Insight into the Mechanism of Formation of Channel Hydrates via Templating

Abstract

Cocrystallization of modafinil, 1, and 1,4-diiodotetrafluorobenzene, 2, in toluene leads to the formation of a metastable modafinil channel hydrate containing an unusual hydrogen bonded dimer motif involving the modafinil molecules that is not seen in anhydrous forms of modafinil. Computational methodologies utilizing bias drift-free differential evolution optimization have been developed and applied to a series of molecular clusters and multicomponent crystals in the modafinil/water and modafinil/water/additive systems for the additive molecules 2 or toluene. These calculations show the channel hydrate is less energetically stable than the anhydrous modafinil but more stable than a cocrystal involving 1 and 2. This provides theoretical evidence for the observed instability of the channel hydrate. The mechanism for formation of the channel hydrate is found to proceed via templating of the modafinil molecules with the planar additive molecules, allowing the formation of the unusual hydrogen-bonded modafini...