Charge density analysis of abiraterone acetate

Area of Science:

• Crystallography
• Quantum Chemistry
• Drug Design

Background:

• Abiraterone acetate is a crucial anticancer drug.
• Understanding its crystal structure and intermolecular forces is key to drug efficacy.
• Cytochrome P450 enzymes are important targets in cancer therapy.

Purpose of the Study:

• To investigate the charge density distribution and intermolecular interactions in abiraterone acetate crystals.
• To analyze the role of various interactions in crystal packing using advanced computational methods.
• To compare the drug's interaction profile in crystal form versus its bound state with cytochrome P450.

Main Methods:

• High-resolution single-crystal X-ray diffraction.
• Quantum theory of `Atoms-in-Molecules' (AIM).
• Non-covalent interaction (NCI) methods and energy framework analysis.
• Voronoi tessellation analysis.

Main Results:

• Dispersion, C-H...H-C, and C-H...π interactions are the primary forces governing abiraterone acetate crystal packing.
• Hydrophobic and hydrophilic interactions' contributions to the molecular surface closely mirror their contribution to total crystal energy.
• The drug's C-H...H-C and C-H...π interactions remain invariant upon binding to cytochrome P450, irrespective of the binding pocket's environment.

Conclusions:

• Abiraterone acetate's crystal structure is stabilized by specific weak interactions.
• The drug's molecular surface interactions are robust and adaptable for target binding.
• These findings provide insights into abiraterone acetate's mechanism of action and potential for drug development.