Distinct Disordered Forms of Promethazine Hydrochloride: A Case of lntergrowth of Polymorphic Domains?
Distinct Disordered Forms of Promethazine Hydrochloride: A Case of lntergrowth of Polymorphic Domains?
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DOI：
10.1021/cg300943b
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发表时间：
2012-12-01
影响因子：
3.8
通讯作者：
Filip, Xenia
中科院分区：
文献类型：
--
作者：
Borodi, Gheorghe;Pop, Mihaela M.;Filip, Xenia
用单晶X射线衍射法测定了抗组胺药物盐酸异丙嗪(PTZ)的第一晶体结构，揭示了多态结构域可能共生的情况，这需要进一步的实验来证实。PTZ的两种晶体结构具有分子构象和晶体堆积高度相似的特点，PTZ脂肪链上的两个不同的无序能级导致晶胞参数略有变化。这些晶胞变化导致晶体结构中分子的微小位移，从而导致不同形式之间的能量、密度和熔点略有差异。尽管PTZ的两种晶型非常相似，但它们是明显不同的无序形式：它们被反复和可重复地获得，到目前为止没有发现中间无序水平，并且通过悬浮液实验证明了它们之间的溶剂介导的转化。此外，固体核磁共振证实了这两个不同的无序水平。我们的研究强调了单晶结构数据对判断相纯度的益处，以及表现出细微结构差异的固体形式。新发现的无序对晶胞尺寸的影响有助于理解不同无序形式之间的相似极限，因此可能为晶体结构预测提供重要线索。
Determination of the first crystalline structures of the antihistaminic drug promethazine hydrochloride (PTZ) by single crystal X-ray diffraction revealed a possible case of intergrowth of polymorphic domains that requires further experimentation for confirmation. The two crystal structures of PTZ are characterized by high similarity of both molecular conformation and crystal packing and slight variations of the unit cell parameters induced by two distinct disorder levels in the PTZ aliphatic chain. These unit cell variations lead to small displacements of the molecules in the crystal structures and, consequently, to slight energy, density, and melting point differences between the forms. Although highly similar, the two crystalline forms of PTZ are clearly distinct disordered forms: they were repeatedly and reproducibly obtained, no intermediate disorder levels were found so far, and solvent-mediated transformation between them was evidenced by slurry experiments. In addition, the two distinct disorder levels were confirmed by solid-state nuclear magnetic resonance. Our study emphasizes the benefit of single-crystal structure data for the judgment of the phase purity and of solid forms exhibiting subtle structural differences. The newly discovered effect of disorder on the unit cell dimensions contributes to understanding the similarity limits between distinct disordered forms and, consequently, may provide important clues for crystal structure prediction.