Hierarchical Noncovalent Interactions between Molecules Stabilize Multicomponent Cocrystals

The formation of multicomponent cocrystals in preference over multi-bicomponent ones has been reported for several systems recently. The factors that drive crystallization of such a multicomponent aggregate is elucidated based on density functional theory and classical molecular dynamics (MD) simulations. Estimating the stabilization energies between the three components of the ternary cocrystal of crownether, thiourea, and perfluoroarenes indicates a hierarchical preference of interactions, namely, crownether···thiourea (H-bonding) > thiourea···perfluoroarenes (halogen bonding). This along with an enhanced stabilization of a ternary system vis-a-vis their binary analogues ensures stability of the three-component system. Generalizing the model further, it is shown that even a quaternary cocrystal consisting of crownether, thiourea, perfluoroarene, and aromatic moieties can be envisioned by further harnessing the rich variety in noncovalent interactions, namely, π···π stacking between perfluoroarene (electron-deficient) and electron-rich planar aromatic molecules such as paradimethylbenzene and hexamethylbenzene. Charge transfer between the cofacial π-surfaces further stabilizes these four-component cocrystals.