Control over crystal polymorphism remains a critical challenge in materials design, with broad implications for pharmaceutical efficacy, device performance, and materials stability. Here, we present a facet-directed strategy for polymorph control of organic molecular crystals using morphology-defined CeO2 nanoparticles as heterogeneous nucleating agents. Cubic and octahedral CeO2, predominantly exposing the (100) and (111) facets, respectively, were employed to regulate the crystallization of three model polymorphic compounds: 5-methyl-2-(2-nitrophenyl)amino-3-thiophenecarbonitrile (ROY), tolfenamic acid (TFA), and carbamazepine (CBZ). Under identical conditions, CeO2(100) consistently induced the formation of thermodynamically stable polymorphs─ON for ROY, Form I for TFA, and Form III for CBZ─whereas CeO2(111) preferentially promoted metastable forms─YN, Form II, and Form II, respectively. In situ optical microscopy revealed distinct nucleation kinetics and growth morphologies between the two facets. Density functional theory (DFT) calculations of ROY adsorption further revealed stronger binding on the (100) surface, rationalizing the observed polymorph selectivity. These findings establish a generalizable framework for facet-directed heterogeneous nucleation, offering a mechanistic basis for polymorph control via surface atomic structure and enabling rational design of nucleating agents in crystal engineering.
Li et al. (Fri,) studied this question.