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

Abstract

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.