Improving separation efficiency of crystallization by ultrasound-accelerated nucleation: The role of solute diffusion and solvation effect

The nucleation rate significantly affects the separation and purification efficiency of crystallization. The proper choice of solvent combined with the intensification of ultrasound can further accelerate the nucleation. However, the difference in the ability of ultrasound to promote nucleation in different solvents needs to be considered. Here, the comparative study of crystal nucleation in various solvent environments under ultrasonic and non-ultrasonic conditions was explored. The probability distribution method was employed to better describe the randomness of nucleation events. Over 1500 nucleation induction time experiments of 3,5-dimethoxybenzoic acid in three solvents (ethanol, acetonitrile, acetone) were performed. The results showed that the enhancement on nucleation rate by ultrasound in different solvents ranged from 1% to 116%, which had obvious differences in different solvents. It is revealed that the enhancement degree is mainly affected by solute diffusion and solvation effect. On the one hand, mean square displacement (MSD) analysis of solute molecule demonstrates that, the weaker the diffusion ability of solute in a certain solvent, the more significant the enhancement effect of ultrasound on the nucleation in such solvent system. On the other hand, molecular dynamics (MD) simulation, density functional theory (DFT) calculation and spectroscopy method indicate that the solvation effect is the main factor determining the order of nucleation rate in the three solvents. The stronger the solvation of solvent on the solute, the more difficult the nucleation. So that in our system, the introduction of ultrasound enhances nucleation in each solvent but does not change the order of nucleation rate in the three solvents.