α-环糊精/乙胺嘧啶包合物的表征、相溶解度及分子模拟
Characterization, phase solubility and molecular modeling of alpha-cyclodextrin/pyrimethamine inclusion complex.
作者信息
de Araujo Marcia Valeria Gaspar, Macedo Osmir F L, Nascimento Cristiane da Cunha, Conegero Leila Souza, Barreto Ledjane Silva, Almeida Luis Eduardo, da Costa Nivan Bezerra, Gimenez Iara F
机构信息
Departamento de Química, Universidade Federal de Sergipe, Av. Marechal Rondon s/n, Campus Universitário Prof. José Aloísio de Campos, CEP 491000-000, São Cristóvão, SE, Brazil.
出版信息
Spectrochim Acta A Mol Biomol Spectrosc. 2009 Feb;72(1):165-70. doi: 10.1016/j.saa.2008.09.011. Epub 2008 Oct 14.
An inclusion complex between the dihydrofolate reductase inhibitor pyrimethamine (PYR) and alpha-cyclodextrin (alpha-CD) was prepared and characterized. From the phase-solubility diagram, a linear increase of PYR solubility was verified as a function of alpha-CD concentration, suggesting the formation of a soluble complex. A 1:1 host-guest stoichiometry can be proposed according to the Job's plot, obtained from the difference of PYR fluorescence intensity in the presence and absence of alpha-CD. Differential scanning calorimetry (DSC) measurements provided additional evidences of complexation such as the absence of the endothermic peak assigned to the melting of the drug. The inclusion mode characterized by two-dimensional (1)H NMR spectroscopy (ROESY) involves penetration of the p-chlorophenyl ring into the alpha-CD cavity, in agreement to the orientation optimized by molecular modeling methods.
制备并表征了二氢叶酸还原酶抑制剂乙胺嘧啶（PYR）与α-环糊精（α-CD）之间的包合物。从相溶解度图可以看出，PYR的溶解度随α-CD浓度呈线性增加，表明形成了可溶性复合物。根据Job曲线，从有和没有α-CD时PYR荧光强度的差异得出，可以提出1:1的主客体化学计量比。差示扫描量热法（DSC）测量提供了络合的额外证据，例如不存在归因于药物熔化的吸热峰。通过二维（1）H NMR光谱（ROESY）表征的包合模式涉及对氯苯基环渗透到α-CD腔内，这与通过分子建模方法优化的取向一致。
Zotero 插件