Insight into the Mechanism of Formation of Channel Hydrates via Templating

Cocrystallization of modafinil, <b>1</b>, and 1,4-diiodotetrafluorobenzene, <b>2</b>, 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 <b>2</b> or toluene. These calculations show the channel hydrate is less energetically stable than the anhydrous modafinil but more stable than a cocrystal involving <b>1</b> and <b>2</b>. 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 modafinil dimer. It is envisaged that the additive is then replaced by water molecules to form the channel hydrate. The formation of the channel hydrate is more likely in the presence of <b>2</b> compared to toluene due to the destabilizing effect of the larger iodine molecules protruding into neighboring modafinil clusters

Utilizing Sulfoxide···Iodine Halogen Bonding for Cocrystallization

The propensity of a range of different sulfoxides and sulfones to cocrystallize with either 1,2- or 1,4-diiodotetrafluorobenzene, via I···O=S halogen bonding, was investigated. Cocrystallization occurred exclusively with 1,4-diiodotetrafluorobenzene in either a 1:1 or 1:2 stoichiometry of the organohalide and the sulfoxide, respectively, depending on the sulfoxide used. It was found that the stoichiometry observed was not necessarily related to whether the oxygen acts as a single halogen bond acceptor or if it is bifurcated; with I···π interactions observed in two of the cocrystals synthesized. Only those cocrystals with a 1:2 stoichiometry exhibit C–H···O hydrogen bonding in addition to I···O=S halogen bonding. Examination of the Cambridge Structural Database shows that (i) the I···O=S interaction is similar to other I···O interactions, and (ii) the I···π interaction is significant, with the distances in the two cocrystals among the shortest known

Utilizing Sulfoxide···Iodine Halogen Bonding for Cocrystallization

The propensity of a range of different sulfoxides and sulfones to cocrystallize with either 1,2- or 1,4-diiodotetrafluorobenzene, via I···O=S halogen bonding, was investigated. Cocrystallization occurred exclusively with 1,4-diiodotetrafluorobenzene in either a 1:1 or 1:2 stoichiometry of the organohalide and the sulfoxide, respectively, depending on the sulfoxide used. It was found that the stoichiometry observed was not necessarily related to whether the oxygen acts as a single halogen bond acceptor or if it is bifurcated; with I···π interactions observed in two of the cocrystals synthesized. Only those cocrystals with a 1:2 stoichiometry exhibit C–H···O hydrogen bonding in addition to I···O=S halogen bonding. Examination of the Cambridge Structural Database shows that (i) the I···O=S interaction is similar to other I···O interactions, and (ii) the I···π interaction is significant, with the distances in the two cocrystals among the shortest known