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Updated: Jan 21, 2026

Author Spotlight: Evaluating Biophysical Assays for Characterizing PROTACS Ternary Complexes
Published on: January 12, 2024
Manipulating the dynamics of mechanochemical ternary cocrystal formation
Hannes Kulla1, Adam A L Michalchuk, Franziska Emmerling
1BAM Federal Institute for Materials Research and Testing, Richard-Willstätter-Strasse 11, 12489 Berlin, Germany. franziska.emmerling@bam.de.
Abstract:
The mechanism of ternary cocrystal formation, and the potential role of intermediate binary phases, has been debated for some time. We report here the first in situ real-time monitoring of two prototypic ternary cocrystals. Our results suggest that the question is more complicated than previously considered. The mechanism of mechanochemical ternary cocrystal formation depends on the milling conditions, here the milling frequency and addition of liquid. Binary phases can form under certain conditions, but do not act as intermediates in the formation of the ternary cocrystals. Rather, binary phases are competitive with the ternary phase, and their formation appears to compete with that of the ternary components. The presence of binary phases leads to an increase in the overall reaction time. The results reported here offer the first insights into the true complexities of mechanochemical multi-component synthesis of higher order multi-component crystals and demonstrate a new understanding of the influence of milling condition for the study of mechanisms and kinetics.
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