Chirality
the reversal of elution order is entirely possible; this could be due to the effects of solvation from different mobile phases or the change between amylose and cellulose stationary phases.
Fundamentally, chiral separation often involves a brute-force, trial-and-error method. The analytes are simultaneously screened through as many columns as possible in order to determine the most enantioselective CSP for that specific racemic mixture. The process of adsorption and desorption of the complex is often slow, and the analysis becomes a matter of leaving the chromatography to run overnights. The aim is to see a baseline resolution where there are well-defined, non-overlapping peaks. What makes the chiral resolutions challenging is usually the presence of giant molecules with multiple chiral centres and requiring many different interactions with the CSP. This usually means that the stereocenters are shielded and hidden away; the molecules are less reactive with the stationary phase. In conclusion, although homochirality triggers the incompatibility of specific enantiomers of chiral drugs in our body, there is nothing that can be done against the primitive existence of chiral environments in our bodies. It can be argued that homochirality is the defence mechanism that designed the complexity of animals and brought about the selectivity and recognition of molecules. In spite of the degree of success in chiral separation, chemists have also constantly been developing methods of asymmetric synthesis to provide an alternate pathway to creating enantiopure drugs. One noteworthy experiment, performed by the Czech chemist Tomas Hudlicky, uses enzymes to oxidize toluene and other aromatics into enantiopure cis-1,2-dihydrocatechols. 7 Intriguingly, their method was centred around using cheap feedstock to produce a compound of high value and is widely used as starting material to produce complex organic molecules. This reaction is quite significant because of the unfavorability in the oxidation of toluene, which is an addition upon the aromatic ring. However, chirality is not the only problem faced by the pharmaceutical industry: the development of cutting- edge technology is also vital in areas such as pharmacokinetics to assess how drugs behave kinetically in the body.
Bibliography
Asuncion, A. (2006) Analyzing the Origin of Homochirality in Life
https://www.ics.uci.edu/~asuncion/homochirality.html Date consulted: 13/07/2021
Berthod, A. (2010) Chiral recognition in separation methods. Villeurbanne Botting, J.H. (2015) Animals and Medicine: The Contribution of Animal Experiments to the Control of Disease. Cambridge Brazil, R. (2015) The origin of homochirality. https://www.chemistryworld.com/features/the-origin-of-homochirality/9073.article Date consulted: 11/07/2021 . Breitbach, Z. (2017) Advancing Chiral Separations . https://www.registech.com/video-library/advancing-chiral- separations/ Date consulted: 13/07/2021 Brooks, W.H., Guida, W.C., & Daniel, K.G. (2011) ‘The significance of chirality in drug design and development’, Current topics in medicinal chemistry 11: 760 – 770. Cabusas M.E.Y. (1998) Chiral Separations on HPLC Derivatized Polysaccharide CSPs: Temperature, Mobile Phase and Chiral Recognition Mechanism Studies. Blacksburg
7 Hudlicky 2018.
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