Aslani Saba, Armstrong Daniel W
Department of Chemistry and Biochemistry, University of Texas at Arlington, 700 Planetarium Place, Arlington, TX, 76019, United States.
Department of Chemistry and Biochemistry, University of Texas at Arlington, 700 Planetarium Place, Arlington, TX, 76019, United States.
Talanta. 2023 Dec 1;265:124857. doi: 10.1016/j.talanta.2023.124857. Epub 2023 Jun 26.
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 sp vs. an sp 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 sp hybridized carbon always had greater retention than the analogous compound where deuterium was connected to an sp 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.
氘代在药物分子中具有多种益处，包括改善药代动力学性质、降低毒性、减少差向异构化等。此外，研究表明氘代的位置会影响药物分子的性质。因此，研究构成氘代库且是较大氘代分子构建单元的低分子量氘代同位素体非常重要。评估了氘原子的位置和数量对23种氘代同位素体在两种不同极性气相色谱固定相上保留情况的影响。观察到，对于每组同位素体，与非极性的PDMS - 5相比，连接到sp与sp杂化碳上的氘原子所产生的计算色谱同位素效应的比率在极性IL - 111i固定相上更大。而且，一个氘原子连接到sp杂化碳的化合物的保留时间总是比氘连接到sp杂化碳的类似化合物更长。所有分析物的范特霍夫图表明，在氘代与质子化同位素体的分离中，熵的影响几乎可以忽略不计，因此这些分离主要由焓驱动。
