Bodor N S, Huang M J, Watts J D
Center for Drug Discovery, College of Pharmacy, Gainesville, FL 32610-0497, USA.
J Pharm Sci. 1995 Mar;84(3):330-6. doi: 10.1002/jps.2600840313.
A series of semiempirical molecular orbital calculations using the AM1 method have been performed on isolated natural and alkylated alpha- and beta-cyclodextrins. For natural cyclodextrins, three geometries were considered: (i) molecular mechanics (MM2); (ii) AM1 fully optimized geometry; (iii) X-ray structures based on the experimental coordinates for heavy atoms with positions of hydrogen atoms optimized by AM1. Large differences between AM1 calculated properties of geometries i-iii were found. The differences between ii and iii are smaller and reflect the intermolecular, crystal packing forces. Comparisons are made between ii and iii and properties determined therefrom, such as cavity diameter, outer diameter, and height. In addition, AM1 semiempirical calculations were performed on the mixed (2,3,6) (hydroxyprophyl)-beta-cyclodextrin, 2,6-dimethyl-beta-cyclodextrin, and 2,6-bis(hydroxypropyl)-beta-cyclodextrin. The results were compared with the substituent effects on monoglucose. It was found that the alkylation and methyl and 2-(hydroxypropyl) functions on beta-cyclodextrin does not introduce significant steric hindrance.
已使用AM1方法对分离出的天然和烷基化的α-和β-环糊精进行了一系列半经验分子轨道计算。对于天然环糊精，考虑了三种几何结构：（i）分子力学（MM2）；（ii）AM1完全优化的几何结构；（iii）基于重原子实验坐标且氢原子位置经AM1优化的X射线结构。发现AM1计算的i - iii几何结构的性质存在很大差异。ii和iii之间的差异较小，反映了分子间的晶体堆积力。对ii和iii以及由此确定的性质（如腔直径、外径和高度）进行了比较。此外，还对混合的（2,3,6）（羟丙基）-β-环糊精、2,6-二甲基-β-环糊精和2,6-双（羟丙基）-β-环糊精进行了AM1半经验计算。将结果与取代基对单葡萄糖的影响进行了比较。发现β-环糊精上的烷基化以及甲基和2-（羟丙基）官能团不会引入显著的空间位阻。
