Enantioselective Degradation of Chiral Insecticide Dinotefuran in Greenhouse Cucumber and Soil

The enantioselective degradation behavior of the chiral insecticide dinotefuran in cucumber and soil was investigated under greenhouse conditions based on the method established with a normal‐phase high‐performance chromatography (HPLC) on a ChromegaChiral CCA column (250 × 4.6 mm, 5 µm, ES Industries). The linearity range, matrix effect, precision, and accuracy of the method were evaluated and the method was then successfully applied for the enantioselective analysis of dinotefuran in cucumber and soil. Significant enantioselectivity of degradation was observed in soil according to the results. The (+)‐dinotefuran was more persistent in soil with half‐life of 21.7 d, which is much longer than that of (–)‐dinotefuran (16.5 d). In cucumber, the (–)‐dinotefuran also tended to be preferentially degraded both in foliar and douche treatment. However, the statistical analysis indicated the enantioselectivity of degradation in cucumber was not significant. The research provides the first report concerning the enantioselective degradation of dinotefuran enantiomers and the results can be used for understanding the insect‐controlling effect and food safety evaluation. Chirality 27:137–141, 2015. © 2014 Wiley Periodicals, Inc.     

Identification of enantioselective extractants for chiral separation of amines and aminoalcohols

The major obstacle for the introduction of fractional reactive extraction as a chiral separation method in the chemical and pharmaceutical industries is the lack of versatile enantioselective extractants. Therefore, a rational approach is developed to transfer the extensive knowledge of chiral selectors reported in the literature on chiral recognition and other chiral separation techniques to extraction. Based on a similarity in separation mechanisms, it was expected that chiral selectors originating from a technique in which chiral recognition takes place in the liquid phase are most likely to function as enantioselective extractant. Using this approach, a selection of promising extractants was made from the literature and experimentally evaluated for the enantioseparation of aminoalcohols and amines. As a result, four enantioselective extractant systems, namely, dibutyl-L-tartrate with boric acid, N-(2-hydroxydodecyl)-L-hydroxyproline Cu(II) complex, N-dodecyl-L-hydroxyproline Cu(II) complex, and azophenolic crown ether, have been identified. The azophenolic crown ether system performed the best and demonstrated an enantioselectivity between 1.3-5.0 for five out of six test compounds. Identification of the enantioselective extractant systems was highly facilitated by the developed rational transfer approach that, although partially qualitative, appeared capable of reducing more than 50 encountered candidates to only three promising systems for further experimental evaluation. Therefore, it is expected that this approach can be successfully applied to identify enantioselective extractants for other classes of enantiomers as well.     

Exploring new methods and materials for enantioselective separations and catalysis

In this article, we will review and highlight some recent computational work on enantioselective adsorption and catalysis in zeolites and metal–organic frameworks. The design, development and understanding of chiral structures will help expand the utility of nanoporous materials into chiral technology. The highlighted works are examples of how molecular simulations can provide a fundamental understanding of chirality in nanoporous materials. This understanding is essential to help in the design and development of next-generation enantioselective separation devices and catalysts.     

Elucidation of the chromatographic enantiomer elution order for praziquantel: An experimental and theoretical assessment

In this work, we have studied both experimentally and theoretically the praziquantel (PZQ) chiral discrimination. According to the main results, the enantioseparation of PZQ was efficiently optimized by HPLC on the reverse phase from the Chiralpak IB column, which has cellulose tris (3,5-dimethylphenylcarbamate) (CDMPC) as a chiral selector. The thermodynamic and structural parameters obtained via density functional theory (DFT) calculations pointed out the chiral discrimination as well as the enantiomeric elution order of PZQ, thus elucidating the experimental data and validating our proposed method. Finally, the hydrogen bonds and π-π stacking interactions played a key role in the discrimination between the PZQ diastereomeric complexes formed.     

Mechanism of chiral recognition in the enantioseparation of 2-aryloxypropionic acids on new brush-type chiral stationary phases

New brush-type chiral stationary phases (CSP I-IV) comprising N-3,5,6-trichloro-2,4-dicyanophenyl-L-alpha-amino acids (1-4) were prepared by binding of chiral selectors 1-4 to gamma-aminopropyl silica gel. To check the role of excess free aminopropyl groups, CSP V was prepared by binding N-3,5,6-trichloro-2,4-dicyanophenyl-L-alanyl-(3-triethoxysilyl)propylamide to unmodified silica gel. The best separation of racemic 2-aryloxypropionic acids (TR-1-13) was obtained with CSP I; the -(-)-S enantiomer were regularly eluted first, as determined by a CD detector. The mechanism of chiral recognition implies a synergistic interaction of carboxylic acid analyte with the chiral selector and achiral free gamma-aminopropyl units on silica. In fact, CSP V, which is lacking an achiral aminopropyl spacer, shows a lower separation ability for 2-aryloxypropionic acids, but a similar enantioselective discrimination of esters TR-19-20, in comparison with CSP I. CSP I-IV retain unaltered separation ability after a few months of continuous work using a large number of various mobile phases.     

Separation and aquatic toxicity of enantiomers of 1-(substituted phenoxyacetoxy)alkylphosphonate herbicides

A series of organophosphorous compounds (OPs), 1-(substituted phenoxyacetoxy)alkylphosphonates containing a chiral carbon atom, show notable herbicidal activities. In this study, the enantioselective separation and biological toxicity of all these compounds were investigated. The enantioselective separation on the columns of Chiralpak AD, Chiralpak AS, Chiralcel OD, and Chiralcel OJ were compared under various chromatographic conditions. All the analytes investigated obtained baseline resolution (R(s) > 1.5) on Chiralpak AD column, which showed best chiral separation capacity. Further investigation was carried out on Chiralpak AD to evaluate the influence of the mobile phase composition and column temperature. The effect of the structural features on discrimination was also examined. The resolved enantiomers were distinguished by their signs of circular dichroism. The acute aquatic toxicity of enantiomers and racemate to Daphnia magna (D. magna) were assessed. The in vivo assays showed that compound 3 was about 2-148.5 times more toxic than the other four analogues to D. magna. The racemates of compounds 3 and 5 showed intermediate toxicity compare to their enantiomers, while those of compounds 1, 2, and 4 showed synergistic or antagonistic effect. These results suggest that the biological toxicity of chiral OPs to nontarget organisms is enantioselective and therefore should be evaluated with their pure enantiomers.     

Simultaneous enantioselective separation of azelastine and three of its metabolites for the investigation of the enantiomeric metabolism in rats. I. Liquid chromatography-ionspray tandem mass spectrometry and electrokinetic capillary chromatography

Enantioselective separation methods and the enantioselective determination of the anti-allergic drug azelastine and of three of its main phase I metabolites in a biological matrix underwent chromatographic and electrophoretic investigations. An enantioselective assay of a coupling of HPLC using a beta-cyclodextrin chiral stationary phase to ionspray tandem mass spectrometry is presented. Additionally, this assay is compared to another enantioselective assay using electrokinetic capillary chromatography with beta-cyclodextrin and carboxymethyl-beta-cyclodextrin in polyacrylamide-coated capillaries. For capillary electrophoresis (CE) the importance of polyacrylamide coating for the validation of this separation method is highlighted. Extracted rat plasma samples of enantioselective metabolism studies were measured by both validated assays. Differences in the pharmacokinetics and pharmacodynamics were evaluated for the main substance azelastine and its main metabolite demethylazelastine. So, a first hint about the enantioselectivity of biotransformation of azelastine in rats was seen after oral application of either enantiomer or the racemate to rats.     

Direct enantioselective HPLC monitoring of lipase-catalyzed kinetic resolution of tiaprofenic acid in nonstandard HPLC organic solvents

The first straightforward lipase-catalyzed enantioselective access to enantiomerically enriched tiaprofenic acid as a versatile method in chiral separation of racemates is demonstrated. The latter was directly monitored by enantioselective HPLC using a 3,5-dimethylphenylcarbamate derivative of cellulose-based chiral stationary phase namely Chiralpak IB (the immobilized version of Chiralcel OD). Non-standard HPLC organic solvents were used as diluent to dissolve the "difficult to dissolve" enzyme substrate (the acid) and as eluent for the simultaneous enantioselective HPLC baseline separation of both substrate and product in one run without any further derivatization. The existence of a non-standard HPLC organic solvent (e.g., methyl tert-butyl ether) in the mobile phase composition is mandatory to accomplish the simultaneous enantioselective HPLC baseline separation of both substrate and product.     

Enantioselective separations using capillary electrophoresis

The preconditions are outlined for enantioselective separations in capillary electrophoresis (CE) with chiral selectors as additives to the background electrolyte. Free solution capillary electrophoresis conditions are characterised by a single solution phase. Chiral separations are reviewed by selector type (chiral ligand exchange, cyclodextrins, crown ethers, glycoproteins) with the extensive studies on cyclodextrins grouped into sections on amino acids, pharmaceuticals, and speciality chemicals, optimisation, biological fluids, and quantitative aspects. In micellar electrokinetic capillary chromatography, enantioselective discrimination occurs by partition in a two-phase system, with a chiral micellar phase as selector. Optimum separation conditions can be readily predicted for a given selector–selectand combination, and absolute values of binding constants determined by CE. Advantages of CE in comparison with HPLC using a chiral stationary phase include robust, rapid assays and the use of small volumes of aqueous solutions; disadvantages include less favourable detection limits. © 1994 Wiley-Liss, Inc.     

Isothermal Titration Calorimetry of Chiral Polymeric Nanoparticles

Chiral polymeric nanoparticles are of prime importance, mainly due to their enantioselective potential, for many applications such as catalysis and chiral separation in chromatography. In this article we report on the preparation of chiral polymeric nanoparticles by miniemulsion polymerization. In addition, we describe the use of isothermal titration calorimetry (ITC) to measure the chiral interactions and the energetics of the adsorption of enantiomers from aqueous solutions onto chiral polymeric nanoparticles. The characterization of chirality in nano‐systems is a very challenging task; here, we demonstrate that ITC can be used to accurately determine the thermodynamic parameters associated with the chiral interactions of nanoparticles. The use of ITC to measure the energetics of chiral interactions and recognition at the surfaces of chiral nanoparticles can be applied to other nanoscale chiral systems and can provide further insight into the chiral discrimination processes of nanomaterials. Chirality 27:613–618, 2015. © 2015 Wiley Periodicals, Inc.     

Enantiomeric analysis of amino acids by using comprehensive two-dimensional gas chromatography

The chiral separation of amino acids (AA) derivatised with ethyl chloroformate by using comprehensive two-dimensional gas chromatography is reported. A commercially available enantioselective capillary column (Chirasil-l-Val) has been tested as first-dimension column. Two nonenantioselective stationary phases (BPX50 and BP1) with different column lengths were combined with the enantioselective column, which represent chiral/polar and chiral/low-polarity column sets, respectively. These column sets were evaluated to determine the most useful column combination to provide improved separation efficiency of enantioselective AA analysis. Separations of AA mixtures derivatised either as their N-trifluoroacetyl methyl esters or with methyl chloroformate, performed on a chiral/low-polarity column set, are also shown. The method was demonstrated for chiral analysis of AAs in different beer samples. The major AA in the beer samples was proline with amounts ranging from around 65-95% with minor contents of glycine and the l-enantiomers of alanine, valine, leucine, and isoleucine. Small amounts of d-alanine, at about 1, 1.5, and 15% were detected in the three samples.     

Enantioselective Separation and Simultaneous Determination of Tolperisone and Eperisone in Rat Plasma by LC‐MS/MS

Tolperisone and eperisone used as muscle relaxants possess one chiral center each and exist as two optical isomers for each drug. Therefore, enantioselective assays to measure each enantiomer in biological matrices are of great importance. In the present study a simple and complete reverse‐phase liquid chromatography tandem mass spectrometric method for separation and enantioselective determination of tolperisone and eperisone in rat plasma was developed. The analytes were extracted from rat plasma by a simple protein precipitation method with acetonitrile as the extraction solvent. The enantioselective separation of analytes was achieved on a Cellulose Tris (4‐chloro‐3‐methylphenylcarbamate) chiral column with a mobile phase of acetonitrile: 10 mM ammonium acetate in an isocratic mode of elution and mass spectrometric detection. The calibration curve for each enantiomer was found to be linear over 0.2 to 20 ng/mL for each enantiomer. The proposed method exhibited good intra‐ and interday precision (% CV) ranged between 0.95–6.05% and 1.11–8.21%, respectively. The intra‐ and interday accuracy for the proposed assay method ranged between 94.0–100.5% and 92.7–102.1%, respectively. The proposed method was validated as per regulatory guidelines. Chirality 25:622–627, 2013. © 2013 Wiley Periodicals, Inc.     

A hierarchical screening approach to enantiomeric separation

The screening of a number of chiral stationary phases (CSPs) with different modifiers in supercritical fluid chromatography to find a chromatographic method for separation of enantiomers can be time‐consuming. Computational methods for data analysis were utilized to establish a hierarchical screening strategy, using a dataset of 110 drug‐like chiral compounds with diverse structures tested on 15 CSPs with two different modifiers. This dataset was analyzed using a combinatorial algorithm, principal component analysis (PCA), and a correlation matrix. The primary goal was to find a set of eight columns resolving a large number of compounds, but also having complementary enantioselective properties. In addition to the hereby defined hierarchical experimental strategy, quantitative structure enantioselective models (QSERs) were evaluated. The diverse chemical space and relatively limited size of the training set reduced the accuracy of the QSERs. However, including separation factors from other CSPs increased the accuracies of the QSERs substantially. Hence, such combined models can support the experimental strategy in prioritizing the CSPs of the second screening phase, when a compound is not separated by the primary set of columns.     

Bioanalytical chiral chromatographic technique and docking studies for enantioselective separation of meclizine hydrochloride: Application to pharmacokinetic study in rabbits

Enantiomeric resolution and molecular docking studies of meclizine hydrochloride on polysaccharide-based chiral stationary phase comprising cellulose tris(4-methylbenzoate) chiral selector (150 × 4.6 mm, 3.0 μm) were presented. The mobile phase used was acetonitrile:10mM ammonium bicarbonate (95:05, v/v). The developed technique was used to perform the enantioselective assay of meclizine hydrochloride in its marketed formulation. The elution order of meclizine hydrochloride enantiomers was determined by docking studies. Target compound was extracted from rabbit plasma using protein precipitation technique, followed by development of bioanalytical chiral separation method using the same matrix. Application of the method to determine pharmacokinetic parameters of meclizine hydrochloride enantiomers was performed using Phoenix WinNonlin 8.1 software. The results demonstrated stereoselective disposition of meclizine hydrochloride enantiomers in rabbits.     

Stereoselective degradation of metalaxyl and metalaxyl-M in soil and sunflower plants.

A high proportion of agrochemicals are chiral compounds. Since stereoisomers often show different biological and physiological properties, the biological and metabolic responses to these compounds and their fate in the environment are expected to be different. In this work we investigate a possible stereo and/or enantioselective degradation in soil and plants (sunflower) of the fungicide Metalaxyl (rac-Metalaxyl) and the new compound Metalaxyl-M ((-)-(R)-Metalaxyl) and propose procedures for extraction, cleanup, chromatographic separation of enantiomers, and determination of the R : S ratio by using an HPLC chiral column. The degradation of the two stereoisomers of Metalaxyl proved to be enantioselective and dependent on the media: the (+)-(S)-enantiomer showed a faster degradation in plants, while the (-)-(R)-enantiomer showed a faster degradation in soil. In this study there was no evidence that racemization of Metalaxyl-M took place either in soil or in sunflowers.     

Optical resolution and mechanism using enantioselective cellulose,sodium alginate and hydroxypropyl‐β‐cyclodextrin membranes

Chiral solid membranes of cellulose, sodium alginate, and hydroxypropyl‐β‐cyclodextrin were prepared for chiral dialysis separations. After optimizing the membrane material concentrations, the membrane preparation conditions and the feed concentrations, enantiomeric excesses of 89.1%, 42.6%, and 59.1% were obtained for mandelic acid on the cellulose membrane, p ‐hydroxy phenylglycine on the sodium alginate membrane, and p ‐hydroxy phenylglycine on the hydroxypropyl‐β‐cyclodextrin membrane, respectively. To study the optical resolution mechanism, chiral discrimination by membrane adsorption, solid phase extraction, membrane chromatography, high‐pressure liquid chromatography ultrafiltration were performed. All of the experimental results showed that the first adsorbed enantiomer was not the enantiomer that first permeated the membrane. The crystal structures of mandelic acid and p ‐hydroxy phenylglycine are the racematic compounds. We suggest that the chiral separation mechanism of the solid membrane is “adsorption – association – diffusion,” which is able to explain the optical resolution of the enantioselective membrane. This is also the first report in which solid membranes of sodium alginate and hydroxypropyl‐β‐cyclodextrin were used in the chiral separation of p ‐hydroxy phenylglycine.     

Chiral Separation and Enantioselective Degradation of Vinclozolin in Soils

Vinclozolin is a chiral fungicide with potential environmental problems. The chiral separation of the enantiomers and enantioselective degradation in soil were investigated in this work. The enantiomers were separated by high‐performance liquid chromatography (HPLC) on Chiralpak IA, IB, and AZ‐H chiral columns under normal phase and the influence of the mobile phase composition on the separation was also studied. Complete resolutions were obtained on all three chiral columns under optimized conditions with the same elution order of (+)/(?). The residual analysis of the enantiomers in soil was conducted using accelerate solvent extraction followed by HPLC determination. The recoveries of the enantiomers ranged from 85.7–105.7% with relative standard deviation (SD) of 0.12–3.83%, and the limit of detection (LOD) of the method was 0.013 µg/g. The results showed that the degradations of vinclozolin enantiomers in the soils followed first‐order kinetics. Preferential degradation of the (?)‐enantiomer was observed only in one soil with the largest |ES| value of 0.047, and no obvious enantioselective degradation was observed in other soils. It was found that the persistence of vinclozolin in soil was related to pH values based on the half‐lives. The two enantiomers disappeared about 8 times faster in basic soils than that in neutral or acidic soils. Chirality 26:155–159, 2014. © 2014 Wiley Periodicals, Inc.     

Novel chiral ionic liquids stationary phases for the enantiomer separation of chiral acid by high‐performance liquid chromatography

Novel chiral ionic liquid stationary phases based on chiral imidazolium were prepared. The ionic liquid chiral selector was synthesized by ring opening of cyclohexene oxide with imidazole or 5,6‐dimethylbenzimidazole, and then chemically modified by different substitute groups. Chiral stationary phases were prepared by bonding to the surface of silica sphere through thioene “click” reaction. Their enantioselective separations of chiral acids were evaluated by high‐performance liquid chromatography. The retention of acid sample was related to the counterion concentration and showed a typical ion exchange process. The chiral separation abilities of chiral stationary phases were greatly influenced by the substituent group on the chiral selector as well as the mobile phase, which indicated that, besides ion exchange, other interactions such as steric hindrance, π‐π interaction, and hydrogen bonding are important for the enantioselectivity. In this report, the influence of bulk solvent components, the effects of varying concentration, and the type of the counterion as well as the proportion of acid and basic additives were investigated in detail.     

Chiral separation and quantification of R/S-amphetamine, R/S-methamphetamine, R/S-MDA, R/S-MDMA, and R/S-MDEA in whole blood by GC-EI-MS

The enantioselective composition of the amphetamines is of interest, as the enantiomers show differences in their pharmacological effects and several methods for chiral separation of amphetamines have been described. Only a few methods have used whole blood as matrix and none of these separates both classic amphetamines (amphetamine and methamphetamine) and designer amphetamines (MDA, MDMA and MDEA). The aim of this study was, therefore, to develop a method for enantioselective analysis of AM, MA, MDA, MDMA, and MDEA in whole blood. The amphetamines were extracted from 0.5 g of whole blood by liquid-liquid extraction. After derivatization with R-MTPCl, the resulting diastereomers were separated by GC on a HP-5MS column and detected by SIM-MS. R-MTPCl was used as derivatization reagent because of the stability of this reagent and good separation of these analytes. Through the method, development time and temperature of the derivatization were optimized, and by admixture of 0.02% triethylamine it became possible to detect the amphetamines in adequately low concentrations as more analytes were derivatized. The method was validated and it was linear from 0.004 to 3 microg/g per enantiomer. The accuracy was within 91-115%, while the repeatability and reproducibility were < or =15% R.S.D. A method suitable for enantioselective separation and analysis of the amphetamines has been achieved, and the method was applied to analysis of whole blood samples originating from traffic and criminal cases and post mortem cases.