Supramolecular Gel Control of Cisplatin Crystallization: Identification of a New Solvate Form Using a Cisplatin-Mimetic Gelator
Supramolecular Gel Control of Cisplatin Crystallization: Identification of a New Solvate Form Using a Cisplatin-Mimetic Gelator
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DOI：
10.1021/acs.cgd.5b00840
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发表时间：
2015-09-01
影响因子：
3.8
通讯作者：
Steed, Jonathan W.
中科院分区：
文献类型：
--
作者：
Dawn, Arnab;Andrew, Katherine S.;Steed, Jonathan W.
合成了一系列铂基低分子量脲基胶凝剂C1、C2和C3，模拟抗癌药物顺铂的结构，作为靶向超分子凝胶相结晶和多态性筛选策略开发的一部分。形态学和流变学研究表明，在凝胶因子（C3）的尿素和顺铂模拟区域之间包含较长的间隔子导致最佳的凝胶化性能。顺铂在凝胶-溶胶两相体系中的界面结晶已被用于解决药物分子在有机溶剂中的不溶性。已经鉴定了一种新的顺铂的N，N-二甲基乙酰胺（DMA）溶剂化物，并且在二甲苯中制备的C3凝胶中的顺铂结晶上观察到已知的顺铂的N，N-二甲基甲酰胺（DMF）溶剂化物形式的晶体习性改变。虽然靶向和非靶向凝胶都导致新的DMA溶剂化物的形成，但只有靶向C3凝胶导致适于通过单晶晶体学表征的高质量单晶。高晶体质量归因于C3的核心几何形状与顺铂的几何形状之间的紧密匹配以及C3的凝胶纤维中的局部有序性。
A series of platinum based low-molecular-weight urea-based gelators C1, C2, and C3, mimicking the structure of the anticancer drug cisplatin has been synthesized, as part of the development of a targeted, supramolecular gel phase crystallization and polymorphism screening strategy. Morphological and rheological studies established that inclusion of a longer spacer between the urea and cisplatin-mimetic regions of the gelator (C3) resulted in optimal gelation performance. Interfacial crystallization of cisplatin in a gel sol biphasic system has been employed to address the insolubility of the drug molecule in organic solvents. A new N,N-dimethylacetamide (DMA) solvate of cisplatin has been identified and a crystal habit modification of the known N,N-dimethylformamide (DMF) solvate form of cisplatin has been observed on crystallization of cisplatin in C3 gels prepared in xylenes. While both targeted and nontargeted gels resulted in the formation of the new DMA solvate, only the targeted C3 gel resulted in high-quality single crystal suitable for characterization by single crystal crystallography. The high crystal quality is attributed to a close match between the core geometry of C3 with that of cisplatin together with local order in the gel fibers of C3.