Simulation and mechanism for the Ultrasound-Assisted Oiling-Out Process: A case study using Fructose-1,6-diphosphate

Abstract

Liquid–liquid separation, commonly referred to as oiling-out, frequently can occurs during crystallization, especially the anti-solvent crystallization process of phosphoryl compounds, and poses potential hurdle for high-quality product. Efficiently regulating oiling-out during crystallization remains a significant challenge. Among various techniques, ultrasound emerges as a green and effective approach to enhance the crystallization process. However, there is a dearth of in-depth research exploring the microscopic mechanisms of this process. Therefore, our research focused on the fructose-1,6-diphosphate (FDP), a typical phosphoryl compound, to gain a deeper understanding of how ultrasound influences the oiling-out process. The focused beam reflectance measurement (FBRM) technology was used to investigate the oiling-out phenomenon of FDPNa3 across various solvent ratios. In addition, the influence of ultrasound on the induction time was studied and the nucleation energy barrier was calculated. Finally, to further unravel the microscopic mechanisms, we utilized molecular simulation techniques to analyze the impact of ultrasound power on the dissolution-precipitation process. Our observations revealed a consistent oiling-out process that attainted a stable state regardless of the solvent employed. Notably, the results of the oiling-out induction time experiments indicated that ultrasound significantly reduced helped lower the nucleation energy barrier of FDP3- ions, thereby dismantling FDP3-clusters in solution. Thus, in turn, shortened the reduced induction time and promoted crystallization. Furthermore, ultrasound reduced the interactions between FDP3-ions and water molecules as well as FDP3- ions themselves. As simulated field intensity increased, these interaction forces gradually diminished, the thickness of the hydration layer surrounding the FDP3- clusters facilitating the disruption of clusters, ultimately enhancing the crystallization process.

Keywords

• Ultrasound
• Molecular simulation
• Fructose-1
• 6-diphosphate
• Oiling-out mechanism
• Nucleation energy barrier