On the Mechanism of Cocrystal Mechanochemical Reaction via Low Melting Eutectic: A Time-Resolved In Situ Monitoring Investigation

Abstract

Mechanochemistry has become a sustainable and attractive cost-effective synthetic technique, largely used within the frame of crystal engineering. Cocrystals, namely, crystalline compounds made of different chemical entities within the same crystal structure, are typically synthesized in bulk via mechanochemistry; however, whereas the macroscopic aspects of grinding are becoming clear, the fundamental principles that underlie mechanochemical cocrystallization at the microscopic level remain poorly understood. Time-resolved in situ (TRIS) monitoring approaches have opened the door to exceptional detail regarding mechanochemical reactions. We here report a clear example of cocrystallization between two solid coformers that proceeds through the formation of a metastable low melting binary eutectic phase. The overall cocrystallization process has been monitored by time-resolved in situ (TRIS) synchrotron X-ray powder diffraction with a customized ball milling setup, currently available at μSpot beamline at BESSY-II, Helmholtz-Zentrum Berlin. The binary system and the low melting eutectic phase were further characterized via DSC, HSM, and VT-XRPD.

Accurate extrinsic and intrinsic peak broadening modelling for time-resolved in situ ball milling reactions via synchrotron powder X-ray diffraction

“…Other features, such as accurate scattering background, are also significant, and can provide crucial insight into the presence of non-crystalline phases. 54 Typically, the quality of XRPD data obtained from TRIS measurements has been suboptimal, leading to significant uncertainties regarding phase identification, crystal structure, particle size, and microstructure quantification. Hence, robust investigation of mechanochemical transformations has been limited to ex situ analysis.…”

“…Additionally, by including the experimental profile of the empty jar in the Rietveld refinement we could deconvolute the extrinsic to the intrinsic contribution of the background which provides exciting opportunities towards the possibility to monitor the formation of amorphous or liquid products as intermediates. 54…”

“…Additionally, by including the experimental prole of the empty jar in the Rietveld renement we could deconvolute the extrinsic to the intrinsic contribution of the background which provides exciting opportunities towards the possibility to monitor the formation of amorphous or liquid products as intermediates. 54 Quantitative phase analyses (QPA) and microstructural evolution XRPD datasets of any sample under investigation were t sequentially considering both the extrinsic and intrinsic components to the peak broadening. The Rietveld renement strategy differed depending on the propensity of the sample powder to adhere to the jar walls.…”

Spiers Memorial Lecture: Mechanochemistry, tribochemistry, mechanical alloying – retrospect, achievements and challenges

“…243–247,249–251,312,336 Contact (eutectic) melting can occur at the interface of two reactant particles. 115,184,337–342 A fluidized state can be a consequence of mechanical impact itself, but also of local heating. 343 Reaction will then occur in the melt, not in the solid state.…”

Dispensing Essential Oil Components through Cocrystallization: Sustainable and Smart Materials for Food Preservation and Agricultural Applications

“…Cocrystals are single-phase crystalline materials composed of different chemical entities in a stoichiometric ratio. They have been widely explored in the field of crystal engineering, − and they have found significant pharmaceutical applications, , although they have appeared only sporadically in the environmental-related literature. − In recent publications, we highlighted how cocrystallization can be an especially viable solution to this problem, allowing us to tune the physical properties and control the delivery of EOs components, thus extending their range of applicability. ,− …”