Chen Shuang, Xi Hanmi, Yu Lian
School of Pharmacy, University of Wisconsin-Madison, 777 Highland Avenue, Madison, Wisconsin 53705-2222, USA.
J Am Chem Soc. 2005 Dec 14;127(49):17439-44. doi: 10.1021/ja056072d.
Cross-nucleation between polymorphs is a newly discovered phenomenon important for understanding and controlling crystal polymorphism. It contradicts Ostwald's law of stages and other theories of crystallization in polymorphic systems. We studied the phenomenon in the spontaneous and seeded melt crystallization of 5-methyl-2-[(2-nitrophenyl)amino]-3-thiophenecarbonitrile (ROY), currently the most polymorphic system of known structures. We observed extensive and sometimes selective cross-nucleation between ROY polymorphs. Certain polymorphs could not nucleate without the aid of others. The new polymorph was found to be more or less thermodynamically stable than the initial one but to always grow faster than or as fast as the initial one. The temperature and surface characteristics of the seed crystals affected the occurrence of cross-nucleation. Our results show that the pathway of crystallization in polymorphic systems is not determined solely by the initial nucleation, but also by cross-nucleation between polymorphs and the different growth rates of polymorphs. This study identified a new metastable polymorph of ROY, the 10th of the family.
多晶型物之间的交叉成核是一种新发现的现象，对于理解和控制晶体多晶型至关重要。它与奥斯特瓦尔德阶段定律及多晶型系统中的其他结晶理论相矛盾。我们在5-甲基-2-[(2-硝基苯基)氨基]-3-噻吩甲腈（ROY，目前已知结构中多晶型最多的系统）的自发和籽晶熔体结晶过程中研究了这一现象。我们观察到ROY多晶型物之间存在广泛且有时具有选择性的交叉成核。某些多晶型物在没有其他多晶型物帮助的情况下无法成核。发现新的多晶型物在热力学上或多或少比初始多晶型物更稳定，但总是比初始多晶型物生长得更快或一样快。籽晶的温度和表面特性影响交叉成核的发生。我们的结果表明，多晶型系统中的结晶途径不仅由初始成核决定，还由多晶型物之间的交叉成核以及多晶型物的不同生长速率决定。本研究鉴定出一种新的ROY亚稳多晶型物，这是该家族中的第10种。
