Chirality
Jefferson Xue
One significant problem faced by the pharmaceutical industry revolves around chiral chemistry and the homochirality of optically active biological molecules in the human body. In 1981, Sir John Cornforth said that the ‘ sad truth is that we still learn most of our chemistry on flatland, to the detriment of our science ’. 1 Chirality exists in three dimensions and gives rise to the distinguishing effects of enantiomers of the same drug. Such a phenomenon first became apparent when Louis Pasteur separated two enantiomers of sodium ammonium tartrate; this led us to his famous conjecture that the ‘universe is chiral’. 2 Following the discovery of the uniformity of biological polymers in our body, the idea of homochirality soon prevailed. There has always been a puzzle about the origin of life and the plausibility of abiogenesis. Homochirality became the root cause for the creation of chiral environments. This is demonstrated by the enantiomeric excess of a specific handedness of different types of biological molecules in the human body. Subsequently, the challenge for chemists has been to explore solutions to the various problems that chirality causes in the pharmaceutical industry. About 60% of prescribed drugs currently used are chiral chemicals, yet 90% of them are sold as racemic mixtures containing equimolar amounts of each enantiomer. 3 Foundationally, it is essential to develop the analysis and separation of racemic drugs in the pharmaceutical industry to eliminate the distomer. As explained by Vladmir Prelog, ‘ an object is chiral if it cannot be brought into congruence with its mirror image by translation and rotation ’ . 4 Originally, Lord Kel vin coined the term ‘chiral’ after deriving it from the Greek word ce·r (hand). It refers to the mirror and non-superimposable characteristics of two molecules. In simple terms, due to the equal probability of the nucleophile attacking either side of the reactant, any chemical reaction producing chiral products will always yield a racemate. The concept of homochirality came to light after discovering that biological molecules such as sugars are always D- chiral, and amino acids are all L-chiral. As it is an unsolved problem in organic chemistry, there have been many theories regarding how homochirality came to predominate living organisms. In 1952, the Miller-Urey Experiment was conducted to mimic the primordial soup and learn about abiogenesis. The experimenters filled a flask with water, methane, ammonia and hydrogen, and ionized the mixture. As a result, a racemic mixture of amino acids was produced. It can therefore be speculated that homochiral life might have purely originated by stochastic processes. Nevertheless, it is known that there must have been two events that must have occurred: symmetry breaking and amplification. Firstly, symmetry breaking denotes breaking the balance between the left and right; theories have concluded that it was a natural and random selection that led to the auto-amplification
1 Hu 2002. 2 Wolf 2007. 3 Nguyen et al. 2006. 4 Prelog 1975.
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