Crystal morphology, absolute configuration

The morphological differences between crystals grown in the presence and absence of the additive would then indicate the direction of the substrate molecule W-Y with respect to the polar axis. Consequently, the absolute configuration of the crystal and of the chiral molecular constituents can be derived. The additive need not be chiral, and even if it is, the assignment of the absolute configuration... 

This anisotropic distribution of the occluded additive provides a second independent method of confirming the absolute configuration assigned by means of the morphological changes, once the mechanism of adsorption is known. This principle will be met again in the growth of centrosymmetric crystals. 

These effects have proved important in improving the methods available for resolution of enantiomers by crystallization (267). Furthermore, by studies of the morphological changes induced, one may determine the faces at which the impurities are dominantly attached (270,271). Then, in suitable systems, it is possible to determine the absolute configuration of a polar crystal if one knows that of the impurity (272), or to determine that of the impurity if one knows the structure of the centrosymmetric crystal with which it interacts (270). 

Addadi and coworkers (1985) have shown that chirality can be induced by the use of selective additives which modify crystal morphology. Thus, when (R, S)-threonine is crystallized in the presence of impurities, enantiomeric excess greater than 95% is readily obtained. The strategy also affords a means of determining the absolute configuration of the additive molecule. 

The stereochemical correlations between the enantiomorphic crystals and their chiral inhibitors, namely that the additive affects only the enantiomer of the same absolute configuration, provides us with a new method for the determination of absolute configuration on a relative scale. This is revealed independently by morphological changes and enantioselective occlusion of additives. The method is related to the quasi-racemate technique of Fredga [18], but has the advantage of a wider applicability. 

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