吡罗昔康多晶型分子间相互作用的分析研究  

Study of intermolecular interactions of piroxicam polymorphs

作　　者：邢文慧 邢逞[1] 喻红梅 房政钰 张丽[1] 龚宁波[1] 吕扬[1] XING Wen-hui;XING Cheng;YU Hong-mei;FANG Zheng-yu;ZHANG Li;GONG Ning-bo;LÜYang(Beijing Key Laboratory of Polymorphic Drugs,Institute of Materia Medica,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100050,China)

机构地区：[1]北京协和医学院、中国医学科学院药物研究所,晶型药物研究北京市重点实验室,北京100050

出　　处：《药学学报》2022年第7期2171-2176,共6页Acta Pharmaceutica Sinica

基　　金：国家科技重大专项(2019ZX09735002);中国医学科学院医学与健康科技创新工程项目(2017-I2M-1-010,2020-I2M-1-003);中国医学科学院中央级公益性科研院所基本科研业务费(2021-RW350-001);北京市自然科学基金(7222261)。

摘　　要：吡罗昔康具有多晶型现象。不同的晶型可呈现不同的理化性质与生物活性,深入探讨分子间相互作用对于揭示多晶型的形成机制及性质差异至关重要。本论文利用Hirshfeld表面分析和半经验方法计算分析了7种吡罗昔康的多晶型中分子间相互作用,结果显示,Hirshfeld表面分析方法能清晰直观地揭示各分子间相互作用,其中H…H,O…H/H…O和N…H/H…N相互作用占据总能量的95%,不同晶型的作用力的比例和分布存在差异。原子间库伦-伦敦-泡利(AA-CLP)能量计算表明,水合物的晶格能明显低于无水晶型的晶格能,在具体的能量分布中,色散力的贡献最为突出。进一步的相互作用能分析发现:在以吡罗昔康分子为中心3.8?距离范围内,不同晶型的吡罗昔康分子与周围分子存在不同的相互作用能。Piroxicam has polymorphism.Different crystalline forms can exhibit different physicochemical properties and biological activities.Analysis of the intermolecular interactions is essential to reveal the formation mechanism and differences of polymorphs.In this paper,Hirshfeld surface analysis and semi-empirical methods were used to calculate and analyze the intermolecular interactions in seven polymorphic forms of piroxicam.The results show that the Hirshfeld surface analysis method can clearly and intuitively reveal the intermolecular interactions,among which H…H,O…H/H…O and N…H/H…N interactions account for 95%of the total energy.There are differences in the proportion and distribution of the forces of different crystal forms.The energy calculation shows that the lattice energy of the hydrate is significantly lower than that of the anhydrous forms,and in the specific energy distribution,the contribution of the dispersion force is the most prominent.Further interaction energy analysis was found that within the distance of 3.8?from the center of the piroxicam molecule,different crystalline forms of piroxicam molecule have different interaction energies with surrounding molecules.

关 键 词：多晶型 Hirshfeld表面分析 晶体结构 吡罗昔康 能量计算 

分 类 号：R917[医药卫生—药物分析学]