Extensive Sequential Polymorphic Interconversion in the Solid State: Two Hydrates and Ten Anhydrous Phases of Hexamidine Diisethionate
Extensive Sequential Polymorphic Interconversion in the Solid State: Two Hydrates and Ten Anhydrous Phases of Hexamidine Diisethionate
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DOI：
10.1021/acs.cgd.9b01170
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发表时间：
2019-12-01
影响因子：
3.8
通讯作者：
Steed, Jonathan W.
中科院分区：
文献类型：
--
作者：
Edkins, Katharina;McIntyre, Garry J.;Steed, Jonathan W.
晶体多态和溶剂包合是制药工业中的一个主要研究领域，并不断地揭示复杂的体系。在这里，我们介绍了六胺二异硫酸酯(HDI)的固态体系，这是一种形成二晶型二水合物的防腐药物化合物，以及10种无水晶型。水合晶型的X射线和中子晶体结构及相应的相互作用能表明，阳离子与水之间没有直接作用，而阳离子与阴离子、阴离子与水之间存在很强的相互作用。这在宏观上是因为水合物对温度和湿度的脱水具有很高的稳定性。无水晶型揭示了一种罕见的顺序和可逆的晶型转变，热分析和变温粉末X射线衍射对其进行了表征。虽然大多数跃迁都伴随着显著的结构变化，但低能跃迁只能被检测到反射位置随温度的微小变化。因此，HDI代表了一种模型化合物，用于研究具有微小结构变化的多态转变。
Crystal polymorphism and solvent inclusion are a dominant research area in the pharmaceutical industry and continue to unveil complex systems. Here, we present the solid-state system of hexamidine diisethionate (HDI), an antiseptic drug compound forming a dimorphic dihydrate as well as 10 anhydrous polymorphs. The X-ray and neutron crystal structures of the hydrated crystal forms and related interaction energies show no direct interaction between the cation and water but very strong interactions between cation and anion, and anion and water. This is observed macroscopically as high stability of the hydrate against dehydration by temperature and humidity. The anhydrous polymorphs reveal a rare case of sequential and reversible polymorphic transformations, which are characterized by thermal analysis and variable-temperature powder X-ray diffraction. While most transitions are accompanied by significant structural changes, the low-energy transitions can only be detected as slight changes in the reflection positions with temperature. HDI thus represents a model compound to investigate polymorphic transitions with small structural changes.