6X射线衍射在药学中的应用rev课件.pptVIP

X-射线晶体学在医药学中的应用 1 微量化合物或新骨架化合物的分子结构测定 随着分离、提取等分析技术的飞速发展,从天然产物中可获得低含量的化合物,单晶X射线衍射分析只需要一颗单晶体(约1/ 4～1/ 6 mg 量) ,就可直接使用单晶X射线分析技术独立完成所需的化合物的全部结构测定工作,而一般不再需要借助其它谱学(NMR、MS等) 信息。 2 以共晶方式存在的混合物分子结构测定 共晶在固体药物样品中是常见的现象,最简单的例子是药物分子与溶剂或结晶水分子以共晶方式存在。共晶分子结构可以由异构体形成,也可以由不同结构分子形成。在药物研究中确切地了解共晶样品的组成成分,以及它们实际存在的比例是至关重要的。单晶X 射线衍射分析技术对药物中的共晶样品可以给出准确、定量的分析结果。 Chemical Pharmaceutical Bulletin (2008), 56(4), 439-442. Different configuration Different Structure 3. Configuration analysis构型分析 An absolute configuration is the spatial arrangement of the atoms of a chiral molecular entity. Description e.g. R or S 32 33 4 Conformation analysis构象分析 Tetrahedron Letters 2002, 43, 2415-2418 Conformation is the spatial arrangement of atoms in a molecule that can change through free rotation of atoms about a single chemical bond. My conformation 5. Solvent molecules in raw material for drugs溶剂分子确定 What is the solvent? What is the ratio? Solvent: Water; ratio: 2:1 Li, Guo Qiang; Li, Yao Lan; Wang, Guo Cai; Liang, Zhi Hong; Jiang, Ren Wang. Acta Crystallographica, Section E: Structure Reports Online 2011, E67(8), o2192 Tubulin-podophyllotoxin complex 微管蛋白-鬼臼毒素 (PDB：1SA1) Androgen receptor-bicalutamide complex 雄激素受体-比卡鲁胺 (PDB no. 1z95) 6. Macromolecular complex大分子复合物 The X-ray diffraction is the main experimental technique used for determination of three-dimensional structures of proteins and their complexes at atomic and subatomic resolution. Though molecular weight less than 50kD could be determined by solution or solid state nmr, proteins with larger molecular weight are depend on X-ray diffraction.