Cross-Nucleation between ROY Polymorphs

Abstract

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.

Surface Crystallization of Indomethacin Below T g

“…Such difference is not surprising given that polymorphs have different internal structures and growth morphologies. Such difference has been observed in other systems and been found to be a key factor controlling the pathways of crystallization (18,19). Today the ability to predict the relative growth rates of polymorphs is lacking, even with the knowledge of the crystal structures and thermodynamics of the polymorphs.…”

Nucleation via an unstable intermediate phase

“…There are numerous examples of one crystalline form of a substance, for example, the equilibrium one, nucleating on another crystalline form of the same substance. For an experimental example of this behavior see the work of Chen et al 22 on a substance known as ROY. The molecule commonly known as ROY is named after its red ͑R͒, orange ͑O͒, and yellow ͑Y͒ polymorphs.…”

Polymorphism and Phase Behaviors of 2-(Phenylamino)nicotinic Acid

“…So far, ROY holds the record of polymorphs characterized by single-crystal X-ray diffraction at seven. 19,20 In 2005, four new polymorphs were reported for oxalyl dihydrazide (ODH). 21 The system described in this report is the newest addition to the "elite club" of organics with four or more polymorphs.…”