Combining Structural Rugosity and Crystal Packing Comparison: A Route to More Polymorphs?

Abstract

In this study, we have combined structural comparisons and the rugosity model to investigate experimental and predicted crystal structures from previous results of a crystal structure prediction study on a group of three rigid, planar small molecules, 2-methyl-, 3-methyl-, and 2,3-dimethyl-benzo[b]thiophene 1,1-dioxide. The results of the crystal structure comparisons provided some insights into the possibility that pairs of predictions, close in energy, might be related by potential phase transitions. In particular, we observed that for some pairs of predictions, a transformation from one type of crystal packing to the other would require only small shifts between adjacent molecules. This raised the question of whether only a few of these predictions can effectively be experimentally isolated. The calculations of the structural rugosity, a parameter that correlates surface rugosity with ease of crystallization, indicated smooth surfaces only for a few predictions. With the aim to isolate new polymorphs, we performed a small experimental study, limited to a few common solvents and crystallizations from the melt. Crystallizations from the melt selectively produced single crystals of new polymorphs for the 3-methyl- and the 2,3-methyl-benzothiophene derivatives. These showed good correlations with the above calculations, suggesting that the combination of crystal structure analysis and experimental screening might represent a useful approach in polymorphism screenings.