Chiral entropically driven

Examples of entropically driven separations are chiral separations and separations that are dominated by size exclusion. However, it must be emphasized that chromatographic separations can not be exclusively "energetically driven" or "entropically driven" but will always contain both components. It is by the careful adjustment of both "energetic" and "entropic" components of the distribution that very difficult and subtle separations can be accomplished. 

Temperature can also be used to optimize enantioselectivity in SFC. The selectivity of most CSPs increases as temperature decreases. For this reason, most chiral separations in SFC are performed at ambient or subambient temperatures [50, 74]. Subambient temperatures are particularly useful for compounds having low conformational stability [75]. Stringham and Blackwell explored the concept of entropically driven separations [76]. As temperature increased, enantioselectivity decreased until the enantiomers co-eluted at the isoelution temperature. Further increases in temperature resulted in reversal of elution order of the enantiomers. The temperature limitations of the CSP should be considered before working at elevated temperatures. 

Examples of entropically driven systems will be those employing chirally active stationary phases. 

This separation is an impressive example of an entropically driven distribution system where the normally random movements of the solute molecules are restricted to different extents depending on the spatial orientation of the substituent groups. For further information the reader is directed to an excellent review of chiral separations by LC (Taylor and Maher (12)) and a monograph on CYCLOBOND materials from ASTEC Inc. (13). 

R. W. Stringham and J. A. Blackwell, Entropically driven chiral separations in supercritical fluid chromatography. Confirmation of isoelution temperature and reversal of elution order, AnaZ. Chem. 68 (1996), 2179-2185. 

Stringham, R. W., Blackwell, J.A. Entropically Driven Chiral Separations in Supercritical Fluid Chromatography. Confirmation of Isoelution Temperature and Reversal of Elution Order, Anal. Chem., 1996, 68, 2179-2185. 

Stringham, R.W. Blackwell, J.A. Factors that control successful entropically driven chiral separations in SEC and HPLC. Anal. Chem. 1997, 69, 1414-1420. 

Stringham RW, Blackwell JA. Entropically driven chiral separations in supercritical fluid chromatography. 

In another study, thermodynamic parameters have been investigated with a tris(4-methyIbenzoate)-derivatized cellulose type CSP (Chiralcel OJ) and a chiral diol compound. It was found that at low temperatures, the enantioselectivity is entropy-driven (region 11), while at higher temperatures the separation is enthalpy-driven (region 1) (see Fig. 9.8). DSC and IR experiments revealed that the transitions between the enthalpic and the entropic regions of the van t Hoff plots are a result of a change in conformation of the stationary phase [76]. 

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