Chiral solid stationary phases

Enantiomer separation becomes very easy when a column with a solid chiral stationary phase (CSP) able to separate a given enantiomer pair is available. Unfortunately, there is no universal phase for solving all separation problems and it is impossible that there ever will be. However, an immense number of CSPs have been developed and many of them are commercially available. A good deal of literature has also been published, from which a promising phase can usually be selected. Sometimes, the sample can be adapted to the phase by nonchiral derivatization. The most important CSPs are listed in Table 22.1. They are based on very different separation principles and can be grouped as follows  

TABLE 22.1 Some chiral stationary phases for HPLC  

Bovine serum albumin Human serum albumin a i-Acid glycoprotein Ovomucoid Avidin 

Section 7.5 outlined how silica can be derivatized with almost any functional group the resulting monomer structures are known as brushes . The first broadly used and still very important CSP is the brush-type dinitrobenzoylphenylglycine (DNBPG), the first one shown in Table 22.1. According to its inventor, William H. Pirkle, it is often called Pirkle-phase , although a more correct name is Pirkle T because it is not the only one of his phases that is on the market. 

Advances in Chromatography, P.R. Brown andE. Grushka, eds, 35,171 (1995) R Gasparrini, 

The DNBPG phase has a number of features which are typical for almost all of the brush-type CSPs. It has two amide groups which are rigid (planar) therefore the whole chiral moiety will prefer a limited (i.e. not an unlimited) number of conformations which is important for chiral recognition. The amide 

N aphthylethylurea Helical polymer phases Cellulose triacetate 

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The use of a chiral solid stationary phase (usually termed chiral stationary phase, CSP). 

With chiral affinity phases, proteins undergo enantioselective interactions with a great variety of drugs. Thus, the resolution on chiral affinity stationary phases is due to interactions of the enantiomers with proteins bonded to the solid support. Typical proteins used for chiral affinity separa-... 

The Adsorption of a Chiral Reagent on the Surface of a Solid Stationary Phase... 

New ILs and coating methods are being developed for high efficiency and high thermostability GC columns. Chiral GC stationary phases with high thermo-stability and broad enantiomeric selectivity are needed. One area that will continue to grow in imp>ortance is the use of ILs as absorbents in solid-phase extractions (SPE) and solid-phase micro-extractions (SPME). It is likely that ILs will fill the role of a polar absorbent for these techniques [Han Armstrong, 2007]. 

Separation of enantiomers by physical or chemical methods requires the use of a chiral material, reagent, or catalyst. Both natural materials, such as polysaccharides and proteins, and solids that have been synthetically modified to incorporate chiral structures have been developed for use in separation of enantiomers by HPLC. The use of a chiral stationary phase makes the interactions between the two enantiomers with the adsorbent nonidentical and thus establishes a different rate of elution through the column. The interactions typically include hydrogen bonding, dipolar interactions, and n-n interactions. These attractive interactions may be disturbed by steric repulsions, and frequently the basis of enantioselectivity is a better steric fit for one of the two enantiomers. ... 

In addition to the development of the powerful chiral additive, this study also demonstrated that the often tedious deconvolution process can be accelerated using HPLC separation. As a result, only 15 libraries had to be synthesized instead of 64 libraries that would be required for the full-scale deconvolution. A somewhat similar approach also involving HPLC fractionations has recently been demonstrated by Griffey for the deconvolution of libraries screened for biological activity [76]. Although demonstrated only for CE, the cyclic hexapeptides might also be useful selectors for the preparation of chiral stationary phases for HPLC. However, this would require the development of non-trivial additional chemistry to appropriately link the peptide to a porous solid support. 

The mixture of deprotected amino acid derivatives in solution was then immobilized onto a polymeric solid support, typically activated 5-)xm macroporous poly(hydroxyethyl methacrylate-co-ethylene dimethacrylate) beads, to afford the chiral stationary phases with a multiplicity of selectors. Although the use of columns... 

The mixture was extracted with diethyl ether (three times). The combined organic layers were washed with brine and dried over sodium sulfate. After concentration in vacuo, the residue was purified by silica gel flash column chromatography (hexane/ethyl acetate = 20/1-3/1) to give (5)-l (426.3 mg, 74%, 98% ee) as a colourless solid. The enantiomeric excess of (5)-l was determined by chiral stationary-phase HPLC analysis DAICEL CHIRALCEL OD-H, j-PrOH/hexane 1/4, flow rate l.OmLmin tR 14.0 min [(R)-isomer)] and 21.3 min [(5)-isomer), detection at 254 nm]. ... 

Cyclodextrin stationary phases utilize cyclodextrins bound to a solid support in such a way that the cyclodextrin is free to interact with solutes in solution. These bonded phases consist of cyclodextrin molecules linked to silica gel by specific nonhydrolytic silane linkages (5,6). This stable cyclodextrin bonded phase is sold commercially under the trade name Cyclobond (Advanced Separation Technologies, Whippany, New Jersey). The vast majority of all reported hplc separations on CD-bonded phases utilize this media which was also the first chiral stationary phase (csp) developed for use in the reversed-phase mode. 

On the other hand, the direct chromatographic approach involves the use of the chiral selector either in the mobile phase, a so-called chiral mobile phase additive (CMPA), or in the stationary phase [i.e., the chiral stationary phase (CSP)]. In the latter case, the chiral selector is chemically bonded or coated or allowed to absorb onto a suitable solid support. Of course chiral selectors still can be used as CMPAs, but the approach is a very expensive one owing to the high amount of chiral selector required for the preparation of the mobile phase, and the large amount of costly chiral selector that is wasted (since there is very little chance of recovering this compound). Moreover, this approach is not successftd in the preparative separation of the enantiomers. 

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