Cyclodextrins Cyclodextrin-type compound

Fig. 7. Schemes of crystalline cyclodextrin inclusion compounds (a) channel type (b) cage herringbone type (c) cage brick type (58).

Fig. 2 Influence of cyclodextrin type on the chiral resolution of the basic drug tocainide and related substances using 40 mM sodium phosphate (pH 3.0) containing (a) 20 mM -CD and (b) 50 mM methyl- -CD and 50 mM heptakis (2,6 di-O-methyl-jS-CD. [Adopted with kind permission from D. Beider and G. Schomburg, Chiral separations of basic and acidic compounds in modified capillaries using cyclodextrin-modified capillary zone electrophoresis, J. Chromatogr. A 666 351 (1994).]...

The chemistry of inclusion compounds also looks back on a lively history There are many events of significance in the area of inclusion chemistry till the middle of the twentieth century including the discovery of new inclusion compounds and hosts (Fig. 1), among them the graphite intercalates, the P-quinol and cyclodextrin inclusion compounds, the Hofmann-type clathrates as well as the inclusion compounds of tri-o-thymotide, Dianin s compound, the choleic acids, of phenols, of urea and others specified in comprehensive monographs... 

Cyclotriveratrylene, by analogy with calixarenes, cyclodextrins and a few other cyclophane-type compounds, can be used as a matrix to preorganize coordination sites for transition metals, either at the edge of the rigid structure, or around an expanded CTV s cavity. Achiral 2- and 3-pyridine tripod ligands have been synthesized together with a bipyridine multichelate. Studies of these new ligands, both by... 

Packing of the cyclodexthn molecules (a, P, P) within the crystal lattice of iaclusion compounds (58,59) occurs in one of two modes, described as cage and channel stmctures (Fig. 7). In channel-type inclusions, cyclodextrin molecules are stacked on top of one another like coins in a roU producing endless channels in which guest molecules are embedded (Fig. 7a). In crystal stmctures of the cage type, the cavity of one cyclodextrin molecule is blocked off on both sides by neighboring cyclodextrin molecules packed crosswise in herringbone fashion (Fig. 7b), or in a motif reminiscent of bricks in a wall (Fig. 7c). 

GC using chiral columns coated with derivatized cyclodextrin is the analytical technique most frequently employed for the determination of the enantiomeric ratio of volatile compounds. Food products, as well as flavours and fragrances, are usually very complex matrices, so direct GC analysis of the enantiomeric ratio of certain components is usually difficult. Often, the components of interest are present in trace amounts and problems of peak overlap may occur. The literature reports many examples of the use of multidimensional gas chromatography with a combination of a non-chiral pre-column and a chiral analytical column for this type of analysis. 

The type of CSPs used have to fulfil the same requirements (resistance, loadabil-ity) as do classical chiral HPLC separations at preparative level [99], although different particle size silica supports are sometimes needed [10]. Again, to date the polysaccharide-derived CSPs have been the most studied in SMB systems, and a large number of racemic compounds have been successfully resolved in this way [95-98, 100-108]. Nevertheless, some applications can also be found with CSPs derived from polyacrylamides [11], Pirkle-type chiral selectors [10] and cyclodextrin derivatives [109]. A system to evaporate the collected fractions and to recover and recycle solvent is sometimes coupled to the SMB. In this context the application of the technique to gas can be advantageous in some cases because this part of the process can be omitted [109]. 

Mourier s report was quickly followed by successful enantiomeric resolutions on stationary phases bearing other types of chiral selectors, including native and deriva-tized cyclodextrins and derivatized polysaccharides. Many chiral compounds of pharmaceutical interest have now been resolved by packed column SFC, including antimalarials, (3-blockers, and antivirals. A summary is provided in Table 12-2. Most of the applications have utilized modified CO, as the eluent. 

The problem of molecular recognition has attracted biologically oriented chemists since Emil Fischer s lock-and-key theory l0). Within the last two decades, many model compounds have been developed micelle-forming detergents11, modified cyclodextrins 12), many kinds of crown-type compounds13) including podands, coronands, cryptands, and spherands. Very extensive studies using these compounds have, however, not been made from a point of view of whether or not shape similarity affects the discrimination. 

Many racemic mixtures can be separated by ordinary reverse phase columns by adding a suitable chiral reagent to the mobile phase. If the material is adsorbed strongly on the stationary phase then selectivity will reside in the stationary phase, if the reagent is predominantly in the mobile phase then the chiral selectivity will remain in the mobile phase. Examples of some suitable additives are camphor sulphonic acid (10) and quinine (11). Chiral selectivity can also be achieved by bonding chirally selective compounds to silica in much the same way as a reverse phase. A example of this type of chiral stationary phase is afforded by the cyclodextrins. 

The theory and development of a solvent-extraction scheme for polynuclear aromatic hydrocarbons (PAHs) is described. The use of y-cyclodextrin (CDx) as an aqueous phase modifier makes this scheme unique since it allows for the extraction of PAHs from ether to the aqueous phase. Generally, the extraction of PAHS into water is not feasible due to the low solubility of these compounds in aqueous media. Water-soluble cyclodextrins, which act as hosts in the formation of inclusion complexes, promote this type of extraction by partitioning PAHs into the aqueous phase through the formation of complexes. The stereoselective nature of CDx inclusion-complex formation enhances the separation of different sized PAH molecules present in a mixture. For example, perylene is extracted into the aqueous phase from an organic phase anthracene-perylene mixture in the presence of CDx modifier. Extraction results for a variety of PAHs are presented, and the potential of this method for separation of more complex mixtures is discussed. 

Metalated container molecules can be viewed as a class of compounds that have one or more active metal coordination sites anchored within or next to a molecular cavity (Fig. 2). A range of host systems is capable of forming such structures. The majority of these compounds represent macrocyclic molecules and steri-cally demanding tripod ligands, as for instance calixarenes (42), cyclodextrins (43,44), and trispyrazolylborates (45-48), respectively. In the following, selected types of metalated container molecules and their properties are briefly discussed and where appropriate the foundation papers from relevant earlier work are included. Porphyrin-based hosts and coordination cages with encapsulated metal complexes have been reviewed previously (49-53) and, therefore, only the most recent examples will be described. Thereafter, our work in this field is reported. 

Many chiral compounds can be used as selectors, for example, chiral metal complexes, native and modified cyclodextrins, crown ethers, macrocyclic antibiotics, noncyclic oligosaccharides, and polysaccharides all have been shown to be useful for efficient separation of different types of compounds. 

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