ABSTRACT
Chiral metal-organic frameworks(CMOFs)with enantiomeric subunits have been employed in chiral chemistry.In this study,a CMOF formed from 6-methoxyl-(8S,9R)-cinchonan-9-ol-3-carboxylic acid(HQA)and ZnCl2,{(HQA)(ZnCl2)(2.5H2O)｝n was constructed as a chiral stationary phase(CSP)via an in situ fabrication approach and used for chiral amino acid and drug analyses for the first time.The{(HQA)(ZnCl2)(2.5H2O)}n nanocrystal and the corresponding chiral stationary phase were systematically characterised using a series of analytical techniques including scanning electron microscopy,X-ray diffraction,Fourier transform infrared spectroscopy,circular dichroism,X-ray photoelectron spectros-copy,thermogravimetric analysis,and Brunauer-Emmett-Teller surface area measurements.In open-tubular capillary electrochromatography(CEC),the novel chiral column exhibited strong and broad enantioselectivity toward a variety of chiral analytes,including 19 racemic dansyl amino acids and several model chiral drugs(both acidic and basic).The chiral CEC conditions were optimised,and the enantioseparation mechanisms are discussed.This study not only introduces a new high-efficiency member of the MOF-type CSP family but also demonstrates the potential of improving the enantiose-lectivities of traditional chiral recognition reagents by fully using the inherent characteristics of porous organic frameworks.
ABSTRACT
Homochiral metal-organic frameworks(MOFs)have attracted considerable attention in many fields of research,such as chiral catalysis and chiral chromatography.However,only few homochiral MOFs can be effectively used in capillary electrochromatography(CEC)and their performances are far from adequate.In this study,we successfully synthesized achiral nanocrystalline MIL-53.A facile post-synthetic modi-fication strategy was then implemented to functionalize the product,yielding a homochiral MOF:L-His-NH-MIL-53.This MOF was then employed as a chiral coating in open-tubular CEC mode(OT-CEC),and,as such,it exhibited high enantioselectivities for several racemic drugs.The homochiral MOF and the fabricated capillary coating were systematically characterized using transmission electron microscopy,scanning electron microscopy(with energy-dispersive X-ray spectrometry),Fourier-transform infrared spectroscopy,X-ray diffractometry,thermogravimetric analysis,circular dichroism spectroscopy,Bru-nauer-Emmett-Teller surface area measurements,and X-ray photoelectron spectroscopy.This study is expected to provide a new strategy for the design and establishment of MOF-based chiral OT-CEC systems.
ABSTRACT
Enantioseparation of three β-blockers,i.e.,atenolol,metoprolol and propranolol,was studied on amylose tris(3-chloro-5-methylphenylcarbamate) immobilized chiral stationary phase using supercritical fluid chromatography (SFC).The effect of organic modifiers (methanol,isopropanol and their mixture),col-umn temperature and back pressure on chiral separation of β-blockers was evaluated.Optimum chro-matographic separation with respect to resolution,retention,and analysis time was achieved using a mixture of CO2 and 0.1％ isopropyl amine in isopropanol:methanol (50:50,V/V),in 75:25 (V/V) ratio.Under the optimized conditions,the resolution factors (Rs) and separation factors (α) were greater than 3.0 and 1.5,respectively.Further,with increase in temperature (25-45 ℃) and pressure (100-150 bars)there was corresponding decrease in retention factors (k),α and Rs.However,a reverse trend (α and Rs)was observed for atenolol with increase in temperature.The thermodynamic data from van't Hoff plots revealed that the enantioseparation was enthalpy driven for metoprolol and propranolol while entropy driven for atenolol.To understand the mechanism of chiral recognition and the elution behavior of the enantiomers,molecular docking studies were performed.The binding energies obtained from simulation studies were in good agreement with the elution order found experimentally and also with the free energy values.The method was validated in the concentration range of 0.5-10 μg/mL for all the enan-tiomers.The limit of detection and limit of quantitation ranged from 0.126 to 0.137 μg/mL and 0.376-0.414 μg/mL,respectively.The method was used successfully to analyze these drugs in pharmaceutical preparations.
ABSTRACT
Carvedilol is a chiral drug with potent antihypertensive and antianginal activities. Although it is clinically used as a racemic mixture, its enantiomers show different pharmacokinetic and pharmacodynamic profiles. Here, the direct chiral separation of racemic drug by high performance liquid chromatography using two immobilized-type amylose-based chiral stationary phases is presented. Some chromato-graphic parameters, such as retention and selectivity, were determined under multimodal eluent con-ditions and different temperatures. A temperature-dependent inversion of the elution order of enantiomers was observed in the operative temperature range of chiral chromatographic support. Finally, an effective direct enantioselective method was successfully applied to the separation of the enantiomers of carvedilol on a semipreparative scale.
ABSTRACT
Objective To establish a self-made chiral column for enantiomeric separation of salbutamol. Methods We used different concentrations of acid,alkali additives in the polar phase flow for enantiomers separation of salbutamol by using 3, 4-dichlorophenyl isocyanate vancomycin chiral column, and discussed the chiral recognition mechanism. Results The ratio of acid to alkali additive in the mobile phase was 0.01%:0.01% (V/V), the flow rate was 1ml/min, the column temperature was 25℃, and the best separation of enantiomers of salbutamol was obtained,the selective factor was 1.16, the separation degree reached 1.41. Conclusion Self-made 3, 4-two chlorophenyl isocyanate vancomycin chiral column is effective for salbutamol separation, and it can be as a reference for developing other similar chiral stationary phase.
ABSTRACT
A method for the rapid enantioseparation of five β-blocker drugs, including alprenolol, propranolol), mexiletine, metoprolol and pindolol was developed by a 5-cm short column packed with perphenylcarbamoylated β-cyclodextrin(CD) chiral stationary phase by HPLC. The results showed that except for alprenolol), the other 4 β-blocker drugs were completely separated using ACN-0.1% thriethylammonium acetate(TEAA), 40∶ 60, V/V, pH=4.0) as mobile phase. The 5-cm short CD-based column exhibited rapid separation ability to the above β-blocker drugs within 5 min, which indicated that the separation has high efficiency. According to the chemical structures of the β-blockers and their chromatographic behavior, related separation mechanisms were also discussed. The proposed method was rapid, effective and repeated.
ABSTRACT
The enantioseparations of 38 racemates on Chiralcel OD, Chiralpak AD, Chiralpak IA and(S, S)-Whelk-01 were presented by HPLC. Those enantiomers come from the amines, alcohols, ethers, ketones, aromatic derivatives, heterocyclic compounds, amide acids and medicines etc. With the mobile phase of n-hexane)/isopropanol(90∶ 10, V/V), n-hexane/isopropanol/trifluoracetic acid(90∶ 10∶ 0.2, V/V) or n-hexane/isopropanol/triethylamine(90∶ 10∶ 0.2, V/V), over 70% enantioseparations were obtained for OD, AD and IA columns). The order of enantioseparation selectivity for four columns was OD>AD>IA>(S,S)-Whelk-01, and among those columns there was a big chiral discriminating complementarity. This investigation was useful for choosing chiral columns to separate chiral compounds.
ABSTRACT
Objective: To develop a capillary electrophoresis system for purity test and enantioseparation of L-pramipexole. Methods: Using β-CD, HP-β-CD, SBE-β-CD and DM-β-CD as chiral selection agents, we investigated the influence of concentration, pH of chiral selection agent and column length and inner diameter on chiral separation. The enantiomers were baseline separated under the following conditions-uncoated fused silica capillary (50 μm X 47 cm) with an effective length of 40 cm, back-ground electrolyte solution, 40 mmol/l trisodium citrate buffer solution, 0.5% SBE-β-CD, pH 4.0 adjusted by phosphoric acid, 5% methanol, 25 mmol·L-1 SDS, 40 mmol·L-1 sodium tetraborate solution as running buffer, and 16 kV separation voltage. The detection wavelength was set at 254 nm and the column temperature was 30*C. Results: The baseline separation of L-pramipexole was obtained under our condition. The optical isomerism had satisfactory resolution (Rs>2.5) and the content of R-pramipexole was less than 0.5%. Conclusion: The proposed method is simple, reliable and can be used for routine purity test and chiral separation.