Separation of Enantiomers of the Chiral Arginine System: Solid-Phase Characterization, Solubility Phase Diagrams, and Preferential Crystallization

The separation of enantiomers is of significant interest for various industrial sectors, such as pharmaceutical production and agrochemistry. The technology requires a comprehensive understanding of chiral structures, thermodynamics, and kinetics to develop sustainable separation strategies. In this work, a systematic investigation was undertaken to characterize the solid phases of both the enantiomer l- and the racemate dl-arginine in aqueous solutions by employing powder X-ray diffraction, thermogravimetry, differential scanning calorimetry, and microscopy analyses. This study discovered the formation of a complex hydrate system of the enantiomer and racemate of arginine. The solubilities of these compounds were determined across a broad range of temperatures and solvent mixtures composed of water and ethanol. Hereby, ethanol acts as an antisolvent in aqueous arginine solutions. The different interactions between the enantiomer, the racemate, and the solvents resulted in varying solubility ratios and had an influence on the eutectic compositions in ternary phase diagrams (TPDs). TPDs were constructed by taking into account different hydrate formations. Observed shifts in the eutectic composition offer possibilities for chiral separation via crystallization. Guided by the TPDs determined, an approach for the enantioseparation of arginine enantiomers was proposed and validated, exploiting isothermal seeded preferential crystallization.