English

Adjective

racemic

1. containing equal amounts of dextrorotatory and levorotatory stereoisomers and therefore not being optically active; typically, will be synthetic rather than natural

In chemistry, a racemic mixture, or racemate, is one that has equal amounts of left- and right-handed enantiomers of a chiral molecule. The first known racemic mixture was 'racemic acid', which Louis Pasteur found to be a mixture of the two enantiomeric isomers of tartaric acid.

Properties

A racemate is optically inactive: because the two isomers rotate plane-polarized light in opposite directions they cancel out, therefore a racemic mixture does not rotate plane-polarized light.

In contrast to the two separate enantiomers, which generally have identical physical properties, a racemate often has different properties compared to either one of the pure enantiomers. Different melting points and solubilities are very common, but different boiling points are also possible.

Pharmaceuticals may be available as a racemate or as pure enantiomer, which might have different potencies.

Crystallization

There are three ways a racemate can crystallize, this is important for the resolution of a racemate by crystallisation. Precise ways to distinguish between these crystal forms were summarised already in 1899 by H. W. B. Roozeboom.

• Conglomerate (sometimes racemic mixture or racemic conglomerate)

A mechanical mixture of enantiomerically pure crystals of one enantiomer and its opposite. Molecules in the crystal structure have higher affinity to the same enantiomer than to the opposite enantiomer. The melting point of the racemic conglomerate is always lower than the pure enantiomer. Addition of a small amount of one enantiomer to the racemic compound increases the melting point.

• Racemic compound (sometimes true racemate)

Molecules have a higher affinity to the opposite enantiomer than to the same enantiomer, the substance forms a single crystalline phase in which the two enantiomers are present in an ordered 1:1 ratio in the elementary cell. By addition of small amount of one enantiomer to the racemic compound, the melting point decreases. But the pure enantiomer can have higher or lower melting point than the racemic compound.

• Pseudoracemate (sometimes racemic solid solution)

Unlike the racemic compound or conglomerate, there is no big difference in affinity between the same and opposite enantiomers. Overall, both enantiomers occur in equal proportions in the crystal but they coexist in an unordered manner in the crystal lattice. By addition of small amount of one enantiomer to the racemic compound, the melting point changes just little bit, or not at all.

• Quasiracemate.

A quasiracemate is a mixture of two similar but distinct compounds one of which is left-handed and the other of opposite handedness. Although chemically different, they are sterically similar (isosteric) and are still able to form a racemic crystalline phase. One of the first such racemates studied, by Pasteur in 1853, forms from a 1:2 mixture of the bis ammonium salt of (+)-tartaric acid and the bis ammonium salt of (-)-malic acid in water. Re-investigated in 2008 , the crystals formed are dumbbell shaped with the central part consisting of ammonium (+)-bitartrate while the outer parts are a quasiracemic mixture of ammonium (+)-bitartrate and ammonium (-)-bimalate.

Resolution

The separation of a racemate into its components, the pure enantiomers, is called a chiral resolution. There are various methods, including crystallization, chromatography and the use of enzymes. The first successful resolution of a racemate was performed by Louis Pasteur, who manually separated the crystals of a conglomerate.

Synthesis

Without a chiral influence (for example a chiral catalyst, solvent or starting material), a chemical reaction that makes a chiral product will always yield a racemate. That can make the synthesis of a racemate cheaper and easier than making the pure enantiomer, because it does not require special conditions. This fact also leads to the question how biological homochirality evolved on a presumably racemic primordial earth.

The reagents of, and the reactions that produce, racemic mixtures are said to be "not stereospecific" or "not stereoselective", for their indecision in a particular stereoisomerism.

Racemic pharmaceuticals

Some drug molecules are chiral and the enantiomers have different effects on biological entities. They can be sold as one enantiomer or as a racemic mixture. Examples include Thalidomide, Ibuprofen, and Salbutamol. Adderall is a mixture of several different enantiomers. A single amphetamine dose combines the neutral sulfate salts of dextroamphetamine and amphetamine, with the dextro isomer of amphetamine saccharate and d, l-amphetamine aspartate monohydrate.

In some cases (e.g. Ibuprofen and Thalidomide) the enantiomers are interconverted in vivo. This means that preparing a pure enantiomer for medication is largely pointless.

In cases like Salbutamol and Thalidomide the inactive isomer may be harmful.

Methamphetamine is available by prescription under the brand name Desoxyn. The active component of Desoxyn is dextro-methamphetamine hydrochloride. This is the right-hand isomer of methamphetamine. The left-handed isomer of methamphetamine, levo-methamphetamine, is less centrally acting and more peripherally acting; therefore a racemic mixture of dextro/levo-methamphetamine isn't used in current medical practice. In the past, due to different levels of restrictions on precursor chemicals and lack of knowledge by those preparing the final product, racemic methamphetamine was produced and sold on the black market. Newer techniques typically use asymmetric synthesis methods and yield a majority of d-methamphetamine and relatively little l-methamphetamine.

See also

• Racemization
• Optical isomerism
• Chirality

References