Date of Award

5-2011

Degree Type

Dissertation

Degree Name

Doctor of Philosophy

Major

Chemistry

Major Professor

Georges Guiochon

Committee Members

Douglas Gordon Hayes, Shawn Campagna, Jon Camden

Abstract

Acid/base modifiers are sometimes used as additives in the elution on columns packed with amylose tris(3,5-dimethylphenylcarbamate) stationary phase to separate enantiomers. When modifiers are removed from the mobile phase, the stationary phase is affected in ways that are not understood because of the lack of systematic studies, making the scale-up of preparative separations difficult to predict. Once a column has been exposed to these modifiers, the selectivity of certain pairs of enantiomers may change, for the better or the worse. Numerous pairs of molecules affected by this phenomenon are listed in the literature. Five pairs of these molecules were chosen, the selectivity of which changes after an acidic or basic solutions has been percolated through the column. The selectivity of the ketoprofen, 4-chlorophenylalanine methyl and ethyl esters improves after a solution of ethanesulfonic acid is percolated through the column. The selectivity of the propranolol HCl and Troger’s base increases after a solution of diiospropylethylamine is percolated through the column. The selectivity of these the 4-chlorophenylalanine ethyl ester, propranolol and Troger's base enantiomers are inversely affected by percolation of the opposite acid/base solution. This residual change in certain enantiomeric separations has been named the Memory Effect. In contrast, trans-stilbene oxide (TSO) was used as a standard to determine the column's stability because no Memory Effect is observed for this separation (the retention, enantioselectivity, and resolution remain constant). Karl Fischer titrations showed that only slight changes in the mobile phase's water content occurred, and that the water to polymer repeat unit ratio is important. Analytical studies of the stationary phase suggest that slow protonation/deprotonation of water bounded to the carbamate moiety may be responsible for the Memory Effect. It has been shown that the Memory Effect can be minimized by percolating through the column a sufficiently concentrated solution of the appropriate acid or base. Thus, columns that were unreliable for method development, due to the Memory Effect, can now be used. As a result, the scale-up of separations can be predicted and successfully performed. Finally, a test was devised to determine if a column was under the influence of the Memory Effect.

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