Fernandes Catarina M, Carvalho Rui A, Pereira da Costa Saúl, Veiga Francisco J B
Laboratory of Pharmaceutical Technology, Faculty of Pharmacy, University of Coimbra, 3000 Coimbra, Portugal.
Eur J Pharm Sci. 2003 Apr;18(5):285-96. doi: 10.1016/s0928-0987(03)00025-3.
Proton nuclear magnetic resonance spectroscopy (1H NMR), which has become an important tool for in vitro study of cyclodextrin (CD) complexes, was used to study and structurally characterize the inclusion compounds formed in solution between nicardipine hydrochloride (NC) and beta-cyclodextrin (betaCD), hydroxypropyl-beta-cyclodextrin (HPbetaCD) and triacetyl-beta-cyclodextrin (TAbetaCD). The large variation of chemical shifts from protons located around the interior of the hydrophobic cavity (i.e. H-3, H-5 and H-6) coupled with minimal variation of shifts from protons located on the outer sphere of the betaCD (i.e. H-1, H-2 and H-4) provided clear evidence of inclusion complexation. In the presence of the different CDs, the aromatic protons of NC were the most affected, suggesting a strong involvement of the phenyl groups in the inclusion mechanism. The application of continuous variation method indicated the presence of complexes with a 1:1 host/guest stoichiometry for all the studied CDs. Two-dimensional rotating frame nuclear Overhauser effect spectroscopy (ROESY) experiments were carried out to further support the proposed inclusion mode. Inspection of the ROESY spectra allowed the establishment of spatial proximities between several aromatic hydrogens of the guest and the CD protons, indicating that the inclusion occurs by accommodation of the two aromatic groups of NC. All the experimental data were further rationalized to elaborate possible three-dimensional geometric models of inclusion complexes. From the aforementioned observations, we concluded there is no preference for inclusion of a particular aromatic ring. Instead, two types of 1:1 complexes with different inclusion structures may exist simultaneously in solution, being alternatively included through the wider side of the cavity, i.e. the so-called multimodal inclusion occurs in the interaction of NC with the different CDs.
质子核磁共振波谱法（1H NMR）已成为环糊精（CD）配合物体外研究的重要工具，用于研究盐酸尼卡地平（NC）与β-环糊精（βCD）、羟丙基-β-环糊精（HPβCD）和三乙酰-β-环糊精（TAbβCD）在溶液中形成的包合物，并对其结构进行表征。疏水腔内质子（即H-3、H-5和H-6）化学位移的大幅变化，以及βCD外球面上质子（即H-1、H-2和H-4）化学位移的微小变化，为包合络合提供了明确证据。在不同CD存在的情况下，NC的芳环质子受影响最大，表明苯基在包合机制中发挥了重要作用。连续变化法的应用表明，所有研究的CD形成的配合物主客体化学计量比均为1:1。进行二维旋转框架核Overhauser效应光谱（ROESY）实验以进一步支持所提出的包合模式。对ROESY光谱的检查确定了客体的几个芳环氢与CD质子之间的空间接近性，表明包合是通过NC的两个芳环的容纳而发生的。所有实验数据都经过进一步合理分析，以构建包合物可能的三维几何模型。根据上述观察结果，我们得出结论，不存在对特定芳环包合的偏好。相反，溶液中可能同时存在两种具有不同包合结构的1:1配合物，它们通过空腔较宽的一侧交替包合，即NC与不同CD相互作用时发生所谓的多模式包合。
