperatures (4, 37 and 65°C) that can be useful for a multi-step food conservation. This paper puts forwards an easy strategy to prepare a functional sustainable edible film with thermo-sensitive antioxidant/antimicrobial activity.

Encapsulation of sulfur, oxygen, and nitrogen mustards by cucurbiturils: a DFT study

A density functional theory analysis on the encapsulation of sulphur mustard (HD), oxygen mustard (OM), and nitrogen mustard (N1) by cucurbit[7]uril (CB[7]) molecule was carried out using the dispersion corrected B3LYP-D/6-311+G(d,p) method. The encapsulation of HD, OM and N1, have favorable interaction energy and are found to be functional dependent. Amongst the encapsulated molecules, N1@CB[7] has the least highest occupied molecular obitual- lowest unoccupied molecular orbital gap, which indicates that nitrogen mustard can be reversible stored inside CB[7]. Molecular electrostatic potential studies shows that charge transfer occurs between the host and guest molecule during the complexation process. Atoms-in-molecules analysis at the intermolecular bond critical points, have positive charge density, negative Laplacian and close to zero value of total energy density, indicating the depletion of electronic charge along the bond paths, which implies an electrostatic nature of bonding. The natural bond order analysis of N1@CB[7] complex with highest strongest second order perturbation energies are due to the donation of lone pair nitrogen of CB molecule to the guest molecule and the back donation of charge, leads to the high interaction energy. Non covalent index isosurface clearly show the existence of hydrogen bonding and van der Walls intermolecular interaction between the guest molecule and the host CB[7].

Toward the Design of Highly Stable Small Colloidal SERS Substrates with Supramolecular Host–Guest Interactions for Ultrasensitive Detection

In this work, we report a simple strategy to obtain ultrasensitive SERS nanostructures by self-assembly of Au nanospheres (NSs). This novel protocol allow us to obtain in a reproducible manner Au NS dimers using cucurbit[6]uril (CB[6]) molecules as linkers. The resulting dimers are stable in colloidal dispersion over several days, generating in this way nanostructures with highly reproducible hot spots. This feature is due to the precise subnanometric control of the molecules that generates interparticle distance and, at the same time, of the capability of placing analyte molecules just within these junctions of ultrahigh field enhancement due to the host–guest properties of the CB[6] molecule. The dimer formation is based on the modification of the metal surface with cysteamine molecules (Cys) previous incubation with CB[6] molecules. The cysteamine-functionalized NSs (Cys/NSs) are positive charged due to the protonation of the amine groups of the Cys molecule at the working pH. These positive groups interact through H-bonds with the carbonyls groups at the portal of the CB[6] molecules. The dimer formation is based on the stoichiometric control between Cys/NPs and CB[6] (ratio 2:1), generating a gap of 1.8 nm and giving rise to SERS enhancements of around 108. The host–guest properties of the CB[6] molecule are used to detect the average SERS enhancement produced by adding methyl viologen (MV) as plasmonic probe. It was found that the average analytical enhancement factor (AEF) for MV is as good as that obtained for the CB[6] itself (around 108).

A novel shell-like supramolecular assembly of 4,4'-bipyridyl derivatives and a twisted cucurbit[14]uril molecule.

This work showed that the 4,4'-bipyridyl group and alkyl chains of 4,4'-bipyridyl derivatives are completely located in the shell-like cavity of the twisted cucurbit[14]uril molecule and formed novel shell-like 1 : 1 inclusion complexes. As it is enthalpy-driven the complexation benefits from ion-dipole interactions.

The origin of the room-temperature stability of [TTF]˙⁺⋅⋅⋅[TTF]˙⁺ long, multicenter bonds found in functionalized π-[R-TTF]₂²⁺ dimers included in the cucurbit[8]uril cavity.

A computational study is performed to identify the origin of the room-temperature stability, in aqueous solution, of functionalized π-[R-TTF]2(2+) dimers (TTF=tetrathiafulvalene; R=(CH2OCH2)5CH2OH) included in the cavity of a cucurbit[8]uril (CB[8]) molecule. π-[R-TTF]2(2+) dimers in pure water are weakly stable, and are mostly dissociated at room temperature. Upon addition of CB[8] to an aqueous π-[R-TTF]2(2+) solution, a (π-[R-TTF]2⊂CB[8])(2+) inclusion complex is formed. The same complex is obtained after the sequential inclusion of two [R-TTF](.+) monomers in the CB[8] molecule. Both processes are thermodynamically and kinetically allowed. π-[R-TTF]2(2+) dimers dissolved in pure water present a [TTF](.+)⋅⋅⋅[TTF](.+) long, multicenter bond, similar to that already identified in π-[TTF]2(2+) dimers dissolved in organic solvents. Upon their inclusion in CB[8], the strength and other features of the [TTF](.+)⋅⋅⋅[TTF](.+) long, multicenter bond are preserved. The room temperature stability of the π-[R-TTF]2(2+) dimers included in CB[8] is shown to originate in the π-[R-TTF]2(2+)⋅⋅⋅CB[8] interaction, the strength of which comes from a strongly attractive electrostatic component and a dispersion component. Such a dominant electrostatic term is caused by the strongly polarized charge distribution in CB[8], the geometrical complementarity of the π-[R-TTF]2(2+) and CB[8] geometries, and the amplifying effect of the 2+ charge in π-[R-TTF]2(2+).

A highly luminescent tetramer from a weakly emitting monomer: acid- and redox-controlled multiple complexation by cucurbit[7]uril.

The tetrahedral, shape-persistent molecule 1(4+), containing four pyridylpyridinium units connected through a central carbon atom, exhibits unexpected photophysical properties including a substantially redshifted absorption (2350 cm(-1)) and a very strong fluorescence (Φem = 40 %), compared with the monomer 2(+) (Φem = 0.4 %). Density functional theory calculations on the structure and spectroscopic properties of 1(4+) and 2(+) show that exciton interactions, homoconjugation, and orbital nature account for the observed differences in their photophysical properties. The protonated tetramer binds four cucurbit[7]uril molecules and the host/guest interactions can be controlled by chemical (acid/base) as well as redox stimuli.

Features of the microstructure of gold nanoparticles inside cavities of cucurbit[7]uril according to XAFS spectra

The Au L3 X-ray absorption fine structure (XAFS) spectra have been measured for gold nanoparticles with the calibrated size dAu ∼ 1 nm in the cavities of cucurbit[7]uril molecules. The features of their electronic structure and microstructure have been characterized. It has been found that gold clusters in cavities of cucurbit[7]uril are characterized by smaller (by 0.01–0.02 A) interatomic distances and a noticeably larger (by a factor of 3 at 12 K) Debye-Waller factor as compared to bulk gold. Analysis of the experimental results and their comparison with the model calculations show that the special properties of atoms on the surface of small metal (gold) particles are not determined by their position at the vertices and edges of small clusters; they are likely attributed to the structural disorder, deformations, and stresses, which increase with a decrease in the size of the particles.

Tetrachloride transition-metal dianion-induced coordination and supramolecular self-assembly of strontium dications to cucurbit[8]uril

In the present work, we describe a kind of novel cucurbit[8]uril-based coordination supramolecular self-assembly taking place in the presence of tetrachloride transition-metal dianions ([MtransCl4]2−, Mtrans = Cd, Zn, Cu, Co) in HCl solution. As reported previously, the “honeycomb effect” of the tetrachloride transition-metal dianion ([MtransCl4]2− has been observed in the coordination of strontium cations to cucurbit[8]uril molecules (Q[8]s). It seems that the [MtransCl4]2− anions form a honeycomb structure with hexagonal cells filled with Sr2+–Q[8] linear coordination polymers in which the Sr2+ cations coordinate to Q[8] molecules and form zigzag coordination polymers.

Synthesis, crystal structures, and properties of [Ca(H2O)2(Dmf@CB[6])(Bdc)] · DMF · 4H2O and [Ca(H2O)3(Dmf@CB[6])]Cl2 · 2H2O

Complexes [Ca(H2O)2(Dmf@CB[6])(Bdc)] · DMF · 4H2O (I) and [Ca(H2O)3(Dmf@CB[6])]Cl2 · 2H2O (II) are synthesized by the heating (95°C) of a mixture of calcium chloride and cucurbit[6]uril (CB[6]) in a mixture of dimethylformamide (DMF) and water with the addition of terephthalic acid (H2Bdc) in the case of complex I or triethylamine for complex II. The compounds are characterized by X-ray diffraction analysis, IR spectroscopy, and thermogravimetric and elemental analyses. The luminescence spectra are also recorded. According to the X-ray diffraction data, the calcium atom is coordinated by the oxygen atoms of the cucurbit[6]uril molecule, water molecules, and terephthalate anion (for I). The internal cavity of the cavitand is occupied by DMF.

Uranyl Ion Complexes with Ammoniobenzoates as Assemblers for Cucurbit[6]uril Molecules

The crystal structures of the complexes formed under hydrothermal conditions by uranyl ions with 4-aminobenzoic (HL1), 4-amino-3-methylbenzoic (HL2), 4-(aminomethyl)benzoic (HL3), and 3-amino-5-hydroxybenzoic (HL4) acids, in the presence of cucurbit[6]uril (CB6), have been determined. These ligands have been chosen because, in their zwitterionic form, they display both a metal-complexing carboxylate group and an ammonium group able to associate with CB6 through ion-dipole and hydrogen bonding interactions. The complexes [H2NMe2]2[(UO2)2(L1)2O(OH)(H2O)]2·CB6·15H2O (1) and [H2NMe2]2[(UO2)2(L2)2O(OH)(H2O)]2·CB6·17H2O (2) were obtained in the presence of dimethylformamide, which gives dimethylammonium ions in situ. The latter are held at the CB6 portals, while the tetranuclear uranyl complex with the aminobenzoate anions is not bound to CB6. The neutral, ammonium-containing form of the ligand is present in [UO2(HL3)(OH)(HCOO)(H2O)]2·2CB6·2DMF·14H2O (3), in which the di(μ2-hydroxo)-bridged, dinuclear uranyl complex displays two diverging, monodentate HL3 ligands. The latter are associated with two CB6 molecules to give a dumbbell-shaped supramolecular assembly. Three CB6 molecules are assembled around a tetranuclear uranyl complex in [(UO2)4(HL3)2(L3)O2(OH)2(H2O)4]·2CB6·0.5CB8·HL3·NO3·20H2O (4), with two of them being bridging and giving rise to a one-dimensional, linear supramolecular architecture. Finally, the 3-amino substituted ligand HL4 gives the highly symmetric complex [UO2(HL4)(L4)2]·3CB6·16H2O (5), in which the uranyl ion is chelated by three carboxylate groups. Three CB6 molecules are assembled around the planar complex to give a triangular, discrete species. In compounds 3–5, the usual packing of CB6 molecules into columns or layers is not retained as it is frequently in the presence of uranyl complexes. This is due to the CB6-assembling role of the heterodifunctional ligands, which hold the CB6 molecules at the periphery of mono-, di-, or tetranuclear uranyl complexes of quite usual, planar geometry.

Novel supramolecular compounds based on Cucurbit[6]uril, 1,8-diaminooctane and octahedral thiohydroxo anions with cluster core [Re 6S 8

Supramolecular compounds {C 8N 2H 22@Cuc[6]}{Re 6S 8(H 2O) 2(OH) 4}·18H 2O ( 1), and K 2{C 8N 2H 22@Cuc[6]}{Re 6S 8(OH) 6}·14H 2O ( 2) were obtained by crystallization from aqueous solutions that contained the macrocyclic cavitand cucurbit[6]uril (C 36H 36N 24O 12), 1,8-diaminooctane and the cluster thiohydroxo complex [Re 6S 8(OH) 6] 4−. The resultant composition of the formed compounds depends on the experiment technique. According to the X-ray diffraction analysis, 1,8-diaminooctane molecules are encapsulated within the cavity of the cucurbit[6]uril molecules in such a way that the aminogroups are above and below the plane of the cavitand. The 1,8-diaminooctane molecules formed hydrogen bonds with the cavitand and the cluster thiohydroxo complexes to give chains.