Application of the Method of Molecular Voronoi–Dirichlet Polyhedra for Analysis of Noncovalent Interactions in Aripiprazole Polymorphs

Aripiprazole (APZ) is a highly polymorphic chemical compound with nine structurally characterized modifications. Using the method of molecular Voronoi–Dirichlet (VD) polyhedra and the k–Φ criterion, we showed that each of the APZ polymorphs is characterized by unique combinations of types of intra- and intermolecular noncovalent contacts. Descriptors of the three-dimensional geometric image of an interatomic interaction of any kind were calculated to quantitatively characterize crystal structures of all the available APZ polymorphs. The identification of differences in interatomic interactions in polymorphic modifications of APZ is important mainly for the pharmaceutical industry (drugs design), as well as for fundamental science to establish the desired relationship between observed types of interactions and certain features of polymorphic modifications, such as relative stability or physicochemical properties. A comparison of calculations performed using molecular VD polyhedra and Hirshfeld surface approach highlights the importance of interactions with low partial contributions for distinguishing polymorphs.