Understanding the Metastability of Theophylline FIII by Means of Low-Frequency Vibrational Spectroscopy
Understanding the Metastability of Theophylline FIII by Means of Low-Frequency Vibrational Spectroscopy
复制标题
DOI：
10.1021/acs.molpharmaceut.1c00476
复制
发表时间：
2021-08-24
影响因子：
4.9
通讯作者：
Zeitler, J. Axel
中科院分区：
文献类型：
--
作者：
Paiva, Eduardo Maia;Li, Qi;Zeitler, J. Axel
虽然茶碱已被广泛研究，发现了多种多晶型物，但目前仍然没有亚稳态茶碱III型的决定性结构。在本工作中，通过将更广泛使用的技术如X射线衍射和热重分析与更新兴的技术如低频拉曼和太赫兹时域光谱相结合，以分析晶体系统的结构和动力学，可以提供进一步的证据，即III型结构具有去除水分子的茶碱一水合物结构。固态密度泛函理论模拟是至关重要的，证明了这种结构是正确的，并解释了晶体结构中的振动模式如何表征和控制多晶型转变和亚稳态形式III。通过模拟和实验结果提供的洞察力，可以决定性地得出茶碱III型的难以捉摸的晶体结构的结论。它还表明，正确的空间群茶碱一水合物不是P21/n，但事实上，Pc。
While theophylline has been extensively studied with multiple polymorphs discovered, there is still currently no conclusive structure for the metastable theophylline form III. In this present work, by combining more widely used techniques such as X-ray diffraction and thermogravimetric analysis with more emerging techniques like low-frequency Raman and terahertz time-domain spectroscopy, to analyze the structure and dynamics of a crystalline system, it was possible to provide further evidence that the form III structure has a theophylline monohydrate structure with the water molecules removed. Solid-state density functional theory simulations were paramount in proving that this proposed structure is correct and explain how vibrational modes within the crystal structures feature and govern polymorphic transitions and the metastable form III. Through the insight provided by both simulated and experimental results, it was possible to decisively conclude the elusive crystal structure of theophylline form III. It was also shown that the correct space group for theophylline monohydrate is not P21/n but, in fact, Pc.