Cyclodextrin Complexes (cyclodextrin + complex)

Distribution by Scientific Domains

Selected Abstracts

Synthesis and Electrochemical Study of an Original Copper(II)-Capped Salen,Cyclodextrin Complex

Elise Deunf
Abstract A new metallocapped cyclodextrin (CD) was synthesized by the regioselective debenzylation, induced by diisobutylaluminium hydride (DIBAL-H), of perbenzylated cyclodextrins. This reaction allowed for the efficient preparation of an unprecedented CD,salen type copper(II) complex. The electrochemical behavior of both the bound and unbound CD,salen compounds was investigated by cyclic voltammetry. Notably, it was shown that the presence of tert -butyl groups at the ortho - and para -positions of the salen aromatic rings stabilized the copper(II) phenoxyl radical species that was generated upon the one-electron oxidation of the starting compound. Importantly, this stabilization remained effective when the salen-type ligand was covalently attached to the CD. This allowed for investigations of the reactivity of the copper(II) phenoxyl radical complex towards a primary alcohol to be performed by cyclic voltammetry. This reaction can be considered as mimicking the behavior of galactose oxidase. However, under these conditions, no reactivity was observed in the presence of benzyl alcohol. This may be due to distortion, either of the initially square planar salen ligand after its grafting to the CD primary face, and/or of the CD itself. On the other hand, the electrochemical reduction of the un-grafted copper(II) salen-type ligand led to a transient anionic species that exhibited significant stability on the time-scale of the slow cyclic voltammetry measurement in the absence of the CD, but was unstable in the presence of the CD. In the latter case, it was demonstrated that the anionic species was protonated by the CD. Importantly, this protonation was not fast enough to prevent catalytic activation of iodomethane by the electro-generated copper(I)-capped salen CD complex. [source]

The Structure of the First Supramolecular ,-Cyclodextrin Complex with an Aliphatic Monofunctional Carboxylic Acid

Saddys Rodríquez-Llamazares
Abstract The crystal structure of the supramolecular complex between ,-cyclodextrin and decanoic acid was determined: The aliphatic chain of the carboxylic acid is threaded through a head-to-head dimer of two cyclodextrin residues, resulting in a 1:2 stoichiometry. Head-to-head orientation is also observed between neighboring complexes. The overall degree of hydration with 25 water molecules per supramolecular complex is remarkably high. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007) [source]

Cyclodextrin complexes of sulfonamide carbonic anhydrase inhibitors as long-lasting topically acting antiglaucoma agents

Francesca Maestrelli
Abstract Complexes of several 1,3,4-thiadiazole-2-sulfonamide derivatives possessing strong carbonic anhydrase (CA) inhibitory properties with ,-cyclodextrin and hydroxypropyl-,-cyclodextrin were obtained and characterized. Although the investigated CA inhibitors possessed very powerful inhibitory properties against the two CA isozymes involved in aqueous humor production within the eye, i.e., CA II and CA IV, these compounds were topically ineffective as intraocular pressure (IOP) lowering agents in normotensive/hypertensive rabbits, due to their very low water solubility. On the contrary, the cyclodextrin,sulfonamide complexes proved to be effective and long-lasting IOP lowering agents in the two animal models of glaucoma mentioned above. © 2002 Wiley-Liss Inc. and the American Pharmaceutical Association J Pharm Sci 91:2211,2219, 2002 [source]

ChemInform Abstract: Asymmetric Synthesis of 2-Azido-1-arylethanols from Azido Aryl Ketone-,-cyclodextrin Complexes and Sodium Borohydride in Water.

CHEMINFORM, Issue 6 2002
M. Arjun Reddy
Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a "Full Text" option. The original article is trackable via the "References" option. [source]

Inhibition of ruminal microbial methane production by ,-cyclodextrin iodopropane, malate and their combination in vitro

N. Mohammed
Summary The objective of this study was to evaluate the effects of different concentrations of l -malate (0, 5, 10 and 20 mm), 2-iodopropane- , -cyclodextrin complex (CD-IP) (0, 0.1, 0.2 and 0.4 mm) and a combination of malate (10 and 20 mm) plus CD-IP (0.2 and 0.4 mm) on methane production from corn starch. Ruminal fluid was collected from dairy cows, mixed with phosphate buffer (1 : 2) and incubated (30 ml) anaerobically at 38 °C for 6 h with or without additives. Fermentation of corn starch in the presence of malate resulted in an increase (p < 0.05) in pH of the medium, total volatile fatty acid (VFA), total gas production and molar proportion of propionate. Acetate and ammonia-N concentration were unchanged. Methane production was decreased (p < 0.05) (15.5 to 20.4%). Addition of CD-IP in corn starch resulted in an increase (p < 0.05) in total VFA and molar proportion of propionate. Acetate, pH and ammonia-N concentration of the medium were decreased (p < 0.05). Total gas production was unchanged. Methane production was decreased (p < 0.05) (25.2 to 97.1%) and hydrogen production was increased (p < 0.05). Addition of l -malate to CD-IP resulted in an increase (p < 0.05) in total VFA, total gas production and molar proportion of propionate. Acetate and ammonia-N concentration were decreased (p < 0.05). No effects were observed on medium pH. Methane production was decreased (p < 0.05) (49.5 to 97.1%). Hydrogen production was also decreased (p < 0.05) (54.5 to 64.1%) compared with those of CD-IP alone. Therefore, these additives may be used as supplements to inhibit methane production as well as to improve rumen fermentation and animal performance. [source]

Enhanced bioavailability of a new thiazolidine derivative FPFS-410, an antidiabetic and lipid-lowering drug, after oral administration of its hydroxypropyl-,-cyclodextrin complex to bile duct-cannulated rats

Takumi Hara
Abstract The effect of bile acids on bioavailability of FPFS-410 (2-(N -Cyanoimino)-5-{(E)-4-styrylbenzylidene}-4-oxothiazolidine) after oral administration of the drug and its 2-hydroxypropyl-,-cyclodextrin (HP-,-CyD) complex was investigated. The complexation with HP-,-CyD increased the oral bioavailability of FPFS-410 in normal rats in a HP-,-CyD concentration-dependent manner, compared with that of drug alone. In bile duct-cannulated rats, bile acid concentrations in pylic serum and biliary were decreased to 18% and 14% of sham-operated rats, respectively. After oral administration of the HP-,-CyD complex, the plasma levels of FPFS-410 were lower in bile duct-cannulated rats than in sham-operated rats up to 1 h, however, this order reversed from 2 to 12 h. The plasma levels of M1, a dominant metabolite of FPFS-410 in rats, significantly decreased until 2 h after administration of the complex in bile duct-cannulated rats, compared with in sham-operated rats. Bioconversion of FPFS-410 to M1 and CYP3A2 expression in the liver was markedly lowered by bile duct-cannulation. Bile duct-cannulation did not, however, affect the serum levels of estradiol. These results suggest that bile acids have a pivotal role for bioavailability of FPFS-410 after oral administration of the FPFS-410 complex with HP-,-CyD through CYP3A2 activity in liver of rats. © 2006 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 95: 1771,1782, 2006 [source]

Improved efficacy and tolerability of retinoic acid in acne vulgaris: a new topical formulation with cyclodextrin complex ,

RY Anadolu
ABSTRACT Objectives, Retinoic acid (RA) has long been used, both topically and systemically, for disorders of keratinization, acne and related disorders. In the present study, the efficacy and tolerability of topical RA prepared as a cyclodextrin beta complex (,-CD) is investigated in 66 acne vulgaris patients. Methods, This randomized, double-blind, placebo-controlled study compares nightly topical application of RA/,-CD complex hydrogel formulation (0.025%), RA/,-CD complex in moisturizing base (0.025%), hydrogel base, moisturizer base or a commercial RA gel (0.05%) in acne vulgaris patients. Improvement of acne was assessed using a 5-point improvement scale and by measuring sebum and moisture content of the skin using an SM 810 sebumeter/corneometer. Results, After 3 months of treatment, mean scores of acne improvement on the 5-point scale were 4 with the RA/,-CD complex hydrogel formulation, 4.1 with the RA/,-CD complex in moisturizing base, 1.2 with hydrogel placebo base, 1.1 with moisturizer placebo base and 3 with the commercial RA product. All patients treated with the commercial product experienced local side-effects. One patient discontinued due to severe irritation. None of the patients treated with the RA/,-CD complex in the moisturizing base and hydrogel formulation experienced significant local irritation, although the sebum content of the skin decreased after application of the RA/,-CD preparations. This change was not significant compared to controls. The moisture content of the skin was better preserved in the group treated with the RA/,-CD complex in the moisturizing base. Conclusion, The topical RA/,-CD complex, in hydrogel and moisturizing base, was more effective than the twice concentrated commercial RA product. There were few topical side-effects with this new formulation, which increases patient compliance. Topical RA/,-CD (0.025% RA) did not significantly reduce sebum secretion but may help to preserve optimum epidermal moisture content with the proper base formulation. This is the first study in the literature reporting efficacy and tolerability of the topical RA/,-CD complex in acne vulgaris. We conclude that the topical RA/,-CD complex displays an improved efficacy and tolerability profile and is an effective treatment alternative for acne vulgaris. [source]

Gas phase isomeric differentiation of oleanolic and ursolic acids associated with heptakis-(2,6-di- O -methyl)-,-cyclodextrin by electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry

Zhan Yu
Abstract Oleanolic acid (OA) and ursolic acid (UA) are isomeric triterpenoid compounds with similar pharmaceutical properties. Usually, modern chromatographic and electrophoretic methods are widely utilized to differentiate these two compounds. Compared with mass spectrometric (MS) methods, these modern separation methods are both time- and sample-consuming. Herein, we present a new method for structural differentiation of OA and UA by Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) with the association of heptakis-(2,6-di- O -methyl)-,-cyclodextrin (DM-,-CD). Exact MS and tandem MS (MS/MS) data showed that there is no perceptible difference between OA and UA, as well as their ,-cyclodextrin and ,-cyclodextrin complexes. However, there is a remarkable difference in MS/MS spectra of DM-,-CD complexes of OA and UA. The peak corresponding to the neutral loss of a formic acid and a water molecule could only be observed in the MS/MS spectrum of the complex of DM-,-CD : OA. Molecular modeling calculations were also employed to further investigate the structural differences of DM-,-CD : OA and DM-,-CD : UA complexes. Therefore, by employing DM-,-CD as a reference reagent, OA and UA could be differentiated with purely MS method. Copyright © 2010 John Wiley & Sons, Ltd. [source]

Influence of response factors on determining equilibrium association constants of non-covalent complexes by electrospray ionization mass spectrometry

Valérie Gabelica
Abstract A method for determining the equilibrium association constant of a complexation reaction A + B , AB by electrospray ionization mass spectrometry is described. The method consists in measuring the relative intensities of the peaks corresponding to A and to AB in equimolar A,B solutions at different concentrations C0. The results are fitted by a non-linear least-squares procedure, with the two variable parameters being the equilibrium association constant Ka and a factor R, defined by I(AB)/I(A) = R × [AB]/[A]. The factor R is the ratio between the response factors of AB and A, and corrects for the relative electrospray responses of the complex and the free substrate A, mass discrimination of instrumental origin and/or moderate in-source dissociation. The method is illustrated with the following two systems: complexes between a double-stranded 12-base pair oligonucleotide and minor groove binders, and cyclodextrin complexes with ,,,-dicarboxylic acids. For the oligonucleotide complexes, it is found that the response of the complex is not dramatically different to the response of the free oligonucleotide duplex, as the double helix conformation is disturbed by the drug only to a minor extent. In the case of cyclodextrin complexes, these complexes were found to have a much higher response than free cyclodextrin. This may be due to the fact that cyclodextrin is neutral in solution, whereas the complex is charged, but it can also stem from the fact that a significant proportion of the complex is in a non-inclusion geometry. The present method requires the exact determination of the concentrations of the reactants and is applicable to 1 : 1 complexes. Copyright © 2003 John Wiley & Sons, Ltd. [source]

Preparation of budesonide/,-cyclodextrin complexes in supercritical fluids with a novel SEDS method

Tarja Toropainen
Abstract The aim was to investigate if solid drug/cyclodextrin complexes could be produced in a single-step process with a solution enhanced dispersion by supercritical fluids (SEDS) method. Budesonide and ,-cyclodextrin (CD) solutions (50% or 99.5% ethanol) were pumped from the same (conventional method) or separate (modified method) containers together with supercritical carbon dioxide through a coaxial nozzle into a particle formation chamber. The pressure was maintained at 100, 150 or 200 bar with a temperature of 40, 60 or 80°C. SEDS-processed powders were characterised with HPLC, DSC and XRPD for budesonide content, complexation and crystallinity. The budesonide dissolution rate was determined in 1% ,-CD aqueous solution. Solid, white budesonide/,-CD complex particles were formed using the conventional and modified SEDS processes. The complexation efficiency was dependent on the processing conditions. For example, with the conventional method (100 bar, 60°C) the yield of the powder was 65,±,12% with 0.14,±,0.02 mg budesonide/mg powder, corresponding to 1:2 drug:CD molar ratio. The dissolution rate of this complexed budesonide (93,±,2% after 15 min) was markedly higher compared to unprocessed micronised budesonide (41,±,10%) and SEDS-processed budesonide without CD (61,±,3%). As a conclusion, SEDS is a novel method to produce solid drug/CD complexes in a single-step process. © 2006 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 95:2235,2245, 2006 [source]

Effect of cyclodextrins on the solubility and antimycotic activity of sertaconazole: Experimental and computational studies

I. Perdomo-López
Abstract This study investigated the effects of the complexation of sertaconazole nitrate with different cyclodextrin (CD) derivatives (,-CD, ,-CD, ,-CD, hydroxypropyl-,-CD, and hydroxypropyl-,-CD) on the aqueous solubility and antimycotic activity of the drug. Phase solubility studies indicated that the solubility of sertaconazole in enzyme-free simulated gastric- and enzyme-free simulated enteric fluids was significantly increased in the presence of cyclodextrins. The observed order of solubility increasing effect was: ,-CD,>,HP,-CD,>,HP,-CD,>,,-CD,>,,-CD. Solid-state sertaconazole,cyclodextrin complexes were prepared by freeze drying, and characterized by X-ray powder difractometry, differential scanning calorimetry (DSC), and infrared spectroscopy (FTIR). Freeze-dried complexes showed markedly higher solubility than both physical mixtures and sertaconazole alone. The antimycotic activities of sertaconazole,cyclodextrin complexes in solution were evaluated by inhibition zone assays with Candida albicans. The activity ranking agrees with the solubility ranking observed for these complexes, with the ,-CD,sertaconazole complex showing the strongest antimycotic activity. Finally, molecular modeling studies were carried out using the MM2 force field method, for complexes in vacuum and in water. This enable indentification of the preferred orientation of sertaconazole in the ,-CD cavity and of the main structural features responsible for the enhancement of its solubility and antimycotic activity. © 2002 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 91:2408,2415, 2002 [source]

An NMR study of cyclodextrin complexes of the steroidal neuromuscular blocker drug Rocuronium Bromide

Kenneth S. Cameron
Abstract The interaction of Rocuronium Bromide, and a model steroid Org 7402, with three cyclodextrins (,-cyclodextrin, ,-cyclodextrin and Org 25969) was studied by solution state NMR experiments. Stoichiometries and binding constants were determined from 1H chemical shift titrations. All of the systems formed 1 : 1 complexes. Most of the complexes were in fast exchange with unbound species on the NMR time scale, but the most tightly bound complex (Rocuronium Bromide,Org 25969) was in the slow exchange regime. The geometry of the complexes was inferred from 1H and 13C NMR shift changes upon complexation and from intramolecular NOE correlations. Rocuronium Bromide forms a weak complex with ,-cyclodextrin (Ka = 3.3 ± 0.5 × 103M,1) and no clear picture of the structure of the complex emerges. The complexes with ,-cyclodextrin (Ka = 1.8 ± 0.2 × 104M,1) and Org 25969 (Ka > 105M,1) are true inclusion complexes with the steroid located inside the central void of the cyclodextrin. Copyright © 2002 John Wiley & Sons, Ltd. [source]