Unraveling the Dynamics of Strain-Induced Mechanisms of Crystal Growth Modifiers

A molecular-level understanding of crystal growth modification is essential for advancing crystallization control across biomedical, pharmaceutical, and materials science applications. Recent studies have shown the role of crystal growth modifiers (CGMs) not only in inhibiting growth through site-blocking mechanisms but also in their ability to induce localized strain-mediated dissolution. In this study, we capture the dual role of CGMs, particularly citrate (CA) and hydroxycitrate (HCA), in modulating crystallization. Specifically, this dual role refers to the concentration-dependent shift in CGM behavior. At low concentrations, CGMs function as traditional step-pinners and kink blockers, reducing crystal growth rates. However, at higher concentrations, they induce lattice strain, leading to localized surface desorption and the formation of distinct etch pits. This transition from growth inhibition to strain-mediated dissolution challenges classical crystallization theories and underscores the significance of modifier-induced lattice perturbations in shaping surface morphology. These insights contribute to a broader understanding of controlled crystallization through CGM-mediated mechanisms, which remain underexplored in the field. By elucidating previously unknown strain-induced mechanisms, this work provides new molecular-level insight into how crystallization modifiers operate, guiding the development of next-generation inhibitors with greater precision and offering new strategies for both preventing pathological crystallization (e.g., kidney stone formation) and improving industrial crystallization processes in the presence of CGMs.