Complexation of quercetin with three kinds of cyclodextrins: an antioxidant study

The slightly water-soluble flavonoid quercetin (QUE) and its inclusion with either beta-cyclodextrin (betaCD), hydroxypropyl-beta-cyclodextrin (HP-betaCD) or sulfobutyl ether-beta-cyclodextrin (SBE-betaCD) were investigated. The stoichiometric ratios and stability constants describing the extent of formation of the complexes have been determined by phase-solubility measurements; in all cases type-A(L) diagrams have been obtained (soluble 1:1 complexes). The results showed that the inclusion ability of betaCD and its derivatives was the order: SBE-betaCD>HP-betaCD>betaCD. Kinetic studies of DPPH with QUE and CDs complexes were done. The results obtained indicated that the QUE-SBE-betaCD complex was the most reactive form. The scavenging capability of QUE and CDs complexes with DPPH and galvinoxyl was studied using ESR spectroscopy. All complexes showed a higher scavenging capability with both radicals, compare quercetin in water. Beside, these results indicated that the complexes formed maintained the quercetin antioxidant activity.     

Electrochemical oxidation of morin and interaction with DNA

A poly (tetrafluroethylene)-deoxyribonucleate acid (PTFE-DNA) film-modified glassy carbon electrode (GCE) has been fabricated. The electrochemical oxidation behaviors of morin as well as its interaction with DNA have been studied at PTFE-DNA film-modified GCE and bare GCE by electrochemical methods. This modified electrode shows an enhanced effectiveness towards the oxidation of morin. Importantly, as to the interaction between morin and DNA in solution, characteristic parameters such as the binding stoichiometry and association equilibrium constant according to the Hill model for cooperative binding have been determined on the basis of linear sweep voltammetry and chronocoulometry.     

桑色素光度法测定痕量铝和聚丙烯酰胺

基于聚丙烯酰胺（ＰＡＭ）作为增稳剂时,Ａｌ＾３＋叠色素（ｍｏｒｉｎ）之间的显色反应,提出了一种简便,快速,高灵敏测定痕量铝的光度法,络合物组成比为Ａｌ：ｍｏｒｉｎ＝１：２;表观摩尔吸光系数ε４０８＝６．３×１０＾７Ｌ．ｍｏｌ＾－１．ｃｍ＾－１;铝浓度在０．０４－０．２８μｇ／Ｌ范围内服从比尔定律;检测限４．０×１０＾－１０ｇ／Ｌ。     

The use of naphthalene fluorescence probes to study the binding sites on cyclodextrin polymers formed from reaction of cyclodextrin monomers with epichlorohydrin

Three naphthalene-based fluorescence probes were used as guest molecules to study host/guest binding with cyclodextrin (CD) polymer hosts prepared by treating -,-, or -cyclodextrin monomers with epichlorohydrin. The fluorescence data indicate that the binding interaction is much stronger for the probes with the CD polymers than with the CD monomers. Moreover, the fluorophore binding site on the CD polymers is also more hydrophobic than that on the CD monomers. Fluorescence lifetime data from one of the bound probes (2-(N-methylanilino) naphthalene-6-sulfonic acid) suggest that more than one type of binding site may exist on the CD polymers with this probe. A comparison of fluorescence data using different molecular weight ranges of the CD polymers appear to rule out the possibility of a 12 host/guest complex, where the two CD units come from the same polymer chain.     

Pseudorotaxanes of Cyclodextrin and Diglycidyl Ether of Bisphenol A as Precursors of New Intramolecularly Reinforced Epoxy-based Thermosets

As a preliminary work in the search of potential monomers for new intramolecularly reinforced epoxy-based materials, this investigation has been aimed at the synthesis and the physico-chemical characterisation of the monomers formed by complexation between β- and γ-cyclodextrin (CD) and diglycidyl ether of bisphenol A (DGEBA). Results from steady-state fluorescence suggest that, even at high temperature, the DGEBA forms very stable complexes with both macrocycles (particularly with the β-CD) in aqueous solution. Regardless of the CD and according to the interproton distances obtained from the ROESY spectrum when compared with the simulated ones by semi-rigid docking, the oxirane ring of the DGEBA monomer can be found outside the cavity, while the bisphenol moiety firmly remains attached and buried in the CD. The stability of the adduct and the lack of steric hindrance at the epoxide functional points, make the complex very interesting for the synthesis of crosslinked epoxy based polymers, in which the bisphenol part would be covered and therefore protected by the CD. The semi-rigid docking scheme applied to this host–guest system reveals itself as a useful tool for the search of conformers that fit the experimental distances obtained by NMR, although its utility for the estimation of the free energies of binding is still limited.     

Complexation study of midazolam hydrochloride with beta-cyclodextrin: NMR spectroscopic study in solution

(1)H NMR spectroscopic study of midazolam hydrochloride (MDL), beta-cyclodextrin (beta-CD) and their mixtures confirmed the formation of beta-CD-MDL inclusion complex in aqueous solution. The stoichiometry of the complexes was determined by Scott's method to be 1:1, and the association constant (K(a)) was calculated to be 108 M(-1). It was confirmed on the basis of 2D ROESY spectral data that only a fluorine-substituted aromatic ring acted as guest in complexation. Most of the aromatic signals of MDL exhibited induced shift changes as well as splitting, in the presence of beta-CD, indicating chiral differentiation of MDL by beta-CD.     

High Resolution NMR Spectroscopic Study of Complexation of Hydroxyzine Hydrochloride with β‐Cyclodextrin in Aqueous Solution

Hydroxyzine hydrochloride forms two 1:1 inclusion complexes with β‐cyclodextrin in aqueous solution as confirmed by the ¹H NMR titration and ROESY studies. One complex is formed by the deep penetration of the chlorophenyl ring from the wider rim side, while the mode of entry of the phenyl ring into the β‐CD cavity is not clear. The stoichiometry and overall association constant of the complexes have been determined by the treatment of ¹H NMR shift data. Some chiral discrimination by the host between the two enantiomers of hydroxyzine hydrochloride is also indicated.     

Computational study on the molecular inclusion of andrographolide by cyclodextrin

Due to the poor water solubility of andrographolide (andro), an inclusion technique has been developed to modify its physical and chemical properties so as to improve its bioavailability. In contrast with the immense experimental studies on the inclusion complexes of andro:cyclodextrin, no computational study has so far been carried out on this system. In this work, preliminary docking experiments with AutoDock were performed. Density Functional Theory (DFT) and Austin Model 1 (AM1) calculations upon the docking instances were applied to investigate the two possible modes of molecular inclusions between andro and x-cyclodextrin (xCD, where x is alpha, beta or gamma). Atoms-in-Molecules (AIM) analysis based on the B3LYP/cc-pVDZ wavefunction was applied to verify the existence of the intermolecular hydrogen bonds. It was found that the most stable complex among the six possible inclusion complexes was the one formed between andro and betaCD with andro's decalin ring moiety wrapped by CD at a ratio of 1:1. The hydrogen bonds between andro and CD were responsible for the stability of the inclusion complexes. The calculated data were found to be consistent with the experimental results. Thus, the results of this study can aid new drug design processes.     

Complexation of hydroxytyrosol with β-cyclodextrins. An efficient photoprotection

The complexation of the potent olive oil antioxidant hydroxytyrosol (HT) with commercial β-cyclodextrin (β-CD) and hydroxypropyl-β-cyclodextrin (HP-β-CD) in aqueous solutions has been studied for the first time. The 1:1 stoichiometries of the complexes were evidenced by Job’s plot and the association constants were determined by linear regressions from Scott’s method. The geometry of the HT/β-CD complex was elucidated by 2D-ROESY experiments, suggesting insertion of the catechol moiety with the hydroxyalkyl chain directed to the primary rim. The antioxidant activity of encapsulated HT was also evaluated by scavenging of the stable DPPH radical, observing an improvement of the scavenging activity upon increase of the cyclodextrin concentration. Complexation of HT with β-CD also provided a strong photoprotection of the polyphenolic compound upon irradiation with UV (λ=254 nm).     

Complexation of sodium picosulphate with beta cyclodextrin: NMR spectroscopic study in solution

Sodium Picosulphate (SPL) is a synthetic drug, widely used for thorough evacuation of the bowel, usually for patients who are preparing to undergo a colonoscopy. Cyclodextrins (CDs) are chiral, truncated cone shaped, cyclic oligosaccharides that can encapsulate a variety of drug molecules into inclusion complexes, thereby increasing their stability and solubility. ¹H NMR spectroscopic studies showed the inclusion complexation between β-CD and SPL, based on the upfield shift changes in the β-CD cavity protons (H-3′ and H-5′) and downfield shift changes in the guest (SPL) protons. The structure of inclusion complexes was determined by 2D ROESY spectral data. The 1:1 stoichiometry and overall association constant (Ka) were determined by using Scott’s plot method to be 450 M^?1.     

A Study of b-Cyclodextrin Inclusion Complexes with Progesterone and Hydrocortisone Using Rotating Frame Overhauser Spectroscopy

Summary.  Inclusion complexes of β-cyclodextrin with two steroid derivatives, progesterone (pregn-4-ene-3,20-dione) and hydrocortisone (11,17,21-trihydroxy-pregn-4-ene-3,20-dione), were studied in the liquid state by NMR spectroscopy. The complex formation process was monitored by intermolecular dipolar interactions between ¹H signals in the hydrophobic β-cyclodextrin cavity (H-3 and H-5 of the α-glucose units) and the steroid moiety in ROESY spectra. The data revealed that progesterone is fully immersed in the β-cyclodextrin cavity; however, complete inclusion of the hydrocortisone molecule was prevented by the polar hydroxyl groups on its surface. Received April 26, 2001. Accepted (revised) May 18, 2001     

Complexation and Sensing Behavior of Dansyl-appended Cyclodextrins and Cyclodextrin Dimers with Bile Salts

The dansyl-modified cyclodextrin derivatives 2 and 3 form complexes with the steroidal bile salts. The selectivity of the monomeric derivative 3 is similar to that of native g -cyclodextrin. All binding constants with 3 are lowered compared to g -cyclodextrin because of the competition for the cavity between the steroids and the dansyl moiety. Cholate ( 4a ) and deoxycholate ( 4b ) form weak complexes, the other bile salts ( 4c - e ) are complexed far more strongly. The difference is attributed to the absence of a 12-hydroxy group in the latter steroids. Data for dimer 2 reveal strongly enhanced binding of 4a and 4b and only slightly stronger complexes with the other steroids. Due to the low binding affinity of 3 for 4a and 4b , this receptor could not be used for their detection by fluorescence spectroscopy. Steroids 4c - e showed a decrease in fluorescence intensity. The detection of all steroids 4a - e was possible using 2 . The fluorescence intensity of the dimer increased or decreased, depending on which steroid was added.     

Application of adsorptive stripping voltammetry to the determination of bismuth and copper in the presence of morin

A new method is presented for the determination of bismuth and copper based on cathodic adsorptive stripping of complexes of Cu(II) and Bi(III) with 2′,3,4′,5,7-pentahydroxyflavone (morin) at a hanging mercury drop electrode (HMDE). The effect of various parameters such as pH, concentration of morin, accumulation potential and accumulation time on the selectivity and sensitivity were studied. The optimum conditions for determination of copper include nitric acid concentration 0.1 M, morin concentration 0.6 μM and accumulation potential of −300 mV. Those conditions for the determination of bismuth include 0.15 M acid concentration, 0.6 μM morin and accumulation potential of −300 mV. Under these optimum conditions and for an accumulation time of 60 s, the measured peak current at −20 to 25 mV is proportional to the concentration of copper and bismuth over the range of 0.2-130 and 5-50 ng ml⁻¹, respectively. At high concentration of morin (35 μM morin) and accumulation potential of −300 mV (versus Ag/AgCl reference electrode) the peak current is proportional only to the concentration of copper and bismuth has no contribution to the current. At low concentration of morin (0.5 μM morin) and accumulation potential of 100 mV (versus Ag/AgCl reference electrode) the peak current is proportional only to the concentration of bismuth. The method was applied to the determination of copper and bismuth in some real and synthetic samples with satisfactory results.     

Complexation of Na-, Ca-, and Cu-montmorillonites with some parent and methylated cyclodextrins

The uptake of -, -, -, hexakis-2,6-di-O-methyl--(DM--), heptakis-2,6-di-O-methyl--(DM--) and heptakis-2,3,6-tri-O-methyl-- (TM--) cyclodextrins (CD's) by Na-, Ca-, and Cu-montmorillonites has been studied at 25°C. Each of -, DM--, DM--, and TM--CD's forms a complex with all of these montmorillonites in which the guest molecules are arranged as a monolayer with their open faces parallel to the silicate sheet of montmorillonite. On the other hand, -CD is intercalated only by the Na form and -CD cannot be taken up by any of the clays used. The interlayer spacing of the -CD complex varies from 18.0 to 21.5 Å with replacement of the interlayer cation, but those of the methylated -and -CD complexes remain unchanged, beingca. 21 and 18 Å, respectively. The different behaviour of the parent and methylated CD's is explained in terms of the structural and physicochemical characteristics of the individual CD's and interlayer cations.     

Lattice self-assembly of cyclodextrin complexes and beyond

While lipids form soft, fluidic membranes (soft assembly), proteins can readily assemble into rigid, crystalline structures such as viral capsids and bacterial compartments (lattice assembly). The key difference has to do with the driving forces, where the former is driven by the weak, directionless hydrophobic effect and the latter, by a combination of relatively strong, directional intermolecular interactions. In synthetic systems, the lipid assembly has been massively replicated but the protein assembly has been rarely rivaled. Herein, we briefly review these two kinds of assemblies with special emphasis on a recently reported lattice self-assembly system of cyclodextrin complexes. The complexes arrange themselves into an in-plane, rhombic lattice that develops into lamellar, tubular, and polygonal structures depending on concentration. We will then cover the formation mechanisms, driving forces, and an application of the tubes in particle encapsulation. We hope that this short review would draw people's attention to this emerging field of lattice self-assembly.     

A combined electrochemical and DFT study of the lattice strain effect on the surface reactivity of Pd

We report a combined study of electrochemical experiments and ab initio calculations on tuning the surface reactivity of Pd via a compressive lattice strain achieved by employing nanoparticles of Pd-Cu alloys with a Pd-rich surface.Surface oxygen-containing species were used as the probing molecule for revealing the surface reactivity.Both density functional theory (DFT) calculations and experiments showed linear relationships,with very close slopes,between the adsorption strength of OH_(ads) and the Pd lattice constant.Not only is this work a successful realization of controllable modulation in the surface reactivity,but it also provides valuable information for the rational design of Pd-based catalysts for fuel cell applications.     

Physicochemical characterisation and cyclodextrin complexation of erlotinib

Erlotinib (ERL), the anticancer drug of poor bioavailability, was quantified in terms of bio-relevant physicochemical parameters, such as acid–base properties, lipophilicity and solubility, and a comprehensive study on its inclusion complexation was carried out. The protonation constant of ERL (log K = 5.32) indicates that it exists mainly in deprotonated form at the pH of blood plasma. The high lipophilicity (log p = 2.75) explains its good permeability, while the very low solubility (S₀ = 12.46 μM) causes its low bioavailability and renders injection formulation a difficult job. This problem could be alleviated by enhancing ERL solubility through cyclodextrin (CD) inclusion complexation. Therefore, ERL–CD interactions were studied by a number of analytical techniques. The apparent stability constants of ERL with seven different CDs were determined using affinity capillary electrophoresis. Results indicated that the seven-membered β-CD and its derivatives were the most suitable hosts. Using UV Job plot titration 1:1 stoichiometry was determined, confirmed by electrospray ionisation-mass spectrometry experiments. The geometry of the inclusion complex was investigated by 2D ROESY NMR techniques, revealing that the ethynylphenyl ring enters the β-CD cavity. Phase-solubility analysis shows greatly enhanced solution concentration by CD complexation. The determined equilibrium and structural information offer molecular basis to elaborate improved drug formulation with enhanced bioavailability.     

Design on head-to-tail directly linked homogeneous and heterogeneous cyclodextrin dimers and their evaluation of hydrophobic cavity

Covalent directly head-to-tail linked homogeneous and heterogeneous cyclodextrin (CD) dimers were synthesized, and that the reaction of 6-tosylated α-, β-, or γ-CD with a β-CD mono-oxyanion linked the second CD to the secondary hydroxyl side of β-CD was demonstrated. Moreover, deprotonation of α- and γ-CD using NaOH gave corresponding mono-oxyanions, which reacted with the 6-tosylated CDs to produce the CD dimers. The binding of the dimers to sodium 6-(4-tert-butylaniline)-2-naphthalenesulfonate (BNS) was investigated. The binding constant of the ⁶β–²β-CD dimer with BNS was estimated as 3.2 × 10⁶ M⁻¹, about 10² times larger than that of β-CD monomer.     

Complexation of carboxylic acids and anions by alpha and beta cyclodextrins

A pH potentiometric method is used to measure complex formation constants of aqueous alpha- and/or beta-cyclodextrin with several carboxylic acids and carboxylate anions: butyric acid/butyrate; valeric acid/valerate; hexanoic acid/hexanoate; octanoic acid/octanoate; decanoic acid/decanoate; cyclohexanecarboxylic acid/cyclohexanecarboxylate and benzoic acid/benzoate. Standard enthalpies and entropies of complex formation are calculated from the temperature dependencies of the equilibrium constants. These thermodynamic parameters of the alpha-cyclodextrin complexes largely conform to a correlation based on complexes with other substrate species previously reported. Both standard enthalpies and entropies of formation of beta-cyclodextrin complexes are found to be more positive than the corresponding complexes of alpha-cyclodextrin with the same substrates. These observations lead to insights into the bonding mechanism of cyclodextrin complexation.     

Complexation of adamantane-ammonium substrates by beta-cyclodextrin and itsO-methylated derivatives

A spectrophotometric method is used to determine formation constants of complexes of-cyclodextrin, the 2,6-di-O-methylated and 2,3,6-tri-O-methylated derivatives of-cyclodextrin as hosts with adamantan-1-ylammonium, adamantan-2-ylammonium and adamantan-1-ylmethylammonium as substrate species. The spectrophotometric method uses methyl orange anion and acid forms as indicator species. Complexes of the cyclodextrins with these species are determined as well as with the adamantane derivatives. Standard enthalpies and entropies of formation of all complexes are calculated from the temperature variation of the equilibrium constants.-Cyclodextrin and its 2,6-O-methyl derivative have comparable complex strengths with adamantaneammonium substrates and these strengths are about two orders of magnitude stronger than the corresponding complexes of the permethylated derivative. Thermodynamic parameters are interpreted in terms of differing intramolecular properties of the cyclodextrin complexes.