The Mechanism of Chromatographic Retention - Chiral Chromatography > Chiral Polysiloxane Stationary Phases > Page 76

It must be remembered that all molecules at the temperatures at which chromatographic separations are carried out are in continuous and violent motion as a result of their thermal energy. Consequently, the diagram can only represent a statistical possibility and the situation as shown could only be transient to say the least. Nevertheless, during the passage of a solute through a column, a molecule may randomly and transitorilly assume a position something like that depicted. Furthermore, inclusion is considered by many as an important factor contributing to retention.

Thus, there are two different interactive processes by which cyclodextrins can retain solutes and resolve enantiomers. One involves molecular interaction after inclusion, in which case the proper cavity size must be chosen to achieve the desired selectivity. The other process involves normal interaction with the surface of the stationary phase. If the enantiomer molecules are small enough so that inclusion can take place, then any of the three cyclodextrins might be appropriate. However, if the enantiomer molecules are relatively large (e.g. 3 to 5 aromatic rings) inclusion is not possible and only the g-cyclodextrin would be appropriate. It is also possible that inclusion is inhibited by the types of interactive groups on the solute molecule itself. In general, if the solute molecule contains dispersive groups, including the halogens, sulfo, and phospho groups, inclusion can readily take place. Conversely, polar groups, amines, aldehydes, ketones, acids etc. do not readily enter the cyclodextrin cavities and interact preferentially with the surface. As a corollary, if a stereogenic center contains a functional group that results in inclusion, then although the enantiomers may be well retained there will be little or no chiral selectivity. A computer model of R-Propanolol oriented in a b-cyclodextrin cavity is shown in figure 39.


Figure 39. A Computer Model of R-Propanolol Oriented in a b-cyclodextrin Cavity