In 1956, Robert Sidney Cahn, Christopher Ingold and Vladimir Prelog developed a nomenclature system that, based on a few simple rules, allows to assign the absolute configuration of each chirality center in a molecule.[1][5]
This nomenclature system, called the RS system, or the Cahn-Ingold-Prelog (CIP) system, when added to the IUPAC system of nomenclature,[3] allows to name accurately and unambiguously the chiral molecules, even when there is more than one asymmetric center.
Chiral molecules are, in most cases, able to rotate plane-polarized light when light passes through a solution containing them. In this regard, it should be emphasized that the sign of the rotation of plane-polarized light caused by a chiral compound provides no information concerning RS configuration of its chiral centers.
The Fischer-Rosanoff convention is another way to describe the configuration of chiral molecules.[6] However, compared to RS system, it labels the whole molecule and not each chirality center, and is often ambiguous for molecules with two or more chirality centers.[7]
Contents
The priority rules of the RS system
The RS system assigns a priority sequence to the groups attached to the chirality center and, tracing a curved arrow from the highest priority group to the lowest, labels each chiral center R or S.[2][4]
First rule
A priority sequence is assigned to the groups based on the atomic number of the atoms directly attached to the chiral center.
- The atom with the highest atomic number is assigned the highest priority.
- The atom with the lowest atomic number is assigned the lowest priority.
For example, if an oxygen atom, O, atomic number 8, a carbon atom, C, atomic number 6, a chlorine atom, Cl, atomic number 17, and a bromine atom, Br, atomic number 35 are attached to the chiral center, the order of priority is: Br > Cl > O > C.
For isotopes, the atom with the highest atomic mass is assigned the highest priority.
Second rule
When different groups are attached to the chiral center through identical atoms, the priority sequence is assigned based on the atomic number of the next atoms bound, then moving outward from the chirality center until the first point of difference is reached.
If, for example, –CH3, –CH2CH3 and –CH2OH groups are attached to a chiral center, there are three identical atoms directly attached to the chiral center. Analyzing the next atoms bound, we have:
| for the methyl group –CH3 | H, H, H |
| for the ethyl group –CH2CH3 | H, H, C |
| for the hydroxymethyl group –CH2OH | H, H, O |
Because the atomic number of oxygen is higher than that of carbon, that, in turn, is higher than that of hydrogen, the order of priority is –CH2OH > –CH2CH3 > –CH3
The order of priority of some groups is:
–I > –Br > –Cl > –SH > –OR > –OH > –NHR > –NH2 > –COOR > –COOH > –CHO > –CH2OH > –C6H5 > –CH3 > –2H > –1H
Note that the groups attached to a chirality center must not have identical priority ranking, because, in that case, the center cannot be chiral.
Once the priority sequence has been established, the molecule is oriented in space so that the group with the lowest priority is pointed away from the viewer, then behind the chiral center. Now, trace a curved arrow, a circle, from the highest priority group to the lowest.
- If you move in a clockwise direction, the configuration of chiral center is R, from the Latin rectus, meaning “right”.
- If you move in a counterclockwise direction, the configuration of chiral center is S, from the Latin sinister, meaning “left”.
Third rule
This is the third rule of the RS system, by which we can determine the configuration of a chirality center when there are double or triple bonds in the groups attached to the chirality center.
To assign priorities, the atoms engaged in double or triple bonds are considered duplicated and tripled, respectively.
In the case of a C=Y double bond, one Y atom is attached to the carbon atom, and one carbon atom is attached to the Y atom.
In the case of a C≡Y triple bond, two Y atoms are attached to the carbon atom, and two carbon atoms are attached to the Y atom.
RS system and multiple chiral centers
When two or more chirality centers are present in a molecule, each center is analyzed separately using the rules previously described.
Consider 2,3-butanediol. The molecule has two chiral centers, carbon 2 and carbon 3, and exists as three stereoisomers: two enantiomers and a meso compound. What is the RS configuration of the chiral centers of the enantiomer shown in figure?
Consider carbon 2. The order of priority of the groups is –OH > –CH2OHCH3 > –CH3 > –H. Rotate the molecule so that the hydrogen, the lowest priority group, is pointed away from the viewer. Tracing a path from –OH, the highest priority group, to –CH3, the lowest priority group, we move in a clockwise direction: the configuration of the carbon 2 is, therefore, R. Applying the same procedure to carbon 3, its configuration is R. Then, the enantiomer shown in figure is (2R,3R)-2,3-butanediol.
Amino acids and gliceraldeide
In the Fischer-Rosanoff convention, all the proteinogenic amino acids are L-amino acids. In the RS system, with the exception of glycine, that is not chiral, and cysteine that, due to the presence of the thiol group, is (R)-cysteine, all the other proteinogenic amino acids are (S)-amino acids.
Threonine and isoleucine have two chirality centers, the α-carbon and a carbon atom on the side chain, and exist as three stereoisomers: two enantiomers and a meso compound. The forms of the two amino acids isolated from proteins are (2S,3R)-threonine and (2S,3S)-isoleucine, in Fischer-Rosanoff convention, L-threonine and L-isoleucine.
In the RS system, L-glyceraldehyde is (S)-glyceraldehyde, and, obviously, D-glyceraldehyde is (R)-glyceraldehyde.
References
- ^ Cahn R.S., Ingold C., Prelog V. Specification of molecular chirality. Angew Chem 1966:5(4); 385-415. doi:10.1002/anie.196603851
- ^ Garrett R.H., Grisham C.M. Biochemistry. 4th Edition. Brooks/Cole, Cengage Learning, 2010
- ^ IUPAC. Compendium of Chemical Terminology, 2nd ed. (the “Gold Book”). Compiled by A. D. McNaught and A. Wilkinson. Blackwell Scientific Publications, Oxford (1997). Online version (2019-) created by S. J. Chalk. ISBN 0-9678550-9-8. doi:10.1351/goldbook
- ^ Moran L.A., Horton H.R., Scrimgeour K.G., Perry M.D. Principles of Biochemistry. 5th Edition. Pearson, 2012
- ^ Prelog V. and Helmchen G. Basic principles of the CIP‐system and proposals for a revision. Angew Chem 1982:21(8);567-583. doi:10.1002/anie.198205671
- ^ Rosanoff M.A. On Fischer’s classification of stereo-isomers. J Am Chem Soc 1906:28(1);114-121. doi:10.1021/ja01967a014
- ^ Voet D. and Voet J.D. Biochemistry. 4th Edition. John Wiley J. & Sons, Inc. 2011