How Many Parameters Can Affect the Solid Form of Cocrystallization Products in Mechanochemical Reactions? A Case Study

Polymorphism of cocrystals is a fascinating research topic in the field of crystal engineering. For the often employed mechanochemical synthesis approach, the solvent polarity and the stoichiometric ratio of starting materials were previously confirmed as significant variables controlling the polymorphic outcomes. In this study, the 1:1 (THP-AH11) and 1:2 (THP-AH12) theophylline-acesulfame cocrystals were obtained by using mechanochemical method with different synthesis parameters. It was found that the solid form of the mechanochemical product can also be altered by grinding energy and forms of starting materials. All these effect factors are understandable from the point of view of energy mechanism, which modified either the energy barrier or the reaction pathway.

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