Interplay between geometry, electron density, and polarizability of the controversial drug atoxyl in crystal and biological environments.

The molecule para-arsanilic acid was historically used and misused as a drug under the name atoxyl. It is a biologically active compound in the class of arsenic-organic molecules. In this study, we aim for an understanding of its mode of action with particular focus on the role of the arsenic atom in the structure. We carried out experimental quantum crystallographic studies of p-arsanilic acid in its zwitterionic form and found that there is a rich network of intermolecular interactions in the small-molecule crystal structure that resembles interactions in the biological environment. However, the arsenic atom is not involved in these interactions, but the internal polarization of the molecule by its environment is governed by the large polarizability of the As-C bond. By adopting different strategies to simulate the interaction density and the interaction electrostatic potential, we delineate effects of conformation and geometry from the pure polarization of the molecule by its neighbors.