TY - JOUR A1 - Kulla, Hannes A1 - Becker, C. A1 - Michalchuk, Adam A1 - Linberg, Kevin A1 - Paulus, B. A1 - Emmerling, Franziska T1 - Tuning the Apparent Stability of Polymorphic Cocrystals through Mechanochemistry T2 - Crystal Growth & Design N2 - Mechanochemistry has become a valuable method for the synthesis of new materials and molecules, with a particular strength for screening and preparing multicomponent crystals. In this work, two novel cocrystals of pyrazinamide (PZA) with pimelic acid (PA) were prepared mechanochemically. Their formation was monitored in real time by in situ synchrotron powder X-ray diffraction. Control over the polymorphic form was obtained through the selective choice of liquid additive via liquid assisted grinding. Slurry experiments and dispersion-corrected density functional theory calculations suggest that Form I is the thermodynamically stable form under ambient conditions. Upon aging, Form II converts to Form I. The stability of Form II upon aging was found to depend strongly on the milling duration, intensity, and material of the milling vessels. Longer or higher energy milling drastically increased the lifetime of the Form II product. For the first time, this work also demonstrates that the choice of milling jar can have a decisive effect on the aging stability of a bulk polymorphic powder. In contrast to material prepared in steel milling vessels, the preparation of Form II in Perspex (PMMA) vessels increased its lifetime 3-fold. These findings offer a new dimension to garnering control over mechanochemical cocrystallization and demonstrate the critical importance of the careful and timely ex situ screening of ball mill grinding reactions. This will be of importance for potential industrial applications of mechanochemical cocrystallization where understanding polymorph longevity is crucial for the development of a robust preparative protocol. PB - ACS Publications KW - Physical and chemical processes KW - Organic compounds KW - Liquids KW - Materials KW - Stability PY - 2019 UR - https://opus4.kobv.de/opus4-bam/frontdoor/index/index/docId/50281 AN - OPUS4-50281 VL - 19 IS - 12 SP - 7271 EP - 7279 AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany