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Profound Effect of the Milling Assembly on Polymorphism in Mechanochemical Cocrystallization

submitted on 10.02.2020, 06:36 and posted on 11.02.2020, 06:54 by Luzia S. Germann, Mihails Arhangelskis, Robin Stein, Martin Etter, Robert E. Dinnebier, Tomislav Friscic
Mechanochemistry provides a highly efficient, but still poorly understood route to synthesize and screen for polymorphs of organic solids. We present a hitherto unexplored approach to control the mechanism and outcome of mechanochemical cocrystallization through changes to the milling assembly, i.e. milling jar and balls. Whereas polymorph control of mechanochemical cocrystallization is typically discussed in terms of liquid additives, real-time synchrotron X-ray diffraction studies reveal a direct impact of the choice of milling media on the rate of formation and interconversion of cocrystal polymorphs. This effect enabled the discovery of a new polymorph of a cocrystal of nicotinamide and adipic acid, whose formation and conversion to the previously known, enantiotropically-related form, was readily controlled by milling in jars made of different materials.


Swiss National Science Foundation, P2SKP2_187638

National Science Center of Poland, 2018/31/D/ST5/03619

NSERC Discovery Accelerator award (RGPAS 507837-17)

NSERC E. W. R. Steacie Memorial Fellowship (SMFSU 507347-17)

NSERC Discovery Grant (RGPIN-2017-06467)


Email Address of Submitting Author


McGill University



ORCID For Submitting Author


Declaration of Conflict of Interest

no conflict of interest