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In chemistry, racemization refers to the conversion of an enantiomerically pure mixture (one where only one enantiomer is present) into a mixture where more than one of the enantiomers are present. An enantiomer, also known as an optical isomer, refers to a stereoisomer of a pair of molecules that are nonsuperposable mirror images of each other. If the racemization results in a mixture where the D and L enantiomers are present in equal quantities, the resulting sample is described as racemic, a racemic mixture, or a racemate.[1][2]


Chiral molecules have two forms (at each point of asymmetry), which differ in their optical characteristics: The levorotatory form (the (−)-form) will rotate the plane of polarization of a beam of light to the left, whereas the dextrorotatory form (the (+)-form) will rotate the plane of polarization of a beam of light to the right. The two forms, which are non-superimposable when rotated in 3-dimensional space, are said to be enantiomers.

Racemization occurs when one pure form of an enantiomer is converted into equal proportion of both enantiomers, forming a racemate. When there are both equal numbers of dextrorotating and levorotating molecules, the net optical rotation of a racemate is zero.[1]

Physical properties[edit]

Racemate may have different physical properties from either of the pure enantiomers because of the differential intermolecular interactions. The change from a pure enantiomer to a racemate can change its density, melting point, solubility, heat of fusion, refractive index, and its various spectra. Crystallization of a racemate can result in separate (+) and (−) forms, or a single racemic compound.

Biological significance[edit]

In general, only one form of a chiral molecule will participate in biochemical reactions while the other simply does not participate or can cause side-effects. Of note, the L form of amino acids and the D form of sugars (primarily glucose) are usually the biologically reactive form. This is due to the fact that many biological molecules are chiral and thus the reactions between specific enantiomers produce pure stereoisomers.[3]

Additionally, many psychotropic drugs show differing activity or efficacy between isomers, e.g. amphetamine is often dispensed as racemic salts while the more active dextroamphetamine is reserved for refractory cases or more severe indications; another example is methadone, of which one isomer has activity as an opioid agonist and the other as an NMDA antagonist.

Racemization of pharmaceutical drugs, however, can occur in vivo. An example is thalidomide: its (R) enantiomer is effective against morning sickness, while the (S) enantiomer is teratogenic, causing birth defects when taken in the first trimester of pregnancy. If only one enantiomer is administered to a human subject, both forms may be found later in the blood serum.[4] The drug is therefore not considered safe for use by women of child-bearing age, and while it has other uses, its use is tightly controlled.[5][6] Thalidomide can be used to treat multiple myeloma. [7]??? Another commonly used drug is ibuprofen which is only anti-inflammatory as one enantiomer while the other is biologically inert. Likewise, only one stereoisomer in Citalopram (Celexa), an antidepressant which inhibits serotonin reuptake, is active. The The study of enantiomers in the pharmaceutical industry is termed chiral organic synthesis.[3][2]

Also notable is the fact that all amino acid residues exist in the L form. However, bacteria produce D-amino acid residues that polymerize into short polypeptides which can be found in bacterial cell walls. These polypeptides are less digestible by peptidases and are synthesized by bacterial enzymes instead of mRNA translation which would normally produce L-amino acids.[3]

Formation of racemic mixtures[edit]

On a trivial level, racemization can be achieved by simply mixing equal quantities of two pure enantiomers. Racemization can also occur in a chemical interconversion. For example, when (R)-3-phenyl-2-butanone is dissolved in aqueous ethanol that contains NaOH or HCl, a racemate is formed. The racemization occurs by way of an intermediate enol form in which the former stereocenter becomes planar and hence achiral.[8] An incoming group can approach from either side of the plane, so there is an equal probability that protonation back to the chiral ketone will produce either an R or an S form, resulting in a racemate.

Racemization can occur through some of the following processes:

The rate of racemization (from L-forms to a mixture of L-forms and D-forms) has been used as a way of dating biological samples in tissues with slow rates of turnover, forensic samples, and fossils in geological deposits. This technique is known as amino acid dating.

Discovery of Optical Activity[edit]

In 1843, Louis Pasteur discovered optical activity in paratartaric, or racemic, acid found in grape wine. He was able to separate two enantiomer crystals that rotated polarized light in opposite directions.[2]


  1. ^ a b Andrew Streitwieser, Clayton H. Heathcock (1985). Introduction to Organic Chemistry (3rd ed.). Maxwell MacMillan. pp. 122–124. ISBN 0029467209. 
  2. ^ a b c Nelson, David L.; Cox, Michael M. (2013). Lehninger Principles of Biochemistry (6th ed.). New York: W.H. Freeman. ISBN 1429234148. 
  3. ^ a b c Voet, Donald; Voet, Judith G.; Pratt, Charlotte W. (2013). Fundamentals of Biochemistry: Life at the Molecular Level (4th ed.). Hoboken, NJ: Wiley. ISBN 0470547847. 
  4. ^ Teo SK, Colburn WA, Tracewell WG, Kook KA, Stirling DI, Jaworsky MS, Scheffler MA, Thomas SD, Laskin OL (2004). "Clinical pharmacokinetics of thalidomide". Clin Pharmacokinet. 43 (5): 311–327. doi:10.2165/00003088-200443050-00004. PMID 15080764. 
  5. ^ Sheryl Gay Stolberg (17 July 1998). "Thalidomide Approved to Treat Leprosy, With Other Uses Seen". New York Times. Retrieved 8 January 2012. 
  6. ^ "Use of thalidomide in leprosy". WHO:leprosy elimination. WHO. Retrieved 22 April 2010. 
  7. ^ Reddy, K. Chandra Sekhara; Kasiviswanath, I.V. (January 2013). "Racimisation of (R)–Alpha–Ethyl-2-Oxo-1-Pyrrolidine Acetic acid with Thionyl Chloride". International Journal for Pharmaceutical Research Scholars (IJPRS) 2 (1): 45–48. 
  8. ^ Andrew Streitwieser, Clayton H. Heathcock (1985). Introduction to Organic Chemistry (3rd ed.). Maxwell MacMillan. p. 373. ISBN 0029467209. 
  9. ^ Jerry March (1985). Advanced Organic Chemistry: reactions, mechanisms, and structure (3rd ed.). John Wiley & Sons. pp. 517–518. ISBN 0-471-85472-7. 
  10. ^ Jerry March (1985). Advanced Organic Chemistry: reactions, mechanisms, and structure (3rd ed.). John Wiley & Sons. p. 610. ISBN 0-471-85472-7. 

See also[edit]