A New Look at the Mechanism of Cocrystal Formation and Coformers Exchange in Processes Forced by Mechanical and/or Thermal Stimuli - ex situ and in situ Studies of Low-Melting Eutectic Mixtures.

Autor: Dudek MK; Centre of Molecular and Macromolecular Studies Polish Academy of Sciences, Sienkiewicza 112, 90-363, Lodz, Poland., Trzeciak K; Centre of Molecular and Macromolecular Studies Polish Academy of Sciences, Sienkiewicza 112, 90-363, Lodz, Poland., Tajber L; School of Pharmacy and Pharmaceuticals Sciences, the SFI Research Centre for Pharmaceuticals, Trinity College Dublin College Green, Dublin 2, Ireland., Zając J; Centre of Molecular and Macromolecular Studies Polish Academy of Sciences, Sienkiewicza 112, 90-363, Lodz, Poland., Kaźmierski S; Centre of Molecular and Macromolecular Studies Polish Academy of Sciences, Sienkiewicza 112, 90-363, Lodz, Poland., Pindelska E; Department of Pharmaceutical Chemistry and Biomaterials, Faculty of Pharmacy, Medical University of Warsaw, Banacha 1, 02-093, Warsaw, Poland., Makowski T; Centre of Molecular and Macromolecular Studies Polish Academy of Sciences, Sienkiewicza 112, 90-363, Lodz, Poland., Svyntkivska M; Centre of Molecular and Macromolecular Studies Polish Academy of Sciences, Sienkiewicza 112, 90-363, Lodz, Poland., Potrzebowski MJ; Centre of Molecular and Macromolecular Studies Polish Academy of Sciences, Sienkiewicza 112, 90-363, Lodz, Poland.
Jazyk: angličtina
Zdroj: Chemistry (Weinheim an der Bergstrasse, Germany) [Chemistry] 2024 Feb 21; Vol. 30 (11), pp. e202302138. Date of Electronic Publication: 2024 Jan 08.
DOI: 10.1002/chem.202302138
Abstrakt: Three different devices: ball mill, hot stage melting, and magic angle spinning (MAS) NMR rotor were used for the preparation of ethenzamide (ET) cocrystals with glutaric acid (GLU), ethylmalonic acid (EMA) and maleic acid (MAL) as coformers. In each case, well-defined binary systems (ET:EMA, ET:GLU, ET:MAL) were obtained. The common features of the two solvent free methods of cocrystal formation (grinding, melting) are presented on the basis of arguments obtained by solid state NMR spectroscopy. Thermal analysis (Differential Scanning Calorimetry) proved that the eutectic phase arises over a wide range of molar ratios of components for each of the binary systems. NMR techniques, supported by theoretical calculations, allowed to provide details about the pathway of the reaction mechanism with atomic accuracy. It was found that the formation of ET cocrystals is a complex process that requires five steps. Each step has been recognized and described. Variable temperature 1D and 2D MAS NMR experiments allowed to track physicochemical processes taking place in a molten state. Moreover, it was found that in a multicomponent mixture consisting of all four components, ET, EMA, GLU, and MAL, ET in the molten phase behaves as a specific selector choosing only one partner to form binary cocrystals according to energy preferences. The process of exchange of coformers in binary systems during grinding, melting, and NMR measurements is described. The stabilization energies (E stab ) and molecular electrostatic potential (MEP) maps computed for the cocrystals under discussion and their individual components rationalize the selection rules and explain the relationships between individual species.
(© 2023 Wiley-VCH GmbH.)
Databáze: MEDLINE
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