Stationary Phase Limitation by Exclusion

In the past the term exclusion chromatography implied that solute retention depends solely on solute molecule size. However, this will be true only if the magnitude of the forces between the solute and both phases is the same. By appropriate choice of the mobile phase this unique situation can be closely approached and under such circumstances the larger molecules, being partially or wholly excluded, will elute first and the smaller molecules elute last. It should be emphasized that, even when the dominant retention mechanism is controlled by molecular forces between the solute and the two phases, if the stationary phase or supporting material has a porosity commensurate with the molecular size of the solutes, exclusion can still play a significant part in retention but this rarely occurs in GC.

Chiral Stationary Phases

The technique of gas chromatography was invented in the early 1950's, progress was rapid and the main developments were completed and the methodology well established by 1960. Nevertheless, although sporadic efforts were made to separate chiral substances in the late 1950s, the use of GC to separate enantiomers was not proved successful until the mid 1960s, The two main reasons, as already explained, were a common lack of interest in chiral separations and, consequently, little impetus to develop the separation of chiral substances generally. In addition, the separation of enantiomers was also very difficult with the phases then available, so it was found quite laborious to obtain adequate selectivity to achieve a separation.

As already discussed, thermodynamically, the separation of two substances can only be achieved in a chromatographic system if their standard energy's differ. Now the difference between enantiomers is spatial and not structural, thus, any separation must be achieved by primarily changing the relative standard entropy contribution to the standard free energy of each isomer. This does not exclude an accompanying significant contribution of standard energy from a simultaneous change in standard enthalpy, but the primary effect must be entropic in order to promote the corresponding change in standard enthalpy. Consequently, to obtain enantiomeric selectivity, the structure of the stationary phase must be such that one isomer will fit more closely to the stationary phase molecules (or surface) than the other(s). It is clear that one way of achieving selectivity would be to use another chiral substance as the stationary phase.