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Niclosamide methanol solvate and niclosamide hydrate: structure, solvent inclusion mode and implications for properties
Author(s) -
Harriss Bethany I.,
Wilson Claire,
Radosavljevic Evans Ivana
Publication year - 2014
Publication title -
acta crystallographica section c
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.304
H-Index - 17
ISSN - 2053-2296
DOI - 10.1107/s2053229614015496
Subject(s) - niclosamide , hydrogen bond , isostructural , methanol , hydrate , crystallography , molecule , chemistry , powder diffraction , solvent , stacking , crystal structure , crystal (programming language) , stereochemistry , organic chemistry , ecology , computer science , programming language , biology
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, C 13 H 8 Cl 2 N 2 O 4 ·CH 3 OH or NCL·MeOH, and niclosamide monohydrate, denoted H A . 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 via π‐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, H A , 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.