Chiral metal-organic cages used as stationary phase for enantioseparations in capillary electrochromatography

Since some metal-organic cages (MOCs) have been synthesized in past several years, the applications of MOCs such as drug delivery, molecular recognition, separation, catalysis, and gas storage, etc. have been witnessed with a significant increase. However, to the best of our knowledge, so far no one has used MOCs as chiral stationary phase to separate chiral compounds in CEC. In this study, three MOCs were developed as the stationary phase for CEC separation of enantiomers. The MOCs coated capillary column showed good chiral recognition ability for some chiral compounds, including amine, alcohols, ketone, etc. The influence of buffer concentration, applied voltage, pH of buffer solution on the chiral separations was also investigated. The RSDs of run-to-run, day-to-day, and column-to-column for retention time were 2.1-4.67%, 1.2-4.36%, and 3.62-6.43%, respectively. This work reveals that the chiral MOCs material is feasible for the enantioseparation in CEC.     

Rational optimization of the Whelk-O1 chiral stationary phase using molecular dynamics simulations

Rational in silico optimization of the Whelk-O1 chiral stationary phase (CSP) has been carried out based on the chiral recognition mechanism extracted from previous molecular dynamics simulations [C.F. Zhao, N.M. Cann, Anal. Chem. 80 (2008) 2426] of this CSP. Three modified CSPs have been examined. The first two are designed to increase selectivity by reducing the docking probability of the less retained analyte. The third modified selector reverses the amide bridge to introduce a structural motif found in the popular carbamate-derivatized polysaccharide CSPs [Y. Okamoto, M. Kawashima, K. Hatada, J. Am. Chem. Soc. 106 (1984) 5357]. For each modified selector, an atomistic model has been obtained through extensive ab initio calculations. The effect of selector modification is then evaluated via simulations of the modified interface in the presence of target analytes. Simulation results show that the separation factors are increased for the modified CSPs but in some cases elution orders are reversed. The Whelk-O1 CSP was originally designed to separate naproxen [W.H. Pirkle, C.J. Welch, B. LAmm, J. Org. Chem. 57 (1992) 3854]. With this in mind, molecular dynamics simulations of naproxen are compared for the original, and the modified, selectors.     

New hybrid polymeric liquid chromatography chiral stationary phase prepared by surface-initiated polymerization

A new hybrid organic/inorganic HPLC chiral stationary phase (CSP1) has been synthesized by the grafting from (g-from) radical polymerization of an enantiopure diacryloyl derivative of trans-1,2-diaminocyclohexane in the presence of mesoporous, azo-activated silica particles. The new chiral stationary phase has been fully characterized by elemental analysis, differential scanning calorimetry, diffuse reflectance infrared spectroscopy, scanning electron microscopy, inverse size exclusion chromatography and Van Deemter analysis. CSP1 shows improved chromatographic performances compared to its analog CSP2 synthesized by the alternative grafting to (g-to) approach in which the azo initiator is kept in solution. CSP1 can successfully resolve several chemically diverse chiral compounds, using both organic and water-based eluents (normal phase, polar organic, etc.).     

An improved version of an old fluorocarbinol chiral stationary phase

A chiral stationary phase (CSP) derived from anthrone is quite effective for the chromatographic resolution of the enantiomers of a wide variety of compounds. Denoted CSP 4, the phase is a chiral 2,2,2-trifluoro-1-(9-anthryl)ethanol tethered to silica by an elevencarbon-atom chain at the 10-position of the anthryl ring. CSP 4 typically provides greater enantioselectivity than its fluoroalcohol predecessor and is synthetically much more accessible.     

The study of enantioseparation of zolmitriptan on vancomycin-bonded chiral stationary phase

In this study, the chiral stationary phase was prepared by bonding vancomycin to 5 microm spherical silica gel according to "one-pot" synthetic strategies, and used to separate the enantiomers of zolmitriptan under polar ionic mode. The influences of mobile phase composition, such as the concentration and ratio of glacial acetic acid (HOAc) and triethylamine (TEA), on the enantioseparation were investigated, and the chiral recognition mechanism is discussed. It was found experimentally that the retention factors were increased with the increase of the HOAc/TEA concentration in a certain extent, and the ionic interactions, hydrogen bondings, and steric interactions may play key role together. The method is suitable for baseline separation of zolmitriptan enantiomers.     

涂敷纤维素类手性固定相对甲霜灵中间体的高效液相色谱拆分

通过在自制的球形氨丙基硅胶上涂敷纤维素－三（3，5－二甲基苯基氨基甲酸酯）（CDMPC）制备了手性固定相，并采用该手性固定相成功地对甲霜灵中间体进行了高效液相色谱拆分；考察了由不同比例的正己烷和异丙醇组成的流动相对甲霜灵中间体分离效果的影响。     

Glucose, cellobiose, lactose and raffinose used as chiral stationary phases in HPLC

This paper presents the enantioseparation using glucose, cellobiose, lactose and raffinose as chiral selector bonded to silica gel via an arm in HPLC. Surprisingly, they also possess high enantioseparation selectivity, may be used in normal-phase and reversed- phase mode, and there is a big chiral discriminating complementary. This work indicates that oligosaccharides could soon become very attractive as a new class of chiral stationary phase for HPLC.     

Separation of the enantiomers of tebuconazole and its potential impurities by high-performance liquid chromatography with a cellulose derivative-based chiral stationary phase

Summary The high-performance liquid chromatographic resolution of the enantiomers of tebuconazole, a new anti-fungal agent with one chiral center, and the enantiomers of some impurities in technical tebuconazole, has been studied on a chiral stationary phase prepared by coating aminopropylated silica gel with celluloseris(3,5-dimethylphenylcarbamate). The effects of solute structure and the amount of the organic mobile-phase modifier, 2-propanol, on retention and resolution were studied. Under optimum conditions excellent enantiomer separations were achieved for tebuconazole and its impurities. As far as we are aware this is the only liquid chromatographic system enabling discrimination of the enantiomers of all of the racemates discussed in this paper.     

The preparative chromatographic enantioseparation of a racemic morphanthridine analog on a chiral stationary phase

Summary The preparative chromatographic enantioseparation of a chiral morphoanthridine analog has been performed on an analytical column using amylose-tris(3,5-dimethylphenylcarbamate) as chiral stationary phase. The racemate (100 mg) was resolved to baseline within 15 min. This paper describes the development of the method, estimation of the capacity of the chiral stationary phase and discussed the potential of the chromatography if performed under preparative conditions. From the results and calculations presented it seems likely that the resolution of 70 tons year⁻¹ could easily be achieved on 30 kg of stationary phase with a mobile-phase consumption of only 720 L day⁻¹.     

直链淀粉手性固定相高效液相色谱法拆分比索洛尔对映体

采用直链淀粉手性固定相高效液相色谱法在正相条件下直接拆分了比索洛尔对映异构体。分别以异丙醇、乙醇为有机改性剂,考察了流动相的组成与配比、流速及柱温等因素对比索洛尔对映体分离的影响。确定了比索洛尔对映体的最佳拆分条件:流动相正己烷-乙醇-二乙胺(体积比为88∶12∶0.1),流速0.6 mL/min,检测波长270 nm,柱温20 ℃。该方法可快捷、简便地拆分比索洛尔对映体。     

(3,5-二甲基苯基氨基甲酸酯)衍生的纤维素手性固定相

纤维素三（3,5-二甲基苯基氨基甲酸酯）是液相色谱中使用最广泛的手性柱。该文详细地研究了不同程度衍生的纤维素（3,5-二甲基苯基氨基甲酸酯）以及不同硅胶（粗制硅胶、氨丙基粗制硅胶、精制硅胶、氨丙基精制硅胶、大孔硅胶、氨丙基大孔硅胶）作为支撑体对该柱手性分离能力的影响。自制了13根手性色谱柱,分别考察了其对16种外消旋体的拆分,分离结果显示：三取代纤维素柱 > 二取代纤维素柱 > 纤维素柱;精制硅胶和大孔硅胶优于粗制硅胶,大孔硅胶的柱压更低;硅胶的氨丙基化对手性选择性有一定的影响;这些手性柱之间具有一定的互补性,尤其是纤维素柱。该文有助于人们更深刻地理解和更好地把握高效液相色谱手性柱的制备。     

Proline-based chiral stationary phases: a molecular dynamics study of the interfacial structure

Proline chains have generated considerable interest as a possible basis for new selectors in chiral chromatography. In this article, we employ molecular dynamics simulations to examine the interfacial structure of two diproline chiral selectors, one with a terminal trimethylacetyl group and one with a terminal t-butyl carbamate group. The solvents consist of a relatively apolar n-hexane/2-propanol and a polar water/methanol mixture. We begin with electronic structure calculations for the two chiral selectors to assess the energetics of conformational changes, particularly along the backbone where the amide bonds can alternate between cis and trans conformations. Force fields have been developed for the two selectors, based on these ab initio calculations. Molecular dynamics simulations of the selective interfaces are performed to examine the preferred backbone conformations, as a function of end-group and solvent. The full chiral surface includes the diproline selectors, trimethylsilyl end-caps, and silanol groups. Connection is made with selectivity measurements on these interfaces, where significant differences are observed between these two very similar selectors.     

Adsorption behaviour of a quinidine carbamate-based chiral stationary phase: Role of the additive

In this study, we incorporate the additive properties into the theoretical model of a general preparative chromatographic system; this is normally not done and this limits a proper process optimization. As a model phase system, we used the adsorption of 9H-fluoren-9-ylmethoxycarbonyl-allylglycine (Fmoc-allylglycine) enantiomers on a quinidine carbamate-based chiral stationary phase (anion exchanger) together with a methanol–glacial acetic acid–ammonium acetate eluent. The inverse method was used to measure the competitive adsorption isotherms of both the Fmoc-allylglycine enantiomers as well as the non-detectable additive acetic acid. It was concluded that this enantioselective preparative system is well described by a non-heterogeneous adsorption model and that the loading capacity is very high. The proposed model is valid over a wide range of additive concentrations, which is important for process optimization.     

锆基纤维素手性固定相直接拆分萘普生衍生物

萘普生是一种消炎镇痛药 ,其 S对映体的抗炎作用是 R构型的 2 8倍 ,萘普生及其衍生物的拆分具有重要意义 .手性固定相 HPLC直接拆分 [1～ 4 ] 是最简便的分析方法 .氧化锆是近年来备受关注的色谱载体 [5,6 ] .Carr等 [7] 对碱性药物快速拆分表明氧化锆在手性分离Scheme1　 Structuresof chiral naproxen and its derivatives中的独特选择性 .萘普生及其衍生物在锆基手性固定相上的分离未见文献报道 .本组利用自制的球形氧化锆制备了涂敷型纤维素 -三 ( 3,5 -二甲基苯基氨基甲酸酯 ) -Zr O2 手性固定相 ( CDMPC- Zr O2 - CSP) ,在正…     

An amylopectin tris(phenylcarbamate) chiral stationary phase for high performance liquid chromatography

Amylopectin tris(phenylcarbamate) has been evaluated as a chiral stationary phase for HPLC; the influence on its cptical resolving capabilities of mobile phase composition and nature of the alcohol used as modifier has been studied. Separation and resolution of twelve arylalcohol racemates were examined. In most instances, the stationary phase exhibited high optical resolving capacity.     

Chromatographic Chiral Recognition and Computer Aided Deconvolution of the Enantiomeric Secondary Alcohol with a Self‐Packed Chiral Stationary Phase HPLC Column

The γ‐aminopropyl‐derivatized silica was treated with the (R)‐(‐)‐N‐(3,5‐dinitrobenzoyl)‐α‐phenylglycine and was packed into a standard 250 mm × 4.5 mm HPLC column to perform the chiral separation of secondary alcohol. Enantiomers of four homologous series of aryl alkyl substituted alcohol were resolved in different degrees. The chiral recognition mechanism was proposed that could be used to rationalize well the elution order and the resolution between the R‐ and S‐configuration of a secondary alcohol. The unresolved peak of the enantiomers of 1‐phenylethanol and the partially resolved peak of the enantiomers of 1‐(1‐naphthyl)ethanol were deconvoluted by the assistance of computer and a program written in BASIC computer language. Two mathematical models were used for the deconvolution and were based on modified Gaussian functions with a fixed baseline that can take into account the skew of a chromatographic peak. Parameters in the mathematical model were estimated by using a nonlinear regression algorithm. The selected mathematical models were suitable for deconvolving the less skewed overlapping peaks of 1‐phenylethanol.     

A chiral stationary phase with special hydrophobic framework for ligand-exchange chromatography

A novel chiral stationary phase (CSP1) for ligand-exchange chromatography (CLEC) was prepared by firstly using dimethyl- chlorosilane as an endcapping reagent for decreasing residual silanol group on the surface of silica gel,and then introducing L-Pro as a chiral selector and hydrophobic octyl group to the silica gel surface simultaneously.The enantioseparations of 14 DL-amino acids on CSP1 were achieved with the enantioselectivityαranging from 1.09 to 2.44 and the resolution Rs being between 0.8 and 6.3.The chromatographic performances of CSP1 with the bonded phase (CSP2) prepared using reference method were compared.The results showed that the column efficiency and resolution Rs of chiral stationary phase could be improved by using the above modifying method.