Interaction Of Cyclodextrins Research Articles

Design of Potentiometric Sensors Based on Interaction of Cyclodextrins with the Enantiomer of Interest

Five enantioselective sensors based on α-, β-, carboxymethyl-β-(as sodium salt), 2-hydroxyl-3-trimethylammoniopropyl -β-(as chloride salt) and γ-cyclodextrins were designed based on results of their molecular interaction with the S- and R-enantiomers of ketoprofen obtained using SPR (surface plasmon resonance) based sensors. SPR proved to be an excellent technique for selecting the best chiral selectors. The best sensor was the one based on β-cyclodextrin. Low detection limits (of 10-8 to 10-9 magnitude orders) were recorded with the enantioselective, potentiometric membrane electrodes. Keywords: Cyclodextrin, enantioanalysis, enantioselective, potentiometric membrane electrode, S-ketoprofen, surface plasmon resonance.

Cyclodextrin supramolecular inclusion-enhanced pyrene excimer switching for time-resolved fluorescence detection of biothiols in serum

We report here an efficient pyrene excimer signaling-based time-resolved fluorescent sensor for the measurement of biothiols (cysteine (Cys), homocysteine (Hcy), glutathione (GSH)) in human serum based on thymine–Hg2+–thymine (T–Hg2+–T) coordination chemistry and the inclusion interaction of cyclodextrin. The sensing mechanism of the approach is based on the competitive ligation of Hg2+ ions by Hcy/Cys/GSH and T–T mismatches in a bis-pyrene-labeled DNA strand with the self-complementary 5′ and 3′ ends. The introduction of γ-cyclodextrin can provide cooperation for the molecular level space proximity of the two labeled pyrene molecules, moreover the hydrophobic cavity of γ-cyclodextrin can also offer protection for the pyrene dimer's emission from the quenching effect of environmental conditions and enhance the fluorescence intensity of the pyrene excimer. When the biothiols are not presented, the sensing ensemble is in the “off” state due to the long distance between the two labeled pyrene molecules resulted from the formation of a more stable T–Hg2+–T structure. While in the presence of biothiols, Hg2+ interacts very strongly with thiol groups and the T–Hg2+–T structure is dehybridized, and then the pyrene excimer will be formed due to the self-complementary 5′ and 3′ ends of the DNA probe and the cooperation interaction of γ-cyclodextrin to pyrene dimer, thus resulting in switching the sensing ensemble to the “on” state. In the optimum conditions described, the linear concentration range of 1.0–100μM with the limit of detection (LOD) of 0.36μM for GSH was obtained. Moreover, due to the much longer lifetime of the pyrene excimer fluorescence than those of the ubiquitous endogenous fluorescent components, the time-resolved fluorescence technique has been successfully used for application in complicated biological samples.

Cyclodextrin Interaction with Specific Channel CymA from K. Oxytoca

The outer membrane acts as a selective uptake barrier in Gram negative bacteria. It contains protein channels (porins) which provide an entry pathway for hydrophilic molecules like small nutrient molecules and β-lactam antibiotics. However the CymA channel is known to take up cyclodextrin molecules giving bacteria the ability to survive on cyclodextrins. Hence understanding uptake of these molecules via porins is vital to comprehend the transport mechanism across the cell membrane. Electrophysiology forms a promising approach to study the permeation of molecules across outer membrane and thereby understanding molecular interactions with the channel. Here we present cyclodextrin interaction studies of CymA from K. oxytoca using single channel electrophysiology. Detailed single channel analysis revealed inherent asymmetric gating characteristics of the channel. Analysis of the ion current reduction through CymA in presence of cyclodextrin led revealed kinetic parameters of substrate binding. To further elucidate the affinity sites of substrate to the channel, mutation of certain channel residues has been performed. An altered channel gating behaviour is observed. To obtain an atomistic view we complement our studies with all-atom molecular dynamics simulation to study the various conductance states of the channel in the absence of cyclodextrin and to get molecular insight into the uptake of cyclodextrins as well.

Determination of the kinetic rate constant of cyclodextrin supramolecular systems by high-performance affinity chromatography.

The kinetics of the association and dissociation are fundamental kinetic processes for the host-guest interactions (such as the drug-target and drug-excipient interactions) and the in vivo performance of supramolecules. With advantages of rapid speed, high precision and ease of automation, the high-performance affinity chromatography (HPAC) is one of the best techniques to measure the interaction kinetics of weak to moderate affinities, such as the typical host-guest interactions of drug and cyclodextrins by using a cyclodextrin-immobilized column. The measurement involves the equilibration of the cyclodextrin column, the upload and elution of the samples (non-retained substances and retained solutes) at different flow rates on the cyclodextrin and control column, and data analysis. It has been indicated that cyclodextrin-immobilized chromatography is a cost-efficient high-throughput tool for the measurement of (small molecule) drug-cyclodextrin interactions as well as the dissociation of other supramolecules with relatively weak, fast, and extensive interactions.

Reversible Janus particle assembly via responsive host-guest interactions.

Reversible assembly of Janus particles was manipulated by host-guest interaction of β-cyclodextrin (β-CD) and azobenzene. One side of every Janus particle was modified with β-CD. Superstructures of Janus particles were formed by adding azobenzene-containing polymers to the dispersion of Janus particles. The superstructures were reversibly disassembled by adding α-CD or light irradiation.

A supramolecular brush polymer via the self-assembly of bridged tris(β-cyclodextrin) with a porphyrin derivative and its magnetic resonance imaging.

Accurate imaging of soft tissues is one of the ultimate goals in biomedical imaging. Different imaging modalities can improve their disadvantages, and promote the imaging ability. However, once an imaging agent has been prepared, it is usually hard to adjust it according to the actual needs. Herein, we developed a supramolecular brush polymer (SBP) as a versatile imaging agent platform. The SBP platform (SBPP) is constructed by the intermolecular inclusion complexation of bridged tris(β-cyclodextrin) (1) with Mn(iii)-porphyrin-bearing poly(ethylene glycol) (PEG) side chains (Mn(iii)-TPP), and can further bind other functional groups by host-guest interactions of cyclodextrin and adamantine. The SBPP is characterized by UV/vis absorption spectroscopy, NMR, dynamic light scattering (DLS), atomic force microscopy (AFM) and transmission electron microscopy (TEM). We demonstrated that this SBPP not only has no cellular toxicity against NIH 3T3 cells in in vitro cell experiments, but it also shows an efficient enhanced T1 relaxivity in in vitro MR imaging experiments. When used as multifunctional imaging agents, different imaging probes and/or targeting agents can be introduced to this SBPP as needed through simple host-guest interactions. In in vitro imaging experiments, it shows accurate imaging of different kinds of cancer cells by choosing on-demand targeting agents. These results suggest a promising strategy for engineering multifunctional imaging agents with SBPs.

Host-guest-driven color change in water: influence of cyclodextrin on the structure of a copper complex of poly((4-hydroxy-3-(pyridin-3-yldiazenyl)phenethyl)methacrylamide-co-dimethylacrylamide).

In the present work we report the synthesis of poly((4-hydroxy-3-(pyridin-3-yldiazenyl)phenethyl)methacrylamide-co-dimethylacrylamide) and its reversible optical and complex-forming properties due to copper and cyclodextrin (CD) interactions. Color changing effects are characterized by UV–vis spectroscopy and the supramolecular behavior is investigated by dynamic light scattering experiments.

Interactions of Native Cyclodextrins with Biorelevant Molecules in the Solid State: A Review

Interactions of Native Cyclodextrins with Biorelevant Molecules in the Solid State: A Review

Multianalyte determination of the kinetic rate constants of drug–cyclodextrin supermolecules by high performance affinity chromatography

The kinetics of the dissociation is fundamental to the formation and the in vivo performance of cyclodextrin supramolecules. The individual determination of the apparent dissociation rate constant (kd,app) using high performance affinity chromatography (HPAC) is a tedious process requiring numerous separate studies and massive data fitting. In this study, the multianalyte approach was employed to simultaneously measure the kd,app values of three drugs through one injection based on the investigation of the dependence of drug–cyclodextrin interaction kinetics on the mobile phase composition. As a result, the kd,app values increased when decreasing the ion strength, increasing the ionization of drugs and adding extra organic solvents. The values of kd,app for acetaminophen, phenacetin and S-flurbiprofen estimated by the multianalyte approach were 8.54±1.81, 5.36±0.94 and 0.17±0.02s−1, respectively, which were in good agreement with those determined separately (8.31±0.58, 5.01±0.42 and 0.15±0.01s−1). For both of the single and multiple flow rate peak profiling methods, the results of the multianalyte approach were statistically equivalent with that of the single compound analysis for all of the three drugs (p>0.05). The multianalyte approach can be employed for the efficient evaluation of the drug–cyclodextrin kinetics with less variance caused by cyclodextrin column bleeding.

Interaction of cyclodextrins with human and bovine serum albumins: A combined spectroscopic and computational investigation

Interaction of cyclodextrins (CDs) with the two most abundant proteins, namely human serum albumin (HSA) and bovine serum albumin (BSA), has been investigated using steady-state and time-resolved fluorometric techniques, circular dichroism measurements and molecular docking simulation. The study reveals that the three CDs interact differently on the fluorescence and fluorescence lifetimes of the serum albumins. However, fluorescence anisotropy and circular dichroism are not affected. Depending on their size, different CDs bind to the serum albumins in different positions, resulting in changes in the spectral behaviour of the proteins. Docking study suggests the probable binding sites of the three CDs with the proteins. Combined experimental and computational studies imply that sufficiently high concentration of CDs causes loosening of the rigid structures of these transport proteins, although their secondary structures remain intact. Thus, CDs are found to be safe for the serum proteins from the structural point of view. Depending on their cavity sizes, cyclodextrins bind to the human and bovine serum albumins in different positions. This leads to loosening of the rigid structures of the serum proteins resulting in a change in the polarity around the microenvironment of the intrinsic fluorophore of these proteins, i.e., the tryptophan moiety.

Biophysical aspects of cyclodextrin interaction with paraoxon

Cyclodextrins are torus-shaped polymers of glucose that can bind organophosphorous compounds such as nerve agents and pesticides. We demonstrate here that cyclodextrin can bind up to two paraoxon molecules with a K(av) of 6775 M(-1). Molecular modeling shows that the paraoxon appears to bind in polar opposite orientation and have an average binding energy of -89 Kcals/mol. Published 2013. This article is a U.S. Government work and is in the public domain in the USA.

Weak antibody–cyclodextrin interactions determined by quartz crystal microbalance and dynamic/static light scattering

In a quest to elucidate the mechanism by which hydroxypropyl β-cyclodextrin (HPβCD) stabilizes antibodies against shaking stress, two heavily debated hypotheses exist, namely that stabilization is due to HPβCD’s surface activity, or due to specific interactions with proteins. In a previous study by Serno et al. (Pharm. Res. 30 (2013) 117), we could refute the first hypothesis by proving that, although HPβCD is slightly surface active, it does not displace the antibody at the air–water interface, and accordingly, its surface activity is not the underlying stabilizing mechanism. In the present study, we investigated the possibility of interactions between HPβCD and monoclonal antibodies as the potential stabilization mechanism using quartz crystal microbalance (QCM) and static as well as dynamic light scattering. In the presence of HPβCD, the adsorption of IgG antibodies in the native state (IgG A) and the unfolded state (IgG A and IgG B) on gold-coated quartz crystals was studied by QCM. Results show that HPβCD causes a reduction in protein adsorption in both the folded and the unfolded states, probably due to an interaction between the protein and the cyclodextrin, leading to a reduced hydrophobicity of the protein and consequently a lower extent of adsorption. These results were supported by investigation of the interaction between the native protein and HPβCD using static and dynamic light scattering experiments, which provide the protein–protein interaction parameters, B22 and kD, respectively. Both B22 and kD showed an increase in magnitude with increasing HPβCD-concentrations, indicating a rise in net repulsive forces between the protein molecules. This is further evidence for the presence of interactions between HPβCD and the studied antibodies, since an association of HPβCD on the protein surface leads to a change in the intermolecular forces between the protein molecules. In conclusion, this study provides evidence that the previously observed stabilizing effect of HPβCD on IgG antibodies is probably due to direct interactions between the cyclodextrin and the protein.

Dynamic Lipid Lateral Segregation Driven by Lauryl Cyclodextrin Interactions at the Membrane Surface

Amphiphilic cyclodextrins, with a cholesterol anchor (βChol) or an aspartic acid moiety esterified by two lauryl acyl chains (βDLC), were designed to combine the inclusion ability of the cyclodextrin cavity with the carrier properties of model membranes. Their insertion in phosphatidylcholine bilayers induces a marked lateral phase separation into a pure lipid phase and a cyclodextrin-rich phase (LCD), organized as a 2D cyclodextrin network stabilized by intermolecular hydrogen bonds between the saccharide headgroups at the membrane surface (Roux, M.; Perly, B.; Djedaïni-Pilard, F. Self-Assemblies of Amphiphilic Cyclodextrins. Eur. Biophys. J.2007, 36, 861-867). We have replaced the dilauryl anchor by a single lauryl chain grafted onto a leucine residue, giving monolauryl-β-cyclodextrin (βMLC), which readily inserts into bilayers of chain-deuterated DMPC-d27. The removal of one lauryl acyl chain leads to a dynamic membrane insertion of this new cyclodextrin derivative, with significant lipid exchange on the deuterium NMR time scale between a loosely packed cyclodextrin-enriched phase (L'CD) and free lipid regions, yielding broadened two-component NMR spectra. Like the LCD phases, the cyclodextrin-enriched L'CD regions remain (partially) fluid below the DMPC-d27 main fluid-to-gel transition but do not undergo a clear transition toward a gel state, as observed at 14.5 °C in the LCD phase induced by the dilauryl derivative. Partially fluid lipids of the βMLC-induced L'CD phase coexist with pure lipids in the Pβ' gel phase with possible exchange between them until all of the lipids undergo a transition toward an Lβ' gel state at around 7 °C. Trimethylated monolauryl-β-cyclodextrins induce only an ordering of the lipid acyl chains just above the main transition, without any lateral phase separation. Similar chain ordering is also observed within the βMLC-induced L'CD phase as a consequence of the deep membrane insertion of the monolauryl nonmethylated cyclodextrin derivative.

Effect of Hydroxypropyl-β-Cyclodextrin on the Solubility of an Antiarrhythmic Agent

The aim of this work was to obtain an inclusion complex between HP-β-CD and amiodarone in order to increase the solubility of this active agent. Drug–cyclodextrin interactions in solution were investigated using phase solubility studies. The Fourier transform infrared spectroscopy (FT-IR) spectra revealed the presence of the interactions between the components of the inclusion complex. Changes in crystallinity of the drug inside the inclusion complex were confirmed by X-ray diffractometry (XRD) and differential scanning calorimetry (DSC). Thermogravimetric (TG) results demonstrated the modification of the drug thermal behavior due to the interactions with the host cyclodextrin. The dissolution rate of amiodarone from the inclusion complex was considerably increased as compared to dissolution of the pure drug. It has been established that the complexation of amiodarone with HP-β-CD offers the possibility to increase its aqueous solubility without the modification of its original structure.

Effect of Cyclodextrin Structure upon Interaction of Cyclodextrin with Different Lipids Incorporated into Model Membrane Vesicles

We have used methyl-beta- cyclodextrin (MbCD) to exchange membrane lipids between different vesicles in order to prepare model membrane vesicles with lipid asymmetry. To determine how to improve the efficiency of this method, the binding of lipids to various cyclodextrins (CDs) was investigated. The decrease in light scattering of multilamellar vesicles and the change in Förster resonance energy transfer (FRET) of labeled lipids incorporated into small unilamellar vesicles comprised primarily of unlabeled lipids were used to detect when vesicles are dissolved by binding of lipids to CD. A different FRET assay was used to detect when CDs catalyzed lipid exchange under conditions that vesicles do not dissolve. The effects of CD ring size (6, 7 or 8 sugar rings), substituants (hydroxy propyl, methyl, carboxymethyl and sulfate) and CD concentration were examined. It was found that while MbCD has the ability to dissolve lipid vesicles, most other CDs do not, although they are able to exchange lipids between vesicles. At lower MbCD concentrations, even MbCD loses the ability to dissolve vesicles, it retains the ability to exchange lipids. For MbCD, the concentration needed to dissolve about half of the vesicles was not strongly affected by lipid headgroup or acyl chain saturation, although there seemed to be some effect of acyl chain length.

シクロデキストリンと無機イオンとの相互作用

ホスト-ゲスト化学の分野において中心的な役割を担ったクラウンエーテルやカリックスアレン，シクロデキストリンに代表される環状化合物は，その後の超分子化学，ボトム→アップ型ナノテクノロジーへと領域が推移拡大する中においても重要な鍵となる化合物として精力的な研究開発の一翼を担っている。一般に，クラウンエーテルやカリックスアレンは，有機溶媒中でアルカリ金属イオンやアルカリ土類金属イオンを取り込むホスト分子として知られている。一方，シクロデキストリンは水溶液中で中性の有機分子を取り込むホスト分子として知られているが，無機イオンとの相互作用に関する認知度は高くない。しかしながら最近，この相互作用がにわかに注目されている。本稿では，特に未修飾のシクロデキストリンと無機イオンとの相互作用に着目し，これについて紹介する。

Redox-switchable supramolecular polymers for responsive self-healing nanofibers in water

Self-healing nanomaterials that respond to new stimuli sources are attractive. In particular, redox potential is one of the most universal and convenient stimuli in nature. Here we report utilization of ferrocene- and cyclodextrin-terminated monomers to form water-soluble AA-BB-type supramolecular polymers on the basis of host–guest interactions of ferrocene (Fc) and cyclodextrin (CD). These noncovalent polymers can further hierarchically assemble into one-dimensional supramolecular nanofiber architectures. The electrochemical-responsive Fc–CD host–guest connections endow these nanofibers with unique self-degradable and -healable features under redox potential control. Moreover, different redox conditions can exactly regulate the self-repairable rates of these nanostructures. It is anticipated that this supramolecular polymer model would open up a way for redox-tunable one-dimensional nanomaterials.

A cellular automata model of enantiomer binding strengths to β-cyclodextrin

As yet, the analytical process of chromatographic enantiomer separation has not been modeled using cellular automata (CA). This approach uses mathematical systems that are easily adaptable to different enantiomer analytical binding interactions. A CA model of analyte to cyclodextrin (CD) interaction accurately (R2=0.9960) predicts one-to-one molecular binding strengths through correlation with experimental complex stability constants while exhibiting established chromatographic behavior (i.e. retention site dependency and band broadening). The model is expanded to enantiomer HPLC retention interactions with β-CD that accurately predicts one-to-one binding strengths through the development of probabilistic rules and factors from chromatographic results. The proposed model predicts the strength of binding interactions and the degree of chromatographic separation (or lack thereof) of six enantiomer pairs that agree with published potential binding energies of enantiomer–(β-CD) complexes and published experimental HPLC separations.

Interaction of cyclodextrins with pyrene-modified polyacrylamide in a mixed solvent of water and dimethyl sulfoxide as studied by steady-state fluorescence

The interaction of β- and γ-cyclodextrins (β-CD and γ-CD, respectively) with polyacrylamide modified with pyrenyl (Py) residues (pAAmPy) was investigated in a mixed solvent of water and dimethyl sulfoxide (DMSO) by steady-state fluorescence. In the absence of CD, the fluorescence spectra indicated that the formation of Py dimers became less favorable with increasing volume fraction of DMSO (xDMSO). The fluorescence spectra at varying xDMSO and CD concentrations indicated that β-CD and γ-CD included monomeric and dimeric Py residues, respectively. Using the fluorescence spectra, equilibrium constants of the formation of Py dimers and the complexation of β-CD and γ-CD with Py residues were roughly estimated based on simplified equilibrium schemes.

Phenoxathiinsulphone derivatives–cyclodextrin interactions: induced chirality and TDDFT calculations

The inclusion process of phenoxathiin-10,10-dioxide and 2-CH2Br-phenoxathiin-10,10-dioxide in α-, β-, γ- and 2-hydroxypropyl-γ-cyclodextrins was studied by circular dichroism spectroscopy. The dependence of the induced circular dichroism signal on the host concentration was analyzed in terms of a nonlinear model yielding the stoichiometry and the association constants of the complexes. Time dependent density functional theory (TDDFT) calculations were used to rationalize the experimental data considering two aspects. Firstly, to support on theoretical grounds the experimentally observed achirality of the studied compounds that present two structural elements to confer chirality: the butterfly motion of the roof-shaped heteroring and the rotation of the CH2Br group. In this last process, some favorable position of the bromine atom could influence the overall chirality. Secondly, the TDDFT calculations of the polarizations of the electronic transitions in correlation with the signs of the induced dichroic bands were used to establish the axial or equatorial way the guest is included in the host cavity.