Persistency of a two-fold embrace in crystalline phases of Bupropion hydrohalides: a thorough ab-initio X-ray powder diffraction study

Bupropion hydrohalide salts yield ten different crystal phases of bupropion (four hydrochloride, two hydrobromide, and four hydroiodide salts). Of these forms, only four have been previously characterized by single crystal or powder diffraction analysis. The structures of the six new crystal forms have been solved using state-of-the art structural powder diffraction methods. All ten phases have been found to be made up of the same supramolecular synthon packed in different ways. The supramolecular synthon common to all phases is a bupropion hydrohalide dimer held together by hydrogen bonding. The true driving force of the polymorphism of bupropion hydrohalides is therefore the ability of the bupropion hydrohalide dimer to pack in several different ways and not the ability of the molecule to form different hydrogen bonding motifs or to exist with aliphatic branches in different stable conformations.