Volume 241, 2023

Controlling polymorphism in molecular cocrystals by variable temperature ball milling

Abstract

Mechanochemistry offers a unique opportunity to modify and manipulate crystal forms, often providing new products as compared with conventional solution methods. While promising, there is little known about how to control the solid form through mechanochemical means, demanding dedicated investigations. Using a model organic cocrystal system (isonicotinamide:glutaric acid), we here demonstrate that with mechanochemistry, polymorphism can be induced in molecular solids under conditions seemingly different to their conventional thermodynamic (thermal) transition point. Whereas Form II converts to Form I upon heating to 363 K, the same transition can be initiated under ball milling conditions at markedly lower temperatures (348 K). Our results indicate that mechanochemical techniques can help to reduce the energy barriers to solid form transitions, offering new insights into controlling polymorphic forms. Moreover, our results suggest that the nature of mechanochemical transformations could make it difficult to interpret mechanochemical solid form landscapes using conventional equilibrium-based tools.

Graphical abstract: Controlling polymorphism in molecular cocrystals by variable temperature ball milling

Associated articles

Supplementary files

Article information

Article type
Paper
Submitted
20 5 2022
Accepted
24 6 2022
First published
24 6 2022
This article is Open Access
Creative Commons BY license

Faraday Discuss., 2023,241, 178-193

Controlling polymorphism in molecular cocrystals by variable temperature ball milling

K. Linberg, B. Röder, D. Al-Sabbagh, F. Emmerling and A. A. L. Michalchuk, Faraday Discuss., 2023, 241, 178 DOI: 10.1039/D2FD00115B

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