Additive strategy for nucleation pathway control based on the understanding of molecular size effect on crystallization

Abstract

Understanding mechanisms involved in particle formation processes is crucial to effectively control crystalline particle characteristics. This study highlights the significant effect of slight changes in molecular size on the crystallization pathway. Molecular dynamics simulations are performed in a binary Lennard-Jones system as a model for systems that undergo two-step nucleation via an intermediate droplet structure. This study analyzed two cases with different solute–solute interaction strengths and found that a larger solute-to-solvent size ratio delayed droplet crystallization in both cases. In systems with strong solute–solute interactions, this delay shifted the pathway from one-step-like to two-step-like nucleation, as droplets with larger solute molecules incorporated more solvent, thereby hindering crystallization. We explained this change in droplet composition by considering the mixing free energy between the solute and solvent. Larger solute molecules form entropically and enthalpically favorable structures by accommodating solvent molecules, which increase the solvent fraction of the droplet. We used a thermodynamic model based on the classical nucleation theory with a core–shell nucleus and revealed that this increased solvent fraction in the droplet lowered the freezing point of the droplet and raised the solid–liquid interfacial tension, ultimately delaying and suppressing crystallization. Based on these findings, we proposed a strategy to control the nucleation pathway using additives. Introducing appropriate additives to modify the stability of intermediates is a promising strategy to control nucleation pathways in various systems.