(359b) Minimum Free Energy Pathways for Nucleation and Polymorph Transformations in Molecular Crystals

Crystallization is extensively used in the pharmaceutical and food industries, among others, to purify chemicals intended for human consumption. Despite its widespread use, however, the design of crystalline materials is far from an easy task. Many molecules can crystallize into different polymorphs depending on the precipitation conditions (e.g. solvent, degree of supersaturation). These polymorphs often exhibit different physical properties, which affects their suitability for various applications. For example, different polymorphs of a drug may have different dissolution profiles, and hence bioavaliabilites, which makes the control of the crystallization process critical in drug manufacturing.

In this work, we combine a novel method to characterize the degree of order in molecular crystals [1] with the string method in collective variables [2] to obtain minimum free energy pathways for the nucleation of benzene from the melt, the polymorph transformation of terephtalic acid, and the nucleation of alpha-glycine from aqueous solution. We compare some of the results from this approach with those obtained using transition path sampling. These results are a first step toward a thorough molecular-level understanding of the mechanisms underlying crystallization and polymorph transformations in molecular systems.

[1] E.E. Santiso and B.L. Trout, J. Chem. Phys. Submitted (2010)

[2] L. Maragliano, et al., J. Chem. Phys. 125, 024106 (2006)