Molecular Requirements for Chiral Recognition

To facilitate the understanding of chiral recognition at the molecular level, a number of attempts have been made to define minimum criteria in terms of the required intermolecular SO-SA interactions [67-74]. The currently most widely accepted concept is known as the three-point rule [67]. This rule states that for chiral recognition to occur a minimum of three simultaneous interactions between SO and at least one of the enantiomers is required, with at least one of these interactions being stereochemicaUy dependent. This concept is graphically illustrated in Fig. 7.3. 

On approaching the SO, each of the SA enantiomers can readily establish a set of two interactions with the SO. Due to the different orientations of their functional sites in space, however, only one of the enantiomers is capable of simultaneously undergoing a third interaction with the SO. Thus, chiral recognition between the SA enantiomers and the SO is ultimately achieved by the presence or absence of this crucial stereochemicaUy dependent interaction. 

Confusion often arises due to misinterpretation of the term interaction within the conceptional framework of the three-point rule. It is important to understand that in this particular context interaction refers to intermolecular physical forces and their steric implication rather than to specific spatial relationships between substructure elements in the SO and SA entities. This distinction is crucial as intermolecular forces, depending on their physical nature, may be of single-point or of multi-point quality. For example, forces acting exclusively between specific 

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