Simulation of aggregation phenomena in solution

How does crystallization begin? An answer to this apparently simple question is out of reach for current experimental techniques, which are blind to transient supramolecular aggregates that may occur in the no man’s land between a homogeneous liquid state and a suspension of crystal nuclei. Despite an increasing understanding of the thermodynamics of crystallization in the framework of Classical and Multi-Step nucleation theories, a predictive theory of nucleation has never been developed so far. Classical Molecular Dynamics can shed light on the events that initiate aggregation phenomena, as in principle it can simulate the very elementary acts that lead to nucleation. The recently developed MiCMoS platform , provides several flexible and cheap tools to investigate small organic molecules in condensed phase. MiCMoS relies on accurately calibrated intermolecular force fields and was successfully applied to investigate several systems, including liquids, crystals, nanodroplets and nanoparticles . In this contribution, the implementation of a biased Molecular Dynamics algorithm to speed up the self-recognition process is reported. The procedure is employed to probe pre-nucleation aggregation phenomena in solutions of benzoic acid, selected as a suitable test case. The algorithm is already available in the most recent release MiCMoS v2.0, which can be downloaded for free at https://sites.unimi.it/xtal_chem_group/index.php/research/5-micmos.