Pharmaceutical polymorph control in a drug-mimetic supramolecular gel.
Pharmaceutical polymorph control in a drug-mimetic supramolecular gel.
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DOI：
10.1039/c6sc04126d
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发表时间：
2017-01-01
期刊：
影响因子：
8.4
通讯作者：
Steed JW
中科院分区：
文献类型：
--
作者：
Foster JA;Damodaran KK;Maurin A;Day GM;Thompson HPG;Cameron GJ;Bernal JC;Steed JW
设计用于化学模拟药物化合物结构的超分子凝胶控制底物结晶的多晶型结果。我们报告的合成的双（脲）胶凝剂的设计，专门模仿高度多态性的药物ROY的化学结构。ROY从该胶凝剂的甲苯凝胶中结晶导致形成亚稳态红色形式而不是热力学黄色多晶型物。相反，所有其他凝胶和溶液对照实验均得到黄色形式。构象和晶体结构的预测方法已被用来提出的凝胶的结构，并表明，模板化的红色形式的目标凝胶的结果从构象匹配的胶凝剂的ROY基板耦合到本地周期性结构的凝胶纤维上的ROY的过度生长。
A supramolecular gel designed to chemically mimic the structure of a pharmaceutical compound controls the polymorphic outcome of the crystallization of the substrate. We report the synthesis of a bis(urea) gelator designed to specifically mimic the chemical structure of the highly polymorphic drug substance ROY. Crystallization of ROY from toluene gels of this gelator results in the formation of the metastable red form instead of the thermodynamic yellow polymorph. In contrast, all other gels and solution control experiments give the yellow form. Conformational and crystal structure prediction methods have been used to propose the structure of the gel and show that the templation of the red form by the targeted gel results from conformational matching of the gelator to the ROY substrate coupled with overgrowth of ROY onto the local periodic structure of the gel fibres.