Micelles chiral

An extremely important aspect in pharmaceutical research is the determination of drug optical purity. The most frequently applied technique for chiral separations in CZE remains the so-called dynamic mode where resolution of enantiomers is carried out by adding a chiral selector directly into the BGE for in situ formation of diastereomeric derivatives. Various additives, such as cyclodextrins (CD), chiral crown ethers, proteins, antibiotics, bile salts, chiral micelles, and ergot alkaloids, are reported as chiral selectors in the literature, but CDs are by far the selectors most widely used in chiral CE. 

Zhao L, Wang X, Li Y et al (2009) Chiral micelles of achiral TPPS and diblock copolymer induced by amino acids. Macromolecules 42 6253-6260... 

Conceptually. CE enantioseparations are mainly applied to charged SAs. Micellar electrokinetic chromatography (MEKC) (introduced by Terabe et al. in 1984 488 ), in contrast, permits the separation of electrically neutral compounds. In enantiomer separation by MEKC. ionic pseudo-stationary phases, such as chiral micelles composed of chiral SO moieties, which migrate according to their electrophoretic mobility, may interact stereoselectively with the solutes to be separated. MEKC with synthetic (e.g. A-dodecoxycarbonylvalines, commercialized as SDVal by Waters) 1489.490) or naturally occurring chiral surfactants (e.g. bile salts) 1491-494). and cyclodextrin-moditied MEKC (most often SDS/CD combinations) 1495-498) are the mo.st widely used selector systems in MEKC. The topic of MEKC enantioseparation has been reviewed by Nishi )499). 

Similarities between CD and absorbance methods are also found between CD and fluorescence and CD and circularly polarized luminescence (CPL). Three prerequisites are needed to produce FDCD and CPL activities. Intense emission signals normally associated with fluorescence are attractive because limits of detection are lowered considerably. FDCD finds more uses as a chromatographic detection device. A CD signal is usually induced by some kind of molecular complexation reaction. Association can be with a simple molecule or with an aggregate of molecules, such as chiral micelles, which are known to be fluorescence enhancers. In cases of color induction combined with fluorescence induction, FDCD can lead to even higher levels of selectivity among analytes that have been derivatized by the same color reagent. 

Mechref, Y. El Rassi, Z. Micellar electrokinetic capillary J chromatography with in-situ charged micelles VI. Eval- Q uation of novel chiral micelles consisting of steroidal- glycoside surfactant-borate complexes. J. Chromatogr., A S... 

Chiral Separations by Micellar Electrokinetic Chromatography with Chiral Micelles... 

Since micellar electrokinetic chromatography (MEKC) was hrst introduced in 1984, it has become one of major separation modes in capillary electrophoresis (CE), especially owing to its applicability to the separation of neutral compounds as well as charged ones. Chiral separation is one of the major objectives of CE, as well as MEKC, and a number of successful reports on enantiomer separations by CE and MEKC has been published. In chiral separations by MEKC, the following two modes are normally employed (a) MEKC using chiral micelles and (b) cyclodextrin (CD)-modilied MEKC (CD-MEKC ... 

An ionic chiral micelle is used as a pseudo-stationary phase it works as a chiral selector. When a pair of enantiomers is injected to the MEKC system, each enantiomer is incorporated into the chiral micelle at a certain extent determined by the micellar solubilization equilibrium. The equilibrium constant for each enantiomer is expected to be different more or less among the enantiomeric pair that is, the degree of solubilization of each enantiomer into the chiral micelle would be different for each. Thus, the difference in the retention factor would be obtained and different migration times would occur. 

In some cases, an ionic chiral micelle (e.g., a bile salt) is also used as a chiral pseudo-stationary phase with a CD. Moreover, cyclodextrin electrokinetic chromatography (CDEKC), where a CD derivative having an ionizable group is used as a chiral pseudo-stationary phase, has become popular recently since several commercially available ionic CD derivatives have appeared. Although the CDEKC technique is actually beyond the field of MEKC, it is an important method for enantiomer separation by CE. 

In this section, chiral separation by MEKC with chiral micelles is mainly treated. The development of novel chiral surfactants adaptable to pseudo-stationary phases in MEKC for enantiomer separation is continuously progressing. It seems somewhat difficult for a researcher to find an appropriate mode of CE when one wants to achieve a specific enantioseparation. However, nowadays, various method development kits for chiral separation have been commercially available and some literature on the topic is also available, so that helpful information may be obtained without difficulty. 

Also, it is expected that the micellar size is controlled easier than with a conventional low-molecular-mass surfactant (EMMS). The first report on enantiomer separation by MEKC using a chiral HMMS appeared in 1994, where poly(sodium A-undecylenyl-L-valinate) [poly(L-SUV)] was used as a chiral micelle and binaphthol and laudanosine were enantioseparated. The optical resolution of 3,5-dinitrobenzoylated amino acid isopropyl esters by MEKC with poly(sodium (10-undecenoyl)-L-valinate) as well as with SDVal, SDAla, and SDThr was also reported. 

Chiral surfactants The chiral separation of anal5des is based on their partition coefficients between the chiral micelle phase and the electrolyte bulk phase. Alkylglucosides, alkylmaltoside, sodium cholate, saponines, sodium dodecyl sulfate, sodium taurocholate. Ephedrine, fenoldopam, hexobarbital, ketamine, pindolol, timolol, etc. 

Various chiral selector additives, such as chiral crown ethers, proteins, antibiotics, bile salts, chiral micelles and ergot alkaloids, have been reported in the literature [15-17]. An extensive review of the numerous selectors of CE is outside the scope of the present chapter. Nevertheless, CDs are by far the most widely used selectors in chiral CE. CD are nonionic cychc oligosaccharides consisting of six, seven or eight glucose units and are called a-, [i-, and y-CD, respectively. 

Less successful was the use of achiral catalysts in chiral micelles. The induced enantioselectivity in the resulting a-amino acid derivatives was in all cases below 10% ee depending on the type of amphiphile [59]. Other asymmetric reac-... 

J Wang, IM Warner. Combined polymerized chiral micelle and gamma-cyclodextrin for chiral separation in capillary electrophoresis. J Chromatogr A 711 297— 304, 1995. 

There are many types of chiral selectors that have been applied to the separation of enantiomers by CE, but the most common are native and derivatized CDs. Other chiral selectors, which have been applied to CE separations, include natural and synthetic chiral micelles, crown ethers, chiral ligands, proteins, peptides, carbohydrates, and macrocyclic antibiotics [105,111-114]. A review by Blanco and Valverde [114] describes the separation capabilities of various chiral selectors and provides criteria for their choice in terms of molecular size, charge, and the presence of specific functional groups or substructures in the analytes. 

Various V-alkanoyl-L-amino acids, such as sodium N-dodecanoyl-L-valinate (SDVal), sodium V-dodecanoyl-L-alaninate (SDAla), sodium V-dodecanoyl-L-glutamate (SDGlu), V-dodecanoyl-L-serine (DSer), V-dodecanoyl-L-aspartic acid (DAsp), sodium V-tetradecanoyl-L-glutamate (STGlu), and sodium V-dodecanoyl-L-threoninate (SDThr) have been employed as synthetic chiral micelles in MEKC several enantiomers have been successfully separated (Fig. 1). In each case, the addition of SDS, urea, and organic modifiers such as methanol or 2-propanol were essential to obtain improved peak shapes and enhanced enantioselectivity. 

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