磺丁基醚-β-环糊精拆分莫达非尼及其立体选择性差异研究  

Stereoselective Differences Research of Sulfobutylether-β-cyclodextrin on Chiral Separation of Modafinil Enantiomers

作　　者：王伟[1] 周晓娟[1] 季一兵[1] 相秉仁 

机构地区：[1]中国药科大学分析化学教研室 [2]分析测试中心,南京210009

出　　处：《分析化学》2013年第10期1566-1570,共5页Chinese Journal of Analytical Chemistry

摘　　要：利用毛细管电泳和分子模拟对磺丁基醚-β-环糊精（SBE-β-CD）在莫达非尼手性拆分中的立体选择性差异进行了研究。考察了环糊精浓度和温度对对映体手性拆分的影响。在15～35℃温度范围内，考察了对映体的保留和分离行为。结果表明，随着温度的升高，手性分离变差，并以lna对1／T作图，得到的Van’t Hoff曲线具有良好线性关系（r=0．995）。热力学结果表明，此手性拆分过程为焓控过程。在5～50mmol／L范围内，考察了SBE-β-CD浓度对分离的影响，采用双倒数法求得莫达非尼S-和R-对映体与SBE-β-CD的结合常数分别为58．0和70．6IMmol。分子模拟实验以Gold对接完成，结果表明，莫达非尼R-对映体相比S-对映体与SBE-β-CD结合更稳定，且两对映体与SBE-β-CD结合的差异主要来源与氢键贡献的差异。The stereoselective differences research of sulfobutylether-β-cyclodextrin （SBE-fl-CD） on the chiral separation of modafinil enantiomers was carried out by molecular docking method and capillary electrophoresis. Several parameters were investigated for the influence on enantiomeric separation of modafinil. By changing the temperature within 15-35 ℃ and the concentration of SBE-β-CD within 5-50 mmol/L, the thermodynamic parameters and binding constants were determined by capillary electrophoresis. The Van＇t Hoff plot of the lna versus 1/T of the enantiomers had a good linearity with a correlation coefficient of 0.995. The binding constants calculated by the method of double reciprocal for S-and R-modafinil were 58.0 L/mol and 70.6 L/tool, respectively. The molecular docking was performed by Gold V3.0.1, and the results showed that the binding energy of R-modafinil with SBE-β-CD was greater than that of S-modafinil with SBE-β-CD and the reason may lie in the difference of hydrogen bonding interaction of modafinil enantiomers with SBE-fl-CD.

关 键 词：磺丁基醚-Β-环糊精 莫达非尼 手性拆分 毛细管电泳 立体选择性差异 

分 类 号：TQ460.72[医药卫生—药物分析学] O657.8[化学工程—制药化工]