A study of solvent selectivity on the crystal morphology of FOX-7 via a modified attachment energy model

Abstract

The crystal morphology of FOX-7 in different solvents was investigated via molecular dynamics simulations. A modified attachment energy (MEA) model was constructed by introducing surface chemistry terms and the associated topography of the habit crystal plane. Solvent has a large effect on the crystal morphology of FOX-7. The calculated results show that the crystal morphology of FOX-7 in vacuum is dominated by six faces, (0 1 1), (1 0 −1), (1 0 1), (1 1 −1), (0 0 2) and (1 10), while that in acetic acid is dominated by three faces, (1 1 −1), (0 1 1) and (1 0 1). The applicability of the model was successfully validated by the study of FOX-7 crystals grown from cyclohexanone, acetonitrile, H₂O/DMF, and H₂O/DMSO. All the predicted results are in good agreement with the experimental results. The crystal morphology of FOX-7 is variable in different crystallization solvents. H₂O/DMF and H₂O/DMSO are good choices for the solvent recrystallization of FOX-7. The results are useful for the formulation design of FOX-7.