Factors That Control Successful Entropically Driven Chiral Separations in SFC and HPLC

With temperature increases, selectivity of chiral separations decreases until enantiomers coelute at an isoelution temperature. Above this temperature, elution order should reverse and selectivity will increase with temperature. In this region, separation is termed "entropically driven". Entropically driven chiral separations hold the promise of being able to concurrently increase selectivity and column efficiency by means of increased temperature. The ability to achieve such separations is hindered by high isoelution temperatures. The isoelution temperature is determined by a balance of enthalpic and entropic contributions. A variety of mobile phase modifiers are evaluated for their ability to moderate these contributions. Results suggest that more use should be made of non-alcohol modifiers. The major barrier to entropically driven separations was found to be the nonspecific retention increase that is characteristic when the critical temperature is traversed. Use of hexane in place of CO(2) shifts the position of the retention increase away from the temperature range used in this study, and dramatically successful entropically driven chiral separations are obtained.