Ran Dou, Ke Chen, Guoli Chi, Jun Luo, Chung F. Wong, Baojing Zhou
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引用次数: 4
摘要
利用β-环糊精(β-CD)及其衍生物手性分离特布他林(TB)引起了广泛的关注。本文基于实验数据,采用分子动力学/量子力学/连续溶剂模型(MD/QM/CSM)方法研究了β-CD和庚基(2,3-二- o -乙酰基)-β-CD (HAD-β-CD)对TB的对映分离机理。我们的方法证实了HAD-β-CD/TB两种实验预测的结合模式之一,并将其归因于r复合物。R-TB被HAD-β- CD紧密包含:芳香环在CD腔内,而烷基部分也包含在CD腔内,并且几乎平行于CD的二级边缘。通过计算的结合亲和力表明,r -配合物的这种紧密结合模式增强了主-客体疏水相互作用,使r -配合物比s -配合物更稳定。相比之下,R- tb和S-TB与β-CD的结合方式相似,这是由于宿主的灵活性较差,危及其区分R- tb和S-TB的能力。
Why heptakis(2,3-di-O-acetyl)-β-cyclodextrin can separate terbutaline enantiomers better than β-cyclodextrin: nonbonding and hydrophobic interactions
The chiral separation of terbutaline (TB) using β-cyclodextrins (β-CD) and its derivatives has aroused intensive interest. Herein, the enantioseparation mechanisms of β-CD and heptakis(2,3-di-O-acetyl)-β-CD (HAD-β-CD) towards TB are investigated by a molecular dynamics/quantum mechanics/continuum solvent model (MD/QM/CSM) approach based on the experimental data. One of the two experimentally predicted binding modes of HAD-β-CD/TB is confirmed by our approach and ascribed to the R-complex. R-TB is compactly included by HAD-β- CD: the aromatic ring is within the CD cavity, while the alkyl moiety is also included and almost parallel to the secondary rim of the CD. As indicated by the computed binding affinity, this tight binding mode of R-complex enhances the host–guest hydrophobic interaction and renders the R-complex significantly more stable than the S-complex. In contrast, the binding modes of R- and S-TB with β-CD are similar due to the poor flexibility of the host, which jeopardizes its ability to differentiate R- and S-TB.
期刊介绍:
The Journal of Inclusion Phenomena and Macrocyclic Chemistry is the premier interdisciplinary publication reporting on original research into all aspects of host-guest systems. Examples of specific areas of interest are: the preparation and characterization of new hosts and new host-guest systems, especially those involving macrocyclic ligands; crystallographic, spectroscopic, thermodynamic and theoretical studies; applications in chromatography and inclusion polymerization; enzyme modelling; molecular recognition and catalysis by inclusion compounds; intercalates in biological and non-biological systems, cyclodextrin complexes and their applications in the agriculture, flavoring, food and pharmaceutical industries; synthesis, characterization and applications of zeolites.
The journal publishes primarily reports of original research and preliminary communications, provided the latter represent a significant advance in the understanding of inclusion science. Critical reviews dealing with recent advances in the field are a periodic feature of the journal.