Chiral Stationary Phases

Recently, there has been a great surge of activity in the field of chirality and the interactions of chiral molecules, driven to a large extent by the needs of the pharmaceutical industry to develop new drugs, many of which are chiral, but also the need to develop new detection technologies for biomedical applications (such as microfluidics), where the targets are of course inherently chiral. One of the more interesting applications is the chiral stationary phase, as developed by Pirkle. This is a form of column chromatography where the silica particles are coated with a chiral molecule anchored to the silicone via a siloxane linkage. The technique depends on the formation of diastereomeric complexes between the selector molecule and the target, as seen in Figure 5.

Figure 5 Schematic of the process of separating enantiomers using a chiral stationary phase.
There are many such columns on the market, with certain selector molecules that are specific to particular types of chiral molecules. In our work, we model these systems using both experimental and theoretical methods, in order to find out just what characteristics of the selector molecule can give rise to chiral selectivity. In the long run, this would allow us to rationally design a selector molecule that is specific to a particular task.

We take two approaches to this work. First, we measure the forces acting between two enantiomers directly, by attaching molecules to an AFM tip and to an oxidized Si surface. This scheme models what really takes place in the chromatographic column. Secondly, in collarboration with Dr. Natalie Cann of the chemistry department, we use molecular dynamics simulations to study the interactions of solvent molecules with the chiral molecules at the sample or tip surface. As an example, Figure 6 shows the interaction forces (in nN) between an AFM tip and Si sample both coated with a derivative of phenylglycine. The data suggests much stronger interactions between the R-R or S-S diastereomers than the R-S or S-R pairs. The molecular dynamics simulations suggest that this is due to the formation of strong H-bonding networks at the interface.

Figure 6 Chiral discrimination using a phenylglycine derivative chiral stationary phase.