Absolute configuration

An absolute configuration refers to the spatial arrangement of the atoms of a chiral molecular entity (or group) and its stereochemical description e.g. R or S, referring to Rectus, or Sinister, respectively. An absolute configuration refers to the spatial arrangement of the atoms of a chiral molecular entity (or group) and its stereochemical description e.g. R or S, referring to Rectus, or Sinister, respectively. Absolute configurations for a chiral molecule (in pure form) are most often obtained by X-ray crystallography. All enantiomerically pure chiral molecules crystallise in one of the 65 Sohncke groups (chiral space groups). Alternative techniques are optical rotatory dispersion, vibrational circular dichroism, 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 (R)-enantiomer. The configuration of other chiral compounds was then related to that of (+)-glyceraldehyde by sequences of chemical reactions. For example, oxidation of (+)-glyceraldehyde (1) with mercury oxide 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 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 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 (R,R) it was deduced that the original guess for (+)-glyceraldehyde was correct. 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 (CIP), 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 (for Rectus, Latin for right), if it decreases in counterclockwise direction, it is S (for Sinister, Latin for left). (R) (S) is written in italics and parentheses. If there are multiple chiral carbons, e.g. (1R,4S), a number specifies the location of the carbon preceding each configuration.