聚合物诱导的托芬那酸异质成核：一种五变体的结构研究
Polymer-induced heteronucleation of tolfenamic acid: structural investigation of a pentamorph.
作者信息
López-Mejías Vilmalí, Kampf Jeff W, Matzger Adam J
机构信息
Department of Chemistry and the Macromolecular Science and Engineering Program, University of Michigan, 930 North University Avenue, Ann Arbor, Michigan 48109-1055, USA.
出版信息
J Am Chem Soc. 2009 Apr 8;131(13):4554-5. doi: 10.1021/ja806289a.
Abstract
The nonsteroidal anti-inflammatory drug (NSAID) tolfenamic acid (TA), previously thought to be dimorphic, is demonstrated to have at least five polymorphs. The new forms were uncovered through the emerging screening technique of polymer-induced heteronucleation (PIHn). The presence of conformational changes among forms, whole molecule disorder, space group diversity, and varying number of molecules in the asymmetric unit occurring within a very narrow free energy window (approximately 0.3 kcal/mol) make the solid-state chemistry of this molecule uniquely complex among pharmaceuticals. These aspects make it a particularly suitable benchmark compound for crystal structure prediction methods.
摘要
非甾体抗炎药托芬那酸（TA），此前被认为是二态的，现被证明至少有五种多晶型物。这些新晶型是通过新兴的聚合物诱导异相成核（PIHn）筛选技术发现的。在非常窄的自由能窗口（约0.3千卡/摩尔）内，各晶型之间存在构象变化、整个分子无序、空间群多样性以及不对称单元中分子数量不同，这些使得该分子的固态化学在药物中具有独特的复杂性。这些方面使其成为晶体结构预测方法特别合适的基准化合物。
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