(252a) Nucleation of Molecular Crystals: Order Parameters and Minimum Free Energy Paths

Crystallization is extensively used in the pharmaceutical and food industries, among others, to purify chemicals intended for human consumption. Many molecules, however, 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 present a new method to characterize the degree of order in molecular crystals. This method provides a way to define order parameters for almost any system that does not have a very large number of intramolecular degrees of freedom. We then combine the order parameters constructed in this way with the String Method in collective variables [1] to obtain minimum free energy pathways for the nucleation of crystals from the melt and from aqueous solution. Our results shed light on the mechanisms by which molecules come together and organize into crystalline structures, which is a first step in understanding the mechanisms of polymorph selection.

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