Abstract
„Amorphous Intermediates and Polymorph Selection in Molecular Crystallization“
When matter crystallizes, thermodynamics dictates that the crystal structure with the lowest free energy will prevail in equilibrium. For typical organic molecules, however, the situation is more complicated: many accessible crystal packings often lie within a narrow free-energy range, and crystallization outcomes are frequently controlled less by thermodynamic stability than by kinetic accessibility. In practice, discovering a new polymorph often means identifying the crystallization conditions that selectively favor one structural pathway over competing alternatives. The Grünwald group uses molecular modeling and computer simulations to uncover crystallization mechanisms in systems ranging from organic molecular crystals to metal–organic frameworks and nanoparticle superstructures. In this presentation, I will discuss recent simulation and experimental results for two representative systems: 3-chloromandelic acid, a drug-like organic molecule, and ZIF-8, a prototypical metal–organic framework. In both cases, crystallization from solution does not proceed by direct, single-step ordering from the dilute phase. Instead, building units first assemble into dense, disordered aggregates, from which crystalline order subsequently emerges. I will show that the local structural motifs and fluctuations of these amorphous intermediates encode information about which polymorph or framework topology is most likely to nucleate. These findings highlight the importance of non-classical nucleation pathways for polymorph selection and suggest ways to improve crystal structure prediction by accounting not only for the relative thermodynamic stability of candidate structures, but also for the kinetic pathways by which they can form.