Analysis of 50 Crystal Structures Containing Carbamazepine Using the Materials Module of Mercury CSD

A set of 50 crystal structures containing the molecule carbamazepine (CBZ) have been analyzed using the Materials module within Mercury CSD 2.0. The similarity relationships between all 50 structures were determined based on the analysis of packing motifs. Packing motifs that define the similarity relationships within three separate groups of structures were found to be exclusive to a particular group. The carboxamide homodimer found in all four of the carbamazepine polymorphs is seen to be disfavored compared to the carboxamide−carboxylic acid heterodimer when a coformer molecule with a carboxylic acid group is present. Etter’s rules are found to be broken in a large percentage of the CBZ structures (24%) compared to the overall CSD statistics (2.5%), apparently due to steric hindrance caused by the dibenzazepine group. A group of 14 similar structures has been identified containing ordered or disordered coformer-filled channels. Thirteen new crystal structures containing CBZ and pharmaceutically relevant carboxylic acid coformers are reported. Pharmaceutically relevant concepts are explored including crystal packing relationships, motif stability, hydrogen-bond competition, isostructurality, void visualization, and rational crystal design.

一套包含50个羧甲噻嗪（CBZ）分子晶体结构的集合已通过Mercury CSD 2.0软件中的材料模块进行分析。基于对堆积模式的解析，确定了这50个结构之间的相似性关系。研究发现，定义三个独立结构群体内部相似性关系的堆积模式具有独特性。在所有四种羧甲噻嗪多晶型体中发现的羧酰胺同二聚体与存在具有羧酸基团的共分子时相比，其存在被观察到是不利的。与整体CSD统计数据（2.5%）相比，在大量CBZ结构（24%）中发现了Etter规则被违反的现象，这显然是由于二苯并噻嗪基团引起的空间位阻。已识别出一组包含有序或无序共分子填充通道的14个相似结构。报道了13个含有CBZ和与药物相关的羧酸共分子的新晶体结构。探讨了包括晶体堆积关系、模式稳定性、氢键竞争、同构性、空腔可视化以及理性晶体设计在内的与药物相关的概念。