Structural study of an unusually large molecular solid from powder diffraction: the sequential unravelling of hydrogen bonding and van der Waals interactions contributing to the Z′ = 2 crystal packing of amcinonide

Abstract

We report the crystal structure analysis of the glucocorticoid drug amcinonide from high-resolution X-ray powder diffraction data, with an uncommonly large number of atoms (142, including H) and Z′ = 2; which was carried out through the stepwise location of the rigid and flexible fragments of the asymmetric unit, using the knowledge of steroidal conformations, bond length and angles, and hydrogen bonding packing motifs extracted from the Cambridge Structural Database. The database search also provided an experimental framework used to compare the main attractive intermolecular interactions found in amcinonide with those of related steroids, in order to contribute to the systematization of likely factors often leading to Z′ > 1 structures in this type of compound. These were found to be the presence of the functional groups –COOH and multiple –OH, as well as hydrated structures, wherein varied H-bonding patterns are formed.