Inclusion complexes of α- andβ-cyclodextrin with α-lipoic acid

A UV spectroscopic study has been performed in neutral aqueous solution to give the complex stability constants. Data analyses assuming 1:1 stoichiometry were successfully applied to both of the host-guest combinations employed, where 1:1 host-guest complex formations were observed at lower concentration of cyclodextrins (CDs). X-ray powder diffraction and IR spectroscopy measurements also demonstrated that inclusion complexes were formed in the solid state. Furthermore, thermogravimetry and DTA were used to investigated the thermal properties of these complexes. The differential thermal analysis, as well as temperature variation experiments below 100°C, indicated that after complexing the 1,2-thiolane moiety of -lipoic acid (LP) penetrated into the cavity of the CD and the S-S linkage was protected against heat.     

Inclusion of α-lipoic acid in β-cyclodextrin. Physical–chemical and structural characterization

The inclusion of α-lipoic acid (LA) in β-cyclodextrin (β-CD) by increasing the aqueous solubility and photostability can enhance its medicinal use in the oral administration. Different preparation methods were employed to obtain an α-lipoic acid-β-cyclodextrin (LA-β-CD) inclusion complex and to determine the physical–chemical characteristics and the interactions present in this compound. The formation of the solid inclusion compound was confirmed by X-ray powder diffraction, differential scanning calorimetry (DSC) and infrared spectroscopy (FTIR). FTIR and DSC data confirm the new obtained compound. The crystalline structure of this compound belongs to the monoclinic system with four molecules in the unit cell. ¹H NMR spectroscopic method was employed to study the inclusion process in aqueous solution. Job plots derived from the ¹H NMR spectral data demonstrated an 1:1 stoichiometry of the inclusion complex in liquid state. 2D NMR data suggest the orientation of LA with the carboxyl group near to narrower rim of the β-CD.     

Stereospecific synthesis of α-lipoic acid

Short and highly stereospecific synthesis of (S)-(-)- and (R)-(+)-α-lipoic acid using menthone as a recyclable chiral auxiliary is presented.     

Inclusion complex of usnic acid with β-cyclodextrin: characterization and nanoencapsulation into liposomes

In this study β-cyclodextrin (β-CD) was used to improve usnic acid (UA) solubility and the inclusion complex (UA:β-CD) was incorporated into liposomes in order to produce a targeted drug delivery system for exploiting the antimycobacterial activity of UA. A phase-solubility assay of UA in β-CD at pH 7.4 was performed. An apparent stability constant of K_1:1 = 234.5 M^?1 and a complexation efficiency of 0.005 was calculated. In the presence of 16 mM of β-CD the solubility of UA (7.3 μg/mL) increased more than 5-fold. The UA:β-CD complex was prepared using the freeze-drying technique and characterized through infrared and ¹HNMR spectroscopy, X-ray diffraction and thermal analyses. The UA:β-CD inclusion complex presented IR spectral modifications when compared with UA and β-CD spectra. ¹HNMR spectrum of UA:β-CD inclusion complex showed significant chemical shifts in proton H5 located inside the cavity of β-CD (Δδ = 0.127 ppm), suggesting that phenyl ring moiety of UA would be expected to be included within the β-CD cavity, interacting with the H-5 proton. A change in UA from its crystalline to amorphous form was observed on X-ray, suggesting the formation of a drug inclusion complex. DSC analysis showed the disappearance of the UA fusion peak UA:βCD complex. No differences between the antimicrobial activity of free UA and UA:βCD were found, supporting the hypothesis that the complexation with cyclodextrin did not interfere with drug activity. Liposomes containing UA:βCD were prepared using hydration of a thin lipid film method with subsequent sonication. Formulations of liposomes containing UA:βCD exhibited a drug encapsulation efficiency of 99.5% and remained stable for four months in a suspension form. Interestingly, the encapsulation of UA:βCD into the liposomes resulted in a modulation of in vitro kinetics of release of UA. Indeed, liposomes containing UA:β-CD presented a more prolonged release profile of free usnic acid compared to usnic acid-loaded liposomes.     

Inclusion complex of (−)-linalool and β-cyclodextrin

(?)-Linalool is a monoterpene alcohol which is present in the essential oils of several aromatic plants. Recent studies suggest that (?)-linalool has antimicrobial, anti-inflammatory, anticancer, antioxidant, and antinociceptive properties in different animal models. The aim of this study was to prepare and characterize inclusion complexes of (?)-linalool with β-cyclodextrin (β-CD). Equimolar binary (?)-linalool/β-CD systems were prepared by physical mixture, paste (PM), and slurry methods (SC) and characterized by differential scanning calorimetry, thermogravimetric analysis, FT-IR spectroscopy, X-ray diffractometry, Karl Fisher titration, and scanning electron microscopy. Thermal characterization indicates the occurrence of complexation, mainly in paste complexes, which is present in the interval from 140 to 280 °C a gradual mass loss (4.6 %), probably related to (?)-linalool loss. FT-IR spectra showed changes that may be related to the formation of intermolecular hydrogen bonds between (?)-linalool and β-CD. The new solid-phase formed using the PM and SC methods, had a crystal structure which was different from the original morphology of β-CD.     

Synthesis and study of new indoline spiropyran and its derivative with α-lipoic acid exhibiting low cytotoxicity

Russian Chemical Bulletin - New indoline spiropyran was synthesized by the cyclocondensation of 5-chlorine-substituted Fischer base with 2,7-dihydroxy-1-naphthaldehyde. This spiropyran was used to...     

Inclusion complex of α-cyclodextrin and the extended viologen dication: a model of an insulated molecular wire

An extended viologen dication 1, containing one viologen subunit, was used as a model for the inclusion complex formation between cyclodextrin (CD) molecules and molecular wires comprising several subunits. UV–Vis and fluorescence spectroscopic measurements confirmed the formation of two types of the inclusion complexes 1:1 and 2:1 between αCD and 1 in the aqueous solution containing 20% of ethanol. The complex formation constants were obtained from the fluorescence spectral changes: K _a  = 25 ± 3 mM^?1 for [αCD–1] complex and K _a  = 0.21 ± 0.07 mM^?2 for [(αCD)₂–1] complex, respectively. Cyclodextrins βCD and γCD do not form the inclusion complexes with 1 in these aqueous solutions. The time-dependent differential capacitance measurements confirmed the adsorption of 1 in the form of a complex at the electrode/electrolyte interface. These studies were conducted with the aim to find the most suitable CD cavity that would separate individual molecular wires from each other on the electrode/electrolyte interface.     

Inhibition of cyclodextrins on the activity of α-amylase

α-amylase activity influences both flour fermentation process and the quality of the fermented products due to its ability of breaking starch into smaller units. The inhibition of cyclodextrins on α-amylase activity was investigated in this paper. Experiment results showed that hydrophobic cavity size was an intrinsic factor during the inhibition processing. Among three types of cyclodextrin (α-, β- and γ-), β-type exhibited the most significant inhibitory activity toward α-amylase. The optimal inhibitory parameters were indicated to be pH 5.9, concentration of β-cyclodextrins 1 mmol/L, reaction temperature 45 °C and reaction time 60 min. Results suggested that the endogenous fluorescence of α-amylase was inhibited by cyclodextrins. Circular dichroism spectrum indicated that the secondary structure of α-amylase, including α-helices, β-sheets and random coils, was changed by cyclodextrins. All the results in this paper aim to provide a further understanding for α-amylase in the industry application.     

Polarity and structure of α-nitrocinnamic acid esters

Polarity and structure of ethyl α-nitrocinnamates have been studied by means of dipole moments method and quantum-chemical calculations. These compounds exist in the form of Z-isomers in solution, that is, nitro group and benzene ring are cis-positioned.     

Liquid chromatographic determination of polythiols based on pre-column excimer fluorescence derivatization and its application to α-lipoic acid analysis

We developed an LC method for the sensitive and selective fluorometric determination of polythiols. This method employs pre-column intramolecular excimer-forming fluorescence derivatization with N-(1-pyrene)iodoacetamide followed by LC separation. Polythiols were converted to the corresponding dipyrene-labeled derivatives, and the derivatives afforded intramolecular excimer fluorescence (440–540 nm). After the optimization using dithiothreitol and dimercaprol as model polythiols, α-lipoic acid (LA) and α-lipoamide were determined with high sensitivity and selectivity. The detection limits for polythiols were 0.6–3.5 fmol on column. Furthermore, this method could be successfully applied to the determination of LA in commercial dietary supplements and in human urine.     

Formation of an α-cyclodextrin/16-mercaptohexadecanoic acid complex and its deposition on gold surfaces

Using ¹H NMR, XRD and XPS techniques we show new findings concerning the nature of the complex formed between 16-mercaptohexadecanoic acid (MHA) and α-cyclodextrin. Stabilization was achieved by dipole-induced dipole interactions between the carboxyl groups of the MHA with the hydroxyls on the cavity rim of the α-cyclodextrin. Deposition of the complex onto a gold substrate with subsequent ethanol washing showed retention of the thiol moiety and removal of cyclodextrin.     

Lipase catalyzed regio- and stereospecific hydrolysis: chemoenzymatic synthesis of both (R)- and (S)-enantiomers of α-lipoic acid

Native lipase of Candida rugosa (EC 3.1.1.3) enantioselectively and regiospecifically hydrolyses the n-butyl ester of 2,4-dithioacetyl butanoic acid either at the carboxylic acid terminus or at the α-thioacetate to provide enantiomerically pure (R)-2,4-dithioacetyl butyric acid and (S)-butyl 2-thio-4-thioacetyl butyrate (ee >98%) while the lipase modified by treatment with diethyl p-nitrophenyl phosphate attacks only the α-thioacetate giving enantiomerically pure (S)-butyl 2-thio-4-thioacetyl butyrate. These enantiomerically pure intermediates can be used as chiral building blocks to obtain both (S)- and (R)-enantiomers of α-lipoic acid and their analogues.     

Encapsulation of alkylparabens with natural and modified α- and β-cyclodextrins

The inclusion complexation between methylparaben, ethylparaben, propylparaben, butylparaben with α-CD, β-CD, hydroxypropyl α-cyclodextrin and hydroxypropyl β-cyclodextrin were carried out by UV–Vis, steady state and time-resolved fluorescence, FT-IR, ¹H NMR techniques and semi-empirical method (PM3). The drug molecules are all given one emission maximum in water where as dual emission in all the CDs. CDs study revealed that the paraben molecules were formed 1:1 inclusion complex. The aliphatic side chain is present in the hydrophilic part whereas hydroxyl group is present in the hydrophobic part of the CD cavity. Nanosecond time-resolved studies indicated that paraben exhibited biexponential decay in water whereas triexponential decay in CDs solution. The complexation energy, thermodynamic parameters and HOMO–LUMO energy structure were calculated using quantum chemical calculation.     

Inclusion complexes of alcohols with α-cyclodextrin

Calorimetric studies of the inclusion complexes of straight and branched alcohols and of diols with alpha-cyclodextrin (-CD) have been carried out in water solvent. The data suggest that straight and branched chain alcohols enter the cavity of -CD alkyl end first. The hydroxyl group hydrogen bonds to the outer oxygen ring of the cyclodextrin. For branched chain alcohols the longer alkyl part of the molecule penetrates the -CD cavity up to the hydroxyl group. Diols form two hydrogen bonds to the outer oxygen ring of the cyclodextrin with some penetration into its interior.     

Reverse-phase liquid chromatographic determination of α-lipoic acid in dietary supplements using a boron-doped diamond electrode

A fast liquid chromatographic separation, coupled with sensitive and straightforward detection using a boron-doped diamond (BDD) electrode, was developed and validated for the determination of α-lipoic acid in dietary supplement samples. The analysis was carried out using a reversed phase C18 (150 mm × 4.6 mm, 5 μm) column with a mobile phase consisting of a 1:1 (v/v) ratio of 0.05 M phosphate solution (pH 2.5):acetonitrile, at a flow rate of 1.0 mL/min. The detection potential obtained from hydrodynamic voltammetry was 1.05 V vs. Ag/AgCl. Under optimized conditions, the chromatographic separation was performed in less than 5 min, a good linear relationship was obtained between the current and the α-lipoic concentration within the range of 0.01-60 μg/mL (correlation coefficient of 0.9971), and a detection limit of 3.0 ng/mL was determined. Furthermore, this method was successfully applied to determine α-lipoic acid concentrations in selected commercial dietary supplement samples. The recovery of α-lipoic acid in spiked samples at 0.5, 5.0 and 30 μg/mL ranged from 94.4% to 103.6% with a relative standard deviation (RSD) of between 1.2% and 3.7%. In real samples, this developed methodology produced results that were highly correlated with the standard HPLC-UV approach. Therefore, the present method can be used for fast, selective and sensitive quantification of α-lipoic acid in dietary supplements.     

Betulonic acid—cyclodextrins inclusion complexes

Journal of Thermal Analysis and Calorimetry - Betulonic acid (BA) is a pentacyclic lupane-type triterpenoid possessing valuable pharmacological activities, exhibiting very low water solubility....     

Investigation of Inclusion Complexes Between α-Cyclodextrin and Ferrocene by ESI-MSn and Cyclic Voltammetry

The inclusion complexes of α-cyclodextrin(α-CD) and FcCO2(CH2)18 (FcSH) and their self-assembled monolayers(SAMs) on gold surface were investigated by electrospray tandem ionization mass spectrometry(ESI-MSn) and cyclic voltammetry, respectively. The interfacial electrochemical response of the SAMs is related to the way in which the inclusion complexes formed.     

Simultaneous determination of uric acid and ascorbic acid at a ferrocenium–thioglycollate modified electrode

Self-assembled monolayers (SAMS) of chemisorbed thioglycollate on a gold electrode surface have been used as a base interface for the electrostatic adsorption of ferrocenium ion. Electrochemical impedance spectra (EIS) and cyclic voltammetry (CV) were used to evaluate the electrochemical properties of the supramolecular film. The bare gold electrode failed to distinguish the oxidation peaks of ascorbic acid (AA) and uric acid (UA) in phosphate buffer solution (PBS, pH 7.0), while the ferricinium–thioglycollate modified electrode could separate them efficiently. In differiential pulse voltammetric measurements, the prepared gold electrode could separate AA and UA signals, allowing the simultaneous determination of AA and UA. Under optimal conditions and within the linear range of 1.0 × 10⁻⁶ to 5.0 × 10⁻⁴ M, the detection limits of AA and UA achieved were 2.0 × 10⁻⁷ and 1.0 × 10⁻⁷ M, respectively. The applicability of the prepared electrode was demonstrated by measuring AA and UA in human urine without any pretreatment. Figure Fabrication process for the modified electrode     

Investigation of Inclusion Complexes Between α-Cyclodextrin and Ferrocene by ESI-MSn and Cyclic Voltammetry

The inclusion complexes of α-cyclodextrin (α-CD) and FcCO2 (CH2)18(FcSH) and their self-as-sembled monolayers (SAMs) on gold surface were investigated by electrospray tandem ionization mass spectrometry (ESI-MS″) and cyclic voltammetry, respectively. The interfacial electrochemical response of the SAMs is related to the way in which the inclusion complexes formed.