Peer-Reviewed Journal Details
Mandatory Fields
Stokes, SP;Seaton, CC;Eccles, KS;Maguire, AR;Lawrence, SE
2014
March
Crystal Growth & Design
Insight into the Mechanism of Formation of Channel Hydrates via Templating
Validated
WOS: 7 ()
Optional Fields
CAMBRIDGE STRUCTURAL DATABASE POWDER DIFFRACTION DATA FORM-II CARBAMAZEPINE DIFFERENTIAL EVOLUTION CRYSTAL-STRUCTURE CO-CRYSTALS PHARMACEUTICAL COCRYSTALS MOLECULAR-CRYSTALS SOLVENT INCLUSION SOLID-STATE
14
1158
1166
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 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 2 compared to toluene due to the destabilizing effect of the larger iodine molecules protruding into neighboring modafinil clusters.
WASHINGTON
1528-7483
10.1021/cg401660h
Grant Details