Space Groups Complexity versus Molecular Interactions in Quinoline Derivatives Crystal Morphology Prediction: A Throughput Evaluation of Different in Silico Approaches

Molecular Mechanics calculations embedded in dedicated software were used to predict crystal morphologies of two very similar quinoline derivatives: they only differ in the presence of a sulfur and a selenium atom, respectively. The crystal structures do not present any hydrogen bond, and the only relevant interactions in the unit cell are some noncovalent T-shaped ones. They were chosen as good candidates to carry out a performance comparison among different crystal morphology prediction theories. Thus, the results obtained by means of the Bravais-Friedel-Donnay-Harker (BFDH) method were compared with calculations performed on periodic bond chain (PBC) theory and relative interaction energies. Moreover, by transforming the experimentally determined orthorhombic symmetry to lower space group symmetries (in the monoclinic and triclinic systems, respectively), the computed results highlighted that one of the PBC methods still confirmed the predicted morphology, no matter what space group was chosen. The differences among the predicted habits inferred by the different approaches increased instead for the other two methods, as the symmetry level decreased. Furthermore, in the more symmetric system, that is, orthorhombic, the symmetry constraints of the group make BFDH predictions more realistic than in lower symmetry ones. The potential role of crystallization solvents on faces growth was also discussed. RI Punzo, Francesco/A-4921-2011 OI Punzo, Francesco/0000-0003-4212-8064