三种甲氧基黄烷酮在纤维素衍生物手性柱上的对映体分离及手性识别机理研究

在四种自制的涂敷型纤维素衍生物手性柱，即纤维素三苯甲酸酚（CTB）、纤 维素三（4-甲基苯甲酸酯）（C素三苯基氨基甲酸酯（CTPC）和纤维素三（3，5- 二甲基苯基氨基甲酸酯）（cDMPC）上对4'-甲氧基黄烷酮，56-甲氧基黄烷酮进行 了对映体分离，研究了溶质的结构及流动相的组成对手性分离的影响，并对手性识 别的机理进行了讨，认为π-π作用很可能是上述三种甲氧基黄烷酮在四种纤维素 衍生物手性固定相上保留与手性识别的主要因素，CDMPC，氢键作用也对手性识别 有非常重要的作用.     

Comparative Study of the Enantioseparation of Uniconazole and Imazalil by HPLC on Various Cellulose Chiral Columns

Abstract

This paper reported the enantioseparation of uniconazole and imazalil using four different self‐prepared cellulose derivative columns, namely, CTB, CTMB, CTPC, and CDMPC. The mobile phase composition including the type of the alcohol modifier and the ethanol concentration in hexane changed, and the influence on the retention factor (k′); for each enantiomer, the separation factor (α) and the resolution (R_S) was studied. The influence of the structures of the analytes on the chiral separation was investigated. The results showed that uniconazole obtained the best resolution of 2.16 on CTPC, while imazalil obtained the best separation on CTMB, with the maximal resolution of 4.83. It was concluded that the structure of solutes and CSP play a key role in the chiral recognition. And the chiral attraction between them is the predominant factor.     

外消旋硫代缩水甘油醚在多糖基质手性柱上的手性拆分

在自行合成的3种多糖基质的手性固定相上直接拆分了7种外消旋硫代缩水甘油醚，初步探讨了手性化合物结构在手性识别过程中对手性拆分的影响，并对手性固定相的手性识别能力进行了评价。     

芳氧苯氧丙酸类除草剂在两种手性柱上的对映体分离

在自制的涂敷型纤维素三(3,5-二甲基苯基氨基甲酸酯)(CDMPC)手性柱和P irkle型(S,S)-W helk-O 1手性柱上对禾草灵,吡氟禾草灵,喹禾灵,噁唑禾草灵4种芳氧苯氧丙酸类除草剂进行了对映体分离。分别考察了在流动相正己烷中,极性醇类添加剂种类、和浓度以及溶质的结构因素对手性分离的影响,探讨了溶质在两种手性柱上的手性识别的机理。结果显示:噁唑禾草灵在(S,S)-W helk-O 1上获得了较好的分离,其它时3种溶质均在CDMPC上获得了较好的分离,各溶质都达到基线分离。两种手性柱的手性识别机理不同,溶质和固定相的结构是手性识别的关键。     

外消旋萘普生酯类在(S,S)-Whelk-O1与CDMPC手性柱上的对映体分离及手性识别机理的比较

在Pirkle型的(S,S)-Whelk-O 1与纤维素衍生物型的CDMPC两种手性柱上对六种 外消旋萘普生酯进行了对映体分离，通过研究烷氧基结构上的差异以及流动相中不 同的醇类添加剂对手性识别的影响，探讨和比较了外消旋萘普生酯在两种手性固定 相上手性识别的机理。对于 (S,S)-Whelk-O 1， 溶质与固定相之间的吸引作用于 手性识别的主要因素，而对于CDMPC，溶质在手性空腔中的空间适应性很可能是手 性识别的关键。     

Direct optical resolution of the enantiomers of novel chiral tetrahedral metal clusters by HPLC on a cellulose tris-(3,5-dimethylphenylcarbamate) stationary phase

The enantioseparation of seven novel chiral transition metal tetrahedral clusters has been achieved for the first time on cellulose derivatized with tris(3,5-dimethylphenylcarbamate) (CDMPC) as chiral stationary phase (CSP) and hexane containing different alcohols as modifiers as mobile phases. The effect of mobile-phase composition on enantioselectivity was studied, and the effect of structural variation of the solutes on their enantioseparation was also investigated. It was found that both the metal in the tetrahedral core and the ligand coordinated to the atom in the tetrahedral core had significant effects on the chromatographic behavior of the analytes.     

外消旋萘普生酯类在四种纤维素衍生物手性柱上分离及手性 识别机理研究

在纯聚合物型的纤维素三醋酸酯(CTA)、纤维素三苯甲酸酯(CTB)与涂敷型的CTB、纤维素三(4-甲基苯甲酸酯)(CTMB)四种纤维素衍生手性柱上成功地分离了几种外消旋萘普生酯,研究了流动相组成以及溶质的结构对手性分离的影响,探讨了纤维素衍生物手性固定相对外消旋萘普生酯手性识别的机理,得出溶质在固定相手性空腔中体积大小的适应性,尤其是立体结构上的空间适应性是手性识别的关键,不同的固定相这种适应性有所不同,     

High-performance liquid chromatographic enantioseparations on capillary columns containing monolithic silica modified with cellulose tris(3,5-dimethylphenylcarbamate)

Monolithic capillary columns containing native silica gel were modified with cellulose tris(3,5-dimethylphenylcarbamate) (CDMPC) and used for enantioseparations in capillary liquid chromatography. The method adopted for in situ enantioselective modification of monolithic fused silica capillary columns by coating with CDPMC appears to be fairly simple and fast. High efficiency enantioseparations of test racemic compounds and s(everal chiral drugs were achieved in a short time. It was possible to increase the amount of chiral selector present by multiple coating of monoliths with CDMPC. The baseline enantioseparation of 2,2,2-trifluoro-1-(9-anthryl)ethanol was achieved in an analysis time less than 30 s with this capillary column. In addition, reproducible enantioseparations were obtained when the chiral selector was removed from the monolithic column by flushing it with appropriate solvent and the column recoated.     

A mesoporous silica nanoparticles immobilized open-tubular capillary column with a coating of cellulose tris(3,5-dimethylphenyl-carbamate) for enantioseparation in CEC

An approach of immobilizing mobile crystalline material (MCM)-41 mesoporous silica nanoparticles on the inner wall of an open-tubular (OT) capillary as the support for coating chiral selector of cellulose tris(3,5-dimethylphenyl-carbamate) (CDMPC) was carried out. By taking advantage of the improved phase ratio of OT capillary with the immobilization of MCM-41 mesoporous material, the cellulose derivative of CDMPC as the chiral selector was simply coated on the MCM-41 nanoparticle layer via the hydrogen-bonding interaction, and the enantioseparation was successively carried out. Eight pairs of acidic, neutral and basic enantiomers were resolved in capillary electrochromatography or capillary liquid chromatography mode. The concentration of CDMPC for coating was systematically investigated to obtain the optimized chromatographic properties on enantioseparation by controlling the supposed film thickness of CDMPC on MCM-41 nanoparticle layer. Comparing with a bare fused silica capillary column coated with CDMPC under the same coating procedure as MCM-41-modified capillary did, the MCM-41-modified capillary column offered much higher enantioselectivity. This result indicated the significance of using the mesoporous nanoparticles as the electrochromatographic support to enhance the phase ratio of OT capillary column in capillary electrochromatography and capillary liquid chromatography. For investigating the effect of experimental conditions on the enantioseparation with this prepared OT capillary column, the content of organic modifier acetonitrile in the mobile phase was thus extensively evaluated to achieve a better chiral separation.     

取代基效应对三苯甲酸纤维素酯类吸附剂的吸附性能的影响

采用催化合成法制备三苯甲酸纤维素酯（CTB）、三（4-甲基苯甲酸）纤维素酯（CTMB）和三（4-氯苯甲酸）纤维素酯（CTCB），将其分别负载于Gas Chrom Q载体上，用不同类型的探针分子及气相色谱法表征其吸附性能，研究取代基团的电子效应和空间效应对其吸附性能的影响。实验结果表明：在三苯甲酸纤维素酯类吸附剂和苯衍生物吸附质的苯环上的取代基效应（电子效应和立体效应）对吸附质在吸附剂上的吸附热（-Δha）的影响显著，但两者的影响各不相同。     

Fast separations of chiral β-blockers on a cellulose tris(3,5-dimethylphenylcarbamate)-coated zirconia monolithic column by capillary electrochromatography

Cellulose tris(3,5-dimethylphenylcarbamate) (CDMPC) is an excellent chiral selector for enantioseparation of a wide variety of chiral compounds. The monolithic chiral columns are becoming popular in liquid chromatography and capillary electrochromatography. In this work, we present the fast separation of chiral β-blockers on a CDMPC-modified zirconia monolithic column by capillary electrochromatography (CEC). The porous zirconia monolithic capillary column was prepared by using the sol-gel technology and then zirconia surface modified with CDMPC. The enantioseparations were performed in reversed-phase (RP) eluents of a phosphate solution (pH 4.4) modified with acetonitrile or alcohol. The enantioseparations of a set of eight chiral β-blockers were achieved in less than one minute. Influences of the applied voltage, column temperature, concentration of acetonitrile and the type of alcohol as the organic modifier in the mobile phase, and sample injection time on enantioseparation were investigated. CEC separations at the applied voltage of 10 kV and 15 °C in the ACN-modified mobile phase provided the best resolutions for the analytes studied. Run-to-run and day-to-day repeatabilities of the column in the RP-CEC separation were less than 1 and 2%, respectively.     

纤维素键合型手性整体柱的制备及其在快速手性分离中的应用

采用N-丙烯酰琥珀酰亚胺(NAS)为基质单体,乙二醇二甲基丙烯酸酯(EDMA)为交联剂,原位聚合制备聚(NAS-co-EDMA)毛细管整体柱,并通过化学键合法将自合成的纤维素-三(4-甲基苯甲酸酯)(CTMB)共价键合到整体柱上,制备用于快速手性分离的纤维素键合型手性整体柱.优化了整体柱制备和衍生化条件;通过对固定相红...     

Enantioseparation Using Chitosan Tris(3-chlorophenylcarbamate) as a Chiral Stationary Phase for HPLC

A novel chiral stationary phase (CSP) consisting of a silica-based chitosan tris(3-chlorophenylcarbamate) derivative was used for the enantioseparation of nine racemic compounds in the normal phase mode by high-performance liquid chromatography (LC). The influence of the type and percentage of modifier in the mobile phase on the optimization of the resolution was investigated. The resolution of epoxiconazole using this system was compared with those achieved using commercially available Chiralcel^® OD-H and Chiralpak^® AD-H columns. Among the tested racemates, seven racemic compounds were separated most quickly on the CSP of chitosan tris(3-chlorophenylcarbamate). Baseline or near-baseline separation was achieved for benzoin, penconazole, hexaconazole, and epoxiconazole, while the others were partially separated. The enantioseparation results for epoxiconazole were not inferior to those of commercially available Chiralcel^® OD-H and Chiralpak^® AD-H columns.     

HPLC-MS/MS enantioseparation of triazole fungicides using polysaccharide-based stationary phases

The enantiomeric separation of 21 triazole fungicides was carried out on four polysaccharide-derived chiral stationary phases in the reversed phase separation mode using high performance liquid chromatography coupled with tandem mass spectrometry. All fungicides were detected in electrospray ionization (ESI) positive mode with selected reaction monitoring (SRM). Complete enantioseparation was achieved for 21 fungicides except for difenoconazole based on cellulose tris (3,5-dimethylphenylcarbamate) and cellulose tris (3-chloro-4-methylphenyl carbamate) columns by optimizing experimental conditions including mobile phase and column temperature. Mobile phase was 0.1% formic acid aqueous solution mixed with methanol or acetonitrile in different proportions. Among all the fungicides, 15 with two enantiomers and three with four stereoisomers (bitertanol, bromuconazole, and cyproconazole) were successfully separated at 25°C. Enantioseparation for the other three fungicides (propiconazole, triadimenol, and difenoconazole) with four stereoisomers could be achieved by changing the column temperature from 10 to 40°C. Propiconazole and triadimenol were enantioseparated on baseline at 40 and at 35°C, respectively, and difenoconazole was enantioseparated partially with the R(s) > 1.1 at 25°C. Moreover, linearities and limits of detection (LODs) of 21 fungicides except for difenoconazole were studied, showing coefficients of determination (R(2)) higher than 0.99 and LODs lower than 2.5 μg/L.     

High-performance chiral separation of fourteen triazole fungicides by sulfated beta-cyclodextrin-mediated capillary electrophoresis

In this paper, sulfated beta-cyclodextrin-mediated capillary electrophoresis (CE) is evaluated as a new approach for the chiral separation of triazole-type fungicides. The 14 fungicides investigated were bitertanol, cyproconazole, difenoconazole, diniconazole, flutriafol, hexaconazole, myclobutanil, paclobutrazol, penconazole, propiconazole, tebuconazole, tetraconazole, triadimefon and triadimenol. Under the optimal conditions, excellent enantioseparation was achieved for all the 14 fungicides, including those fungicides containing two chiral centers. To our knowledge, this is the only system to date that offers outstanding enantiodiscrimination towards all triazole-type fungicides. The impact of the molecular structures of the triazole compounds on their migration behavior was studied. Similar to other chemical systems involving host-guest complexation, the interaction between sulfated beta-cyclodextrin and the triazole compounds was found to be affected by a variety of factors, including electrostatic force, hydrogen bonding, steric effect and hydrophobicity. These factors, coupled with the countercurrent electroosmotic flow (EOF), were believed to be the major forces behind the exceptional chiral selectivity.     

几种除草剂农药在高效液相色谱手性固定相上的对映体分离

采用正己烷-极性醇正相体系为色谱流动相,稳杀得、萘丙胺等几种不同种类的除草剂农药在Pirkle刷型(S,S)-Whelk-O1手性柱或自制的纤维素三(3,5-二甲苯基氨基甲酸酯)(CDMPC)手性柱上获得了成功的手性分离。研究了流动相中醇类改性剂对手性识别的影响,初步探讨了手性识别的机理,并摸索出最佳的对映体分离条件。     

Enantioseparation on cellulose dimethylphenylcarbamate-modified zirconia monolithic columns by reversed-phase capillary electrochromatography

This work reports the preparation of monolithic zirconia chiral columns for separation of enantiomeric compounds by capillary electrochromatography (CEC). Using sol–gel technology, a porous monolith having interconnected globular-like structure with through-pores is synthesized in the capillary column as a first step in the synthesis of monolithic zirconia chiral capillary columns. In the second step, the surface of the monolith is modified by coating with cellulose tris(3,5-dimethylphenylcarbamate) (CDMPC) as the chiral stationary phase to obtain a chiral column (CDMPCZM). The process of the preparation of the zirconia monolithic capillary column was investigated by varying the concentrations of the components of the sol solution including polyethylene glycol, water and acetic acid. CDMPCZM is mechanically stable and no bubble formation was detected with the applied current of up to 30 μA. The enantioseparation behavior of the CDMPCZM columns was investigated by separating a set of 10 representative chiral compounds by varying the applied voltage and pH and organic composition of the aqueous organic mobile phases.     

Comparison of separation performance of polysaccaride-based chiral stationary phases in enantioseparation of 1-(4-chlorobenzhydryl)piperazine benzamide derivatives by HPLC

Analytical high-performance liquid chromatographic enantioseparation of 1-(4-chlorobenzhydryl) piperazine benzamide derivatives was accomplished on different chiral stationary phases. The enantiomers of the compounds were resolved by normal-phase chromatography on silica-based amylose tris(3,5-dimethylphenylcarbamate) (Chiralpak AD-H), cellulose tris(3,5-dimethylphenylcarbamate) (Chiralcel OD-H) and cellulose tris(4-methylbenzoate) (Chiralcel OJ) columns with mobile phases consisting of mixtures of n-hexane and ethanol in different proportions (90: 10, 80: 20). The mobile phase and the chiral stationary phase were varied to achieve the best resolution. The effect of the concentration of ethanol in the mobile phase was studied. The resolution obtained on the three columns was significant.     

16种手性化合物在不同自制手性固定相上的拆分比较

采用高效液相色谱法,在自制的纤维素-三(3,5-二甲基苯基氨基甲酸酯)(ATEO-OD)、纤维素-三(4-甲基苯基氨基甲酸酯)(ATEO-OG)和纤维素-三(4-甲基苯基甲酸酯)(ATEO-OJ)3种手性柱上对16种不同结构的手性化合物进行了拆分和比较.试验结果表明:16个手性样品在这3种手性固定相上分别获得了不同程度的拆分,A TEO-OD对所分析样品具有更好的手性识别能力,ATEO-OG和ATEO-OJ的手性识别能力相当.     

Enantiomeric resolution of new triazole compounds by high-performance liquid chromatography

Cellulose tris(3,5-dimethylphenylcarbamate) (CDMPC) was synthesized and coated on aminopropylsilica to prepare a chiral stationary phase (CSP). HPLC methods were developed for the direct enantioseparation of 12 chiral triazole compounds on the CSP. The separations were made using normal phase methodology with a mobile phase consisting of n-hexane-alcohol (ethanol, 1-propanol, 1-butanol, 2-propanol, and t-butanol) in various portions. The column temperatures were studied for the optimization of the resolutions. The effects of structural features of the solutes on the discrimination between the enantiomers were examined. Baseline separation was easily obtained in many cases.