Chirality
decongestant as opposed to dextro-methamphetamine, an illegal drug known for its addictiveness and potent euphoric effect. The need for separation is crucial if only a specific enantiomer is sought. Nevertheless, thalidomide epitomizes the dangers that chirality can pose because it racemizes in vivo . Conventionally, thalidomide was sold as a racemic mixture: the R-isomer was used for treating morning sickness. On the contrary, the teratogenic S-isomer causes congenital disabilities for pregnant women when giving birth to their babies. Prior to Pasteur’s separation, the foundation for his discovery of chirality was built on Jean Baptiste Biot’s discovery of the abi lity of tartaric acid to rotate polarized light. Moving on from this, when Pasteur observed the differences in the shapes of crystals, he noticed that some crystals were mirror images of the others and separated them. By dissolving the separated enantiomers in water, he managed to demonstrate the difference in the direction rotation in the presence of plane polarized light. This experiment marked the most compelling evidence for the beginning of chiral chemistry. On the downside, very few enantiomers crystalize into separate mirror images. Nevertheless, this provided a robust basis for chiral separation. Following on, the enzymic resolution became common, as it uses the enantioselective property of enzymes to convert the racemates into different diastereomeric derivatives. The reason that this works is that diastereomers, which have two more stereocenters, can be separated by recrystallization due to the difference between their chemical and physical properties. Nowadays, the use of high-performance liquid chromatography has been popularized in chiral technology. This method involves chiral selectors being coated to the surface of inert solid silica micro- particles to create a chiral stationary phase, abbreviated as CSP. The function of a chiral selector in the separation column is to have enantioselective interactions with the racemic mixture. Companies such as Daicel have been researching chiral selectors with a high number of chiral sites to separate various racemates. Polysaccharides are described as the universal class of chiral selectors, and are subdivided into two main types: amylose and cellulose. Despite their poor chiral discrimination ability, it is drastically magnified when the R groups are replaced by derivatives. In general, the idea is to pass the racemic analyte through the column to form transient diastereomeric complexes between the enantiomers and the CSP. For example, CHIRALPAK® IJ – a recent development from Daicel – is a CSP made from cellulose derivatized with tris(4-methylbenzoate). These molecules have a helical structure containing small pockets called chiral grooves; this is where a process called chiral recognition occurs. The analyte interacts with distinctive pockets through forces such as π - π interactions, hydrogen bonds and steric hindrance to form a complex. As illustrated earlier in the Easson-Stedman model, the selector effectively offers the binding sites; one enantiomer might bind more tightly to the stationary phase to form a more stable complex and moves more slowly through the column. On the other hand, the other enantiomer might prefer to interact with the mobile phase and elutes faster. This difference in stability and energy level of the complexes causes the retention time and the time that they elute the column to vary. Similarly, chromatographic conditions, such as temperature and column length, and the chemical nature of the analyte, are also important factors. The choice and components of the mobile phase dictate the conformational preferences as well as the ionization state. Hence, it is crucial to consider additives that match the pH of the analyte; this ensures that the two peaks do not overlap. Moreover,
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