Yang Pengpeng, Wu Qian, Liu Haodong, Zhou Shuyang, Chen Wensu, Zhong Huamei, Zhang Keke, Zou Fengxia, Ying Hanjie
College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, Nanjing 211816, China.
Biology+ Joint Research Center, School of Chemical Engineering and Technology, Zhengzhou University, Zhengzhou 450001, China.
Ultrason Sonochem. 2024 Aug;108:106953. doi: 10.1016/j.ultsonch.2024.106953. Epub 2024 Jun 12.
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 FDPNa 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 FDP ions, thereby dismantling FDPclusters in solution. Thus, in turn, shortened the reduced induction time and promoted crystallization. Furthermore, ultrasound reduced the interactions between FDPions and water molecules as well as FDP ions themselves. As simulated field intensity increased, these interaction forces gradually diminished, the thickness of the hydration layer surrounding the FDP clusters facilitating the disruption of clusters, ultimately enhancing the crystallization process.
液-液分离，通常称为“出油”，在结晶过程中经常发生，特别是在磷酰化合物的反溶剂结晶过程中，这对高质量产品构成了潜在障碍。有效控制结晶过程中的“出油”现象仍然是一项重大挑战。在各种技术中，超声作为一种绿色有效的方法出现，可用于强化结晶过程。然而，目前缺乏深入研究来探索这一过程的微观机制。因此，我们的研究聚焦于典型的磷酰化合物1,6-二磷酸果糖（FDP），以更深入地了解超声如何影响“出油”过程。采用聚焦光束反射测量（FBRM）技术研究了不同溶剂比例下FDPNa的“出油”现象。此外，研究了超声对诱导时间的影响并计算了成核能垒。最后，为了进一步揭示微观机制，我们利用分子模拟技术分析了超声功率对溶解-沉淀过程的影响。我们的观察结果表明，无论使用何种溶剂，“出油”过程都是一致的，并能达到稳定状态。值得注意的是，“出油”诱导时间实验结果表明，超声显著降低了FDP离子的成核能垒，从而拆散了溶液中的FDP簇。进而缩短了诱导时间并促进了结晶。此外，超声减少了FDP离子与水分子以及FDP离子自身之间的相互作用。随着模拟场强的增加，这些相互作用力逐渐减弱，FDP簇周围水化层的厚度有利于簇的破坏，最终强化了结晶过程。
