Racemic
Encyclopedia
In chemistry
, a racemic mixture, or racemate (icon), is one that has equal amounts
of left- and right-handed enantiomer
s of a chiral
molecule. The first known racemic mixture was "racemic acid
", which Louis Pasteur
found to be a mixture of the two enantiomeric isomer
s of tartaric acid
.
If the ratio is not 1:1 (or is not known), the prefix (+)/(−), - or d/l- (with a slash) is used instead.
The usage of d and l is strongly discouraged by IUPAC.
, meaning that there is no net rotation of plane-polarized light. Although the two enantiomers rotate plane-polarized light in opposite directions, the rotations cancel because they are present in equal amounts.
In contrast to the two pure enantiomers, which have identical physical properties except for the direction of rotation of plane-polarized light, a racemate sometimes has different properties from either of the pure enantiomers. Different melting points are most common, but different solubilities and boiling point
s are also possible.
Pharmaceuticals may be available as a racemate or as the pure enantiomer, which might have different potencies.
had distinguished by 1899:
. There are various methods, including crystallization, chromatography
, and the use of enzyme
s. The first successful resolution of a racemate was performed by Louis Pasteur
, who manually separated the crystals of a conglomerate.
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 of how biological homochirality
evolved on what is presumed to be a 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
.
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 amphetamine
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. The prescription analgesic tramadol
is also a racemate.
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. However, sometimes samples containing pure enantiomers may be made and sold at a higher cost in cases where the use requires specifically one isomer (e.g., for a stereospecific reagent); compare omeprazole
and esomeprazole
.
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 dextromethamphetamine hydrochloride. This is the right-hand isomer of methamphetamine. The left-handed isomer of methamphetamine, levomethamphetamine, is an OTC
drug that is less centrally-acting and more peripherally-acting.
) states that racemic
crystals tend to be denser than their chiral
counterparts. This rule has been substantiated by crystallographic database analysis
Chemistry
Chemistry is the science of matter, especially its chemical reactions, but also its composition, structure and properties. Chemistry is concerned with atoms and their interactions with other atoms, and particularly with the properties of chemical bonds....
, a racemic mixture, or racemate (icon), is one that has equal amounts
Amount of substance
Amount of substance is a standards-defined quantity that measures the size of an ensemble of elementary entities, such as atoms, molecules, electrons, and other particles. It is sometimes referred to as chemical amount. The International System of Units defines the amount of substance to be...
of left- and right-handed enantiomer
Enantiomer
In chemistry, an enantiomer is one of two stereoisomers that are mirror images of each other that are non-superposable , much as one's left and right hands are the same except for opposite orientation. It can be clearly understood if you try to place your hands one over the other without...
s of a chiral
Chirality (chemistry)
A chiral molecule is a type of molecule that lacks an internal plane of symmetry and thus has a non-superimposable mirror image. The feature that is most often the cause of chirality in molecules is the presence of an asymmetric carbon atom....
molecule. The first known racemic mixture was "racemic acid
Racemic acid
Racemic acid is an old name for an optically inactive or racemic form of tartaric acid. It is an equal mixture of two mirror-image isomers , optically active in opposing directions....
", which Louis Pasteur
Louis Pasteur
Louis Pasteur was a French chemist and microbiologist born in Dole. He is remembered for his remarkable breakthroughs in the causes and preventions of diseases. His discoveries reduced mortality from puerperal fever, and he created the first vaccine for rabies and anthrax. His experiments...
found to be a mixture of the two enantiomeric isomer
Isomer
In chemistry, isomers are compounds with the same molecular formula but different structural formulas. Isomers do not necessarily share similar properties, unless they also have the same functional groups. There are many different classes of isomers, like stereoisomers, enantiomers, geometrical...
s of tartaric acid
Tartaric acid
Tartaric acid is a white crystalline diprotic organic acid. It occurs naturally in many plants, particularly grapes, bananas, and tamarinds; is commonly combined with baking soda to function as a leavening agent in recipes, and is one of the main acids found in wine. It is added to other foods to...
.
Nomenclature
A racemic mixture is denoted by the prefix (±)- or dl- (for sugars the prefix - may be used), indicating an equal (1:1) mixture of dextro and levo isomers. Also the prefix rac- (or racem-) or the symbols RS and SR (all in italic letters) are used.If the ratio is not 1:1 (or is not known), the prefix (+)/(−), - or d/l- (with a slash) is used instead.
The usage of d and l is strongly discouraged by IUPAC.
Properties
A racemate is optically inactiveOptical rotation
Optical rotation is the turning of the plane of linearly polarized light about the direction of motion as the light travels through certain materials. It occurs in solutions of chiral molecules such as sucrose , solids with rotated crystal planes such as quartz, and spin-polarized gases of atoms...
, meaning that there is no net rotation of plane-polarized light. Although the two enantiomers rotate plane-polarized light in opposite directions, the rotations cancel because they are present in equal amounts.
In contrast to the two pure enantiomers, which have identical physical properties except for the direction of rotation of plane-polarized light, a racemate sometimes has different properties from either of the pure enantiomers. Different melting points are most common, but different solubilities and boiling point
Boiling point
The boiling point of an element or a substance is the temperature at which the vapor pressure of the liquid equals the environmental pressure surrounding the liquid....
s are also possible.
Pharmaceuticals may be available as a racemate or as the pure enantiomer, which might have different potencies.
Crystallization
There are four ways in which a racemate can crystallize, three of which H. W. B. RoozeboomHendrik Willem Bakhuis Roozeboom
H. W. Bakhuis Roozeboom was a Dutch chemist who gained his reputation for works on phase behaviour in physical chemistry.H. W. Bakhuis Roozeboom was born in Alkmaar in the Netherlands. Financial difficulties did not allow him to directly pursue a university education, and he left school to work...
had distinguished by 1899:
- 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 a greater affinity for the same enantiomer than for the opposite enantiomer. The melting pointMelting pointThe melting point of a solid is the temperature at which it changes state from solid to liquid. At the melting point the solid and liquid phase exist in equilibrium. The melting point of a substance depends on pressure and is usually specified at standard atmospheric pressure...
of the racemic conglomerate is always lower than that of the pure enantiomer. Addition of a small amount of one enantiomer to the conglomerate increases the melting point.
- Racemic compound (sometimes true racemate)
- Molecules have a greater affinity for the opposite enantiomer than for 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. Adding a small amount of one enantiomer to the racemic compound decreases the melting point. But the pure enantiomer can have a higher or lower melting point than the compound.
- Pseudoracemate (sometimes racemic solid solution)
- In contrast to 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. Addition of a small amount of one enantiomer changes the melting point 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 right-handed. 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 ammoniumAmmoniumThe ammonium cation is a positively charged polyatomic cation with the chemical formula NH. It is formed by the protonation of ammonia...
saltSaltIn chemistry, salts are ionic compounds that result from the neutralization reaction of an acid and a base. They are composed of cations and anions so that the product is electrically neutral...
of (+)-tartaric acidTartaric acidTartaric acid is a white crystalline diprotic organic acid. It occurs naturally in many plants, particularly grapes, bananas, and tamarinds; is commonly combined with baking soda to function as a leavening agent in recipes, and is one of the main acids found in wine. It is added to other foods to...
and the bis ammonium salt of (−)-malic acidMalic acidMalic acid is an organic compound with the formula HO2CCH2CHOHCO2H. It is a dicarboxylic acid which is made by all living organisms, contributes to the pleasantly sour taste of fruits, and is used as a food additive. Malic acid has two stereoisomeric forms , though only the L-isomer exists...
in water. Re-investigated in 2008, the crystals formed are dumbbellDumbbellThe dumbbell, a type of free weight, is a piece of equipment used in weight training. It can be used individually or in pairs .-History:...
-shape with the central part consisting of ammonium (+)-bitartrate, whereas 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 resolutionChiral resolution
Chiral resolution in stereochemistry is a process for the separation of racemic compounds into their enantiomers. It is an important tool in the production of optically active drugs...
. There are various methods, including crystallization, chromatography
Chromatography
Chromatography is the collective term for a set of laboratory techniques for the separation of mixtures....
, and the use of enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
s. The first successful resolution of a racemate was performed by Louis Pasteur
Louis Pasteur
Louis Pasteur was a French chemist and microbiologist born in Dole. He is remembered for his remarkable breakthroughs in the causes and preventions of diseases. His discoveries reduced mortality from puerperal fever, and he created the first vaccine for rabies and anthrax. His experiments...
, who manually separated the crystals of a conglomerate.
Synthesis
Without a chiralChirality (chemistry)
A chiral molecule is a type of molecule that lacks an internal plane of symmetry and thus has a non-superimposable mirror image. The feature that is most often the cause of chirality in molecules is the presence of an asymmetric carbon atom....
influence (for example a chiral catalyst, solvent
Solvent
A solvent is a liquid, solid, or gas that dissolves another solid, liquid, or gaseous solute, resulting in a solution that is soluble in a certain volume of solvent at a specified temperature...
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 of how biological homochirality
Homochirality
Homochirality is a term used to refer to a group of molecules that possess the same sense of chirality. Molecules involved are not necessarily the same compound, but similar groups are arranged in the same way around a central atom. In biology homochirality is found in the chemical building blocks...
evolved on what is presumed to be a 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
Stereoisomerism
Stereoisomers are isomeric molecules that have the same molecular formula and sequence of bonded atoms , but that differ only in the three-dimensional orientations of their atoms in space. This contrasts with structural isomers, which share the same molecular formula, but the bond connections...
.
Racemic pharmaceuticals
Some drug moleculesSmall molecule
In the fields of pharmacology and biochemistry, a small molecule is a low molecular weight organic compound which is by definition not a polymer...
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
Thalidomide
Thalidomide was introduced as a sedative drug in the late 1950s that was typically used to cure morning sickness. In 1961, it was withdrawn due to teratogenicity and neuropathy. There is now a growing clinical interest in thalidomide, and it is introduced as an immunomodulatory agent used...
, ibuprofen
Ibuprofen
Ibuprofen is a nonsteroidal anti-inflammatory drug used for relief of symptoms of arthritis, fever, as an analgesic , especially where there is an inflammatory component, and dysmenorrhea....
, and salbutamol
Salbutamol
Salbutamol or albuterol is a short-acting β2-adrenergic receptor agonist used for the relief of bronchospasm in conditions such as asthma and chronic obstructive pulmonary disease. It is marketed as Ventolin among other brand names....
. Adderall
Adderall
Adderall is a brand name of amphetamine salts–based medication used for attention-deficit hyperactivity disorder and narcolepsy. It is a brand-name psychostimulant medication composed of racemic amphetamine aspartate monohydrate, racemic amphetamine sulfate, dextroamphetamine saccharide, and...
is a mixture of several different amphetamine
Amphetamine
Amphetamine or amfetamine is a psychostimulant drug of the phenethylamine class which produces increased wakefulness and focus in association with decreased fatigue and appetite.Brand names of medications that contain, or metabolize into, amphetamine include Adderall, Dexedrine, Dextrostat,...
enantiomers. A single amphetamine dose combines the neutral sulfate salts of dextroamphetamine
Dextroamphetamine
Dextroamphetamine is a psychostimulant drug which is known to produce increased wakefulness and focus as well as decreased fatigue and decreased appetite....
and amphetamine, with the dextro isomer of amphetamine saccharate and D/L-amphetamine aspartate monohydrate. The prescription analgesic tramadol
Tramadol
Tramadol hydrochloride is a centrally acting synthetic opioid analgesic used in treating moderate pain. The drug has a wide range of applications, including treatment for restless legs syndrome and fibromyalgia...
is also a racemate.
In some cases (e.g., ibuprofen
Ibuprofen
Ibuprofen is a nonsteroidal anti-inflammatory drug used for relief of symptoms of arthritis, fever, as an analgesic , especially where there is an inflammatory component, and dysmenorrhea....
and thalidomide
Thalidomide
Thalidomide was introduced as a sedative drug in the late 1950s that was typically used to cure morning sickness. In 1961, it was withdrawn due to teratogenicity and neuropathy. There is now a growing clinical interest in thalidomide, and it is introduced as an immunomodulatory agent used...
), the enantiomers are interconverted in vivo
In vivo
In vivo is experimentation using a whole, living organism as opposed to a partial or dead organism, or an in vitro controlled environment. Animal testing and clinical trials are two forms of in vivo research...
. This means that preparing a pure enantiomer for medication is largely pointless. However, sometimes samples containing pure enantiomers may be made and sold at a higher cost in cases where the use requires specifically one isomer (e.g., for a stereospecific reagent); compare omeprazole
Omeprazole
Omeprazole is a proton pump inhibitor used in the treatment of dyspepsia, peptic ulcer disease , gastroesophageal reflux disease , laryngopharyngeal reflux and Zollinger–Ellison syndrome...
and esomeprazole
Esomeprazole
Esomeprazole is a proton pump inhibitor developed and marketed by AstraZeneca which is used in the treatment of dyspepsia, peptic ulcer disease , gastroesophageal reflux disease and Zollinger-Ellison syndrome...
.
In cases like salbutamol
Salbutamol
Salbutamol or albuterol is a short-acting β2-adrenergic receptor agonist used for the relief of bronchospasm in conditions such as asthma and chronic obstructive pulmonary disease. It is marketed as Ventolin among other brand names....
and thalidomide
Thalidomide
Thalidomide was introduced as a sedative drug in the late 1950s that was typically used to cure morning sickness. In 1961, it was withdrawn due to teratogenicity and neuropathy. There is now a growing clinical interest in thalidomide, and it is introduced as an immunomodulatory agent used...
, the inactive isomer may be harmful.
Methamphetamine
Methamphetamine
Methamphetamine is a psychostimulant of the phenethylamine and amphetamine class of psychoactive drugs...
is available by prescription under the brand name Desoxyn. The active component of Desoxyn is dextromethamphetamine hydrochloride. This is the right-hand isomer of methamphetamine. The left-handed isomer of methamphetamine, levomethamphetamine, is an OTC
OTC
OTC may refer to:* Oakwood Technology College* Owatonna Tool Company* Oklahoma Tax Commission* Odenton Town Center* Officer in Tactical Command* Officer Training Corps* Offshore Technology Conference* Ohio Turnpike Commission...
drug that is less centrally-acting and more peripherally-acting.
Wallach's rule
Wallach's rule (first proposed by Otto WallachOtto Wallach
Otto Wallach was a German chemist and recipient of the 1910 Nobel prize in Chemistry for his work on alicyclic compounds.-Biography:...
) states that racemic
Racemic
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.- Nomenclature :A...
crystals tend to be denser than their chiral
Chirality (chemistry)
A chiral molecule is a type of molecule that lacks an internal plane of symmetry and thus has a non-superimposable mirror image. The feature that is most often the cause of chirality in molecules is the presence of an asymmetric carbon atom....
counterparts. This rule has been substantiated by crystallographic database analysis
See also
- ChiralityChirality (chemistry)A chiral molecule is a type of molecule that lacks an internal plane of symmetry and thus has a non-superimposable mirror image. The feature that is most often the cause of chirality in molecules is the presence of an asymmetric carbon atom....
- HandednessHandednessHandedness is a human attribute defined by unequal distribution of fine motor skills between the left and right hands. An individual who is more dexterous with the right hand is called right-handed and one who is more skilled with the left is said to be left-handed...
- Optical isomerism
- RacemizationRacemizationIn chemistry, racemization refers to the converting of an enantiomerically pure mixture into a mixture where more than one of the enantiomers are present...