Effect of position of deuterium atoms on gas chromatographic isotope effects

Abstract

Deuterium substitution provides various benefits in drug molecules, including improvement in pharmacokinetic properties, reduction of toxicity, reduction of epimerization, etc. Also, it has been shown that the position of deuterium substitution affects the properties of drug molecules. Therefore, it is important to study low molecular weight deuterated isotopologues which constitute the deuterated pool and are building blocks of larger deuterated molecules. The effect of the position and number of deuterium atoms on the retention of 23 deuterated isotopologues on two gas chromatography stationary phases of different polarities was evaluated. It was observed that the ratio of calculated chromatographic isotope effects resulting from a deuterium atom connected to an sp2 vs. an sp3 hybridized carbon was more on the polar IL-111i stationary phase compared to the nonpolar PDMS-5, for each group of isotopologues. Also, a compound with a deuterium atom connected to an sp2 hybridized carbon always had greater retention than the analogous compound where deuterium was connected to an sp3 hybridized carbon. The van't Hoff plots for all analytes showed that the effect of entropy was almost negligible in the separation of deuterated vs. protiated isotopologues, thus these separations were mainly enthalpy driven.