Absolute Configuration
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Absolute configuration refers to the spatial arrangement of
atom Every atom is composed of a nucleus and one or more electrons bound to the nucleus. The nucleus is made of one or more protons and a number of neutrons. Only the most common variety of hydrogen has no neutrons. Every solid, liquid, gas ...
s within a
chiral Chirality is a property of asymmetry important in several branches of science. The word ''chirality'' is derived from the Greek (''kheir''), "hand", a familiar chiral object. An object or a system is ''chiral'' if it is distinguishable from i ...
molecular entity (or group) and its resultant stereochemical description. Absolute configuration is typically relevant in organic molecules, where
carbon Carbon () is a chemical element with the symbol C and atomic number 6. It is nonmetallic and tetravalent—its atom making four electrons available to form covalent chemical bonds. It belongs to group 14 of the periodic table. Carbon makes ...
is bonded to four different
substituent A substituent is one or a group of atoms that replaces (one or more) atoms, thereby becoming a moiety in the resultant (new) molecule. (In organic chemistry and biochemistry, the terms ''substituent'' and '' functional group'', as well as '' ...
s. This type of construction creates two possible
enantiomer In chemistry, an enantiomer ( /ɪˈnænti.əmər, ɛ-, -oʊ-/ ''ih-NAN-tee-ə-mər''; from Ancient Greek ἐνάντιος ''(enántios)'' 'opposite', and μέρος ''(méros)'' 'part') – also called optical isomer, antipode, or optical ant ...
s. Absolute configuration uses a set of rules to describe the relative positions of each bond around the chiral center atom. The most common labeling method uses the descriptors ''R'' or ''S'' is based on the
Cahn–Ingold–Prelog priority rules In organic chemistry, the Cahn–Ingold–Prelog (CIP) sequence rules (also the CIP priority convention; named for R.S. Cahn, C.K. Ingold, and Vladimir Prelog) are a standard process to completely and unequivocally name a stereoisomer of a ...
. R and S refer to Rectus and Sinister, which are Latin for right and left, respectively. Chiral molecules can differ in their chemical properties, but are identical in their physical properties, which can make distinguishing enantiomers challenging. Absolute configurations for a chiral molecule (in pure form) are most often obtained by
X-ray crystallography X-ray crystallography is the experimental science determining the atomic and molecular structure of a crystal, in which the crystalline structure causes a beam of incident X-rays to diffract into many specific directions. By measuring the angle ...
, although with some important limitations. All enantiomerically pure chiral molecules crystallise in one of the 65 Sohncke groups (chiral space groups). Alternative techniques include optical rotatory dispersion, vibrational circular dichroism, ultraviolet-visible spectroscopy, the use of chiral shift reagents in
proton NMR Proton nuclear magnetic resonance (proton NMR, hydrogen-1 NMR, or 1H NMR) is the application of nuclear magnetic resonance in NMR spectroscopy with respect to hydrogen-1 nuclei within the molecules of a substance, in order to determine the str ...
and Coulomb explosion imaging.


History

Until 1951, it was not possible to obtain the absolute configuration of chiral compounds. It was at some time decided that (+)-
glyceraldehyde Glyceraldehyde (glyceral) is a triose monosaccharide with chemical formula C3 H6 O3. It is the simplest of all common aldoses. It is a sweet, colorless, crystalline solid that is an intermediate compound in carbohydrate metabolism. The word ...
was the -enantiomer. The configuration of other chiral compounds was then related to that of (+)-glyceraldehyde by sequences of
chemical reaction A chemical reaction is a process that leads to the chemical transformation of one set of chemical substances to another. Classically, chemical reactions encompass changes that only involve the positions of electrons in the forming and break ...
s. For example, oxidation of (+)-glyceraldehyde (1) with
mercury oxide Mercury oxide can refer to: * Mercury(I) oxide (mercurous oxide), Hg2O * Mercury(II) oxide Mercury(II) oxide, also called mercuric oxide or simply mercury oxide, is the inorganic compound with the formula Hg O. It has a red or orange color. Mer ...
gives (−)- glyceric acid (2), a reaction that does not alter the stereocenter. Thus the absolute configuration of (−)-glyceric acid must be the same as that of (+)-glyceraldehyde.
Nitric acid Nitric acid is the inorganic compound with the formula . It is a highly corrosive mineral acid. The compound is colorless, but older samples tend to be yellow cast due to decomposition into oxides of nitrogen. Most commercially available ni ...
oxidation of (+)- isoserine (3) gives (–)-glyceric acid, establishing that (+)-isoserine also has the same absolute configuration. (+)-Isoserine can be converted by a two-stage process of bromination and
zinc Zinc is a chemical element with the symbol Zn and atomic number 30. Zinc is a slightly brittle metal at room temperature and has a shiny-greyish appearance when oxidation is removed. It is the first element in group 12 (IIB) of the periodic t ...
reduction to give (–)-
lactic acid Lactic acid is an organic acid. It has a molecular formula . It is white in the solid state and it is miscible with water. When in the dissolved state, it forms a colorless solution. Production includes both artificial synthesis as well as natur ...
, therefore (–)-lactic acid also has the same absolute configuration. If a reaction gave the enantiomer of a known configuration, as indicated by the opposite sign of optical rotation, it would indicate that the absolute configuration is inverted. : In 1951, Johannes Martin Bijvoet for the first time used in
X-ray crystallography X-ray crystallography is the experimental science determining the atomic and molecular structure of a crystal, in which the crystalline structure causes a beam of incident X-rays to diffract into many specific directions. By measuring the angle ...
the effect of anomalous dispersion, which is now referred to as resonant scattering, to determine absolute configuration. The compound investigated was (+)-sodium rubidium tartrate and from its configuration (''R'',''R'') it was deduced that the original guess for (+)-glyceraldehyde was correct. Despite the tremendous and unique impact on access to molecular structures, X-ray crystallography poses some challenges. The process of crystallization of the target molecules is time- and resource-intensive, and can not be applied to relevant systems of interest such as many biomolecules (some proteins are an exception) and ''in situ'' catalysts. Another important limitation is that the molecule must contain ‘heavy’ atoms (for example, bromine) to enhance the scattering. Furthermore, crucial distorsions of the signal arise from the influence of the nearest neighbors in any
crystal structure In crystallography, crystal structure is a description of the ordered arrangement of atoms, ions or molecules in a crystalline material. Ordered structures occur from the intrinsic nature of the constituent particles to form symmetric patterns t ...
and of solvents used during the
crystallization Crystallization is the process by which solid forms, where the atoms or molecules are highly organized into a structure known as a crystal. Some ways by which crystals form are precipitating from a solution, freezing, or more rarely de ...
process. Just recently, novel techniques have been introduced to directly investigate the absolute configuration of single molecules in gas-phase, usually in combination with ''ab initio'' quantum mechanical theoretical calculations, therefore overcoming some of the limitations of the X-ray crystallography.


Conventions


By absolute configuration: ''R''- and ''S''-

The ''R / S'' system is an important nomenclature system for denoting enantiomers. This approach labels each chiral center ''R'' or ''S'' according to a system by which its substituents are each assigned a ''priority'', according to the
Cahn–Ingold–Prelog priority rules In organic chemistry, the Cahn–Ingold–Prelog (CIP) sequence rules (also the CIP priority convention; named for R.S. Cahn, C.K. Ingold, and Vladimir Prelog) are a standard process to completely and unequivocally name a stereoisomer of a ...
(CIP), based on atomic number. When the center is oriented so that the lowest-priority substituent of the four is pointed away from the viewer, the viewer will then see two possibilities: if the priority of the remaining three substituents decreases in clockwise direction, it is labeled ''R'' (for '' Rectus'', Latin for right); if it decreases in counterclockwise direction, it is ''S'' (for '' Sinister'', Latin for left). (''R'') or (''S'') is written in italics and parentheses. If there are multiple chiral carbons, e.g. (1''R'',4''S''), a number specifies the location of the carbon preceding each configuration. The ''R / S'' system also has no fixed relation to the system. For example, the side-chain one of
serine Serine (symbol Ser or S) is an α-amino acid that is used in the biosynthesis of proteins. It contains an α- amino group (which is in the protonated − form under biological conditions), a carboxyl group (which is in the deprotonated − for ...
contains a hydroxyl group, -OH. If a thiol group, -SH, were swapped in for it, the labeling would, by its definition, not be affected by the substitution. But this substitution would invert the molecule's ''R / S'' labeling, because the CIP priority of CH2OH is lower than that for CO2H but the CIP priority of CH2SH is higher than that for CO2H. For this reason, the system remains in common use in certain areas of biochemistry, such as amino acid and carbohydrate chemistry, because it is convenient to have the same chiral label for the commonly occurring structures of a given type of structure in higher organisms. In the system, nearly all naturally occurring amino acids are all , while naturally occurring carbohydrates are nearly all . All proteinogenic amino acids are ''S'', except for
cysteine Cysteine (symbol Cys or C; ) is a semiessential proteinogenic amino acid with the formula . The thiol side chain in cysteine often participates in enzymatic reactions as a nucleophile. When present as a deprotonated catalytic residue, s ...
, which is ''R''.


By optical rotation: (+)- and (−)- or ''d-'' and ''l-''

An enantiomer can be named by the direction in which it rotates the plane of polarized light. Clockwise rotation of the light traveling toward the viewer is labeled (+) enantiomer. Its mirror-image is labeled (−). The (+) and (−) isomers have been also termed ''d-'' and ''l-'' (for ''dextrorotatory'' and ''levorotatory''); but, naming with ''d-'' and ''l-'' is easy to confuse with - and - labeling and is therefore discouraged by
IUPAC The International Union of Pure and Applied Chemistry (IUPAC ) is an international federation of National Adhering Organizations working for the advancement of the chemical sciences, especially by developing nomenclature and terminology. It is ...
.


By relative configuration: - and -

An optical isomer can be named by the spatial configuration of its atoms. The system (named after Latin dexter and laevus, right and left), not to be confused with the ''d-'' and ''l-''system, see above, does this by relating the molecule to
glyceraldehyde Glyceraldehyde (glyceral) is a triose monosaccharide with chemical formula C3 H6 O3. It is the simplest of all common aldoses. It is a sweet, colorless, crystalline solid that is an intermediate compound in carbohydrate metabolism. The word ...
. Glyceraldehyde is chiral itself and its two isomers are labeled and (typically typeset in
small caps In typography, small caps (short for "small capitals") are characters typeset with glyphs that resemble uppercase letters (capitals) but reduced in height and weight close to the surrounding lowercase letters or text figures. This is technica ...
in published work). Certain chemical manipulations can be performed on glyceraldehyde without affecting its configuration, and its historical use for this purpose (possibly combined with its convenience as one of the smallest commonly used chiral molecules) has resulted in its use for nomenclature. In this system, compounds are named by analogy to glyceraldehyde, which, in general, produces unambiguous designations, but is easiest to see in the small biomolecules similar to glyceraldehyde. One example is the chiral amino acid
alanine Alanine (symbol Ala or A), or α-alanine, is an α-amino acid that is used in the biosynthesis of proteins. It contains an amine group and a carboxylic acid group, both attached to the central carbon atom which also carries a methyl group side ...
, which has two optical isomers, and they are labeled according to which isomer of glyceraldehyde they come from. On the other hand,
glycine Glycine (symbol Gly or G; ) is an amino acid that has a single hydrogen atom as its side chain. It is the simplest stable amino acid ( carbamic acid is unstable), with the chemical formula NH2‐ CH2‐ COOH. Glycine is one of the proteinog ...
, the amino acid derived from glyceraldehyde, has no optical activity, as it is not chiral (it's achiral). The labeling is unrelated to (+)/(−) - it does not indicate which enantiomer is dextrorotatory and which is levorotatory. Rather, it indicates the compound's stereochemistry relative to that of the dextrorotatory or levorotatory enantiomer of glyceraldehyde. The dextrorotatory isomer of glyceraldehyde is, in fact, the isomer. Nine of the nineteen -amino acids commonly found in proteins are dextrorotatory (at a wavelength of 589 nm), and -fructose is also referred to as levulose because it is levorotatory. A rule of thumb for determining the isomeric form of an amino acid is the "CORN" rule. The groups :COOH, R, NH2 and H (where R is the side-chain) are arranged around the chiral center carbon atom. With the hydrogen atom away from the viewer, if the arrangement of the CO→R→N groups around the carbon atom as center is counter-clockwise, then it is the form. If the arrangement is clockwise, it is the form. As usual, if the molecule itself is oriented differently, for example, with H towards the viewer, the pattern may be reversed. The form is the usual one found in natural proteins. For most amino acids, the form corresponds to an ''S'' absolute stereochemistry, but is ''R'' instead for certain side-chains.


See also

*
Molecular configuration The molecular configuration of a molecule is the ''permanent'' geometry that results from the spatial arrangement of its bonds. The ability of the same set of atoms to form two or more molecules with different configurations is stereoisomerism. ...


References

{{Navbox stereochemistry Stereochemistry