Cyclodextrin Host Research Articles

A cyclodextrin host–guest recognition approach to a label-free electrochemical DNA hybridization biosensor

A novel label-free electrochemical DNA hybridization biosensor using a β-cyclodextrin/poly(N-acetylaniline)/carbon nanotube composite modified screen printed electrode (CD/PNAANI/CNT/SPE) has been developed. The proposed DNA hybridization biosensor relies on the intrinsic oxidation signals of guanine (G) and adenine (A) from single-stranded DNA entered into the cyclodextrin (CD) cavity. Due to the binding of G and A bases to complementary cytosine and thymine bases in dsDNA, the signals obtained for ssDNA were much higher than that of dsDNA. The synergistic effect of the multi-walled carbon nanotubes provides a significantly enhanced voltammetric signal, and the CD encapsulation effect makes anodic peaks of G and A shift to less positive potentials than that at the bare SPE. The peak heights of G and A signals are dependent on both the number of the respective bases in oligonucleotides and the concentration of the target DNA sequences. Hybridization of complementary strands was monitored through the measurements of oxidation signal of purine bases, which enabled the detection of target sequences from 0.01 to 1.02 nmol μl(-1) with the detection limit of target DNA as low as 5.0 pmol μl(-1) (S/N = 3). Implementation of label-free and homogeneous electrochemical hybridization detection constitutes an important step toward low-cost, simple, highly sensitive and accurate DNA assay. Discrimination between complementary, noncomplementary, and two-base mismatch targets was easily accomplished using the proposed electrode.

Structural diversity in native cyclodextrins/folic acid complexes – from [2]-rotaxane to exclusion compound

The formation of different complexes of folic acid depending on the size of the host cyclodextrin resulting in either an exclusion compound (with the smallest α-cyclodextrin) or 2-rotaxane, where cyclodextrin is threaded over folic acid (with β- and γ-cyclodextrins), is presented. The formation is carried out in water which allows both possible application in pharmaceutical sciences and usage of environmentally friendly "green chemistry". The obtained compounds are thoroughly characterized using one and two dimensional NMR, mass spectrometry, differential scanning calorimetry and thermogravimetric analysis.

Supramolecular Host–Guest Interaction for Labeling and Detection of Cellular Biomarkers

Be my guest: A supramolecular host-guest interaction is utilized for highly efficient bioorthogonal labeling of cellular targets. Antibodies labeled with a cyclodextrin host molecule bind to adamantane-labeled magnetofluorescent nanoparticles (see picture) and provide an amplifiable strategy for biomarker detection that can be adapted to different diagnostic techniques such as molecular profiling or magnetic cell sorting.

An electrochemical study in aqueous solutions on the binding of dopamine to a sulfonated cyclodextrin host

Clear evidence for the formation of a weak inclusion complex between dopamine (DA) and a sulfonated β-CD host in aqueous solution was obtained using a combination of electrochemical approaches. Using cyclic voltammetry, a distinct increase in the oxidation potential of DA and a reduction in the peak oxidation current were observed on adding an excess concentration of the sulfonated β-CD to the electrolyte solution. Equally, a clear increase in the half-wave oxidation potential of DA was observed in the presence of the sulfonated β-CD using rotating disc voltammetry. The association constant, K, was computed as 331.3 ± 5.8, indicating the formation of a weak inclusion complex, while a 1:1 stoichiometry for the inclusion complex was deduced from a Job's plot analysis. The rate constant for the oxidation of DA was found to decrease on formation of the inclusion complex. This was attributed to higher reorganization energy for the oxidation of the included DA. These changes in the electrochemistry of DA were not observed when an excess of the smaller sulfonated α-CD was added to the electrolyte, indicating that these variations are not connected with simple electrostatic interactions between the protonated DA and the anionic sulfonated groups. It is proposed that the aromatic ring of the DA molecule includes within the cyclodextrin cavity, while the protonated amine group remains outside the cavity, bound electrostatically with the anionic sulfonated groups.

A spectrophotometric and NMR study on the formation of an inclusion complex between dopamine and a sulfonated cyclodextrin host

The formation of an inclusion complex between the sulfonated β-cyclodextrin (Sβ-CD) with dopamine (DA) was confirmed using UV–vis measurements and NMR methods. It was also established that a 1:1 complex was formed between the Sβ-CD and the DA, where the inclusion occurred predominantly through the aromatic ring of the DA and the hydrophobic CD cavity. The results also suggest that a change in the anion, of supporting electrolyte, had an influence on the DA-Sβ-CD complexation while no change was observed for the cation.

Strong Guest Binding by Cyclodextrin Hosts in Competing Nonpolar Solvents and the Unique Crystalline Structure

6-O-Modified β-cyclodextrins, such as heptakis(6-O-triisopropylsilyl)-β-cyclodextrin (TIPS-β-CD) and heptakis(6-O-tert-butyldimethylsilyl)-β-cyclodextrin (TBDMS-β-CD), formed 2:1 inclusion complexes with pyrene in benzene and cyclohexane with high association constants. The X-ray crystalline structure of the TIPS-β-CD-pyrene complex obtained from the benzene solution showed that one pyrene molecule was incorporated in the form of a sandwich-type complex with two benzene molecules within the cavity of the dimer formed by two TIPS-β-CD molecules.

Electronic transport between Au surface and scanning tunnelling microscope tip via a multipodal cyclodextrin host–metallo‐guest supramolecular system

An elementary supramolecular conducting system was constructed using a novel (±)‐thioctic acid‐functionalized β‐cyclodextrin host deposited on a gold (Au) surface and an iridium‐bearing guest molecule with biphenyl tails to insert specifically into the cyclodextrin cavity. The resulting supramolecular system was used to investigate remote electron communication between the flat Au surface and the platinum (Pt)/iridium (Ir) tip of a scanning tunnelling microscope. The morphology of the surfaces after successive deposition of host molecules followed by guest molecules was investigated. Formation of features of 2 nm size was shown on the Au surface functionalised with the supramolecular system. I–V spectroscopic analysis of the tunnelling current through this supramolecular layer revealed the relation between the effective barrier height and tunnelling distance. Thus, in the supramolecular host–metallo‐guest system, a small increase of conductance is observed, compared to the layer without the guest. This can be attributed to the presence of the Ir‐guest, which eventually creates intermediate energy states between the Au substrate and the Pt/Ir tip. Copyright © 2011 John Wiley & Sons, Ltd.

Controlled Fragrant Molecule Release from Surface-Tethered Cyclodextrin Host–Guest Inclusion Complexes

β-cyclodextrin barrels can be tethered to solid surfaces using the Williamson ether synthesis reaction via an intermediate pulsed plasma deposited poly(4-vinylbenzyl chloride) linker layer. The loading and release of perfume molecules through host-guest inclusion complex formation with surface tethered β-cyclodextrin has been followed by infrared spectroscopy and quartz crystal microbalance measurements. Fragrance release lasts for several months and can be easily recharged.

A cyclodextrin host–guest recognition approach to an electrochemical sensor for simultaneous quantification of serotonin and dopamine

An electrochemical sensor for simultaneous quantification of serotonin (5-hydroxytryptamine, 5-HT) and dopamine (DA) using a β-cyclodextrin/poly(N-acetylaniline)/carbon nanotube composite modified carbon paste electrode has been developed. Synergistic effect of multi-walled carbon nanotube (MWCNT) in addition to the pre-concentrating effect of β-cyclodextrin (β-CD) as well as its different inclusion complex stability with 5-HT and DA was used to construct an electrochemical sensor for quantification of these important neurotransmitters. The overlapping anodic peaks of 5-HT and DA at 428 mV on bare electrode resolved in two well-defined voltammetric peaks at 202 and 363 mV vs. Ag/AgCl respectively. The oxidation mechanism of 5-HT and DA on the surface of the electrode was investigated by cyclic voltammetry and it was found that the electrode processes are pH dependent and electrochemical oxidation of 5-HT is totally irreversible while the electrode gave a more reversible process to DA. Under optimized conditions, linear calibration curves were obtained in the range of about 4–200 μM with a detection limits down to sub-μM levels (S/N = 3) after 20-s accumulation, for both. The proposed sensor was shown to be remarkably selective for 5-HT and DA in matrices containing different species including ascorbic acid and uric acid. The suitability of the developed method was tested for the determination of 5-HT and DA in the Randox Synthetic Plasma samples and acceptable recoveries were obtained for a set of spiked samples.

Constrained polymer chain behavior observed in their non-stoichiometric cyclodextrin inclusion complexes

Much has been learned from inclusion compounds (IC’s) formed between guest polymers and host cyclodextrins (CDs) [polymer-CD-ICs] by examining the properties of the fully covered guest polymers, as well as those coalesced neat bulk samples of guest polymers obtained upon removal of the host CDs. However, what can be gained from studying the properties of the restrained unthreaded portions of polymer chains that “dangle” from non-stoichiometric (n-s)-polymer-CD-IC’s? We attempt to assist in answering this question by observing (n-s)-polymer-CD-IC’s formed between amorphous atactic-poly(methyl methacrylate) (PMMA) and γ-CD, as well as the IC formed between a synthesized poly(e-caprolactone)-poly(propylene glycol)-poly(e-caprolactone) (PCL-PPG-PCL) triblock copolymer and β-CD, which was presumed to have threaded and unthreaded PPG and PCL blocks. Though our (n-s)-PMMA-γ-CD-IC samples were found to exhibit extremely heterogeneous behaviors, glass transition temperature increases of up to 27 °C above that of neat PMMA were observed. X-ray diffraction data indicates modest γ-CD crystallinity at partial coverages of PMMA, with a crystal structure similar to that of the IC with full coverage. On the other hand, XRD, DSC and FTIR data revealed an almost total disruption of PCL block crystallinity upon complexation of PCL-PPG-PCL with β-CD, suggesting either partial threading and coverage of the PCL blocks by β-CD or their partial mixing with the PPG blocks covered with β-CD.

Controlling the size of electrostatically self-assembled nanoparticles with cyclodextrin as external trigger

This study shows how electrostatic self-assembly of polyelectrolytes and organic counterions can be combined with cyclodextrin host–guest chemistry into a novel route to size-controllable supramolecular nanoparticles in aqueous solution. Nanoparticles are formed from fourth generation polyamidoamine dendrimers (PAMAM G4) as positively charged macroions and an excess of the oppositely charged anionic diazo dye Acid Yellow 38 (Ay38), yielding negatively charged supramolecular particles with hydrodynamic radii of 30–60 nm. Stepwise complexation of the dye by α-cyclodextrin leads to a decreasing charge density and thereby caused stepwise size increase up to particles with a hydrodynamic radius of 240 nm. Dynamic light scattering and ζ-potential measurements were used to elucidate assembly size and stabilization and isothermal titration calorimetry to determine association stoichiometry, enthalpies and equilibrium constants.

Melt-crystallized nylon-6 nucleated by the constrained chains of its non-stoichiometric cyclodextrin inclusion compounds and the nylon-6 coalesced from them

Non-covalently bonded crystalline inclusion compounds (ICs) have been formed by threading host cyclic starches, cyclodextrins (CDs), onto guest nylon-6 (N-6) chains. When excess N-6 is employed, non-stoichiometric (n-s)-N-6-CD-ICs, with partially uncovered and “dangling” N-6 chains, result. While the host crystalline CD lattice is stable to ∼300 °C, the uncovered, yet constrained, portions of the N-6 chains emanating from the CD-IC surfaces may crystallize below, or be molten above ∼225 °C, and confer upon them shape-memory. When heated between the Tm of N-6 and the decomposition temperature of the (n-s)-N-6-CD-IC, they may be deformed into a new shape, which is retained following a rapid quench below Tm. When this newly-shaped sample is heated above the Tm of the un-included and crystalline portions of N-6, it reverts back to its original shape in response to the constraining CD-IC crystals.When added at low concentrations, the non-toxic (n-s)-N-6-CD-ICs serve as effective nucleating agents for the bulk crystallization of N-6 from the melt. This is a consequence of the ability of the N-6 chains protruding from their (n-s)-CD-ICs to crystallize more rapidly and at higher temperatures than bulk N-6 chains when their molten mixture is cooled, thereby providing finely dispersed crystalline nuclei for the subsequent crystallization of the bulk N-6 chains. Melt-crystallized N-6 nucleated with (n-s)-N-6-CD-ICs have finer grained more homogeneous morphologies than un-nucleated N-6 samples. Furthermore, N-6s coalesced from their CD-ICs by appropriate removal of the host CD are also found to effectively nucleate the melt-crystallization of bulk N-6, even after long periods of annealing above the Tm of N-6. N-6 coalesced from stoichiometric CD-ICs, with full N-6 coverage, and from (n-s)-N-6-CD-ICs, with only partial N-6 coverage, show very similar crystallization behaviors and both are effective as nucleants, and this is reflected by their higher densities and improved mechanical properties.

α‐Cyclodextrin Host–Guest Binding: A Computational Study of the Different Driving Forces

AbstractFree‐energy differences govern the equilibrium between bound and unbound states of a host and its guest molecules. The understanding of the underlying entropic and enthalpic contributions, and their complex interplay are crucial for the design of new drugs and inhibitors. In this study, molecular dynamics (MD) simulations were performed with inclusion complexes of α‐cyclodextrin (αCD) and three monosubstituted benzene derivatives to investigate host–guest binding. αCD Complexes are an ideal model system, which is experimentally and computationally well‐known. Thermodynamic integration (TI) simulations were carried out under various conditions for the free ligands in solution and bound to αCD. The two possible orientations of the ligand inside the cavity were investigated. Agreement with experimental data was only found for the more stable orientation, where the substituent resides inside the cavity. The better stability of this conformation results from stronger Van der Waals interactions and a favorable antiparallel host–guest dipole–dipole alignment. To estimate the entropic contributions, simulations were performed at three different temperatures (250, 300, and 350 K) and using positional restraints for the host. The system was found to be insensitive to both factors, due to the large and symmetric cavity of αCD, and the nondirectional nature of the host–guest interactions.

Preclinical comparison of intravenous melphalan pharmacokinetics administered in formulations containing either (SBE)7 m‐β‐cyclodextrin or a co‐solvent system

The aim of this work was to evaluate the impact of sulfobutyl ether β-cyclodextrin ((SBE)(7 m)-β-CD; Captisol(®)) on the in vivo pharmacokinetics of melphalan in rats. Melphalan is a chemically unstable antineoplastic drug which in the current commercial formulation (Alkeran(®) for Injection) has some limitations with regard to solubility, stability and biocompatibility. Melphalan formulations containing (SBE)(7 m)-β-CD have previously been evaluated in vitro and shown to significantly reduce the rate of degradation and to simplify the reconstitution procedure for lyophilised melphalan. In this study, melphalan was administered intravenously in rats in formulations that either contain (SBE)(7 m)-β-CD or a co-solvent system (i.e. the commercial formulation). Pharmacokinetic parameters, including half-life, volume of distribution, clearance and extent of renal elimination of melphalan were essentially unchanged between the two formulations. These findings indicate that the pharmacokinetics of melphalan are not altered in the presence of (SBE)(7 m)-β-CD consistent with a rapid shift in the equilibrium to the fully dissociated drug from the fraction associated with the cyclodextrin host molecule upon intravenous administration.

Orthogonal Covalent and Noncovalent Functionalization of Cyclodextrin-Alkyne Patterned Surfaces

The creation of cyclodextrin patterns on a fluorescent reporter surface by microcontact printing provides a versatile orthogonal surface modification method. The alkyne-beta-cyclodextrin surface is prepared through a "click" reaction on alkyne-terminated coumarin monolayers. The resulting alkyne-beta-cyclodextrin surface can be functionalized through supramolecular microcontact printing on cyclodextrin host patterns and by reactive microcontact printing-induced click chemistry on the alkyne-terminated patterns. The orthogonal covalent and supramolecular "host-guest" functionalization of the surface, and its specificity as well as selectivity, is demonstrated by sequential and one-step printing procedures.

Development of a Web Service for the Investigation of Complexation by Cyclodextrins

A free web service (http://Cycloserver.organic.hu) was developed whereby cyclodextrin complexation of molecules can be estimated using molecular docking methodology. 98 various cyclodextrins were prepared in a dock-ready form on the server. Besides docking energy, the contact surface of the complex and dimerization energy of cyclodextrin hosts were calculated as well. Keywords: Cyclodextrin, Docking, Web server, Interaction surface, Complexation

Tailoring Polymeric Hydrogels through Cyclodextrin Host–Guest Complexation

A close correllation between molecular-level interactions and macroscopic characteristics of polymer networks exists. The characteristics of the polymeric hydrogels assembled from β-cyclodextrin (β-CD) and adamantyl (AD) substituted poly(acrylate)s can be tailored through selective host-guest complexation between β-CD and AD substituents and their tethers. Dominantly, steric effects and competitive intra- and intermolecular host-guest complexation are found to control poly(acrylate) isomeric inter-strand linkage in polymer network formation. This understanding of the factors involved in polymeric hydrogel formation points the way towards the construction of increasingly sophisticated biocompatible materials.

β-Cyclodextrin 10.41-hydrate

The crystal structure of β-cyclo­dextrin, C42H70O35·10.41H2O, consists of truncated cone-shaped β-cyclo­dextrin mol­ecules that are herringbone packed. The primary hydr­oxy groups form an intra­molecular hydrogen-bonded array. The semipolar cavity of the cyclo­dextrin host is filled with water mol­ecules, which show partial occupancy and disorder.

Electrospray ionization mass spectrometry studies of cyclodextrin‐carboxylate ion inclusion complexes

Aqueous solutions containing simple model aliphatic and alicyclic carboxylic acids (surrogates 1-4) were studied using negative ion electrospray mass spectrometry (ESI-MS) in the presence and absence of alpha-, beta-, and gamma-cyclodextrin. Molecular ions were detected corresponding to the parent carboxylic acids and complexed forms of the carboxylic acids; the latter corresponding to non-covalent inclusion complexes formed between carboxylic acid and cyclodextrin compounds (e.g., beta-CD, alpha-CD, and gamma-CD). The formation of 1:1 non-covalent inclusion cyclodextrin-carboxylic complexes and non-inclusion forms of the cellobiose-carboxylic acid compounds was also observed.Aqueous solutions of Syncrude-derived mixtures of aliphatic and alicyclic carboxylic acids (i.e. naphthenic acids; NAs) were similarly studied using ESI-MS, as outlined above. Molecular ions corresponding to the formation of CD-NAs inclusion complexes were observed whereas 1:1 non-inclusion forms of the cellobiose-NAs complexes were not detected. The ESI-MS results provide evidence for some measure of inclusion selectivity according to the 'size-fit' of the host and guest molecules (according to carbon number) and the hydrogen deficiency (z-series) of the naphthenic acid compounds. The relative abundances of the molecular ions of the CD-carboxylate anion adducts provide strong support for differing complex stability in aqueous solution. In general, the 1:1 complex stability according to hydrogen deficiency (z-series) of naphthenic acids may be attributed to the nature of the cavity size of the cyclodextrin host compounds and the relative lipophilicity of the guest.

Competitive Enantiodifferentiating Anti-Markovnikov Photoaddition of Water and Methanol to 1,1-Diphenylpropene Using A Sensitizing Cyclodextrin Host

UV-vis, circular dichroism (CD), fluorescence, and NMR spectral studies on the self-inclusion behavior of a newly synthesized sensitizing host, 6-(5-cyanonaphthyl-1-carboamido)-6-deoxy-beta-cyclodextrin (1), showed that the appended naphthalene moiety of 1 perches laterally on the cyclodextrin rim in aqueous methanol but is shallowly included and somewhat tilted in its own cavity in water. UV-vis and CD spectral examinations of the complexation of guest substrate 1,1-diphenylpropene (DPP) with host 1 revealed the formation of a stoichiometric 1:1 complex of DPP with 1. The naphthyl fluorescence of 1 was efficiently quenched by the addition of DPP in aqueous solutions of low methanol contents (<or=25%) but was less efficiently quenched in more hydrophobic solvents (>or=50% methanol), where the fluorophore is not included in the cavity and allows the external attack of DPP to form an exciplex in the bulk solution. Upon irradiation in aqueous solutions of different methanol contents, competitive photoaddition of water and methanol to DPP occurred to give chiral water adduct 3 and methanol adduct 4, favoring the latter product by a factor of 2.5 due to the higher nucleophilicity of methanol. The enantiomeric excess (ee) values of the photoadducts were generally low in highly methanolic solutions, but was greatly improved by increasing the water content to reach 18% ee for 3 and 13% ee for 4 in 10% methanol solution at -10 degrees C. Interestingly, the ee of methanol adduct 4 was consistently lower than that of water adduct 3 particularly in water-rich solvents, revealing that the product's ee is not a simple thermodynamic function of the enantioface-selectivity upon complexation of DPP by chiral host 1 but also kinetically controlled by the subsequent photoinduced enantioface-differentiating nucleophilic attack of water and methanol to radical cationic DPP generated photochemically. Compatible with this mechanism, the compensation plot of the differential activation enthalpy versus entropy, which were obtained from the van't Hoff analysis of the temperature-dependent ee's obtained in aqueous solutions of varying methanol contents, gave an excellent straight line for water adduct 3 but an unprecedented bent plot for methanol adduct 4, indicating a switching of the mechanism in between 35 and 50% methanol solution. By using high pressure, low temperature, and/or added salt, the ee of water adduct 3 was further enhanced to 24-26%.