On the predictability of supramolecular interactions in molecular cocrystals - the view from the bench

A series of theophylline cocrystals involving fluorobenzoic acids was prepared and structurally characterised. The cocrystals display compositions and hydrogen-bond patterns that could not be predicted based on extensive literature/database surveys and the use of other tools. The study demonstrates that - without the use of first-principles crystal structure prediction methods - it is still remarkably difficult to predict and understand the outcomes of cocrystallisation attempts involving small and rigid molecules.