Single-isomer science: the phenomenon and its terminology

Abstract

Single-isomer drugs are of great importance in modern therapeutics. In this article, the basics of the underlying phenomenon are explained. Some molecules are chiral, ie, their mirror image is not superposable on the original. The most common element producing molecular chirality is a chiral center, typically a carbon atom carrying four different groups. The mirror-image molecules are termed enantiomers, but the less specific terms stereoisomers and isomers are also used. A substance consisting of only one of the two enantiomers is a single enantiomer or single isomer, and the 1:1 mixture of the enantiomers is the racemic mixture or racemate. A graphical convention that conveys the three-dimensional aspects of chiral molecules drawn in two dimensions, as well as two nongraphical conventions, based on optical rotation and configuration, are used to identify enantiomers. Optical rotation is a physical property of single enantiomers and involves rotation of the plane of plane-polarized light, each pure enantiomer rotating with equal magnitude but in the opposite direction (dextro and levo). Configuration is the actual arrangement in space of the atoms of chiral molecules. Two systems of indicating configuration are in use. One employs D and L to denote the respective enantiomers, and is applicable only to a-amino acids and carbohydrates. The other is a universal system using R and S as descriptors for the two possible arrangements, respectively, of the atoms around the chiral center. Interest in chiral drugs stems from the frequently observed biological differences between enantiomers. Such enantioselectivity is the result of different interactions of the drug enantiomers with target receptors that are themselves chiral and single-enantiomeric.