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 its 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 the light to the right (dextrorotatory) begins to be added to it, its optical activity will decrease until it is inactivated..
When this happens it is said that there are equal amounts of the left and right enantiomers; If a molecule rotates polarized light to the left, its effect will be immediately canceled when it "stumbles" on 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.
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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 be able to fit..
The right shoe, to say, deflects the polarized light to the left; while the left shoe does it 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 we have a racemic mixture, which is also optically inactive, since the deviations suffered by the light inside 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..
Returning to tartaric acid, its racemic mixture was the first to be known. In the upper image its two enantiomers are shown, each one capable of forming crystals with morphological "left" or "right" faces. Pasteur, through the aid of 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 the polarized light to the right or left, respectively. If both crystals are dissolved in water in equal molar proportions, an optically inactive racemic mixture will be obtained..
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 OHs 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..
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).
However, it is difficult to determine which of the stereoisomers of quinine will deflect polarized light to the right or to the left..
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 your racemic mixture to the chiral resolution already mentioned, in such a way that the pure R enantiomer is obtained.
In the upper image you have the enantiomeric 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.
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, CH3, 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.
More important than the existence or not of 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..
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