Durham D G, Liang H
School of Pharmacy, Robert Gordon University, Aberdeen, Scotland.
Chirality. 1994;6(4):239-44. doi: 10.1002/chir.530060405.
Molecular modelling of beta-cyclodextrin and optimisation of its potential energy suggests that a favoured conformation is that distorted from a symmetrical torus. The inclusion of water molecules into the torus cavity simulates the increased stability in an aqueous solvent. Complexes of beta-cyclodextrin with (R)- and (S)-enantiomers of methylphenobarbitone have been modelled and energetically optimised by the application of molecular mechanics. The simulations suggests that the guest molecules adopt an orientation in which the phenyl ring is projected into the torus cavity, with in each case the plane of the ring parallel to a longer axis of the distorted torus and slightly displaced from the axis through the torus cavity. It is suggested that the asymmetry in the macrocyclic ring contributes to chiral recognition as a result of additional discriminatory binding to the barbiturate ring residue of each enantiomer, which occupy different 3D geometries. The enantiomers form complexes of different minimum potential energies. The resulting difference in complex stability can be related to the behaviour of beta-cyclodextrin, as a mobile phase additive in reverse-phase HPLC to effect chiral separation of rac-methylphenobarbitone during chromatography.
β-环糊精的分子建模及其势能优化表明，一种有利的构象是偏离对称环面的扭曲构象。水分子进入环腔模拟了在水性溶剂中稳定性的增加。通过应用分子力学对β-环糊精与甲基苯巴比妥的（R）-和（S）-对映体的复合物进行了建模和能量优化。模拟结果表明，客体分子采取的取向是苯环伸入环腔，在每种情况下，环平面与扭曲环面的较长轴平行，并稍微偏离穿过环腔的轴。有人认为，大环的不对称性导致了手性识别，这是由于对每种对映体的巴比妥环残基有额外的选择性结合，而这些残基占据不同的三维几何形状。对映体形成具有不同最小势能的复合物。复合物稳定性的差异可与β-环糊精作为反相高效液相色谱流动相添加剂在色谱过程中实现外消旋甲基苯巴比妥手性分离的行为相关。
