摘要
目的研究制备尼莫地平新晶型,并分析尼莫地平3种晶型的分子间作用力差异及形成机制。方法通过溶剂挥发法制备得到尼莫地平新晶型C,采用单晶X射线衍射分析方法获得晶C型晶体的三维立体结构,通过Crystal Explorer软件对3种晶型进行Hirshfeld表面分析,计算分子间氢键的相互作用力。结果晶C型为尼莫地平与DMSO以1:1比例形成的新晶型,根据已报道的单晶数据得知晶A型和晶B型为不同构型的无溶剂尼莫地平。3种晶型具有近似的分子相互作用,H…H、H…O、H…C 3种作用力占据了90%以上的贡献,且3种作用力大小存在差异。结论尼莫地平分子含有二氢吡啶环,N原子作为主要的氢键供体与O原子形成氢键,成为尼莫地平晶型分子中主要作用力,通过Hirshfeld表面分析方法能清晰直观地揭示各分子间相互作用。
Objective New crystal form of nimodipine was prepared.The formation mechanism of the three crystal forms of nimodipine and the differences in the intermolecular interaction were studied.Methods The new crystal form of nimodipine(C)was prepared by solvent evaporation.The structure was obtained through the single crystal X-ray diffraction(SXRD)and the intermolecular interaction was analyzed by Hirshfeld surface method.Results The form C of nimodipine was formed in 1:1 ratio of nimodipine and DMSO.According to the reported single crystal data,the crystal A and B are solvent-free nimodipine molecules with different configurations.These three crystal forms have similar molecular interactions.The three interactions of H…H,H.…O,and H…C account for more than 90%of the total forces,and the magnitudes of the three forces are different.Conclusion Nimodipine contains dihydropyridine ring.As the main hydrogen bond donor,NH forms hydrogen bond with O atom,which becomes the main force in nimodipine crystal molecule.The interaction between molecules can be clearly revealed by Hirshfeld surface analysis method.
作者
王雪
张宝喜
邢逞
龚宁波
吕扬
WANG Xue;ZHANG Baoxi;XING Cheng;GONG Ningbo;LYU Yang(Beijing Key Laboratory of Polymorphs Drugs Research,Institute of Materia Medica,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing 100050,China)
出处
《医药导报》
CAS
北大核心
2021年第8期1090-1093,共4页
Herald of Medicine
基金
国家自然科学基金资助项目(81703473)
国家重点研发计划(2016YFC1000900)
国家科技重大专项-重大新药创制(2017ZX09101001003,2018ZX09711001-010)
中国医学科学院医学与健康科技创新工程(2017-I2M-1-010)。
