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首页> 外文期刊>Crystal growth & design >Predictable disorder versus polymorphism in the rationalization of structural diversity: A multidisciplinary study of eniluracil
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Predictable disorder versus polymorphism in the rationalization of structural diversity: A multidisciplinary study of eniluracil

机译:结构多样性合理化中可预测的疾病与多态性:依尿嘧啶的多学科研究

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摘要

Detailed analysis of X-ray diffraction data from four single crystals of eniluracil, prepared under different crystallization conditions, confirms a picture in which the crystals exhibit different degrees of disorder, which is also suggested by the computed low energy crystal structures. Since several of these crystal structures that effectively differ by an interchange of the oxygen and hydrogen atoms on C(4) and C(6) are essentially equi-energetic, growth errors that may be difficult to reverse are practically inevitable. The structural variations observed for the crystals of eniluracil studied are more appropriately described in terms of variable degrees of disorder rather than polymorphism. Analysis of the computed crystal energy landscape for interchangeable hydrogen-bonded (or other strong) motifs is, therefore, shown to be a valuable complement to X-ray diffraction and solid-state NMR for understanding and characterizing disorder in organic solid state systems. In the case of eniluracil, this detailed picture probably accounts for the challenges in devising a robust production process for this anticancer agent in the 1990s. The specific nature of the disorder accounts for different structures being obtained from powder X-ray diffraction data of different samples, and the possibility of publishable single crystal X-ray refinements also being interpreted as polymorphism rather than disorder.
机译:对在不同结晶条件下制备的四种恩尿嘧啶单晶进行的X射线衍射数据的详细分析,证实了其中晶体表现出不同无序度的图像,这也由计算出的低能晶体结构所暗示。由于通过C(4)和C(6)上的氧原子和氢原子的交换而有效地不同的这些晶体结构中的几个基本上是等能量的,因此实际上难以避免可能难以逆转的生长误差。对于所研究的恩尿嘧啶晶体观察到的结构变化更恰当地描述为无序度变化而不是多态性。因此,对于可互换的氢键(或其他牢固的)基序,计算出的晶体能态图的分析显示出对X射线衍射和固态NMR的宝贵补充,有助于理解和表征有机固态系统中的无序。就恩尼尿嘧啶而言,这一详细情况可能解释了在1990年代为该抗癌药设计可靠的生产工艺所面临的挑战。无序的特殊性质解释了从不同样品的粉末X射线衍射数据获得的不同结构,可发布的单晶X射线细化的可能性也被解释为多态性而不是无序。

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