Characterization, crystal structure and stability analysis of dianhydrodulcitol polymorphs

1,2:5,6-Dianhydrogalactitol (DAG), an anticancer drug with different crystal structures, is investigated in order to get a comprehensive understanding of its polymorphism. Two polymorphs of DAG were prepared by different methods using DAG form I as the starting material. The formation of new crystal forms was confirmed by means of PXRD and other characterization methods. The single crystals of three polymorphs, including a new discovered crystal form II, were prepared and studied. The crystal structure of the new crystal form II was determined by single crystal X-ray diffraction, and the difference in hydrogen bonding structure of the DAG polymorphs was analyzed. The intermolecular interactions of the DAG polymorphs were studied by Hirshfeld surface analysis. The stability relationship between three polymorphs under different conditions was studied. DAG form I is stable at low temperatures and form III is more stable at high temperatures. Form II is a metastable crystal form and can be transformed into the other two crystal forms by solvent-mediated crystallization.