Constantina P. Kapnissi-Christodoulou

Chiral selectors in CE: Recent developments and applications

This review article provides an overview of the recent advances in enantioanalysis by use of electrophoretic techniques. Due to the big number of publications in the subject mentioned above, this article is focused on chiral method developments and applications published from 2008 until 2011, and it demonstrates chiral selectors used in CE. Numerous chiral selectors have been used over the years, and these include the cyclic and the linear oligo‐ and polysaccharides, the branched polysaccharides, the polymeric and monomeric surfactants, the macrocyclic and other antibiotics, and the crown ethers. Different dual‐selector systems are also presented in this article, and the results are compared with those obtained by use of a single chiral selector. Finally, several pharmaceutical and biomedical applications based on chiral recognition are summarized.

Chiral selectors in CE: recent developments and applications (2012-mid 2014).

There is a large number of chiral selectors (CSs) that have, over the years, been synthesized and used in electrophoretic enantioseparations. This report highlights the most important CSs applied in CE during the period 2012 to mid‐2014. It is mainly focused on method developments and validations, along with pharmaceutical and biomedical applications. Even though numerous publications have, through the years, reported the utilization of CSs in enantioseparations, only the ones applied in electrophoretic techniques the last approximately three years are demonstrated in this review article. In particular, cyclodextrins, cyclofructants, linear and branched oligo‐ and polysaccharides, antibiotics, and polymeric surfactants are presented, and their advantages, their chiral recognition mechanisms, and their performance are discussed.

Chiral ionic liquids in chromatographic and electrophoretic separations

This report provides an overview of the application of chiral ionic liquids (CILs) in separation technology, and particularly in capillary electrophoresis and both gas and liquid chromatography. There is a large number of CILs that have been synthesized and designed as chiral agents. However, only a few have successfully been applied in separation technology. Even though this application of CILs is still in its early stages, the scientific interest is increasing dramatically. This article is focused on the use of CILs as chiral selectors, background electrolyte additives, chiral ligands and chiral stationary phases in electrophoretic and chromatographic techniques. Different examples of CILs, which contain either a chiral cation, a chiral anion or both, are presented in this review article, and their major advantages along with their potential applications in chiral electrophoretic and chromatographic recognition are discussed.

Use of chiral amino acid ester-based ionic liquids as chiral selectors in CE

In this study, the applicability of a chiral ionic liquid (CIL) as the sole chiral selector in CE was investigated for the first time. In particular, five amino acid ester‐based CILs were synthesized and used as additives in the BGE in order to evaluate their chiral recognition ability. The performance of these CILs as the sole chiral selectors was evaluated by using 1,1′‐binaphthyl‐2,2‐diylhydrogenphosphate (BNP) as the analyte and by comparing the resolution values. Different parameters were examined, such as the alkyl group bulkiness and the configuration of the cation, the anion type of the CIL and its concentration, and the pH of the BGE, in order to optimize the separation of the enantiomers and to demonstrate the effect that each parameter has on the chiral‐recognition ability of the CIL. Baseline separation of BNP within 13 min was achieved by using a BGE of 100 mM Tris/10 mM sodium tetraboratedecahydrate (pH 8) and a chiral selector of 60 mM l‐alanine tert butyl ester lactate. The run‐to‐run and batch‐to‐batch reproducibilities were also evaluated by computing the %RSD values of the EOF and the two enantiomer peaks. In both cases, very good reproducibilities were observed, since all %RSD values were below 1%.

Tranilast-induced stress alleviation in solid tumors improves the efficacy of chemo- and nanotherapeutics in a size-independent manner

Accumulation of mechanical stresses during cancer progression can induce blood and lymphatic vessel compression, creating hypo-perfusion, hypoxia and interstitial hypertension which decrease the efficacy of chemo- and nanotherapies. Stress alleviation treatment has been recently proposed to reduce mechanical stresses in order to decompress tumor vessels and improve perfusion and chemotherapy. However, it remains unclear if it improves the efficacy of nanomedicines, which present numerous advantages over traditional chemotherapeutic drugs. Furthermore, we need to identify safe and well-tolerated pharmaceutical agents that reduce stress levels and may be added to cancer patients’ treatment regimen. Here, we show mathematically and with a series of in vivo experiments that stress alleviation improves the delivery of drugs in a size-independent manner. Importantly, we propose the repurposing of tranilast, a clinically approved anti-fibrotic drug as stress-alleviating agent. Using two orthotopic mammary tumor models, we demonstrate that tranilast reduces mechanical stresses, decreases interstitial fluid pressure (IFP), improves tumor perfusion and significantly enhances the efficacy of different-sized drugs, doxorubicin, Abraxane and Doxil, by suppressing TGFβ signaling and expression of extracellular matrix components. Our findings strongly suggest that repurposing tranilast could be directly used as a promising strategy to enhance, not only chemotherapy, but also the efficacy of cancer nanomedicine.

Combined use of cyclofructans and an amino acid ester-based ionic liquid for the enantioseparation of huperzine A and coumarin derivatives in CE

Cyclofructans (CFs) and their derivatives have recently been proven to be efficient chiral selectors (CSs) for the enantioseparation of several analytes in CE, HPLC, and GC. In this study, the chiral separation ability of a number of native and derivatized CFs was examined in CE. Particularly, six different CFs, with different derivatization groups and cavity sizes [native CF‐6 and CF‐7, isopropyl cyclofructan‐6 (IPCF‐6), IPCF‐7, sulfated cyclofructan‐6 (SCF‐6), and SCF‐7] were used as CSs for the enantioseparation of huperzine A, warfarin, and coumachlor. Almost all of the examined CFs, except from SCF‐6 & ‐7, demonstrated relatively low and sometimes no chiral separation ability for huperzine A. In an effort to improve both resolution and efficiency, the chiral ionic liquid D‐Alanine tert butyl ester lactate (D‐AlaC4Lac) was added into the BGE. In most of the cases, the combination of CF with D‐AlaC4Lac resulted in an improvement in peak efficiency and/or resolution. When CF‐6 was utilized with D‐AlaC4Lac, a resolution of 1.4 was obtained, while the use of IPCF‐6/D‐AlaC4Lac provided a baseline enantioseparation. Although the combination of SCF‐7 and 40 mM D‐AlaC4Lac did not affect resolution, it dramatically increased peak efficiency from 24 000 to 117 000. In the case of warfarin and coumachlor, IPCF‐6 and IPCF‐7 proved to be the most effective CSs. It is, therefore, concluded that the size of the cavity and the CF derivatization are the key parameters for the chiral separation capability. It is also clear from this study that D‐AlaC4Lac is necessary for improved peak efficiencies and resolutions.

Facile preparation of polysaccharide-coated capillaries using a room temperature ionic liquid for chiral separations

In this study, the dissolution of polysaccharides into an ionic liquid was investigated and applied as a coating onto the capillary walls of a fused‐silica capillary in open‐tubular CEC. The coating was evaluated by examining the chiral separation of two analytes (thiopental, sotalol) with three cellulose derivatives (cellulose acetate, cellulose acetate phthalate, and cellulose acetate butyrate). Baseline separation of thiopental enantiomers was achieved by use of each polysaccharide coating (Rs: 7.0, 8.1, 7.1), while sotalol provided partial resolution (Rs: 0.7, 1.0, 0.9). In addition, reproducibility of the cellulose‐coated capillaries was evaluated by estimating the run‐to‐run and capillary‐to‐capillary RSD values of the EOF. Both stability and reproducibility were very good with RSD values of less than 7%.

Analysis of polyphenols using capillary zone electrophoresis - determination of the most effective wine sample pre-treatment method.

A simple CZE method has been developed for the simultaneous determination of eight polyphenolic compounds. The influence of several experimental conditions such as buffer (concentration and pH) and temperature were studied. Optimum separation was achieved in less than 25 min by using a BGE of 50 mM Na2B4O7 and 10 mM Na2HPO4 at pH 9.6, a temperature of 25°C and an applied voltage of 25 kV. Good linearities for all eight analytes were obtained with correlation coefficients higher than 0.99. The LODs were between 0.03 and 5.05 μg/mL and the RSD values of the migration times were found to be less than 1%. The optimal separation conditions were then used for the identification and the quantitation of polyphenolic compounds in Cypriot wine samples using six different sample preparation procedures. In particular, two direct injection methods (without any extraction step), three different liquid–liquid extraction procedures and an SPE procedure were examined. These sample pre‐treatment methods were also compared in order to determine the one that is the most effective, in regard to analyte recovery, time, difficulty, and reproducibility. Liquid–liquid extraction using diethyl ether as the organic solvent proved to be the most effective.

Enantioseparations in open-tubular capillary electrochromatography: Recent advances and applications.

This review highlights recent advances and applications in open-tubular capillary electrochromatography (OT-CEC) for enantioseparations during the last decade. Although extensive research has been conducted in the area of separations by use of CEC, and a big number of reviews have been published, there is not a review on exclusively the use of chiral stationary phases (CSPs) in OT-CEC for enantioseparations. Therefore, in this review, the design and synthesis of different CSPs are presented, and their potential applications in OT-CEC for enantioseparations are discussed. The different approaches to CSP development include chiral nanomaterials, porous layers, molecular imprinting, sol-gel technique, polyelectrolyte multilayer coating, polymeric coating and others.

Chiral separation of Huperzine A using CE - method validation and application in pharmaceutical formulations.

The aim of this work is the development, validation and application of an MEKC method for the chiral separation of Huperzine A. Huperzine A is an important compound that is used to treat Alzheimers disease. However, only the (−)‐form of this compound is biologically active and behaves as a potential acetylcholinesterase inhibitor. Therefore, the separation of the (−)‐form from the (+)‐form is of greatest importance. Optimal conditions, regarding resolution and analysis time, were established by altering several experimental parameters, such as temperature, field strength, pH, type and concentration of BGE and chiral selector. A major problem that had to be solved in this study was the low intensity and efficiency of the peaks. More parameters were examined, such as the addition of modifiers, to optimize further the separation, and particularly the efficiency. Baseline enantioseparation was achieved by using a BGE of 50 mM acetate (pH 5.0), supplemented with 0.2% w/v poly(sodium N‐undecanoyl‐ll‐alanyl‐valinate) and 10% v/v tert‐butanol. Finally, the optimum conditions were applied to a pharmaceutical formulation, to demonstrate the ability of the method to control the purity of the (−)‐Huperzine A in pharmaceutical formulations.