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.
Keywords: drug discovery; intermolecular interactions; multipole refinement; structure determination.