Preparation and recrystallization of amorphous l-glutamic acid

Abstract

Amino acids, as essential biological molecules and industrial raw materials, exhibit polymorphic behavior that significantly impacts their physicochemical properties and applications. Non-classical crystallization pathways involving amorphous intermediates are commonly observed in the crystallization process of amino acids including L-glutamic acid (Glu). An effective research approach in the field of non-classical crystallization is to synthesize metastable intermediates to study the crystallization mechanisms. Herein, amorphous Glu was successfully synthesized using CaCl₂ as a stabilizer through ball milling (1 : 1 Glu–CaCl₂ molar ratio), spray drying (1 : 1 and 2 : 1 ratios) and aqueous evaporation (up to 5 : 1 ratio). The metastable amorphous Glu with high Glu content (87 wt% for the 5 : 1 ratio) was prepared via evaporation for the first time. The amorphous nature of the samples was confirmed by powder X-ray diffraction and low-frequency Raman spectroscopy. IR, mid-frequency Raman, and ¹³C solid-state NMR spectroscopy confirmed the main existence form of Glu neutral zwitterions in the amorphous Glu, while IR and mid-frequency Raman spectroscopy revealed that the structure of the amorphous Glu resembles Glu aqueous solution. Solubility and pH measurements indirectly showed that Glu are coordinated with Ca²⁺. Suspension recrystallization demonstrated that α polymorph is the primary recrystallization product of the amorphous Glu. The discovery of metastable amorphous intermediates would provide new insights into the non-classical crystallization of amino acids.