Absolute configuration


An absolute configuration refers to the spatial arrangement of the atoms of a chiral molecular entity and its stereochemical description e.g. R or S, referring to Rectus, or Sinister, respectively.
Absolute configurations for a chiral molecule are most often obtained by X-ray crystallography. All enantiomerically pure chiral molecules crystallise in one of the 65 Sohncke groups.
Alternative techniques are optical rotatory dispersion, vibrational circular dichroism, ultraviolet-visible spectroscopy, use of chiral shift reagents in proton NMR and Coulomb explosion imaging.
When the absolute configuration is obtained the assignment of R or S is based on the Cahn–Ingold–Prelog priority rules.
Absolute configurations are also relevant to characterization of crystals.
Until 1951 it was not possible to obtain the absolute configuration of chiral compounds. It was at some time decided that -glyceraldehyde was the -enantiomer. The configuration of other chiral compounds was then related to that of -glyceraldehyde by sequences of chemical reactions. For example, oxidation of -glyceraldehyde with mercury oxide gives -glyceric acid, 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 oxidation of -isoserine 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 reduction to give -lactic acid, 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 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 it was deduced that the original guess for -glyceraldehyde was correct.

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, based on atomic number. If the center is oriented so that the lowest-priority of the four is pointed away from a viewer, the viewer will then see two possibilities: If the priority of the remaining three substituents decreases in clockwise direction, it is labeled R, if it decreases in counterclockwise direction, it is S.
is written in italics and parentheses. If there are multiple chiral carbons, e.g., 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 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, they are nearly all consistent—naturally occurring amino acids are all, while naturally occurring carbohydrates are nearly all. In the R / S system, they are mostly S, but there are some common exceptions.

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- ; But, naming with d- and l- is easy to confuse with - and - labeling and is therefore discouraged by IUPAC.

By relative configuration: - and -

An optical isomer can be named by the spatial configuration of its atoms. The system, not to be confused with the d- and l-system,, does this by relating the molecule to glyceraldehyde. Glyceraldehyde is chiral itself, and its two isomers are labeled and . Certain chemical manipulations can be performed on glyceraldehyde without affecting its configuration, and its historical use for this purpose 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, which has two optical isomers, and they are labeled according to which isomer of glyceraldehyde they come from. On the other hand, glycine, the amino acid derived from glyceraldehyde, has no optical activity, as it is not chiral.
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, 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:
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.