A multi-technique approach to the study of structural stability and desolvation of two unusual channel hydrate solvates of finasteride.
A multi-technique approach to the study of structural stability and desolvation of two unusual channel hydrate solvates of finasteride.
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DOI：
10.1002/jps.22740
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发表时间：
2012
影响因子：
3.8
通讯作者：
S. Byard;Anuji Abraham;Paul J T Boulton;R. Harris;P. Hodgkinson
中科院分区：
文献类型：
--
作者：
S. Byard;Anuji Abraham;Paul J T Boulton;R. Harris;P. Hodgkinson
用固体核磁共振、粉末X射线衍射、热重分析（包括与质谱联用）和动态气相吸附研究了两种重要的药物化合物非尼泊特的水合物溶剂化物（即双非尼泊特一水合物单四氢呋喃和双非尼泊特一水合物单-1，4-二氧六环）的脱水/去溶剂化。这种结构的不寻常之处在于，水通过氢键将主溶剂分子结合在一起，形成溶剂所在的通道。虽然溶剂客体分子与主体的结合力不强，但它们的存在对于结构稳定性至关重要。未发现去溶剂化在明确定义的温度下发生，甚至不一致地产生相同的无水形式（形式I与形式II），而是高度依赖于物理环境，因此依赖于所使用的技术。这种行为使研究复杂化，但互补方法的组合确实可以理解去溶剂化。水和溶剂被证明是同时失去的，没有证据的中间形式或增加的氢键水分子的流动性。的结果是一致的模型，其中结构崩溃和重排以下的一小部分的溶剂分子从通道结构的损失，与产生的最终形式是非常敏感的水蒸气的存在下，在去溶剂化。
The dehydration/desolvation of two hydrate solvates of the pharmaceutically important compound finasteride (namely, bisfinasteride monohydrate monotetrahydrofuran and bisfinasteride monohydrate mono-1,4-dioxane) has been studied by solid-state nuclear magnetic resonance, powder X-ray diffraction, thermogravimetric analysis (including coupling with mass spectrometry) and dynamic vapour sorption. The structure is unusual in that water holds the host finasteride molecules together by hydrogen bonding to form channels in which the solvent is sited. Whilst the solvent guest molecules are not strongly bound to the host, their presence is essential for structural stability. Desolvation is not found to occur at a well-defined temperature or even to consistently produce the same anhydrous form (form I vs. form II), but is instead highly dependent on the physical environment and, therefore, on the technique used. This behaviour complicates investigations, but the combination of complementary methods does allow the desolvation to be understood. Water and solvent are shown to be lost simultaneously, with no evidence of an intermediate form or increased mobility of the hydrogen-bonded water molecules. The results are consistent with a model in which structural collapse and rearrangement follows the loss of a small fraction of the solvent molecules from the channel structure, with the final form produced being very sensitive to the presence of water vapour during desolvation.