Characterising the role of water in sildenafil citrate by NMR crystallography
Characterising the role of water in sildenafil citrate by NMR crystallography
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DOI：
10.1039/c5ce02234g
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发表时间：
2016-01-01
期刊：
影响因子：
3.1
通讯作者：
Hodgkinson, Paul
中科院分区：
文献类型：
--
作者：
Abraham, Anuji;Apperley, David C.;Hodgkinson, Paul
采用固体核磁共振技术，包括C-13/H-1相关、H-2魔角旋转核磁共振和第一性原理计算，研究了水在枸橼酸西地那非不同水化状态中的作用。C-13光谱是完全指定的第一次和直接相关的晶体结构。H-2魔角旋转NMR被证明是一个强大的工具，在复杂的水合物系统中的动态和交换过程的研究，允许在多个溶剂化物网站的行为进行表征，而不需要昂贵的和选择性的标记。使用H-2双量子频率可以分辨不同的位点，从而进行数据拟合以确定不同位点之间的自旋扩散速率。水被证明是高度动态的，经历C-2旋转，与不同的水分子之间的化学交换，也与主机结构。所采用的方法适用于研究在药物原料药中发现的广泛的水合类型。
A combination of solid-state NMR techniques, including C-13/H-1 correlation, H-2 magic-angle spinning NMR and first principles calculation are employed to characterise the role of water in different hydration states of sildenafil citrate. The C-13 spectrum is fully assigned for the first time and direct correlations made with respect to the crystal structure. H-2 magic-angle spinning NMR is demonstrated to be a powerful tool for the study of dynamic and exchange processes in complex hydrate systems, allowing the behaviour at multiple solvate sites to be characterised without the need for expensive and selective labelling. Use of the H-2 double-quantum frequency allows resolution of the different sites and, consequently, data fitting to determine rates of spin-diffusion between the different sites. The water is shown to be highly dynamic, undergoing C-2 rotation, with chemical exchange between different water molecules and also with the host structure. The methods adopted are applicable to the investigation of an extensive range of hydration types found in pharmaceutical drug substances.