TY - JOUR

T1 - Expanding the structural landscape of niclosamide: a high Z ' polymorph, two new solvates and monohydrate HA

AU - Sovago, Ioana

AU - Bond, Andrew D.

PY - 2015/5

Y1 - 2015/5

N2 - Three new crystalline phases are reported for the drug niclosamide [5-chloro-N-(2-chloro-4-nitrophenyl)-2-hydroxybenzamide], C13H8Cl2N2O4. A new high-Z' polymorph (denoted Form II) is described, with four molecules in the asymmetric unit in the space group P2/n. The structure exhibits pseudosymmetry, including local translations and screw-type operations. The niclosamide molecules are linked by O-H...O hydrogen bonds into chains, and the chains are packed so that the molecules form face-to-face (stacking) and end-to-end interactions within layers perpendicular to the chains. There are two different layer arrangements, giving a structure that is relatively complex. In the acetone and acetonitrile solvates, the incorporated solvent molecules accept hydrogen bonds from the OH groups of niclosamide, and the niclosamide molecules are stacked in a face-to-face manner. In the acetone solvate, C13H8Cl2N2O4·C3H6O, V-shaped arrangements are formed in which the nitrobenzene ends of the niclosamide molecules are brought into face-to-face contact. In the acetonitrile solvate, C13H8Cl2N2O4·CH3CN, stacking occurs by translation along a short axis (ca 3.8 Å) and the crystals are frequently observed to be twinned by twofold rotation around that axis. The acetonitrile molecules occupy channels in the structure. A complete structure is provided for niclosamide monohydrate, C13H8Cl2N2O4·H2O, polymorph HA, obtained by Rietveld refinement against laboratory powder X-ray diffraction data. It has been suggested that this compound is related to the methanol solvate of niclosamide [Harriss, Wilson & Radosevljevic Evans (2014). Acta Cryst. C70, 758-763], but it is found that the two are not fully isostructural: they contain isostructural two-dimensional layers, but the layers are arranged differently in the two structures. This suggests that HA may have the potential for polytypism, and features in the Rietveld difference curve indicate that a polytype fully isostructural with the methanol solvate might be present.

AB - Three new crystalline phases are reported for the drug niclosamide [5-chloro-N-(2-chloro-4-nitrophenyl)-2-hydroxybenzamide], C13H8Cl2N2O4. A new high-Z' polymorph (denoted Form II) is described, with four molecules in the asymmetric unit in the space group P2/n. The structure exhibits pseudosymmetry, including local translations and screw-type operations. The niclosamide molecules are linked by O-H...O hydrogen bonds into chains, and the chains are packed so that the molecules form face-to-face (stacking) and end-to-end interactions within layers perpendicular to the chains. There are two different layer arrangements, giving a structure that is relatively complex. In the acetone and acetonitrile solvates, the incorporated solvent molecules accept hydrogen bonds from the OH groups of niclosamide, and the niclosamide molecules are stacked in a face-to-face manner. In the acetone solvate, C13H8Cl2N2O4·C3H6O, V-shaped arrangements are formed in which the nitrobenzene ends of the niclosamide molecules are brought into face-to-face contact. In the acetonitrile solvate, C13H8Cl2N2O4·CH3CN, stacking occurs by translation along a short axis (ca 3.8 Å) and the crystals are frequently observed to be twinned by twofold rotation around that axis. The acetonitrile molecules occupy channels in the structure. A complete structure is provided for niclosamide monohydrate, C13H8Cl2N2O4·H2O, polymorph HA, obtained by Rietveld refinement against laboratory powder X-ray diffraction data. It has been suggested that this compound is related to the methanol solvate of niclosamide [Harriss, Wilson & Radosevljevic Evans (2014). Acta Cryst. C70, 758-763], but it is found that the two are not fully isostructural: they contain isostructural two-dimensional layers, but the layers are arranged differently in the two structures. This suggests that HA may have the potential for polytypism, and features in the Rietveld difference curve indicate that a polytype fully isostructural with the methanol solvate might be present.

KW - pharmaceutical compounds

KW - niclosamide

KW - polymorphism

KW - crystal structure

KW - polytypism

KW - solvates and hydrates

KW - PXRD measurements

U2 - 10.1107/S2053229615005847

DO - 10.1107/S2053229615005847

M3 - Journal article

C2 - 25940896

VL - 71

SP - 394

EP - 401

JO - Acta Crystallographica Section C: Crystal Structure Communications

JF - Acta Crystallographica Section C: Crystal Structure Communications

SN - 0108-2701

IS - 5

ER -