Niclosamide Methanol Solvate and Niclosamide Hydrate: Structure, Solvent Inclusion Mode and Implications for Properties

Harriss, Bethany; Wilson, Claire; Evans, Ivana R

Abstract

Structural studies have been carried out of two solid forms of niclosamide [5-chloro-N-(2-chloro-4-nitrophenyl)-2-hydroxybenzamide, NCL], a widely used anthelmintic drug, namely niclosamide methanol monosolvate, C13H8Cl2N2O4·CH3OH or NCL·MeOH, and niclosamide monohydrate, denoted HA. The structure of the methanol solvate obtained from single-crystal X-ray diffraction is reported for the first time, elucidating the key host–guest hydrogen-bonding interactions which lead to solvate formation. The essentially planar NCL host molecules interact viaπ-stacking and pack in a herringbone-type arrangement, giving rise to channels along the crystallographic a axis in which the methanol guest molecules are located. The methanol and NCL molecules interact via short O—H...O hydrogen bonds. Laboratory powder X-ray diffraction (PXRD) measurements reveal that the initially phase-pure NCL·MeOH solvate readily transforms into NCL monohydrate within hours under ambient conditions. PXRD further suggests that the NCL monohydrate, HA, is isostructural with the NCL·MeOH solvate. This is consistent with the facile transformation of the methanol solvate into the hydrate when stored in air. The crystal packing and the topology of guest-molecule inclusion are compared with those of other NCL solvates for which the crystal structures are known, giving a consistent picture which correlates well with known experimentally observed desolvation properties

Citation

Harriss, B., Wilson, C., & Evans, I. R. (2014). Niclosamide Methanol Solvate and Niclosamide Hydrate: Structure, Solvent Inclusion Mode and Implications for Properties. Acta Crystallographica Section C: Structural Chemistry, 70(8), 758-763. https://doi.org/10.1107/s2053229614015496

• Journal Article Type: Article
• Publication Date: Aug 1, 2014
• Deposit Date: Oct 15, 2014
• Publicly Available Date: Jan 28, 2015
• Journal: Acta Crystallographica Section C: Structural Chemistry
• Electronic ISSN: 2053-2296
• Publisher: International Union of Crystallography
• Peer Reviewed: Peer Reviewed
• Volume: 70
• Issue: 8
• Pages: 758-763
• DOI: https://doi.org/10.1107/s2053229614015496
• Keywords: Crystal structure, Niclosamide methanol solvate, Niclosamide hydrate, Solvent inclusion mode, Hydrogen bonding, Pharmaceutical compounds, PXRD measurements, Desolvation
• Public URL: https://durham-repository.worktribe.com/output/1452382