Sovago Ioana, Bond Andrew D
Department of Pharmacy, University of Copenhagen, Universitetsparken 2, Copenhagen, DK-2100, Denmark.
Acta Crystallogr C Struct Chem. 2015 May;71(Pt 5):394-401. doi: 10.1107/S2053229615005847. Epub 2015 Apr 15.
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.
已报道了药物氯硝柳胺[5-氯-N-(2-氯-4-硝基苯基)-2-羟基苯甲酰胺]（C13H8Cl2N2O4）的三种新晶相。描述了一种新的高Z'多晶型物（表示为晶型II），在空间群P2/n中，不对称单元中有四个分子。该结构表现出假对称性，包括局部平移和螺旋型操作。氯硝柳胺分子通过O-H...O氢键连接成链，并且这些链堆积在一起，使得分子在垂直于链的层内形成面对面（堆积）和端对端相互作用。存在两种不同的层排列，给出了一个相对复杂的结构。在丙酮和乙腈溶剂化物中，掺入的溶剂分子接受来自氯硝柳胺OH基团的氢键，并且氯硝柳胺分子以面对面的方式堆积。在丙酮溶剂化物C13H8Cl2N2O4·C3H6O中，形成V形排列，其中氯硝柳胺分子的硝基苯端面对面接触。在乙腈溶剂化物C13H8Cl2N2O4·CH3CN中，沿着短轴（约3.8 Å）平移发生堆积，并且经常观察到晶体围绕该轴通过二次旋转形成孪晶。乙腈分子占据结构中的通道。通过对实验室粉末X射线衍射数据进行Rietveld精修得到了氯硝柳胺一水合物C13H8Cl2N2O4·H2O多晶型物HA的完整结构。有人认为该化合物与氯硝柳胺的甲醇溶剂化物[哈里斯、威尔逊和拉多塞维利耶维奇·埃文斯（2014年）。《晶体学报》C70，758 - 763]有关，但发现两者并非完全同构：它们包含同构的二维层，但两层在两种结构中的排列不同。这表明HA可能具有多型性的潜力，并且Rietveld差值曲线中的特征表明可能存在与甲醇溶剂化物完全同构的多型体。
