盐酸倍他洛尔与β-环糊精包合物核磁共振研究

目的: 研究盐酸倍他洛尔和β-环糊精包合物化学计量比、结构信息和稳定常数。 方法: 配制不同浓度比例盐酸倍他洛尔和β-环糊精混合溶液,测定了它们的¹H NMR数据,绘制出Job's曲线。并测定了包合物的二维ROESY和排序扩散谱(DOSY)数据。 结果: 盐酸倍他洛尔和β-环糊精的Job's曲线拐点均在r=0.5处。¹H NMR显示盐酸倍他洛尔的H-4'~H-8'包合后向高场位移。ROESY图谱的交叉峰信号出现在H-5'~H-8'和β-环糊精的H-3、H-5、H-6之间。DOSY获得了包合物的扩散系数。 结论: 盐酸倍他洛尔与β-环糊精形成了化学计量比1∶1的包合物。盐酸倍他洛尔由窄口端进入β-环糊精内部,H-4'至H-8'部分完全进入疏水空腔,其余部分在空腔外部。用β-环糊精的表观扩散系数近似代替包合物的扩散系数可方便地计算出包合物稳定常数,结果为153.2 M^-1。

Objective: To study stoichiometry,3D geometry and formation constant of betaxolol hydrochloride and β-cyclodextrin complex were studied. Method: Betaxolol hydrochloride and β-cyclodextrin solution were prepared in various concentration ratio.Job's curve was depicted base on ¹H NMR,2D ROESY and diffusion ordered spectroscopy (DOSY) were also obtained and analysed. Result: Inflection point on Job's curve was appeared at r=0.5.Chemical shifts of betaxolol hydrochloride H-4' to H-8' change to upfield.Cross peaks on ROESY spectra appear between betaxolol hydrochloride H-5' to H-8' and β-cyclodextrin H-3,H-5,H-6.Formation constant of complex was calculated as 153.2M^-1 by DOSY. Conclusion: Job's curve indicates that 1∶1 stoichiometry complex was form between betaxolol hydrochloride and β-cyclodextrin.H-4' to H-8' of betaxolol hydrochloride are included into the β-cyclodextrin hydrophobic cavity,and other parts are outside the cavity.Formation constant of complex is conveniently calculated by DOSY method using apparent diffusion coefficient of β-cyclodextrin as complex diffusion coefficient alternative parameter.

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