Korlyukov Alexander A, Vologzhanina Anna V, Trzybinski Damian, Malinska Maura, Wozniak Krzysztof
A.N. Nesmeyanov Institute of Organoelement Compounds RAS, 28 Vavilova str., Moscow, 119991, Russian Federation.
Biological and Chemical Research Centre, Department of Chemistry, University of Warsaw, Żwirki i Wigury 101, Warsaw, 02089, Poland.
Acta Crystallogr B Struct Sci Cryst Eng Mater. 2020 Dec 1;76(Pt 6):1018-1026. doi: 10.1107/S2052520620013244. Epub 2020 Nov 12.
A high-resolution single-crystal X-ray diffraction study of abiraterone acetate (1) has been carried out. The charge density distribution in the crystal of this anticancer drug is reconstructed from experimental data. The nature and the contributions of various intermolecular interactions to the total crystal energy are studied by means of the quantum theory `Atoms-in-Molecules', a non-covalent interactions method and energy framework plots. In general, dispersion C-H...H-C and C-H...π interactions play the main role in crystal packing of 1. The Voronoi tessellation analysis of 1 confirmed that contribution of hydrophobic and hydrophilic interactions to the molecular surface is close to their contribution to the total crystal energy. Similar analysis of abiraterone complexes with the cytochrome P450 family demonstrated that contribution of the C-H...H-C and C-H...π interactions to the molecular surface of the drug remains unchanged to fit the binding pocket, despite the presence of water and heme molecules, and hydrophilic groups within the pocket.
已对醋酸阿比特龙（1）进行了高分辨率单晶X射线衍射研究。该抗癌药物晶体中的电荷密度分布是根据实验数据重建的。借助量子理论“分子中的原子”、一种非共价相互作用方法和能量框架图，研究了各种分子间相互作用对总晶体能量的性质和贡献。一般而言，色散C-H...H-C和C-H...π相互作用在1的晶体堆积中起主要作用。对1的Voronoi镶嵌分析证实，疏水和亲水相互作用对分子表面的贡献与其对总晶体能量的贡献相近。对阿比特龙与细胞色素P450家族复合物的类似分析表明，尽管存在水、血红素分子以及口袋内的亲水基团，但C-H...H-C和C-H...π相互作用对药物分子表面的贡献保持不变以适应结合口袋。
