Polymer-Induced Heteronucleation of Tolfenamic Acid: Structural Investigation of a Pentamorph

被引:115
作者
Lopez-Mejias, Vilmali
Kampf, Jeff W.
Matzger, Adam J. [1 ]
机构
[1] Univ Michigan, Dept Chem, Ann Arbor, MI 48109 USA
关键词
CRYSTAL-STRUCTURES; POLYMORPH; ROY;
D O I
10.1021/ja806289a
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
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 (similar to 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.
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收藏
页码:4554 / +
页数:3
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