Selector optical

Figure B2.1.1 Femtosecond light source based on an amplified titanium-sapphire laser and an optical parametric amplifier. Symbols used P, Brewster dispersing prism X, titanium-sapphire crystal OC, output coupler B, acousto-optic pulse selector (Bragg cell) FR, Faraday rotator and polarizer assembly DG, diffraction grating BBO, p-barium borate nonlinear crystal.

Traditionally, chiral separations have been considered among the most difficult of all separations. Conventional separation techniques, such as distillation, Hquid—Hquid extraction, or even some forms of chromatography, are usually based on differences in analyte solubiUties or vapor pressures. However, in an achiral environment, enantiomers or optical isomers have identical physical and chemical properties. The general approach, then, is to create a "chiral environment" to achieve the desired chiral separation and requires chiral analyte—chiral selector interactions with more specificity than is obtainable with conventional techniques. 

Enantiomeric separations have become increasingly important, especially in the pharmaceutical and agricultural industries as optical isomers often possess different biological properties. The analysis and preparation of a pure enantiomer usually involves its resolution from the antipode. Among all the chiral separation techniques, HPLC has proven to be the most convenient, reproducible and widely applicable method. Most of the HPLC methods employ a chiral selector as the chiral stationary phase (CSP). 

The screening of libraries of compounds for the desired property constitutes an essential part of the combinatorial process. The easier and the faster the screening, the higher the throughput and the more compounds can be screened in a unit of time. This paradigm has led Still s group to develop a combinatorial approach to chiral selectors that involves a visual screening step by optical microscopy that enables the manual selection of the best candidates [81]. 

Figure 5.6. Diagram of a low-energy, high-angle electron-impact spectrometer. (A) Electron gun (B) monochromator (180° spherical electrostatic energy selector) (C) electron optics (D) scattering chamber (E) analyzer (180° spherical electrostatic energy selector) (F) electron multiplier (G) amplifier and pulse discriminator (H) count-rate meter (I) multichannel scaler (J) X Y recorder (K) digital recorder. (After Kupperman et a/.<42))...

A few synthetic helical polymers are known to act as chiral selectors.7a,918d l8k i9d i9h ancj are widely used as chiral stationary phases (CSP) in gas or liquid chromatography.73,53 Recently, it has been reported that the preference of one helical sense in isotropic solution can be induced by some interaction between optically inactive polymers and chiral solvents/additives. Examples of this include poly(n-hexyl isocyanate)18d l8k and poly(phenylacetylene)s bearing functional group.19d 19h The polysilane derivatives also show chiral recognition ability in solution at room temperature. Poly(methyl-ft-pinanylsilane) includes two chiral centers per bulky hydrophobic pinanyl side group28 and... 

When micelles are used, the CE technique becomes a micellar elec-trokinetic chromatography (MEKC) one. Natural surfactants, such as bile salts, digitonin and saponins, optically active synthetic surfactants, e.g., amino-acid derived ones, alkylglycoside-, tartaric acid- and steroidal glucoside-based surfactants, and high-molecular mass or polymerized surfactants, have been used as chiral selectors in In the lat-... 

The concentration of the chiral selector, for instance, has considerable influence on the mobility and separation of the enantiomers. Optical resolution varies with the chiral selector concentration and reaches a maximum value at a given optimum concentration. Wren and Rowe proposed a model that describes the influence of the selector concentration on selectivity, and which was extended by Vigh s group ° by including the pH as a separation parameter for weak acidic enantiomers. The latter model shows that the chiral selectivity is determined by the complex s relative mobility, the CD concentration, the degree of dissociation... 

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. 

As discussed earlier, the concepts of chiral chromatography can be divided into two groups, the indirect and the direct mode. The indirect technique is based on the formation of covalently bonded diastereomers using an optically pure chiral derivatizing agent (CDA) and reacting it with the pair of enantiomers of the chiral analyte. The method of direct enantioseparation relies on the formation of reversible quasi diastereomeric transient molecule associates between the chiral selector, e.g., i /t)-SO, and the enantiomers of the chiral selectands, [R,S)-SAs [(Ry SA + (S)-SA] (Scheme 1). 

As stated earlier, this technique relies essentially on the formation of covalently bonded diastereomers derived from a pair of chiral analytes (SAs pair of enantiomers) which have been converted to a pair of diastereomers using an optically pure chiral derivatizing agent (CDA) which, in this case, serves as a chiral selector (SO). In this context the definition of " optical purity of the CDA is critical (see Section 3.2.1.2.) and has to be evaluated by complementary methods. 

However, in order to separate enantiomers via formation of diastereomers, the chiral selector (CDA) must be optically pure, e.g., 99.9% of ( )-SO, otherwise the separated diastereomeric reaction products will still be contaminated with the reaction products derived from (S)-SO, leading to optically impure reaction products (mixture of enantiomers) and false results when evaluating the optical purity data of the analyte. 

Another method for creating a chiral environment is lo add an optically pure chiral selector to a bulk liquid phase. Chiral additives have several advanlages over chiral stationary phases and continue lo be the predominant mode for chiral separations by tic and capillary electrophoresis (cc). First of all, the chiral selector added to a bulk liquid phase can be readily changed. The use of chiral additives allows chiral separations lo be done using less expensive, conventional stationary phases. A wider variety of chiral selectors are available [ be used as chiral additives than are available as chiral stationary phases, thus, providing the analyst with considerable flexibility. Finally, the use of chiral additives may provide valuable insight into (he chromatographic conditions and/or likelihood ol success with a potential chiral stationary-phase chiral selector. This is particularly important for the development of new chiral stationary phases because of the difficulty and cosl involved. 

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