Preparation and Characterization of Trans‐Resveratrol Imprinted Polymers

Abstract

In order to selectively extract trans‐resveratrol from Chinese herbs, molecularly imprinted polymers (MIPs) were prepared with trans‐resveratrol as the template molecule. The influences of porogenic solvents and functional monomers on the recognition properties of the polymer were studied. The MIP, which was prepared in acetone using 4‐vinylpyridine as functional monomer, displayed good affinity and recognition property for the template molecule. This indicates that the 4‐vinylpyridine can form hydrogen‐bonding or ionic interaction with trans‐resveratrol. Experimental result also indicated that the MIP column can separate trans‐resveratrol from matrix components in the Polygonum cuspidatum extract.     

Separation of chiral compounds using magnetic molecularly imprinted polymer nanoparticles as stationary phase by microchip capillary electrochromatography

In this work, a simple and rapid approach was developed for separation and detection of chiral compounds based on a magnetic molecularly imprinted polymer modified poly(dimethylsiloxane) (PDMS) microchip coupled with electrochemical detection. Molecularly imprinted polymers were prepared employing Fe₃O₄ nanoparticles (NPs) as the supporting substrate and norepinephrine as the functional monomer in the presence of template molecule in a weak alkaline solution. After extracting the embedded template molecules, Fe₃O₄@polynorepinephrine NPs (MIP–Fe₃O₄@PNE NPs) showed specific molecular recognition selectivity and high affinity towards the template molecule, which were then used as stationary phase of microchip capillary electrochromatography for chiral compounds separation. Mandelic acid and histidine enantiomers were used as model compounds to test the chiral stationary phase. By using R‐mandelic acid as the template molecule, mandelic acid enantiomer was effectively separated and detected on the MIP‐Fe₃O₄@PNE NPs modified PDMS microchip. Moreover, the successful separation of histidine enantiomers on the MIP–Fe₃O₄@PNE NPs modified microchip using L‐histidine as template molecule was also achieved.     

腈菌唑分子印迹聚合物的制备及识别性能研究

以腈菌唑为模板分子,采用原位分子印迹技术,制备具有特定识别性能的连续棒状分子印迹聚合物。考察了流动相中酸量对分离的影响,研究了几种结构类似物在所得分子印迹柱上的保留特性。结果表明,这种棒状分子印迹聚合物比相应的空白聚合物有高的识别性能和选择性。     

A molecularly imprinted monolith for the fast chiral separation of antiparasitic drugs by pressurized CEC

Molecularly imprinted polymer (MIP) monoliths with (S)‐ornidazole ((S)‐ONZ) as the template molecule have been designed and prepared by the simple thermal polymerization of methacrylic acid, 4‐vinylpyridine, and ethylene dimethacrylate in the presence of a binary porogenic mixture of toluene and dodecanol. The influences of polymerization mixture composition on the chiral recognition of ONZ have been evaluated, and the imprint effect in the optimized MIP monolith has been clearly demonstrated. The new monolithic stationary phase with optimized porous property and good selectivity was used for the chiral separation of ONZ by pressurized CEC. The pressurized CEC conditions were also optimized to obtain the good chiral separation. The enantiomers were rapidly separated within 9 min on the MIP‐based chiral stationary phase, whereas the chiral separation was not obtained on the nonimprinted polymer. Additionally, the proposed method has been successfully applied to the chiral separation of ONZ in tablet samples by injection of the crude sample. The cross‐selectivity for similar antiparasitic drug was investigated. The results indicated that the chiral separation of secnidazole could also be obtained on the optimized MIP monolith within 14 min.     

Linear Solvation Energy Relationships in the Determination of Specificity and Selectivity of Stationary Phases

The retention of fifty structurally different compounds has been studied using linear solvation energy relationships. Investigations were performed with the use of six various stationary phases with two mobile phases (50/50 % v/v methanol/water and 50/50 % v/v acetonitrile/water). Packing materials were home-made and functionalized with octadecyl, alkylamide, cholesterol, alkyl-phosphate and phenyl molecules. This is the first attempt to compare all of these stationary phases synthesized on the same silica gel batch. Therefore, all of them may be compared in more complex and believable way, than it was performed earlier in former investigations. The phase properties (based on Abraham model) were used to the classification of stationary phases according to their interaction properties. The hydrophilic system properties s, a, b indicate stronger interactions between solute and mobile phase for most of the columns. Both e and v cause greater retention as a consequence of preferable interactions with stationary phase by electron pairs and cavity formation as well as hydrophobic bonds. However, alkyl-phosphate phase has different retention properties, as it was expressed by positive sign of s coefficient. It may be concluded that most important parameters influencing the retention of compounds are volume and hydrogen bond acceptor basicity. The LSER coefficients showed also the dependency on the type of organic modifier used as a mobile phase component.

     

The Study of Separation and Thermodynamics of Adsorption of the Enantiomers of Ethofumasate on a Modified Cellulose

Abstract

Cellulose and cellulose derivatives are biopolymers that are often used as stationary phases for the separation of enantiomers. Describing the mechanism of such separations is a difficult task due to the complexity of these phases. In the present study, direct enantiomeric resolution of ethofumesate has been achieved, using hexane as the mobile phase with various alcoholic modifiers on cellulose tri(3,5‐dimethylphenylcarbamate) chiral stationary phase (CDMPC CSP). The influence of the mobile phase composition and the column temperature on the chiral separation was studied. It was found that at a constant temperature and within a certain range of alcohol modifier concentration, the conformation of the polymeric phase, and the selective adsorption sites were not affected by alcohol modifier concentration. The type and the concentration of the alcoholic modifiers influenced the retention factor and the separation factor. Ethofumesate gained the best enantioseparation using sec‐butanol as alcoholic modifier at 25°C with α‐value 1.70. And the separation factor decreased with the increase of the column temperature. The van't Hoff plots were linear (R ²>0.96) for ethofumesate from 25°C to 50°C. That showed the enantioselective interactions do not change over the temperature range studied. Furthermore the values of ΔH° and ΔS° were both negative, which indicated an enthalpy‐driven separation. And the possible chiral recognition mechanism of the analyte and CDMPC was discussed. It was found that hydrogen bonding plays an important role on enantioseparation of CDMPC CSP. The inclusion and fitness of solute shape in the chiral cavity significantly contributed to the enantioseparation of solute.     

Sulfonamide imprinted polymers using co-functional monomers

Molecular imprinted polymers (MIPs) prepared using combination of acrylamide (ACM) and 4-vinylpyridine (4-Vpy) as co-functional monomers exhibited efficient recognition properties in both organic and aqueous media as HPLC stationary phase. The results indicate that amide and pyridine groups in functional monomers formed strong hydrogen-bonding interaction with the template molecule, and specific recognition sites were created within the polymer matrix during the imprinting process. When sulfamethoxazole (SMO) was used as template, a MIP prepared in a polar organic solvent (acetonitrile) using the combination of ACM and 4-Vpy showed better recognition of template than the polymer prepared in the same solvent using the combination of acidic monomer (methacrylic acid) and basic monomer 4-Vpy. On the contrary, when sulfamethazine (SMZ) was used as template, a MIP prepared using the combination of methacrylic acid (MAA) and 4-Vpy showed better recognition of template than the polymer prepared using the combination of ACM and 4-Vpy. Our results indicate that in organic media the degree of retention of the sample molecules on the imprinted polymers was controlled by the hydrogen-bonding interaction between the sample molecules and the polymer, while in aqueous media it was determined to a considerable extent by hydrophobic interactions. In both media the shape, size and the electronic structure of the template molecule were all-important factors in the recognition process.     

Cellulose Derivatives Used as Chiral Stationary Phases in Capillary Gas Chromatography

Abstract

In this work, we present the first separation of enantiomers in gas chromatography (GC) using a fused‐silica capillary column containing cellulose triacetate, cellulose triphenylcarbamate, or cellulose tris(3,5‐dimethylphenylcarbamate) as the new chiral stationary phase. The separated solutes included alcohols, amine, ketone, ether, ester, and amino acid. Their column efficiency, polarity, and chiral selectivity were studied. The retention mechanism was discussed. The results showed that those derivatives had relatively high chiral recognition abilities and can be used as the chiral stationary phases in GC.     

Preparation and Evaluation of P-tert-Butyl-calix[8]arene-bonded Silica Stationary Phase for High Performance Liquid Chromatography

ABSTRACT

A new p-fert-butyl-calix[8]arene-bonded silica gel stationary phase was synthesized through heterogeneous functionalisation of suspended porous silica. A characterization of its structure was carried out by using elemental analysis, FTIR and ¹³C solid state NMR spectroscopy. Chromatographic performance of the new packing material was investigated by employing polycyclic aromatic hydrocarbons (PAHs) as probes and using methanol-water as mobile phase. The investigations show that the new stationary phase behaves as a reversed phase stationary phase. The liquid chromatographic separation of PAHs solutes on the new bonded phase was compared with that on a p-tert-butyl-calix[4]arene-bonded silica stationary phase. The new p-tert-butyl-calix[8]arene-bonded phase exhibited higher retention and better separation selectivity, although the carbon content and coverage of the new packing material was lower than that of the p-tert-butyl-calix[4]arene bonded silica stationary phase. A possible retention mechanism for the new packing material was also proposed.     

Preparation and Characterization of Prometryn Molecularly Imprinted Solid‐Phase Microextraction Fibers

Abstract

A novel reproducible solid‐phase microextraction (SPME) coating was prepared on the surface of silanized silica fibers by molecularly imprinted polymerization using prometryn as template molecule. The structure and extraction performance of molecularly imprinted polymer (MIP) coating was studied with the scanning electron microscope and high performance liquid chromatography (HPLC). Specific selectivity was found with the prometryn MIP‐coated fiber to prometry and its structural analogues such as atrazine, simetryn, terbutylazin, ametryn, propazine and terbutryn. In contrast, these triazines could not be selectively extracted by the non‐imprinted polymer fiber or commercial polydimethylsiloxane (PDMS), polydimethylsiloxane/divinylbenzene (PDMS/DVB), polyacrylate (PA) fibers.     

A novel molecularly imprinted method with computational simulation for the affinity isolation and knockout of baicalein from Scutellaria baicalensis

A novel molecularly imprinted polymer (MIP) was synthesized by precipitation polymerization with baicalein (BAI) as the template and used as solid‐phase extraction (SPE) adsorbent, aiming at the affinity isolation and selective knockout of BAI from Scutellaria baicalensis Georgi (SB). We used computational simulation to predict the optimal functional monomer, polymerization solvent and molar ratio of template to functional monomer. Characterization and performance tests revealed that MIP exhibited uniform spherical morphology, rapid binding kinetics, and higher adsorption capacity for BAI compared with nonimprinted polymer (NIP). The application of MIP in SPE coupled with high‐performance liquid chromatography to extract BAI from SB showed excellent recovery (94.3%) and purity (97.0%). Not only the single BAI compound, but also the BAI‐removed SB extract was obtained by one‐step process. This new method is useful for isolation and knockout of key bioactive compounds from herbal medicines. Copyright © 2015 John Wiley & Sons, Ltd.     

Evaluation of the Analytical Potentialities of a Composite Electrode Modified with Molecularly Imprinted Polymers

Abstract

The preparation of a methacrylate polymer molecularly imprinted (MIP) with paracetamol (APAP) was performed. After extraction of the APAP template molecule, the MIPs were incorporated into a graphite–polyurethane (GPU) matrix, and the resulting composites were used to prepare modified electrodes intended to be used in APAP determination. The best results were found using a 2.5% MIP in the GPU electrode and a 500-µm MIP particle size. This electrode was used in the determination of APAP in pharmaceutical formulations, reaching a 6.7 × 10^?8 mol L^?1 limit of detection. The 2.5% MIP-GPU-modified electrode showed better sensitivity than the nonimprinted methacrylate GPU-modified electrodes. Interference of phenacetin in the APAP response decreased remarkably when the proposed electrode was used.     

Separation of Epigallocatechin Gallate from Natural Plant Extracts Using Crowding Agents—Assisted Imprinted Polymers

A methodology-based molecularly imprinted polymer (MIP) was proposed to separate epigallocatechin gallate (EGCG) from natural plant extracts. A molecular crowding agent was introduced to improve the affinity and recognizing ability of EGCG in the preparation of an MIP monolith. Acrylamide was used as the functional monomer, and ethylene glycol dimethacrylate was the crosslinking monomer, using a solution of polystyrene in tetrahydrofuran as a molecular crowding agent with isooctane as a coporogen. In addition, it was found that the ratio of the macromolecule agent, the amount of templates and crosslinking degree, and the composition of the mobile phase greatly affected the retention of the template and performance of molecular recognition. The imprinting factor of the resulting MIP monolith obtained was up to 9.67. The resulting MIP can be used to purify EGCG from crude tea polyphenol efficiently with mean recoveries of 87.42 %.

     

Synthesis and study of a molecularly imprinted polymer for specific solid‐phase extraction of vinflunine and its metabolite from biological fluids

A molecularly imprinted polymer (MIP) was synthesized in order to specifically extract vinflunine, an anticancer agent, and its metabolite (4‐O‐deacetylvinflunine) from bovine plasma and artificial urine by solid‐phase extraction (SPE). Vinorelbine, a non‐fluorinated analogue of vinflunine, was selected as a template for MIP synthesis. The selectivity of MIP versus the template (vinorelbine) and other alkaloids (catharanthine, vinblastine, vincristine, vinflunine and 4‐O‐deacetylvinflunine) was shown by a SPE protocol carried out with non‐aqueous samples. A second protocol was developed for aqueous samples with two consecutive washing steps (AcOH–NH₂OH buffer (pH 7, I=10 mM)–MeOH mixture 95:5 v/v and ACN–AcOH mixture 99:1 v/v) and an elution step (MeOH–AcOH mixture 90:10 v/v). Thus, MIP‐SPE of bovine plasma brought high recoveries, 81 and 89% for vinflunine and its metabolite, respectively. This protocol was slightly modified for artificial urine samples in order to obtain a good MIP/NIP selectivity; furthermore, elution recoveries were 73 and 81% for vinflunine and its metabolite, respectively. Repeatability was assessed in both biological matrices and RSD (%) were inferior to 4%. The MIP also showed a suitable linearity (r² superior to 0.99), between 0.25 and 10 μg/mL for plasma, and between 1 and 5 μg/mL for artificial urine.     

分子烙印聚合物固定相分离咖啡因和茶碱的研究

分子烙印是一种新兴的分子识别技术,利用该技术可制备对烙印分子具有“预定”识别能力的高分子聚合物,即分子烙印聚合物（MIP）,从而可以对性质和组成相近的组如对映体等进行分离^[1,2],咖啡因与茶碱的分子烙印聚合物的制备以及二者分析已有报道^[3-9],但存在两种完全相反的结论。一种观点认为,即使以咖啡因为烙印分子,所制备的聚合物对咖啡因分子的选择性吸附能力也小于茶碱^[3-6]。而另一种观点则认为,在一定条件下,如以咖啡因分子为烙印分子的烙印聚合物对咖啡因分子具有更强的吸附能力^[7-9]。本文分别采用茶碱和咖啡因作为烙印分子,以甲基丙烯酸等为功能单体,在不同条件下制备了多种非共价型分子烙印聚合物,并系统地考察了其作 为HPLC固定相对咖啡因和茶碱的分离能力,同时也对烙印分子应具备的条件加以探讨。     

电色谱模式下四肽印迹整体柱分子识别机理的研究

本文采用原位聚合法制备了以四肽YPLG为模板的毛细管分子印迹整体柱,在毛细管电色谱模式下以模板分子和它的结构类似物YPGL为样品,对分子印迹聚合物的识别机理进行了研究。这两种四肽由于化学结构相似且等电点非常相近,普通的电色谱和毛细管电泳方法分离非常困难。但我们的实验表明,印迹整体柱对模板分子具有特异性识别能力,因此YPLG与YPGL之间的分离因子为1.73,分离度达3.72。实验中系统地研究了流动相中有机溶剂的含量、缓冲溶液的pH值、缓冲溶液的盐浓度以及柱温对四肽识别的影响。实验中我们观察到模板在印迹柱上具有非线性的Van’t Hoff行为,揭示可能存在多重保留机理。本研究结果表明,在毛细管电色谱模式下,分子印迹整体柱的分子识别主要决定于样品与印迹聚合物之间的氢键作用以及印迹孔穴的三维结构。     

Synthesis of molecularly imprinted polypyrrole as an adsorbent for solid‐phase extraction of warfarin from human plasma and urine

The aim of this work was to develop a method for the clean‐up and preconcentration of warfarin from biological sample employing a new molecularly imprinted polymer (MIP) as a selective adsorbent for solid‐phase extraction (SPE). This MIP was synthesized using warfarin as a template, pyrrole as a functional monomer and vinyl triethoxysilane as a cross‐linker. The molar ratio of 1:4:20 (template–functional monomer–cross‐linker) showed the best results. Nonimprinted polymers (NIPs) were prepared and treated with the same method, but in the absence of warfarin. The prepared polymer was characterized by Fourier transmission infrared spectrometry and scanning electron microscopy. An adsorption process (SPE) for the removal of warfarin using the fabricated MIPs and NIPs was evaluated under various conditions. Effective parameters on warfarin extraction, for example, type and volume of elution solvent, pH of sample solution, breakthrough volume and maximum loading capacity, were studied. The limits of detection were in the range of 0.0035–0.0050 µg mL^?1. Linearity of the method was determined in the range of 0.0165–10.0000 µg mL^?1 for plasma and 0.0115–10.0000 µg mL^?1 for urine with coefficients of determination (R²) ranging from 0.9975 to 0.9985. The recoveries for plasma and urine samples were >95%. Copyright © 2015 John Wiley & Sons, Ltd.     

选择性提取单取代磺酰脲除草剂的印迹聚合物的合成及评价

以丙烯酰胺为功能单体合成了新型的单嘧磺隆印迹聚合物,用平衡吸附及液相色谱的方法研究了印迹聚合物对于印迹分子及其结构类似化合物NK#94827的识别特性及亲和能力.研究结果表明,以丙烯酰胺为功能单体得到的印迹聚合物对NK#94827具有较强的识别能力;为印迹聚合物应用于环境样品中NK#94827及其结构类似化合物的分析打下了基础.     

Laboratory to Laboratory Reproducibility of High Performance Liquid Chromatographic Retention Indices

Abstract

Using seven typical drugs, the intra-and inter-laboratory reproducibility of the measured HPLC retention indices, relative retention times, and adjusted relative retention times using the same mobile phase and various reversed-phase C-18 columns were determined. Within a given laboratory, the respective relative standard deviations were ± 0.99%, ± 1.78%, and ± 2.63%. Between laboratories, the respective relative standard deviations were found to be ± 12.6%, ± 30.2%, and ± 34.8%. These results indicated that the HPLC retention index scale may be more useful in comparing data between laboratories.     

Chiral separation of racemic mandelic acids by use of an ionic liquid-mediated imprinted monolith with a metal ion as self-assembly pivot

A new chiral stationary phase based on molecularly imprinted polymers (MIP) was prepared in ionic liquid by use of the metal pivot concept. Imprinted monoliths were synthesized by use of a mixture of R-mandelic acid (template), 4-vinylpyridine, ethylene glycol dimethacrylate, and several metal ions as pivot between the template and functional monomer. A ternary mixture of dimethyl sulfoxide–dimethylformamide–[BMIM]BF₄ containing metal ions was used as the porogenic system. Separation of the enantiomers of rac-mandelic acid was successfully achieved on the MIP thus obtained, with resolution of 1.87, whereas no enantiomer separation was observed on the imprinted monolithic column in the absence of metal ions. The effects of polymerization conditions, including the nature of the metal ion and the ratios of template to metal ions and template to functional monomer, on the chiral separation of mandelic acid were investigated. The results reveal that use of metal ions as a pivot, in combination with ionic liquid, is an effective method for preparation of a highly efficient MIP stationary phase for chiral separation.