Predicting Cocrystallization Based on Heterodimer Energies: Part II

Many crystal engineering studies employ urea functionalities for their predictable association into one-dimensional hydrogen bonded chains. Previously, we showed (Cryst. Growth Des., 2015, 15 (10), 5068–5074) that the urea chain motif usually seen in structures of diphenylureas (PUs) with meta-substituents could be disrupted in several cases by cocrystallization with the strong hydrogen bond acceptor triphenylphosphine oxide (TPPO). Computed differences in the urea···urea and urea···TPPO dimer energies of ∼5.3–6 kcal/mol were a reasonably accurate indicator for cocrystallization success. The current study attempts to reassess the limits of this computational approach using a larger set of 16 ortho- and para-substituted PUs. Seven of the 10 PU systems predicted to cocrystallize on the basis of dimer energy calculations were experimentally realized, along with an eighth whose difference in homo/heterodimer energies fell below the threshold. The absence of cocrystallization in two of the predicted systems is likely due to preferred urea···substituent hydrogen bonding over both urea···urea and urea···TPPO interactions, a factor that was not considered in the homo/heterodimer energy comparisons. When taken in combination with the previous study, energy predictions were 87% accurate over the 30 systems investigated.