{"title":"达沙替尼溶胶的相似性与差异性:晶体学视角","authors":"Aija Trimdale-Deksne, Ilze Grante, Anatoly Mishnev*, Lia̅na Orola and Agris Be̅rziṇš*, ","doi":"10.1021/acs.cgd.4c00248","DOIUrl":null,"url":null,"abstract":"<p >Detailed crystallographic and computational analysis of solvates of dasatinib (DAS), an inhibitor of multiple tyrosine kinases, was performed by confirming the high structural similarity of most of the DAS crystal structures and identifying the differences in molecular conformation, hydrogen bonding, and molecular packing. The crystal structures of 14 new DAS solvates are presented, allowing the crystallographic analysis of 23 DAS solvates and one nonsolvated phase. The analysis of molecular conformation revealed that in most of the structures DAS adopts three slightly different conformations, even though computational analysis indicated the existence of alternative energetically competitive conformations. In almost all structures, DAS molecules form identical hydrogen-bonded layers. The lack of structural variation is believed to be the result of the limited ways for efficient packing of the large sized and specifically shaped DAS molecules. Detailed analysis, however, revealed three similar but somewhat different ways these layers are packed, resulting in the classification of DAS solvates in three structure groups I, II, and III. The different arrangements of the layers result in different hydrogen bonds formed by O1–H and the space available for the solvent, but, interestingly, this is not linked with the exact DAS conformation or solvent functionality, properties, or bonding with DAS molecules.</p>","PeriodicalId":34,"journal":{"name":"Crystal Growth & Design","volume":null,"pages":null},"PeriodicalIF":3.2000,"publicationDate":"2024-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Similarity and Differences of Dasatinib Solvates: A Crystallographic Perspective\",\"authors\":\"Aija Trimdale-Deksne, Ilze Grante, Anatoly Mishnev*, Lia̅na Orola and Agris Be̅rziṇš*, \",\"doi\":\"10.1021/acs.cgd.4c00248\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p >Detailed crystallographic and computational analysis of solvates of dasatinib (DAS), an inhibitor of multiple tyrosine kinases, was performed by confirming the high structural similarity of most of the DAS crystal structures and identifying the differences in molecular conformation, hydrogen bonding, and molecular packing. The crystal structures of 14 new DAS solvates are presented, allowing the crystallographic analysis of 23 DAS solvates and one nonsolvated phase. The analysis of molecular conformation revealed that in most of the structures DAS adopts three slightly different conformations, even though computational analysis indicated the existence of alternative energetically competitive conformations. In almost all structures, DAS molecules form identical hydrogen-bonded layers. The lack of structural variation is believed to be the result of the limited ways for efficient packing of the large sized and specifically shaped DAS molecules. Detailed analysis, however, revealed three similar but somewhat different ways these layers are packed, resulting in the classification of DAS solvates in three structure groups I, II, and III. The different arrangements of the layers result in different hydrogen bonds formed by O1–H and the space available for the solvent, but, interestingly, this is not linked with the exact DAS conformation or solvent functionality, properties, or bonding with DAS molecules.</p>\",\"PeriodicalId\":34,\"journal\":{\"name\":\"Crystal Growth & Design\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.2000,\"publicationDate\":\"2024-06-04\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Crystal Growth & Design\",\"FirstCategoryId\":\"92\",\"ListUrlMain\":\"https://pubs.acs.org/doi/10.1021/acs.cgd.4c00248\",\"RegionNum\":2,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"CHEMISTRY, MULTIDISCIPLINARY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Crystal Growth & Design","FirstCategoryId":"92","ListUrlMain":"https://pubs.acs.org/doi/10.1021/acs.cgd.4c00248","RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
引用次数: 0
摘要
对多种酪氨酸激酶抑制剂达沙替尼(DAS)的溶胶进行了详细的晶体学和计算分析,确认了大多数 DAS 晶体结构的高度相似性,并确定了分子构象、氢键和分子堆积的差异。该研究展示了 14 种新的 DAS 溶剂的晶体结构,从而对 23 种 DAS 溶剂和一种非溶解相进行了晶体学分析。对分子构象的分析表明,在大多数结构中,DAS 采用了三种略有不同的构象,尽管计算分析表明存在其他能量竞争性构象。在几乎所有结构中,DAS 分子都形成了相同的氢键层。结构缺乏变化被认为是由于大尺寸和特殊形状的 DAS 分子有效堆积的途径有限。然而,详细分析发现,这些层的堆积方式有三种相似但略有不同的方式,因此将 DAS 溶剂分为 I、II 和 III 三个结构组。层的不同排列方式导致 O1-H 形成的氢键和溶剂的可用空间不同,但有趣的是,这与 DAS 的确切构象或溶剂的功能、特性或与 DAS 分子的结合并无关联。
Similarity and Differences of Dasatinib Solvates: A Crystallographic Perspective
Detailed crystallographic and computational analysis of solvates of dasatinib (DAS), an inhibitor of multiple tyrosine kinases, was performed by confirming the high structural similarity of most of the DAS crystal structures and identifying the differences in molecular conformation, hydrogen bonding, and molecular packing. The crystal structures of 14 new DAS solvates are presented, allowing the crystallographic analysis of 23 DAS solvates and one nonsolvated phase. The analysis of molecular conformation revealed that in most of the structures DAS adopts three slightly different conformations, even though computational analysis indicated the existence of alternative energetically competitive conformations. In almost all structures, DAS molecules form identical hydrogen-bonded layers. The lack of structural variation is believed to be the result of the limited ways for efficient packing of the large sized and specifically shaped DAS molecules. Detailed analysis, however, revealed three similar but somewhat different ways these layers are packed, resulting in the classification of DAS solvates in three structure groups I, II, and III. The different arrangements of the layers result in different hydrogen bonds formed by O1–H and the space available for the solvent, but, interestingly, this is not linked with the exact DAS conformation or solvent functionality, properties, or bonding with DAS molecules.
期刊介绍:
The aim of Crystal Growth & Design is to stimulate crossfertilization of knowledge among scientists and engineers working in the fields of crystal growth, crystal engineering, and the industrial application of crystalline materials.
Crystal Growth & Design publishes theoretical and experimental studies of the physical, chemical, and biological phenomena and processes related to the design, growth, and application of crystalline materials. Synergistic approaches originating from different disciplines and technologies and integrating the fields of crystal growth, crystal engineering, intermolecular interactions, and industrial application are encouraged.