1H-NMR and molecular modelling techniques for the investigation of the inclusion complex of econazole with α-cyclodextrin in the presence of malic acid
1H-NMR and molecular modelling techniques for the investigation of the inclusion complex of econazole with α-cyclodextrin in the presence of malic acid
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DOI：
10.1016/s0731-7085(00)00260-0
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发表时间：
2000-08-01
影响因子：
3.4
通讯作者：
Mura, P
中科院分区：
文献类型：
--
作者：
Faucci, MT;Melani, F;Mura, P
进行一项研究，发现α-cyclodestrin和苹果酸的组合在改善益康唑（一种水溶性非常差的抗真菌药物）的溶解度方面最有效，在本工作中，H-1-NMR和核奥弗豪泽效应（NOE）进行了实验和分子模拟研究，以深入了解这三种组分之间在溶液中的相互作用和假定的多组分络合物研究结果表明，两种不同的复合物可以同时存在于溶液中，涉及，分别，从环糊精腔的伯羟基侧的主机腔内的益康唑一氯-苯基基团，或通过腔的相对侧的其他苯基基团的内容物。结果表明，苹果酸也严格参与了复合物的分子组装，特别是通过与环糊精分子的伯羟基基团的相互作用。分子建模研究允许详细说明可能的几何模型的多组分复合物，并选择更积极有利的构象，更好地符合实验数据。结果表明，在溶液中可能形成的稳定的低聚物聚集体构成的三个组件的重复连接。(C)2000爱思唯尔科技有限公司。保留所有权利。
Carrying on a study where the combination of alpha-cyclodestrin and malic acid was found to be the most effective in improving the solubility of econazole, an antifungal drug very poorly water soluble, in the present work H-1-NMR and nuclear overhauser effect (NOE) experiments and molecular modelling studies were performed to gain insight into the interactions in solution between such three components and the structure of the supposed multicomponent complex. Findings demonstrated that two different complexes can be simultaneously present in solution involving, respectively, the inclusion of econazole monochloro-phenyl group within the host cavity from the primary hydroxyl side of the cyclodextrin cavity, or that of the other phenyl group through the opposite side of the cavity. It was shown that also melic acid is strictly involved in the molecular assembly of the complex, particularly through interactions with primary hydroxyl groups of the cyclodextrin molecule. Molecular modelling studies allowed to elaborate possible geometric models of the multicomponent complex and to select the more energetically favourable conformations which complied better with experimental data. Results suggested the possible formation in solution of stable oligomeric aggregates constituted by the repeated concatenation of the three components. (C) 2000 Elsevier Science B.V. All rights reserved.