Diverse modes of solvent inclusion in crystalline pseudopolymorphs of the anthelmintic drug Niclosamide

Single crystal X-ray structures of solvated forms of the anthelmintic drug Niclosamide reveal distinctly different modes of inclusion for different solvents. These modes are, respectively, cavity occupation by water molecules in 1:1 niclosamide.H2O, channel occupation by tetrahydrofuran molecules in 1:1 niclosamide.THF, and intercalation by tetraethylene glycol molecules in 2:1 niclosamide.TEG. In all three compounds the host drug molecule adopts the same, nearly planar conformation, which is maintained by an intramolecular N-H ... O hydrogen bond. Host-guest recognition invariably involves hydrogen bonding between the drug hydroxyl group and an oxygen acceptor atom of the solvent molecule. The observed modes of solvent inclusion can be reconciled with the behaviour of the crystals on heating.