Electron density study of the anti-Alzheimer's disease drug donepezil from conventional x-ray data and invariom database application.

Background: The crystal structures of a very large number of compounds with biological relevance are known. Application of the invariom formalism provides the aspherical electron density distribution.
Results and Discussion: The electron density distribution of the anti-Alzheimer's disease drug donepezil was derived from its x-ray structure reported in the literature, using the invariom database. The electrostatic potential mapped on the electron density isosurface shows how the positive charge of the donepezilium cation is distributed over a wide surface range. The presence of intermolecular contacts can be illustrated by the Hirshfeld surface. Comparable interactions are found in both the small-molecule structure and an acetylcholinesterase complex with donezepil from the literature.
Conclusion: The electron density of donepezil in the small-molecule crystal structure mimics the intermolecular interactions within the receptor site. Complementing steric properties with electronic information can be a valuable procedure in the examination of molecular recognition of systems with biological activity.