The Concept of Chirality and the Basic Properties of Chiral Structures

Introduction

Before one can consider how to separate a chiral mixture, be it by gas chromatography (GC) or liquid chromatography (LC), it is essential to understand how chiral substances differ from each other and, conversely, to what extent they resemble one another. It will be seen from future discussions, that most chiral pairs are almost chemically identical and only differ significantly in the spatial arrangement of their composite atoms and/or chemical groups. It follows, that the unique properties of each chiral isomer will not be determined so much by the strength and nature of their interaction with a host molecule, but by the geometry and spatial disposition of the interacting parts which, in turn, will determine how close the isomer molecules and the host molecule can approach each other to interact. The great chemical similarity between chiral pairs can make their separation extremely difficult and, as a consequence, chiral separations usually demand the use of highly efficient separating devices in conjunction with exceptionally selective distribution systems.

Up till about 1980 there was very limited interest in chiral materials but this attitude changed rapidly with the discovery that the pharmacology of the geometric isomers of physiologically active compounds could differ very greatly. In drugs, the effect of this difference, under extreme circumstances could be very dangerous and possibly fatal. As a result, commercial interest in the separation of chiral substances (in particular chiral drugs) increased very rapidly. The FDA now insists that for any drug that can exist as chiral isomers, the physiological activity of each chiral isomer must be individually tested and the physiological effect of each clearly and unambiguously identified. It follows that the separation and identification of isomers has now become a very important analytical problem and it has been shown that chromatographic techniques can be very effective in the resolution of such mixtures. The use of GC for the separation of spatial isomers is not so widely applicable as LC, but the GC system is generally two to three orders of magnitude more sensitive than LC and can be much faster. In addition, as a result of the high number of theoretical plates available from capillary columns, GC has potentially a much higher resolving power and, consequently, is often the method of choice for many chiral analyses providing the chiral isomers are volatile or volatile derivatives can be formed.