Structure-Related Additive-Induced Morphological Transformation of Isovanillin Crystals: Insights from Molecular Dynamics Simulations

The alteration of the crystal morphology by structure-related additives has gained great attention in various fields associated with crystallization. However, an insufficient understanding of the underlying incorporation mechanism has hindered the rational design of such additives. In this study, the effect of the structure-related additive 3-anisaldehyde on the morphology transformation of isovanillin crystals was investigated experimentally, complemented by molecular simulation to elucidate the incorporation mechanism. Systematic analyses of energy and conformational changes revealed that 3-anisaldehyde can be incorporated into specific growth sites, where it undergoes a transition from a metastable to a stable conformation. The resulting morphology change was further elucidated through surface chemistry analysis using electrostatic potential mapping and adsorption locator analysis. The findings indicate that incorporated 3-anisaldehyde disrupts solute recognition at growth sites, thereby inhibiting the development of the corresponding crystal face. This work provides new insight into the incorporation mechanism of the structure-related additive and provides a potential molecular-simulation-based strategy for the prescreening and rational design of structure-related additives.