Β-cyclodextrin Host Research Articles

Inclusion induced second harmonic generation in low dimensional supramolecular crystals

A host–guest inclusion complexation self-assembly strategy was developed for the synthesis of SHG-active low dimensional supramolecular crystals (LDSCs). p-Nitroaniline guest molecules with high inherent second-order polarizability were introduced into the cavities of the β-cyclodextrin host to form supramolecular inclusion complexes, which were then assembled into microscale crystalline structures with an anti-solvent diffusion combined solvent-evaporation-induced self-assembly method. Two distinct types of LDSCs with controllable dimensions were obtained by altering the polarity of anti-solvents and the concentration of supramolecular monomers. Each type of LDSCs exhibited its characteristic SHG response to the polarized incident signals, which is attributed to the inherent crystal structures.

Large scale affinity calculations of cyclodextrin host-guest complexes: Understanding the role of reorganization in the molecular recognition process.

Host-guest inclusion complexes are useful models for understanding the structural and energetic aspects of molecular recognition. Due to their small size relative to much larger protein-ligand complexes, converged results can be obtained rapidly for these systems thus offering the opportunity to more reliably study fundamental aspects of the thermodynamics of binding. In this work, we have performed a large scale binding affinity survey of 57 β-cyclodextrin (CD) host guest systems using the binding energy distribution analysis method (BEDAM) with implicit solvation (OPLS-AA/AGBNP2). Converged estimates of the standard binding free energies are obtained for these systems by employing techniques such as parallel Hamitionian replica exchange molecular dynamics, conformational reservoirs and multistate free energy estimators. Good agreement with experimental measurements is obtained in terms of both numerical accuracy and affinity rankings. Overall, average effective binding energies reproduce affinity rank ordering better than the calculated binding affinities, even though calculated binding free energies, which account for effects such as conformational strain and entropy loss upon binding, provide lower root mean square errors when compared to measurements. Interestingly, we find that binding free energies are superior rank order predictors for a large subset containing the most flexible guests. The results indicate that, while challenging, accurate modeling of reorganization effects can lead to ligand design models of superior predictive power for rank ordering relative to models based only on ligand-receptor interaction energies.

Simultaneous detection of CMPA and PMPA, hydrolytes of soman and cyclosarin nerve agents, by nanopore analysis

A sensitive nanopore-based analytical method was developed for the detection of cyclohexyl methylphosphonic acid (CMPA) and pinacolyl methylphosphonate (PMPA), hydrolytes of nerve agents soman and cyclosarin, respectively. The method uses a multi-functionalized α-hemolysin protein ion channel as the sensing element, with a host molecule β-cyclodextrin lodged in the lumen of the channel as a molecular adapter. The capture and release of CMPA/PMPA by the β-cyclodextrin host caused current modulations in the nanopore. Since the event residence times and amplitudes were significantly different, CMPA and PMPA could conveniently be differentiated and simultaneously quantitated.

Solid-state NMR and wide-angle X-ray diffraction study of hydrofluoroether/β-cyclodextrin inclusion complex

An inclusion complex (IC) composed of a hydrofluoroether (HFE) guest and a β-cyclodextrin (β-CD) host was newly prepared, and the crystalline structure and the thermal stability of the IC were examined using several analytical methods, including wide-angle X-ray diffraction (WAXD), solid-state NMR, thermogravimetric analysis (TGA), TG–mass spectrometry (TG–MS), and quantum chemical calculation. The WAXD patterns and elemental analysis identified that the IC of an HFE/β-CD form of a channel-type structure, in which one HFE molecule is included in a common cavity of two β-CD molecules. TGA and TG–MS analysis indicated that the HFE molecules included in β-CD are hardly evaporated or degraded up to the decomposition temperature of the β-CD host. Solid-state 13C NMR indicated that the β-CD ring structure was deformed by including an HFE molecule in it, and that the 19F NMR signals of the HFE guest were significantly shifted to higher frequencies by the inclusion due to the dielectric media effect in the cavity of β-CD. Moreover, the 19F NMR signals of HFE included in IC were further shifted after annealing at 150 °C, which reflected structural changes in HFE/β-CD IC caused at elevated temperatures. The WAXD patterns also confirmed that the packing structure along the crystalline b-direction of HFE/β-CDs, which penetrates the cavities of β-CDs, was compressed by annealing and transformed to a more stable structure.

Construction and transformation of stimuli-responsive vesicles from the ferrocene derivative supramolecular amphiphiles

The tough stimuli-responsive vesicles were prepared via electrochemical oxidation on the mixture solution of ferrocenylmethyl-trimethylammonium iodide (FcMI) and sodium deoxycholate (NaDC). The vesicle structure and morphology are characterized respectively by transmission electron microscopy (TEM), dynamic light scattering (DLS) and atomic force microscopy (AFM). The vesicle shells can be clearly observed by TEM with the thickness ranging from several to several tens of nanometers and their outer diameters at the range of 50–200nm. The formation of vesicular structures is also supported via AFM measurements. Such tough vesicles made up of ferrocene and deoxycholate blocks are redox-responsive, and their assembly or disassembly behaviors may be controlled by electrochemical methods through the change of ferrocene states between the neutral hydrophobic and the hydrophilic ferrocenium cation. In addition, the stimuli-responsive vesicles can also be formed from the supramolecular inclusion complex between the ferrocene blocks and the β-cyclodextrin hosts, which can then be transformed into nanotubes with time. The obtained results are significant for the preparation of smart supramolecular aggregates.

Fabrication of thermo-responsive hydrogels from star-shaped copolymer with a biocompatible β-cyclodextrin core

A thermally reversible hydrogel composed of a three-arm star copolymer with a specific host β-cyclodextrin (β-CD) center has been developed. The synthesis of this star copolymer initiates with β-CD core, from which sequential polymerization of a temperature-responsive poly(N-isopropylacrylamide) (PNIPAM) block and a hydrophilic poly(N,N-dimethylacrylamide) (PDMA) block as asymmetric arms (named β-CD-g-(PNIPAM-b-PDMA)3) is performed via RAFT protocol. Below the lower critical solution temperature (LCST) of PNIPAM segment, the polymer is of good water-solubility and exhibits a sol state. Upon thermal stimulus, free-standing hydrogels can be formed rapidly at sufficiently high concentrations. By comparing the sol–gel transition of the star polymer with that of its linear counterpart without this feature, we concluded that the special star-shape topology and the thermal-collapsed PNIPAM chains were responsible for this gelation behavior. The rheology measurements indicate the mechanical properties of the polymer hydrogels and the thermal reversibility of the sol–gel transition. Using Rhodamine B as a molecule to model a typical drug, we realize the favorable encapsulation and releasing process from the hydrogel, demonstrating that this star polymer has the potential to function as an injectable hydrogel for drug delivery and gene transport.

Electrochemical study of weak inclusion complex interactions by simultaneous MCR-ALS analyses of potential step-chronoamperometric data matrices

In this article, the analytical information obtained from the chronoamperometric data of a weak host–guest complexation was analyzed by multivariate curve resolution-alternative least square (MCR-ALS) as a powerful chemometrics method. As a model system, the complexation of dopamine with β-cyclodextrin was investigated. Whilst the voltammetric behavior of dopamine does not change significantly upon complexation, its chronoamperogram is changed due to the formed complex. The analysis was performed by titrating dopamine (guest) with variable amounts of β-cyclodextrin (host). In each mole ratio of host : guest, the solution was subjected to a potential step experiment, where in each step the current was measured as a function of time. Thus, for each potential a two-fold array of current data with molar ratio in one direction and time in another direction (data matrix) was obtained. The data matrices collected at different potentials were simultaneously analyzed by MCR-ALS to earn thermodynamic parameters (e.g., stoichiometric ratio and formation constant) of cyclodextrin–dopamine complex. This is the first report of simultaneous analysis of potential step-chronoamperometric data matrices by MCR-ALS.

Poly(vinylidene fluoride) Graft Copolymer Membranes with “Clickable” Surfaces and Their Functionalization

PVDF-g-PPMA copolymers bearing pendant propargyl functionalities were prepared by thermally induced graft copolymerization of propargyl methacrylate (PMA) from the ozone-preactivated poly(vinylidene fluoride) (PVDF) backbones. Microporous membranes were fabricated from the PVDF-g-PPMA comb copolymers by phase inversion in aqueous media. The PVDF-g-PPMA membrane and pore surfaces with pendant propargyl moieties from the PPMA side chains could be further functionalized via the one-step surface-initiated thiol−yne click reaction or alkyne−azide click reaction. The electrolyte-responsive PVDF-g-P[PMA-click-MPS] membranes were prepared via thiol−yne click reaction with 3-mercapto-1-propanesulfonic acid sodium salt (MPS) on the microporous PVDF-g-PPMA membranes. The permeability of aqueous solutions through the PVDF-g-P[PMA-click-MPS] membranes exhibited a dependence on the electrolyte concentration. The PVDF-g-P[PMA-click-β-CD] membranes were synthesized via the alkyne−azide click reaction of mono(6-azido-6-desoxy)-β-cyclodextrin (azido-β-CD) on the PVDF-g-PPMA membranes. The PVDF-g-P[PMA-click-β-CD-guest-PEO] membranes, from surface inclusion complexation of diadamantyl-poly(ethylene oxide) (AD-PEO) guest polymer with the β-cyclodextrin (β-CD) host molecules, exhibited good resistance to protein adsorption and fouling under continuous-flow conditions.

Modulation of fluorescence properties of MMeAQ in micelles and cyclodextrins

The interactions of the N-methylquinoline-3-amine (MMeAQ) with three cyclodextrins and micelles have been investigated using fluorescence spectroscopic techniques. It is shown that cationic and neutral surfactants enhance the fluorescence quantum yield of the MMeAQ in water by breakup of aggregates of MMeAQ and incorporation into the micelles. However such enhancement is not observed in SDS micelle. The fluorescence enhancement of MMeAQ in β-cyclodextrin host is rationalized in the light of the stoichiometry of the inclusion complexes. There is no such interaction is observed for α-CD and γ-CD. Quantum chemical calculation has also been performed in order to support the experimental findings of cationic species.

Complex packing motifs templated by a pseudo-spherical guest: the structure of β-cyclodextrin–adamantaneinclusion compounds

β-Cyclodextrin has been shown to form inclusion compounds with a wide variety of suitably sized guest molecules. In the present study a pseudo-spherical van der Waals guest molecule, adamantane, has been shown to template surprisingly complex packing motifs when incorporated into β-cyclodextrin host frameworks.

Inclusion of parabens in β-cyclodextrin: A solution NMR and X-ray structural investigation

A parallel study was conducted of the inclusion of alkyl parabens (guests) in the host β-cyclodextrin (β-CD). 1H NMR data indicated an insertion of the guest phenyl ring into the β-CD cavity. The stoichiometry of each complex was 1:1, as determined by a continuous variation method that utilises the chemical shifts of the host protons. These chemical shifts were additionally used to determine the association constant yielding K values of 1631, 938, 460 and 2022 M− 1 at 298 K for the methyl-, ethyl-, propyl- and butyl paraben solution state complexes, respectively. NOE experiments conducted on the methyl paraben solution complex indicated that the phenolic group of the guest was located at the secondary rim of the cyclodextrin cavity. Solid state structure analyses of the methyl and propyl paraben β-CD complexes were performed. Both complexes crystallised at ambient temperature in the space group C2, Z = 4 with a host to guest ratio of 1:1. Additionally, a second crystal structure between methyl paraben and β-CD is reported. This complex crystallised at 7oC in the space group P1, Z = 2 with a 1:1 host–guest stoichiometry. 1H NMR and solid state structure analyses were conducted on the inclusion of alkyl parabens in the host β-cyclodextrin. Both indicated an insertion of the guest phenyl ring into the β-CD cavity.

Raman spectroscopy is a convenient technique for the efficient evaluation of cyclodextrin inclusion molecular complexes of azo-dye colorants and largely polarisable guest molecules

Raman spectroscopy has been successfully employed in order to investigate the formation of β-cyclodextrin host–guest inclusion molecular complexes with several different azo-dye structures. The Raman pattern of the carbohydrate framework results negligible when neared to the magnificent intensity of the highly polarisable guest systems and a complete and feasible comparison of the spectral features between the free and the complexed situation of the guest molecule is allowed. In general, with respect to the free guest state, it was found within the complex that a hampering of Raman intensity displays, accompanied by a levelling directed variation of the relative peak intensities, and peculiar Raman peak broadening with shifts occur, relatable to the host–guest settling of inclusive intermolecular interactions. Supportively to the other commonly established characterising methods, or in valid alternative, Raman technique has proved astoundingly useful under the perspective of the diagnostic evaluation of cyclodextrin host–guest molecular inclusion for azo-dyes and, more generally, for a highly polarisable guest structure. It features sample non-destructivity, handiness, fastness and sensitive reproducibility, occasionally providing useful suggestions about the complexation topology.

A new approach to the synthesis of N-monosubstituted aniline and its derivatives via β-cyclodextrin host–guest complexes

A novel method for the synthesis of N-monosubstituted aniline and its derivatives via β-cyclodextrin (CD) host–guest complexes has been presented. The mild reaction gives the title compounds with high selectivity in good yields of 90–98%.

Structure and Dynamics of Perfluoroalkane/β-Cyclodextrin Inclusion Compounds As Studied by Solid-State 19F MAS and 1H →19F CP/MAS NMR Spectroscopy

The molecular structure and dynamics of novel inclusion compounds (ICs) consisting of n-perfluoroalkane (PFA) guests and beta-cyclodextrin (beta-CD) host (PFA/beta-CD) have been investigated using 19F magic angle spinning (MAS) and 1H-->19F cross polarization (CP)/MAS NMR spectroscopy with the aid of thermal analyses, FT-IR spectroscopy, and X-ray diffraction method. The ICs of C9F20/beta-CD and C20F42/beta-CD were successfully obtained as precipitates from mixtures of respective PFAs and saturated aqueous solution of beta-CD. The wide-angle X-ray diffraction (WAXD) revealed that C9F20/beta-CD forms a channel-type crystallite, while C20F42/beta-CD is nearly amorphous at room temperature. The structural orders in both ICs increase at elevated temperatures. The 19F NMR signals obtained by the direct polarization (DP) method for PFA/beta-CD are resonated at higher frequencies than those for original PFA. This can be ascribed to the lower dielectric environment of the beta-CD cavity. Above 80 degrees C, 1H-->19F CP/MAS NMR technique revealed that C9F20 molecules undergo vigorous molecular motion and partly come out of the beta-CD channel. However, the guests hardly degrade or evaporate unless the host is pyrolytically decomposed above ca. 300 degrees C. The spin-lattice relaxation times in the laboratory frame for 19F (T1F) are almost identical for all the fluorines in PFA/beta-CD at each temperature, while significantly different values were observed for fluorines in neat PFA. This indicates that effective intramolecular spin diffusion occurs within a PFA molecule included in beta-CD.

Modeling Competitive Guest Binding to β-Cyclodextrin Molecular Printboards

Anchoring of functionalized guest molecules to self-assembled monolayers (SAMs) is key to the development of molecular printboards for nanopatterning. One very promising system involves guest binding to immobilized beta-cyclodextrin (beta-CD) hosts, with guest:host recognition facilitated by a hydrophobic interaction between uncharged anchor groups on the guest molecule and beta-CD hosts self-assembled at gold surfaces. We use molecular dynamics free energy (MDFE) simulations to describe the specificity of guest:beta-CD association. We find good agreement with experimental thermodynamic measurements for binding enthalpy differences between three commonly used phenyl guests: benzene, toluene, and t-butylbenzene. van der Waals interaction with the inside of the host cavity accounts for almost all of the net stabilization of the larger phenyl guests in beta-CD. Partial and full methylation of the secondary rim of beta-CD decreases host rigidity and significantly impairs binding of both phenyl and larger adamantane guest molecules. The beta-CD cavity is also very intolerant of guest charging, penalizing the oxidized state of ferrocene by at least 7 kcal/mol. beta-CD hence expresses moderate specificity toward uncharged organic guest molecules by van der Waals recognition, with a much higher specificity calculated for electrostatic recognition of organometallic guests.

Facile Light-Triggered One-Step Synthesis of Small and Stable Platinum Nanoparticles in an Aqueous Medium from a β-Cyclodextrin Host−Guest Inclusion Complex

It is shown, for the first time, that small (ca. 2 nm) and stable platinum nanoparticles can be easily obtained in one step through visible light irradiation of a host-guest inclusion complex between beta-cyclodextrin and platinum acetylacetonate in a water solution. The exclusive control of the reaction by an external trigger, the removal of the undesired reaction products without any manipulation of the sample, and the absence of ionic repulsions between the metal nanoparticles represent the main remarkable advantages offered by this synthetic methodology.

Chiral discrimination of 2,2′-dihydro-1,1′-binaphthyl by β-cyclodextrin: a first-principles study

We have investigated the conformational space of the host–guest complex formed between β-cyclodextrin and 2,2′-dihydroxy-1,1′-binaphthyl by means of molecular dynamics simulation using a density-functional-based tight-binding method. In a previous study we explored the mode of entry and the most probable orientation of the guest within the host cavity by studying the time dependence of complex formation. This includes hydrogen bond formation between the guest molecule and the torus-like macro ring of the host β-cyclodextrin, leading to the formation of a stable adduct within the lipophilic cavity of the host. Here, we concentrate on the behavioural activities of the two chiral compounds of binaphthyl in the host cavity of β-cyclodextrin in order to investigate the chiral properties of cyclodextrin on both enantiomers. Our study shows that S-binaphthyl forms a more stable complex with β-cyclodextrin than the corresponding R-enantiomer, as judged from the binding energy difference of the two diastereomeric complexes and the significant structural differences of the two enantiomers in β-cyclodextrin.

Formation of an Inclusion Complex of a New Transition Metal Ligand in β-Cyclodextrin

The inclusion complex of a new transition metal ligand, 2,4,9-trithia-tricyclo[3.3.1.13,7]decane-7-carboxylic acid (2,4,9-trithia-adamantane-7-carboxylic acid, TPCOOH) in β-cyclodextrin was studied by 1H NMR, 2D NOESY NMR spectroscopy, host-induced CD spectroscopy, and tandem mass spectrometry. 1H NMR, MS–MS and NOESY data show that the TPCOOH guest forms a 1:1 inclusion complex with the host β-cyclodextrin. The NOESY experiments also show that TPCOOH is oriented in the complex with the thioketal end preferentially located at the larger opening of β-cyclodextrin. The orientation of the guest in the host molecule is also confirmed by the induced CD of the ligand, which shows a positive Cotton effect. An association constant of 660±20 M−1 was determined by 1H NMR titration for the complex at room temperature in D2O.

Supramolecular Polymers Formed from β-Cyclodextrins Dimer Linked by Poly(ethylene glycol) and Guest Dimers

Novel supramolecular polymers have been prepared from a β-cyclodextrin dimer and a ditopic guest dimer having adamantyl groups. β-Cyclodextrins were bound to poly(ethylene glycol) (PEG, Mn 600). Adamantyl groups were also bound to PEG (Mn 600). The ROESY NMR spectrum of a 1:1 mixture of the β-cyclodextrin dimer and the ditopic adamantane guest dimer showed ROE correlations between the protons of adamantyl substituents and the inner protons of β-cyclodextrin. Molecular weights and molecular sizes of the supramolecular polymer constructed by the mixture of the β-cyclodextrin dimer and the ditopic adamantane guest dimer were investigated by the pulse field gradient spin echo (PFGSE) NMR and by vapor pressure osmometry (VPO). The results have shown that the mixture of the β-cyclodextrin host dimer and the adamantane guest dimer gave linear supramolecular polymers with high molecular weight (Mn = 100 000).

Interaction between β-cyclodextrin and 1,10-phenanthroline: uncommon 2:3 inclusion complex in the solid state

The crystallographic structure of the complex formed by β-cyclodextrin with 1,10-phenanthroline has been studied by X-ray diffraction. The result shows that the complex adopts an uncommon 2:3 stoichiometry in solid state, that is, every complex unit contains three 1,10-phenanthroline molecules and two β-cyclodextrin molecules, where two 1,10-phenanthroline molecules individually occupy two cyclodextrin cavities, and the third guest molecule is located in the interstitial space between two head-to-head cyclodextrin molecules. The intermolecular hydrogen bonds between the adjacent complex units further link these individual monomers to a channel-type assembly. Furthermore, 1H and 2D NMR spectroscopy has been employed to investigate the inclusion behavior between the host β-cyclodextrin and guest 1,10-phenanthroline in aqueous solution.