- Shoes and chirality
- Examples
- Tartaric acid
- Quinine
- Thalidomide
- 1,2-Epoxypropane
- 1-Phenylethylamine
- Final comment
- References
A racemic mixture or racemate is one composed of two enantiomers in equal parts and which is therefore optically inactive. This optical activity refers to the ability of your solutions to rotate, clockwise or counterclockwise, a beam of polarized light that travels through them in one direction.
An enantiomer has the ability to rotate polarized light, say, to the left (left-handed), so its pure solution will be optically active. However, if the enantiomer that rotates light to the right (dextrorotatory) begins to be added to it, its optical activity will decrease until it is inactivated.
Clusters of grapes, which share a kinship with racemic mixtures beyond etymology. Source: Pexels.
When this happens, it is said that there are equal amounts of the levorotatory and dextrorotatory enantiomers; If a molecule rotates polarized light to the left, its effect will immediately be canceled when it "encounters" another molecule that rotates it to the right. And so on. Therefore, we will have a racemic mixture.
The first sighting of the enantiomerism was made by the French chemist Louis Pasteur in 1848, who was studying a mixture of enantiomeric crystals of tartaric acid (at that time called racemic acid). As this acid came from the grapes used to make wines, this mixture ended up being applied in a general way for all molecules.
Shoes and chirality
First of all, for there to be a racemic mixture, there must be two enantiomers (usually), which implies that both molecules are chiral and that their mirror images are not superimposable. A pair of shoes illustrates this perfectly: no matter how hard you try to superimpose the left shoe on the right, they will never fit.
The right shoe, in other words, deflects polarized light to the left; while the left shoe moves to the right. In a hypothetical solution where the shoes are the molecules, if there are only straight, chiral shoes, this will be optically active. The same will happen if there are only left shoes in solution.
However, if there are a thousand left shoes mixed with a thousand right shoes, then there is a racemic mixture, which is also optically inactive, since the deviations that the light undergoes inside it cancel each other out.
If instead of shoes they were balls, objects that are achiral, it would be impossible for racemic mixtures of these to exist, since they would not even be capable of existing as pairs of enantiomers.
Examples
Tartaric acid
Enantiomers of tartaric acid. Source: Dschanz
Returning to tartaric acid, its racemic mixture was the first to be known. The upper image shows its two enantiomers, each capable of forming crystals with "left" or "right" morphological faces. Pasteur, using a microscope and rigorous effort, succeeded in separating these enantiomeric crystals from each other.
The crystals of the L (+) and D (-) enantiomers, separately, show optical activity by deflecting polarized light to the right or left, respectively. If both crystals in equal molar proportions dissolve in water, an optically inactive racemic mixture will be obtained as a result.
Note that both enantiomers have two chiral carbons (with four different substituents). In L (+), the OHs lie behind the plane formed by the carbon skeleton and the COOH groups; while in D (-) these OH are above said plane.
Those who synthesize tartaric acid will get a racemic mixture. To separate the L (+) enantiomer from the D (-), a chiral resolution is necessary, in which this mixture is reacted with a chiral base to produce diastereoisomeric salts, capable of being separated by fractional crystallization.
Quinine
Structural skeleton of the quinine molecule. Source: Benjah-bmm27.
In the example above, to refer to a racemic mixture of tartaric acid it is usually written as (±) -tartaric acid. Thus, in the case of quinine (upper image) it will be (±) -kinine.
The isomerism of quinine is complex: it has four chiral carbons, giving rise to sixteen diastereoisomers. Interestingly, two of its enantiomers (one with the OH above the plane and the other below it) are actually diastereoisomers, since they differ in the configurations of their other chiral carbons (those of the bicyclo with the N atom).
Now, it is difficult to determine which of the stereoisomers of quinine will deflect polarized light to the right or to the left.
Thalidomide
Thalidomide enantiomers. Source: Vaccinationist
The enantiomers of thalidomide are shown above. It only has one chiral carbon: the one that is linked to the nitrogen that joins both rings (one of phthalimide and the other of gluteramide).
In the R enantiomer (with sedative properties), the phthalimide ring (the one on the left) is oriented above the plane; while in the S enantiomer (with mutagenic properties), below.
It is not known to the eye per cent which of the two deflects the light to the left or the right. What is known is that a 1: 1 or 50% mixture of both enantiomers forms the racemic mixture (±) -talidomide.
If you only want to market thalidomide as a hypnotic sedative, it is mandatory to subject its racemic mixture to the chiral resolution already mentioned, in such a way that the pure R enantiomer is obtained.
1,2-Epoxypropane
1,2-epoxypropane enantiomers. Source: Gabriel Bolívar.
In the upper image you have the enantiomer pair of 1,2-epoxypropane. The R enantiomer deflects polarized light to the right, while the S enantiomer deflects it to the left; that is, the first is (R) - (+) - 1,2-epoxypropane, and the second is (S) - (-) - 1,2-epoxypropane.
The racemic mixture of the two, again, in a 1: 1 or 50% ratio, becomes (±) -1,2-epoxypropane.
1-Phenylethylamine
Enantiomers of 1-Phenylethylamine. Source: Gabriel Bolívar.
Shown above is another racemic mixture formed by the two enantiomers of 1-Phenylethylamine. The R enantiomer is (R) - (+) - 1-Phenylethylamine, and the S enantiomer is (S) - (-) - 1-Phenylethylamine; one has the methyl group, CH 3, pointing out of the plane of the aromatic ring, and the other pointing below it.
Note that when the configuration is R, it sometimes coincides with the fact that the enantiomer rotates the polarized light to the right; however, it does not always apply and cannot be taken as a general rule.
Final comment
More important than the existence or not of the racemic mixtures is their chiral resolution. This applies especially to compounds with pharmacological effects that depend on said stereoisomerism; that is, one enantiomer can be beneficial to the patient, while the other can affect it.
That is why these chiral resolutions are used to separate the racemic mixtures into their components, and thus be able to market them as pure drugs free of harmful impurities.
References
- Morrison, RT and Boyd, R, N. (1987). Organic Chemistry. 5th Edition. Editorial Addison-Wesley Interamericana.
- Carey F. (2008). Organic Chemistry. (Sixth edition). Mc Graw Hill.
- Graham Solomons TW, Craig B. Fryhle. (2011). Organic Chemistry. Amines. (10th edition.). Wiley Plus.
- Steven A. Hardinger. (2017). Illustrated Glossary of Organic Chemistry: Racemic Mixture. Department of Chemistry & Biochemistry, UCLA. Recovered from: chem.ucla.edu
- Nancy Devino. (2019). Racemic Mixture: Definition & Example. Study. Recovered from: study.com
- James Ashenhurst. (2019). Stereochemistry and Chirality: What's a Racemic Mixture? Recovered from: masterorganicchemistry.com
- John C. Leffingwell. (2003). Chirality & Bioactivity I.: Pharmacology.. Recovered from: leffingwell.com