Sulfated Β-cyclodextrin Research Articles

A modeling study by response surface methodology (RSM) on Th(IV) adsorption optimization using a sulfated β-cyclodextrin inclusion complex

The inclusion complex (sulfated-β-CD@NAA) of sulfated β-cyclodextrin and α-naphthylacetic acid was synthesized for adsorption of low concentrations of thorium from aqueous solutions. The structure and property of sulfated-β-CD@NAA were characterized by Fourier transform infrared spectroscopy, thermogravimetric, X-ray diffraction, proton nuclear magnetic resonance, specific surface area measurement and scanning electron microscopy. The characterization analysis confirmed the formation of new solid phase. The results indicated that α-naphthylacetic acid embedded into the cavity of sulfated β-cyclodextrin partly from the secondary face and the thermal stability of inclusion complex was significantly increased. The experiments were designed by Box–Behnken design combined with response surface methodology. The adsorption parameters of pH value, contact time, initial concentration were used as the independent variables and their effects were investigated on the Th(IV) adsorption capacity. Second-order polynomial regression models were derived and analysis of variance was utilized to judge the adequacy of the chosen models. The maximum Th(IV) adsorption capacity (12.75 mg g−1) was achieved under the following conditions: pH value 2.5, contact time 35 min, initial concentration 30 mg L−1. Prediction of models was in good agreement with experimental results. The experimental adsorption kinetic data followed a pseudo-second-order equation with the correlation of 0.9996, indicating the chemical adsorption. The obtained equilibrium isotherm data were fitted well with Langmuir model in the concentration range considered. The thermodynamic parameters (∆H0 < 0, ∆S0 < 0, ∆G0 < 0) indicated that the adsorption process was exothermic and spontaneous. Regeneration of Th(IV)-loaded sulfated-β-CD@NAA with 0.1 M HNO3 solution, and the regenerated sulfated-β-CD@NAA can be reused for adsorption of Th(IV).

Development of a capillary electrophoresis method for the determination of the chiral purity of dextromethorphan by a dual selector system using quality by design methodology.

Dextromethorphan is a centrally acting antitussive drug, while its enantiomer levomethorphan is an illicit drug with opioid analgesic effects. As capillary electrophoresis has been proven as an ideal technique for enantiomer analysis, the present study was conducted in order to develop a capillary electrophoresis-based limit test for levomethorphan. The analytical target profile was defined as a method that should be able to determine levomethorphan with acceptable precision and accuracy at the 0.1 % level. From initial scouting experiments, a dual selector system consisting of sulfated β-cyclodextrin and methyl-α-cyclodextrin was identified. The critical process parameters were evaluated in a fractional factorial resolution IV design followed by a central composite face-centered design and Monte Carlo simulations for defining the design space of the method. The selected working conditions consisted of a 30/40.2cm, 50μm id fused-silica capillary, 30mM sodium phosphate buffer, pH6.5, 16mg/mL sulfated β-cyclodextrin, and 14mg/mL methyl-α-cyclodextrin at 20°C and 20kV. The method was validated according to ICH guideline Q2(R1) and applied to the analysis of a capsule formulation. Furthermore, the apparent binding constants between the enantiomers and the cyclodextrins as well as complex mobilities were determined to understand the migration behavior of the analytes.

Supramolecular Dye Aggregate Assembly Enables Ratiometric Detection and Discrimination of Lysine and Arginine in Aqueous Solution.

Constructing sensor systems for rapid and selective detection of small biomolecules such as amino acids is a major area of focus in bioanalytical chemistry. Considering the biological relevance of arginine and lysine, significant efforts have been directed to develop fluorescent sensors for their detection. However, these developed sensors suffer from certain disadvantages such as poor aqueous solubility, technically demanding and time-consuming synthetic protocols, and more importantly, most of them operate through single wavelength measurements, making their performance prone to small variations in experimental conditions. Herein, we report a ratiometric sensor that operates through lysine- and arginine-induced dissociation of a supramolecular assembly consisting of emissive H-aggregates of a molecular rotor dye, thioflavin-T (ThT), on the surface of a polyanionic supramolecular host, sulfated β-cyclodextrin. This disassembly brings out the modulation of monomer–aggregate equilibrium in the system which acts as an ideal scheme for the ratiometric detection of lysine and arginine in the aqueous solution. Besides facile framework of our sensor system, it employs a commercially available inexpensive probe molecule, ThT, which provides an added advantage over other sensor systems that employ synthetically demanding probe molecules. Importantly, the distinctive feature of the ratiometric detection of arginine and lysine provides an inherent advantage of increased accuracy in quantitative analysis. Interestingly, we have also demonstrated that arginine displays a multiwavelength distinctive recognition pattern which distinguishes it from lysine, using a single supramolecular ensemble. Furthermore, our sensor system also shows response in heterogeneous, biologically complex media of serum samples, thus extending its possible use in real-life applications.

Computer simulation and enantioselective capillary electrophoresis to characterize isomer mixtures of sulfated β-cyclodextrins.

The enantiomeric separation of methadone in the presence of multiple isomer mixtures of sulfated β-cyclodextrin (S-β-CD) was studied experimentally with CZE and theoretically using computer simulation. Experiments were performed over many years with several lots of S-β-CD from the same manufacturer with a specified degree of substitution of 7-11. Large differences in the migration patterns were observed between certain lots and it was concluded that the extent of labelling in lots released after a transition time was higher than originally specified. The migration pattern was observed to be associated with (i) the ionic strength increase resulting from using S-β-CDs with a higher charge state and (ii) differences in buffer composition. Apparent binding constants between methadone and the S-β-CD and complex mobilities were determined for different lots of S-β-CD at varying ionic strength using phosphate and 3-morpholino-2-hydroxypropanesulfonic acid buffers. The obtained values were used as input for simulations. For a given ionic strength, agreement between predicted and experimentally observed behavior was obtained for different buffers. R-methadone has a stronger interaction with S-β-CD than S-methadone. For any given configuration there is a distinct S-β-CD concentration range which results in the cationic migration of S-methadone while the migration direction of R-methadone is reversed. This configuration was demonstrated to be applicable for micropreparative CZE separations.

Development of thin film nanocomposite membranes incorporated with sulfated β-cyclodextrin for water vapor/N2 mixture gas separation

In this work, thin film nanocomposite (TFN) membranes incorporated with sulfated β-cyclodextrin (sb-CD) were fabricated by interfacial polymerization using aliphatic diethylene triamine (DETA) and trimesoyl chloride (TMC) for water vapor separation. Aromatic m-phenylenediamine (MPD) was used for performance comparison with DETA. The intrinsic properties of fabricated TFN membranes were investigated by Attenuated total reflectance-Fourier transformed infrared (ATR-FTIR), field-emission scanning electron microscopy (FE-SEM), energy dispersive X-ray spectroscopy (EDX), atomic force microscopy (AFM) and water contact angle (WCA). The contact angle (35°) of the TFC membranes with DETA was very lower than that (59°) of The TFC with MPD. Moreover, the TFN membrane with sb-CD loading of 0.15wt% showed the lowest contact angle of 14°, implying that many hydrophilic sulfonic acid groups of sb-CD nanoparticles contributed to decreased contact angle. The effect of sb-CD loading on water vapor permeance and selectivity was studied. Increase in sb-CD loading caused synergistic increase in both permeance and selectivity below the agglomeration point due to its hydrophilic and packable nature. The maximal selectivity of 503 along with 1597 GPU in permeance was obtained with the sb-CD loading of 0.15wt%. In addition, the structural characteristics were found to have a bigger impact on TFN membrane performance than intrinsic properties.

Sulfated cyclodextrins as water-soluble chiral NMR solvating agents for cationic compounds

The utility of a series of sulfated cyclodextrins as water-soluble chiral NMR solvating agents for cationic substrates is described. Sulfated α-, β- and γ-cyclodextrin with degrees of substitution of 12, 13 and 14, respectively, a sulfated β-cyclodextrin with a degree of substitution of 9 and a sulfobutyl ether β-cyclodextrin with a degree of substitution of 6.3 are examined. Results with 33 water-soluble cationic organic salts are reported. Chiral differentiation with the sulfated cyclodextrins is compared to prior results obtained with anionic carboxymethylated and phosphated cyclodextrins. The highly sulfated cyclodextrins are often more effective at causing enantiomeric differentiation in 1H NMR spectra than the sulfobutyl ether, carboxymethylated and phosphated cyclodextrins, and are recommended as the first choice of a chiral solvating agent for the analysis of chiral cationic organic salts in aqueous solution.

The Selective Electrochemical Detection of Dopamine Using a Sulfated β-Cyclodextrin Carbon Paste Electrode

The present work describes a novel approach for the determination of dopamine (DA) using carbon paste electrodes modified with sulfated β-cyclodextrin (S-β-CDCPE). The electrodes show high affinity towards DA electrochemical oxidation. DA returned a concentration detection range 5 × 10−7 M to 5 × 10−4 M and a detection limit of 1.33 × 10−7 M. DA, ascorbic acid (AA), and serotonin (5-HT) in a solution mixture can be simultaneously oxidized at significantly different potentials in the presence of S-β-CDCPE, while the unmodified CPE returned an overlapping response. In particular, S-β-CD-modified carbon paste microelectrode exhibits clear peak potential separations of 0.161, 0.101, and 0.258 V (vs. Ag/AgCl) for AA/DA, DA/5-HT, and AA/5-HT, respectively, in artificial cerebrospinal fluid (aCSF).

Stimulus-Responsive Supramolecular Aggregate Assembly of Auramine O Templated by Sulfated Cyclodextrin.

Self-aggregation of organic molecules is rarely seen with macrocyclic hosts like β-cyclodextrin, as they preferentially involve the formation of inclusion complexes with the guest molecule. In this contribution, we report the self-aggregation of a guest molecule induced by negatively charged sulfated β-cyclodextrin (SCD) to yield highly emissive aggregates of a recently projected amyloid marker dye, Auramine O (AuO). The SCD templated AuO aggregates display very different photophysics when compared to its reported behavior in a wide range of various chemical and biological environment but show a remarkable similarity with the recently reported photophysical behavior of AuO in human insulin fibrillar media, thus providing important insights into the molecular form of AuO responsible for its amyloid sensing ability. The self-assembled AuO aggregates formed in the presence of SCD display a significantly long excited-state lifetime, suggesting the retardation of the torsional relaxation of dye in the aggregated state, which otherwise leads to a very short excited-state lifetime for the monomeric form of the dye in the isolated form. Detailed time-resolved emission spectra (TRES) measurements show a dynamic Stokes shift suggesting excitonic migration within the AuO aggregates. The supramolecular aggregate assembly displays remarkable sensitivity to important external stimuli like temperature or ionic strength of the medium, pitching for its possible application in designing stimuli-responsive sensing schemes for important analytes.

Separation of hydroxynorketamine stereoisomers using capillary electrophoresis with sulfated β‐cyclodextrin and highly sulfated γ‐cyclodextrin

The racemic N-methyl-d-aspartate receptor antagonist ketamine is used in anesthesia, analgesia and the treatment of depressive disorders. It is known that interactions of hydroxylated norketamine metabolites and 5,6-dehydronorketamine (DHNK) with the α7 -nicotinic acetylcholine receptor and the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor are responsible for the antidepressive effects. Ketamine and its first metabolite norketamine are not active on these receptors. As stereoselectivity plays a role in ketamine metabolism, a cationic capillary electrophoresis based method capable of resolving and analyzing the stereoisomers of four hydroxylated norketamine metabolites, norketamine and DHNK was developed. The assay is based on liquid/liquid extraction of the analytes from the biological matrix, electrokinetic sample injection across a buffer plug and analysis of the stereoisomers in a phosphate background electrolyte (BGE) at pH 3 comprising a mixture of sulfated β-cyclodextrin (5 mg/mL) and highly sulfated γ-cyclodextrin (0.1%). The method was used to analyze samples of an in vitro study in which ketamine was incubated with equine liver microsomes and in plasma samples of dogs and horses that were collected after an i.v. bolus injection of racemic ketamine.

Preparation and characterization of magnetic Fe3O4@sulfonated β-cyclodextrin intercalated layered double hydroxides for methylene blue removal

Nanocage structures derived from sulfated β-cyclodextrin (SCD) intercalated MgAl layered double hydroxides (MgAl-NO3 LDHs) were prepared through ion-exchange reactions. Coprecipitation method was used to prepare the composites of magnetic Fe3O4@sulfonated β-cyclodextrin intercalated LDH (Fe/SCD-LDH), which was demonstrated having an efficient adsorption capability to cationic pollutants and an excellent reuseability. X-ray diffraction and Fourier transform infrared spectroscopy confirmed that SCD was intercalated successfully and the basal spacing was expanded to 1.63 nm. N2-adsorption/desorption and scanning electron microscopy displayed that the resulting Fe/SCD-LDH possessed high crystallinity, hierarchical structure as well as large specific surface area. Energy-dispersive X-ray spectroscopy was used to investigate the type and content of the elements in Fe/SCD-LDH. Batch adsorption experiments were carried out to investigate the removal of methylene blue (MB) from aqueous solution using Fe/SCD-LDH as the adsorbent. MB was selected owing to its toxic and carcinogenic features as a kind of cationic dye. The adsorption process could be well described by the pseudo-second-order kinetic model and fitted well with the Langmuir isotherm model.

Enantioseparation of citalopram analogues with sulfated β-cyclodextrin by capillary electrophoresis.

Capillary electrophoresis methods were developed for the enantiomeric separation of 27 citalopram analogues. Sulfated β-cyclodextrin was the most broadly selective and useful chiral selector. The separations of most of the citalopram analogue compounds reported in this work have not been reported previously. Excellent enantiomeric separations were obtained for 26 out of 27 compounds, and most of the separations were achieved within 10 min. The effects of chemical parameters such as chiral selector types, buffer types, chiral selector and buffer concentrations, buffer pH and organic modifiers on the separation were investigated. The influence of analyte structure on separation also was examined and discussed.

Evaluation of the enantioselective binding of imazalil to human serum albumin by capillary electrophoresis

In this work, a methodology for the evaluation of enantioselective binding of imazalil (IMA) enantiomers to human serum albumin (HSA) that does not require the separation of free and bound to HSA fractions is developed. This methodology comprises the incubation of IMA-HSA designed mixtures for 30 min directly in the capillary electrophoresis system and the subsequent direct injection and chiral separation of IMA employing highly sulfated β-cyclodextrin as chiral selector and the complete filling technique. Two mathematical approaches were used to estimate apparent affinity constants (K1), protein binding and enantioselectivity (ES) for both enantiomers of IMA. Moderate enantioselective binding of IMA enantiomers to HSA (ES = 2.0) was shown by the 1:1 stoichiometry and log K1 values of 3.4 ± 0.4 and 3.1 ± 0.3 for the first and second eluted enantiomers, respectively.

Separation and Determination of Cold Medicine Ingredients by Capillary Zone Electrophoresis Using Sulfated β‐Cyclodextrin as an Electrolyte Modifier and Chiral Selector

AbstractCapillary zone electrophoretic separations of cold medicine ingredients, including acetaminophen (AC), dextromethorphan (DMF) and racemates of phenylpropanolamine (PPA) and chlorpheniramine maleate (CPM) using randomly sulfated‐β‐CD (S‐β‐CD) as an electrolyte modifier and a chiral selector were investigated. The results indicate that S‐β‐CD is an excellent chiral selector and a suitable electrolyte modifier as well for the separation of those cold medicine ingredients. Influences of S‐β‐CD concentration and buffer concentration on the separation were examined. Baseline separation of these cold medicine ingredients with 1.0 % (w/v) S‐β‐CD could be simultaneously and successfully achieved within 11.8 minutes. In addition, S‐β‐CD could also act as a chiral selector for enantioseparation of PPA and CPM. A high enantioselectivity was obtained for these two analytes. Linear relationships between the peak area and its concentration for the calibration curves of AC and DMF were obtained (correlation coefficients: 0.9987 for AC, 0.9965 for DMF, respectively). The relative standard deviations of the migration time and peak area of AC and DMF were 0.19, 2.44 % and 0.34, 2.99 %, respectively. Detection limits were 0.93 and 2.57 μg/mL for AC and DMF, respectively. Recoveries of AC and DMF ranging between 102.42 and 97.28 % were observed. The proposed method was successfully applied to the determination of AC and DMF in cold medicines.

Experimental and theoretical study on chiral recognition mechanism of ketoconazole enantiomers using heptakis (2,3,6-tri-O-methyl)-β-cyclodextrin

Capillary electrokinetic chromatography (EKC) has been established as a versatile and robust capillary electrophoresis (CE) method for the separation of enantiomers. One of the most attractive advantages of EKC for the separation of enantiomers is its ease of change of separation media in method development. The separation solution can easily be altered to find the optimum separation media and one can also use an expensive chiral selector because small amounts of it are required. This work aims to develop experimental and theoretical analysis of the chiral separation of ketoconazole using EKC and molecular modelling study, respectively. In the first part of the study, several cyclodextrins (CD) as the chiral selectors (CS) namely α-cyclodextrin, sulfated β-cyclodextrin, (2-hydroxylpropyl)-β-cyclodextrin, heptakis(2,6-di-O-methyl)-β-cyclodextrin, and heptakis(2,3,6-tri-O-methyl)-β-cyclodextrin were screened. CDs were initially chosen as they are easily available and cheap. Heptakis (2,3,6-tri-O-methyl)-β-cyclodextrin (TMβCD) exhibited a higher enantioselectivity power compared with other tested CDs. The influence of TMβCD concentration, buffer pH, buffer concentration, separation temperature and applied voltage were investigated. The optimum conditions for chiral separation of ketoconazole was achieved using 10 mM phosphate buffer at pH 3.0 containing 20 mM TMβCD with an applied voltage of 30 kV at 35°C with 5 s injection time (hydrodynamic injection). The ketoconazole enantiomers were resolved in less than 10 min (Rs 1.79). In order to understand possible chiral recognition mechanisms of ketoconazole with TMβCD, host-guest binding procedures of TMβCD and ketoconazole were studied using the semi-empirical PM3 calculations.________________________________________GRAPHICAL ABSTRACT

Experimental design-guided development of a stereospecific capillary electrophoresis assay for methionine sulfoxide reductase enzymes using a diastereomeric pentapeptide substrate

A capillary electrophoresis method has been developed and validated to evaluate the stereospecific activity of recombinant human methionine sulfoxide reductase enzymes employing the C-terminally dinitrophenyl-labeled N-acetylated pentapeptide ac-KIFM(O)K-Dnp as substrate (M(O)=methionine sulfoxide). The separation of the ac-KIFM(O)K-Dnp diastereomers and the reduced peptide ac-KIFMK-Dnp was optimized using experimental design with regard to the buffer pH, buffer concentration, sulfated β-cyclodextrin and 15-crown-5 concentration as well as capillary temperature and separation voltage. A fractional factorial response IV design was employed for the identification of the significant factors and a five-level circumscribed central composite design for the final method optimization. Resolution of the peptide diastereomers as well as analyte migration time served as responses in both designs. The resulting optimized conditions included 50mM Tris buffer, pH 7.85, containing 5mM 15-crown-5 and 14.3mg/mL sulfated β-cyclodextrin, at an applied voltage of 25kV and a capillary temperature of 21.5°C. The assay was subsequently applied to the determination of the stereospecificity of recombinant human methionine sulfoxide reductases A and B2. The Michaelis–Menten kinetic data were determined. The pentapeptide proved to be a good substrate for both enzymes. Furthermore, the first separation of methionine sulfoxide peptide diastereomers is reported.

Modeling the chiral resolution ability of highly sulfated β-cyclodextrin for basic compounds in electrokinetic chromatography

Despite the fact that extensive research in the field of enantioseparations by capillary electrophoresis has been carried out, it is difficult to predict whether a concrete chiral selector would be useful for the separation of a racemic compound. Hence, several experimental effort is necessary to test the abilities of individual chiral selectors, usually by trial and error procedures. Thus, the enantioseparation of a new racemate becomes a time- and money-consuming task. In this work, the ability of highly sulfated β-cyclodextrin (HS-β-CD) as chiral selector in electrokinetic chromatography (EKC) is modeled for the first time, using exclusively directly-available structural data of forty compounds (structurally unrelated basic drugs and pesticides). A discriminant partial least squares (PLS)-based quantitative structure–property relationship (QSPR) approach is simplified, resulting in a consistent, predictive and descriptive model. It is converted into an explicit equation able to predict the enantioresolution level (Rs) of new compounds, from four structure properties available in an on-line open database: logarithm of octanol-water partition coefficient estimated at pH 7.4 (lgD), polar surface area (PSA), number of hydrogen bond donors (HBD) and acceptors (HBA). For the cases in which the model predicts good Rs only in concrete experimental conditions, a Box–Behnken experimental design is proposed for the fast PLS-based optimization of the most influential experimental variables: cyclodextrin concentration, temperature and pH.

The antiangiogenic properties of sulfated β-cyclodextrins in anticancer formulations incorporating 5-fluorouracil

Sulfated β-cyclodextrins (S-β-CDs) are useful excipients for improving the solubility of drugs. One such formulation incorporating 5-fluorouracil (5-FU), termed FD(S), showed improved efficacy over 5-FU alone in orthotopic carcinoma xenograft models. S-β-CDs have heparin-like anticoagulant properties, which may have contributed toward the improved antitumor effect of FD(S). S-β-CDs have also been reported to modify a number of processes involved in angiogenesis. Although the anticoagulant nature of S-β-CDs was established, the antiangiogenic properties of S-β-CDs within FD(S) were unknown. The effect of S-β-CD and FD(S) on the proliferation and migration of endothelial cells in live-cell kinetic assays, and the reorganization of human umbilical vein endothelial cells into tubule structures in vitro was assessed. The effects of S-β-CD on angiogenesis in vitro were validated ex vivo using the rat aorta ring assay and the chick embryo chorioallantoic membrane assay. S-β-CD does not alter proliferative endothelial cell sensitivity to 5-FU cytotoxicity. S-β-CD alone and within FD(S) significantly inhibited angiogenesis by impeding endothelial cell migration, resulting in the inhibition of tubule formation and hence new vasculature. In addition to the cytotoxic action of the drug 5-FU, therapeutic inhibition of angiogenesis by S-β-CDs within FD(S) could potentially limit local invasion and metastases. This has important implications for the exploitation of S-β-CDs for drug formulation improvements or for drug delivery of anticancer biologics.

Characterizing the interaction between enantiomers of eight psychoactive drugs and highly sulfated‐β‐cyclodextrin by counter‐current capillary electrophoresis

The estimation of apparent binding constants and limit mobilities of the complexes of the enantiomers that characterize the interaction of enantiomers with chiral selectors, in this case highly sulfated β-cyclodextrin, was approached using a simple and economic electrophoretic modality, the complete filling technique (CFT) in counter-current mode. The enantiomers of eight psychoactive drugs, four antihistamines (dimethindene, promethazine, orphenadrine and terfenadine) and four antidepressants (bupropion, fluoxetine, nomifensine and viloxazine) were separated for the first time for this cyclodextrin (CD). Estimations of thermodynamic and electrophoretic enantioselectivies were also performed. Results indicate that, in general, thermodynamic enantioselectivity is the main component explaining the high resolution found, but also one case suggests that electrophoretic enantioselectivity itself is enough to obtain a satisfactory resolution. CFT results advantageous compared with conventional capillary electrophoresis (CE) and partial filling technique (PFT) for the study of the interaction between drugs and chiral selectors. It combines the use of a simple fitting model (as in CE), when the enantiomers do not exit the chiral selector plug during the separation (i.e. mobility of electroosmotic flow larger than mobility of CD), and drastic reduction of the consumption (and cost; ~99.7%) of the CD reagent (as in PFT) compared with the conventional CE.

In-line capillary electrophoretic evaluation of the enantioselective metabolism of verapamil by cytochrome P3A4

In this paper a methodology for the in-line evaluation of enantioselective metabolism by capillary electrophoresis has been developed and applied to the study of verapamil metabolism by cytochrome P3A4. The developed methodology comprises an in-capillary reaction step carried out by electrophoretically mediated microanalysis and a separation step in which highly sulfated β-cyclodextrin with partial filling technique has been employed as chiral selector for verapamil and norverapamil enantiomers resolution, joining the advantages of both methodologies in a unique assay. Kinetic parameters of the enzymatic reaction (Km and Vmax) have been evaluated for both verapamil enantiomers by non-linear fitting of experimental data obtained under intermediate precision conditions to Michaelis–Menten equation. Km and Vmax estimated values were 51±9μM and 22±2pmolmin−1(pmolCYP)−1 for S-VER and 47±9μM and 21±2pmolmin−1(pmolCYP)−1 for R-VER. Consequently, slight enantioselectivity was found for the CYP3A4 metabolism of verapamil. However, since confidence intervals of estimates overlap, we cannot assure a significant enantioselectivity. Intrinsic clearance values were also estimated from Km and Vmax for both enantiomers.

Comparative enantioseparation of talinolol in aqueous and non-aqueous capillary electrophoresis and study of related selector–selectand interactions by nuclear magnetic resonance spectroscopy

The enantiomers of the chiral β-blocker drug talinolol were separated with two single component sulfated β-cyclodextrin (CD) derivatives, namely heptakis (2,3-di-O-methyl-6-sulfo)-β-CD) (HDMS-β-CD) and heptakis (2,3-di-O-acetyl-6-sulfo)-β-CD) (HDAS-β-CD), in aqueous and non-aqueous capillary electrophoresis (CE). The enantiomer affinity pattern of talinolol toward these two CDs was opposite in both aqueous and non-aqueous CE. However, the enantiomer affinity pattern for a given CD derivative did not change when aqueous buffer was replaced with non-aqueous background electrolyte. The structures of the analyte–selector complexes in both, aqueous and non-aqueous electrolytes were studied using rotating frame nuclear Overhauser effect (ROESY) NMR spectroscopy. Inclusion complex formation between the enantiomers of talinolol and HDAS-β-CD was confirmed in aqueous buffer, while the complex between the enantiomers of talinolol and HDMS-β-CD was of the external type. The complex of the talinolol enantiomers with HDAS-β-CD in non-aqueous electrolyte was also of the external type. In spite of external complex formation excellent separation of the enantiomers was observed in non-aqueous CE.