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.     

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.     

Chiral Discrimination of Ofloxacin Enantiomers Using DNA Double Helix Regulated by Metal Ions

DNA‐based chiral selectors are constructed to discriminate ofloxacin enantiomers through metal‐ion anchoring on a special DNA double helix that contains successive GC pairs. The effects of metal ions involving Mg²⁺, Ni²⁺, Cu²⁺, Ag⁺, and Pt²⁺ were studied on the regulation of DNA chiral discrimination towards ofloxacin enantiomers. It is shown that DNA‐Cu(II) complexes exhibit the highest enantioselectivities at the [Cu²⁺]/base ratio of 0.1. The enantiomeric excess can reach 59% in R‐enantiomer after being adsorbed by the RET‐Cu(II) complex. Stereoselective recognition of ofloxacin enantiomers on the double helix is tunable via external stimulus, providing a programmable desorption process to regenerate DNA. This DNA‐based chiral selector exhibits excellent reusability without apparent loss of enantioselectivity after three cycles of adsorption and desorption. Chirality 26:249–254, 2014. © 2014 Wiley Periodicals, Inc.     

Enantioselective degradation of indoxacarb in cabbage and soil under field conditions

The enantioselective degradation of indoxacarb in cabbage and soil has been investigated in Beijing and Anhui under open conditions. Indoxacarb enantiomers in samples were extracted with acetonitrile, cleaned up by florisil SPE column, separated on high performance liquid chromatography with a cellulose-tris-(3, 5-dimethylphenylcarbamate)-based chiral stationary phase (CDMPC-CSP), and determined by a photodiode array detector. The validation of the developed method by fortification rac-indoxcarb in cabbage and soil showed good accuracy and precision. The results of field trials indicated that the dissipation of indoxacarb enantiomers followed pseudo-first-order kinetics or first-order kinetics in cabbage and soil at two locations. The half-lives of two enantiomers in cabbage ranged from 2.8 to 4.6 d which were shorter than those in soil ranging from 23 to 35 d. The changes of enantiomeric fraction values proved that enantioselective degradation of indoxacarb happened in cabbage and soil. The (-)-indoxacarb showed faster degradation in the Beijing cabbage, whereas in the Anhui cabbage, (+)-indoxacarb preferentially degraded. In soil, preferential degradation of (+)-indoxacarb was observed at two locations.     

Stereoselective degradation of benalaxyl in tomato, tobacco, sugar beet, capsicum, and soil

The stereoselective degradation of the racemic benalaxyl in vegetables such as tomato, tobacco, sugar beet, capsicum, and the soil has been investigated. The two enantiomers of benalaxyl in the matrix were extracted by organic solvent and determined by validated chiral high-performance liquid chromatography with a cellulose-tris-(3, 5-dimethylphenylcarbamate)-based chiral column. Rac-benalaxyl was fortified into the soil and foliar applied to vegetables. The assay method was linear over a range of concentrations (0.5-50 microg ml(-1)) and the mean recoveries in all the samples were more than 70% for the two enantiomers. The limit of detection for both enantiomers was 0.05 microg g(-1). The results in soil showed that R-(-)-enantiomer dissipated faster than S-(+)-enantiomer and the stereoselectivity might be caused by microorganisms. In tomato, tobacco, sugar, beet, and capsicum plants, there was significantly stereoselective metabolism. The preferential absorption and degradation of S-(+)-enantiomer resulted an enrichment of the R-(-)-enantiomer residue in all the vegetables.     

Enantioselective degradation of tebuconazole in cabbage, cucumber, and soils

The enantioselective degradation of tebuconazole has been investigated to elucidate the behaviors in agricultural soils, cabbage, and cucumber fruit. Rac-tebuconazole was fortified into three types of agricultural soils and sprayed foliage of cabbage and cucumber, respectively. The degradation kinetics, enantiomer fraction and enantiomeric selectivity were determined by reverse-phase high-performance liquid chromatography (HPLC) and liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) on a Lux amylose-2 chiral column. The process of the degradation of tebuconazole enantiomers followed first-order kinetic in the test soils and vegetables. It has been shown that the degradation of tebuconazole was enantioselective. The results indicated that the (+)-S-tebuconazole showed a faster degradation in cabbage, while the (-)-R-tebuconazole dissipated faster than (+)-S-form in cucumber fruit and the test soils.     

Preparation and Studies of Chiral Stationary Phases Containing Enantiopure Acridino‐18‐Crown‐6 Ether Selectors

The enantiomeric separation ability of the newly prepared chiral stationary phases containing acridino‐18‐crown‐6 ether selectors was studied by high‐performance liquid chromatography (HPLC). The chiral stationary phases separated the enantiomers of selected protonated primary aralkylamines efficiently. The best results were found for the separation of the mixtures of enantiomers of NO₂‐PEA. Chirality 26:651–654, 2014. © 2014 Wiley Periodicals, Inc.     

Chiral stationary phases in HPLC for the stereoselective determination of methadone

An extensive study of the behavior of three chiral stationary phases (CSP) used in liquid chromatography (LC) is presented for the stereoselective determination of methadone. The following chromatographic columns were selected: a cellulose, Chiralcel OJ; a modified cyclodextrin, Cyclobond I 2000 RSP, and a protein, Chiral‐AGP. Retention factors, enantioselectivity, efficiency, and resolution were tested by modifying the composition of the mobile phase as well as the temperature. The mechanism for the chiral recognition of methadone on each support was discussed. Optimal chromatographic parameters were obtained for the three supports tested, and methadone enantiomers were separated in less than 20 minutes. The cellulose‐based column gave the best resolution, but this CSP was not adapted to clinical analyses of methadone. Under optimized conditions, the cyclodextrin‐ and protein‐based columns allowed an excellent separation of methadone enantiomers, but no interference with the primary metabolite was found only with Chiral‐AGP. Chirality 11:319–325, 1999. © 1999 Wiley‐Liss, Inc.     

Stereoselective Degradation of Chiral Fungicide Myclobutanil in Rat Liver Microsomes

Myclobutanil, (RS)‐2‐(4‐chlorophenyl)‐2‐(1H‐1, 2, 4‐triazol‐1‐ylmethyl)hexanenitrile is a broad‐spectrum systemic triazole fungicide which consists of a pair of enantiomers. The stereoselective degradation of myclobutanil was investigated in rat liver microsomes. The concentrations of myclobutanil enantiomers were determined by high‐performance liquid chromatography (HPLC) with a cellulose‐tris‐(3,5‐dimethyl‐phenylcarbamate)‐based chiral stationary phase (CDMPC‐CSP) under reversed phase condition. The t_1/2 of (+)‐myclobutanil is 8.49 min, while the t_1/2 of (–)‐myclobutanil is 96.27 min. Such consequences clearly indicated that the degradation of myclobutanil in rat liver microsomes was stereoselective and the degradation rate of (+)‐myclobutanil was much faster than (–)‐myclobutanil. In addition, significant differences between two enantiomers were also observed in enzyme kinetic parameters. The V_max of (+)‐myclobutanil was about 4‐fold of (–)‐myclobutanil and the CL_int of (+)‐myclobutanil was three times as much as (–)‐myclobutanil after incubation in rat liver microsomes. Corresponding consequences may shed light on the environmental and ecological risk assessment for myclobutanil and may improve human health. Chirality 26:51–55, 2013. © 2013 Wiley Periodicals, Inc.     

Enantiomeric separation of malathion and malaoxon and the chiral residue analysis in food and environmental matrix

Malathion is a widely used chiral phosphorus insecticide, which has a more toxic chiral metabolite malaoxon. In this work, the enantiomers of malathion and malaoxon were separated by high-performance liquid chromatography-mass/mass (HPLC-MS/MS) with chiral columns using acetonitrile/water or methanol/water as mobile phase, and the chromatographic conditions were optimized. Based on the chiral separation, the chiral residue analysis methods for the enantiomers in soil, fruit, and vegetables were set up. Two pairs of the enantiomers were better separated on CHIRALPAK IC chiral column, and baseline simultaneous separations of malathion and malaoxon enantiomers were achieved with acetonitrile/water (40/60, v/v) as mobile phase at a flow rate of 0.5 mL/min. The elution orders were −/+ for both malathion and malaoxon measured by an optical rotation detector. The chiral residue analysis in soil, fruit, and vegetables was validated by linearity, recovery, precision, limit of detection (LOD), and limit of quantification (LOQ). The LODs and LOQs for the enantiomers of malathion were 1 μg/kg and 3–5 μg/kg and 0.08 μg/kg and 0.20–0.25 μg/kg for malaoxon enantiomers. Good linear calibration curves for each enantiomer in the matrices were obtained within the concentration range of 0.02–12 mg/L. The mean recoveries of the enantiomers of malathion and malaoxon ranged from 82.26% to 109.04%, with RSDs of 0.71–8.63%.The results confirmed that this method was capable of simultaneously determining the residue of malathion and malaoxon in food and environmental matrix on an enantiomeric level.     

Enantiomeric Separations of Ruthenium (II) Polypyridyl Complexes Using HPLC With Cyclofructan Chiral Stationary Phases

The enantiomeric separation of 21 ruthenium (II) polypyridyl complexes was achieved with a novel class of cyclofructan‐based chiral stationary phases (CSPs) in the polar organic mode. Aromatic derivatives on the chiral selectors proved to be essential for enantioselectivity. The R‐napthylethyl carbamate functionalized cyclofructan 6 (LARIHC CF6‐RN) column proved to be the most effective overall, while the dimethylphenyl carbamate cyclofructan 7 (LARIHC CF7‐DMP) showed complementary selectivity. A combination of acid and base additives was necessary for optimal separations. The retention factor vs. acetonitrile/methanol ratio plot showed a U‐shaped retention curve, indicating that different interactions take place at different polar organic solvent compositions. The separation results indicated that π–π interactions, steric effects, and hydrogen bonding contribute to the enantiomeric separation of ruthenium (II) polypyridyl complexes with cyclofructan chiral stationary phases in the polar organic mode. Chirality 27:64–70, 2015. © 2014 Wiley Periodicals, Inc.     

Enantioselective Degradation of Metalaxyl in Grape,Tomato, and Rice Plants

Enantioselective biodegradation of chiral pesticide metalaxyl in grape, tomato, and rice plants under field conditions were studied. Metalaxyl enantiomers were completely separated with a resolution (Rs) of 5.01 by high‐performance liquid chromatography (HPLC) based on a cellulose tris (3‐chloro‐4‐methyl phenyl carbamate) chiral column (Lux Cellulose‐2). Metalaxyl enantiomers from matrixes were extracted by acetonitrile and purged using Cleanert Alumina‐A solid phase extraction (SPE). The linearity, recovery, precision, sensitivity, and matrix effect of the method were assessed. The result showed that significant stereoselectivity occurred in grape, tomato, and rice plants. In grape, (+)‐S‐metalaxyl with a half‐life of 5.5 d degraded faster than (–)‐R‐metalaxyl with that of 6.9 d, and the enantiomer fraction (EF) value reached 0.37 at 21 d. The same enantioselectivity was observed in tomato, and the half‐life was 2.2 d for the S‐enantiomer and 3.0 d for the R‐enantiomer. The EF values decreased from 0.49 of 0 d to 0.26 of 14 d. On the other hand, a preferential degradation of the R‐form was found in rice plants, with an EF value of 0.70 at 14 d, and the corresponding half‐life was 2.3 d for the R‐form and 2.8 d for the S‐form. Chirality 27:109–114, 2015. © 2014 Wiley Periodicals, Inc.     

Enantioselective synthesis and teratogenicity of propylisopropyl acetamide,a CNS‐active chiral amide analogue of valproic acid

Propylisopropyl acetamide (PID), an amide analogue of the major antiepileptic drug valproic acid (VPA), possesses favorable anticonvulsant and CNS properties. PID contains one chiral carbon atom and therefore exists in two enantiomeric forms. The purpose of this work was to synthesize the two PID enantiomers and evaluate their enantiospecific teratogenicity. Enantioselective synthesis of PID enantiomers was achieved by coupling valeroyl chloride with optically pure (4S)‐ and (4R)‐benzyl‐2‐oxazolidinone chiral auxiliaries. The two oxazolidinone enolates were alkylated with isopropyl triflate, hydrolyzed, and amidated to yield (2R)‐ and (2S)‐PID. These two PID enantiomers were obtained with excellent enantiomeric purity, exceeding 99.4%. Unlike VPA, both (2R)‐ and (2S)‐PID failed to exert teratogenic effects in NMRI mice following a single 3 mmol/kg subcutaneous injection. From this study we can conclude that individual PID enantiomers do not demonstrate stereoselective teratogenicity in NMRI mice. Due to its better anticonvulsant activity than VPA and lack of teratogenicity, PID (in a stereospecific or racemic form) has the potential to become a new antiepileptic and CNS drug. Chirality 11:645–650, 1999. © 1999 Wiley‐Liss, Inc.     

Preparation and Enantioselectivity Binding Studies of a New Chiral Cobalt(II)porphyrin‐Tröger's Base Conjugate

A new bis[cobalt(II)porphyrin]‐Tröger's base conjugate was studied as a potential receptor for methyl esters of several amino acids. The conjugate was prepared as racemate, and then resolved via preparative high‐performance liquid chromatography (HPLC) on a chiral column. The high affinity to lysine, histidine, and proline methyl esters was found by complexation studies followed by UV‐Vis spectroscopy. The studies of pure enantiomers, followed by UV‐Vis and electronic circular dichroism spectroscopy, revealed the highest enantioselectivity for lysine methyl ester. Chirality 26:361–367, 2014. © 2014 Wiley Periodicals, Inc.     

Chiral analysis of ammuxetine enantiomers in dog plasma using online SPE/liquid chromatography with tandem mass spectrometric detection after precolumn chiral derivatization

Ammuxetine (AMT), a novel chiral antidepressant candidate compound, exhibits better antidepression effects than duloxetine in different animal models. In this article, a chiral derivatization method, combined with online solid phase extraction (online SPE) and liquid chromatography–tandem mass spectrometry (LC–MS/MS), was developed for the chiral separation of AMT enantiomers after administration of racemic AMT to dogs. The derivatization reaction employed 2,3,4,6‐tetra‐O‐acetyl‐b‐glucopyr‐anosyl isothiocyanate (GITC) as a precolumn chiral derivatization reagent. A SPE column Retain PEP Javelin (10 × 2.1 mm) was used to remove proteins and other impurities in plasma samples. The enantiomeric derivatives were separated on a ZORBAX SB‐C₁₈ column (50 × 2.1 mm × 3.5 μm) with an isocratic elution procedure. The selected multiple reaction monitoring mode of the positive ion was performed and the parent to the product transitions m/z 681.0/543.1 and m/z 687.4/543.1 were used to measure the derivatives of AMT and duloxetine (internal standard) with electrospray ionization. The method was validated in terms of specificity, linearity, sensitivity, precision, accuracy, matrix effect, and stability. The method was applied to a pharmacokinetics study of AMT racemate in dogs. The results suggested that the pharmacokinetic of AMT enantiomers might be stereoselective in dogs.     

Enantioselective determination of triazole fungice tetraconazole by chiral high-performance liquid chromatography and its application to pharmacokinetic study in cucumber, muskmelon, and soils

A simple chiral high-performance liquid chromatography method with diode array detector was developed and validated for stereoselective determination of tetraconazole enantiomers in cucumber, muskmelon, and soils. Good separation was achieved at 20°C using cellulose tris-(4-methylbenzoate) as chiral stationary phase, a mixture of n-hexane and ethanol (90:10) as mobile phase at a flow rate of 0.8 ml/min. The assay method was linear over a range of concentrations (0.5-50 μg/ml) and the mean recoveries in all samples were more than 85% for the two enantiomers. The limits of detection for both enantiomers in plant and soil samples were 0.06 and 0.12 μg/g, respectively. Then, the proposed method was successfully applied to the study of enantioselective degradation of rac-tetraconazole in cucumber, muskmelon, and soils. The results showed that the degradation of two enantiomers of tetraconazole followed first-order kinetics and significantly stereoselective behavior was observed in cucumber, muskmelon, and Beijing soil. The preferential absorption and degradation of (-)-S-tetraconzole resulted in an enrichment of the (+)-R-tetraconazole residue in plant samples, whereas the (+)-R-tetraconazole showed a faster degradation in Beijing soil and the stereoselectivity might be caused by microorganisms. No stereoselective degradation was observed in Heilongjiang soil.     

Highly Enantioselective Michael Addition Promoted by a New Diterpene‐Derived Bifunctional Thiourea Catalyst: A Doubly Stereocontrolled Approach to Chiral Succinimide Derivatives

A doubly stereocontrolled organocatalytic asymmetric Michael addition to the synthesis of substituted succinimides is described. Starting from aldehydes and maleimides, both enantiomers of the succinimides could be obtained in high to excellent yields (up to 98%) and enantioselectivities (up to 99%) when one of the two special chiral diterpene‐derived bifunctional thioureas was individually used as a catalyst. Moreover, these catalysts can be efficiently used in large‐scale catalytic synthesis with the same level of yield and enantioselectivity. Chirality 00:000–000, 2014. © 2014 Wiley Periodicals, Inc.     

Determination of zopiclone enantiomers in plasma by liquid chromatography using a chiral cellulose carbamate column

The enantiomers of zopiclone were determined in human plasma using a sequential achiral—chiral liquid chromatographic method. Zopiclone was separated from the biological matrix and quantified on an achiral silica column. The limit of detection was 5 ng/ml. The eluent fraction containing zopiclone was collected, evaporated, reconstituted with the mobile phase and injected onto a chiral cellulose carbamate column where the enantiomeric ratio was calculated. This validated method, applied to a pilot study, suggests that pharmacokinetics of zopiclone is stereoselective.     

Enantioselective Degradation and Chiral Stability of Metalaxyl‐M in Tomato Fruits

Metalaxyl is an important chiral acetanilide fungicide, and the activity almost entirely originates from the R‐enantiomer. Racemic metalaxyl has been gradually replaced by the enantiopure R‐enantiomer (metalaxyl‐M). In this study a chiral residue analysis method for metalaxyl and the metabolite metalaxyl acid was set up based on high‐performance liquid chromatography tandem mass spectroscopy (HPLC‐MS/MS). The enantioselective degradation and chiral stability of metalaxyl‐M in tomato fruits in two geographically distinct regions of China (Heilongjiang and Hunan Province) were evaluated and the enantioselectivity of metalaxyl acid was also investigated. Tomato plants grew under field conditions with a one‐time spray application of metalaxyl‐M wettable powder. It was found that R‐metalaxyl was not chirally stable and the inactive S‐metalaxyl was detected in tomato fruits. At day 40, S‐metalaxyl derived from R‐metalaxyl accounted for 32% and 26% of the total amount of metalaxyl, respectively. The metabolites R‐metalaxyl acid and S‐metalaxyl acid were both observed in tomato, and the ratio of S‐metalaxyl acid to the sum of S‐ and R‐metalaxyl acid was 36% and 28% at day 40, respectively. For both metalaxyl and metalaxyl acid, the half‐life of the S‐enantiomer was longer than the R‐enantiomer. The results indicated that the enantiomeric conversion should be considered in the bioactivity evaluation and environmental pollution assessment. Chirality 28:382–386, 2016. © 2016 Wiley Periodicals, Inc.     

Chiral HPLC separation and CD spectra of the enantiomers of the alkaloid tacamonine and related compounds.

The HPLC enantiomeric separation of racemic indole alkaloids tacamonine, 17 alpha-hydroxytacamonine, deethyleburnamonine, and vindeburnol was accomplished using Chiralpak AD and Chiralcel OD as chiral stationary phases. Small structural differences affect the enantioselectivity ability of these phases. Single enantiomers of tacamonine and vindeburnol were isolated by semipreparative HPLC and their CD spectra and optical rotations were measured.