O'Brien T, Crocker L, Thompson R, Thompson K, Toma P H, Conlon D A, Feibush B, Moeder C, Bicker G, Grinberg N
Merck Research Laboratories, R80Y-115, P.O. Box 2000, Rahway, New Jersey 07065.
Anal Chem. 1997 Jun 1;69(11):1999-2007. doi: 10.1021/ac961241l.
Cellulose and cellulose derivatives are biopolymers which are often used as stationary phases for the separation of enantiomers. Describing the mechanism of such separations is a difficult task due to the complexity of these phases. In the present study, we attempt to elucidate the types of interactions occurring between a diol intermediate for a LTD(4) antagonist and a tris(4-methylbenzoate)-derivatized cellulose stationary phase. Thermodynamic studies indicate that, at low temperatures, the enantioselectivity is entropy driven. At higher temperatures, the separation is enthalpy driven. DSC and IR experiments reveal 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. Investigation of chromatographic kinetic parameters reveals that, at low temperature, the second eluted enantiomer undergoes sluggish inclusion interactions. Subtle changes in the structure of the analyte indicates that π-π interactions do not contribute to enantioselectivity. Finally, molecular modeling of (R)- and (S)-diol and the stationary phase suggests that hydrogen bonding is a primary factor in the separation, and the calculated energy values obtained from the molecular modeling correlate well with the chromatographic elution order.
纤维素及纤维素衍生物是生物聚合物，常被用作对映体分离的固定相。由于这些固定相的复杂性，描述此类分离的机制是一项艰巨的任务。在本研究中，我们试图阐明白三烯D4（LTD4）拮抗剂的二醇中间体与三（4-甲基苯甲酸酯）衍生化纤维素固定相之间发生的相互作用类型。热力学研究表明，在低温下，对映选择性是由熵驱动的。在较高温度下，分离是由焓驱动的。差示扫描量热法（DSC）和红外光谱（IR）实验表明，范特霍夫曲线中焓区和熵区之间的转变是固定相构象变化的结果。对色谱动力学参数的研究表明，在低温下，第二个洗脱的对映体经历缓慢的包合相互作用。分析物结构的细微变化表明，π-π相互作用对对映选择性没有贡献。最后，（R）-和（S）-二醇与固定相的分子模拟表明，氢键是分离的主要因素，从分子模拟获得的计算能量值与色谱洗脱顺序具有良好的相关性。
