依匹哌唑晶体结构的实验及理论分析

Experimental and theoretical analysis of brexpiprazole crystal structure

以探究依匹哌唑晶体结构为目的,溶剂扩散法制备获得依匹哌唑单晶体。单晶X射线衍射分析法解析的结果是:属单斜晶系,P21/n空间群,晶胞参数a=9. 4083(5),b=25. 9910(14),c=10. 2293(6),α=90,β=113. 061(7),γ=90,Z=4。差热和热重分析结果表明,依匹哌唑的熔点为182℃,低于该熔点温度时,依匹哌唑具有良好的稳定性,不发生吸热、放热及失重现象。应用"赫希菲尔德"表面分析的结果是:酰胺基团中氧分别与C5氢、C7氢和N3氢形成三个氢键;相邻依匹哌唑分子的苯环有部分重叠,导致晶体中存在弱的π-π堆积作用。相互作用能分析结果表明:依匹哌唑分子间存在11种数值不同的总相互作用能,其中包含酰胺二聚体的相邻分子因形成较强N3—H_3…O_2氢键,分子间相互作用能最大(-86. 8kJ·mol^(-1))。能量框架可视化的结果显示:酰胺二聚体分子间作用能转换为半径最大的圆柱体,并形成反向平行的主体框架结构。本文实验和理论分析相结合,系统地分析了依匹哌唑的晶体结构,探究了依匹哌唑晶体结构中分子间的作用关系。

The purpose of this study is to analyze the structure of brexpiprazole crystal which has been prepared by antisolvent diffusion.Brexpiprazole crystal structure solved by SXRD belongs to monoclini crystal system with space group P2 1/n,the cell parameters are a =9.4083(5), b =25.9910(14), c =10.2293(6),α=90,β=113.061(7),γ=90, Z =4.Thermal analysis reveals that the melting point of brexpiprazole is 182 ℃,brexpiprazole is stable when temperature is lower than melting point because there aren’t any endothermic,exothermic and weightless phenomena.According to Hirshfeld surface analysis,Oxygen atom of amide group forms three hydrogen bonds with hydrogen atom of C5,C7 and N3,respectively,and there are weak π-π stacking interactions in the crystal structure of brexpiprazole because of the overlap of the benzene rings.The result of interaction energy analysis is that 11 kinds of intermolecular interaction energies exist in brexpiprazole crystal structure.It should be noted that the highest interaction energies(-86.8 kJ·mol^-1 )are associate with amide dimers linked by two duplicate N3-H3…O2 hydrogen bonds.The interaction energies of amide dimmers are converted into cylinders with the largest radius and form an antiparallel frame structure by“energy framework”module of CrystalExplorer.In this study,we comprehensively analyzed the crystal structure of brexpiprazole and explored the intermolecular interactions in the crystal structure of brexpiprazole combining experimental and theoretical methods.