Jirapongphan Siricharn S, Warzywoda Juliusz, Budil David E, Sacco Albert
Department of Chemical Engineering, Center for Advanced Microgravity Materials Processing, Northeastern University, Boston, Massachusetts 02115, USA.
Chirality. 2007 Jun;19(6):508-13. doi: 10.1002/chir.20408.
Insight into enantioselective separation utilizing chiral-modified zeolite HY could be useful in designing a chiral stationary phase for resolving pharmaceutical compounds. A model was employed to better understand the enantioseparation of valinol in zeolite HY that contains (+)-(1R;2R)-hydrobenzoin as a chiral modifier. This model incorporates the zeolite support and accounts for the flexible change. Results from grand canonical Monte Carlo and molecular dynamics simulations indicate that the associated diastereomeric complex consists of a single (+)-(1R;2R)-hydrobenzoin and a single valinol molecules located in the zeolite HY supercage. Supercage-based docking simulation predicted an enantioselectivity of 2.6 compared with that of 1.4 measured experimentally. Also, the supercage-based docking simulation demonstrated a single binding motif in the S complex, and two binding motifs in the R complex. The multiple binding modes in the R complex resulted in its lower stability. This is hypothesized to be the origin of the weaker binding between (-)-(R)-valinol and the chiral modifier, and explains why (+)-(R)-valinol is retained more in the chiral-modified zeolite system studied.
深入了解利用手性修饰的HY沸石进行对映体分离，可能有助于设计用于拆分药物化合物的手性固定相。采用一个模型来更好地理解在含有(+)-(1R;2R)-氢化苯偶姻作为手性修饰剂的HY沸石中缬氨醇的对映体拆分。该模型纳入了沸石载体并考虑了柔性变化。巨正则蒙特卡罗模拟和分子动力学模拟结果表明，相关的非对映体复合物由单个(+)-(1R;2R)-氢化苯偶姻和位于HY沸石超笼中的单个缬氨醇分子组成。基于超笼的对接模拟预测对映选择性为2.6，而实验测得的对映选择性为1.4。此外，基于超笼的对接模拟表明，S复合物中有一个单一的结合基序，而R复合物中有两个结合基序。R复合物中的多种结合模式导致其稳定性较低。据推测，这是(-)-(R)-缬氨醇与手性修饰剂之间结合较弱的原因，并解释了为什么(+)-(R)-缬氨醇在研究的手性修饰沸石体系中保留得更多。
