Enantioselective adsorption of racemic mixtures is crucial for therapeutic drug purification and synthesis. Pure enantiomeric precursors are needed for the recent emphasis on direct synthesis of pure enantiomers that precludes synthesis and subsequent resolution of racemic mixtures. Layered clays can be modified to resolve racemic mixtures. Clays have a substantial potential because they have large adsorptive capacities, their interactions with molecules can be designed to be quite selective, and they are insoluble in aqueous, polar, and non-polar solvents. The last advantage is important for the actual physical separation step. Resolution with clays is direct chromatography which is preferred to the classical multi-step derivatization technique where losses of product are compounded at each step. Another advantage with clays is that they can be designed to be porous to address a major problem in racemic drug resolution that other methods cannot attack. The ideal Pirkle, enantiomer recognition interactions are chiral three-point attractive interactions between drug and adsorbent. However, many therapeutic drugs are enantiomeric and yet not all of the three sites of recognition have functional groups for attractive interactions; i.e., one or two of the branches on the chiral center may be alkyl in nature. Porous clays may be useful in this regard because they have the advantage of size and shape exclusion. This repulsive selectivity can be one of the three chiral recognition interactions; this is not possible with many of the commercial adsorbents. Preliminary bulk studies have shown some modified clays that produce quantitative resolution of racemic mixtures. Physicochemical measurements of clay-adsorbate interactions need to be made. The relation of modified clay structure to enantiomeric selectivity needs further investigation and the bulk studies will be converted to accepted chromatographic techniques.
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