(196f) Polymorph Selection during Crystal Nucleation and Growth

Understanding the phenomenon of crystallization is of great fundamental and technological importance [1,2]. The structure (or polymorph), in which a compound crystallizes, dictates many of its properties. For instance, the bioavailability of a pharmaceutical solid will depend on its structure: the formation, after a few months of production, of a less soluble polymorph led Abbott Laboratories to reformulate the anti-Aids drug Norvir [3]. Similarly, the nonlinear optical properties of a crystal depend on the overall dipole moment of the crystal and hence on the structure in which the compound crystallizes [4]. Finally, properties like the rigidity of polymer crystals vary over several orders of magnitude depending on the molecular arrangement of the chains in forming the crystal.

In previous work, we used the umbrella sampling technique together with an appropriate reaction coordinate to study the crystallization process in supercooled liquids of N2 [5] and CO2. This simulation method allows to simulate the crystallization phenomenon at a degree of supercooling typical of those used in experiments [6]. These studies shed light on the microscopic mechanisms underlying the early stages of crystallization. In the case of N2, the nucleation and the subsequent growth of the critical nucleus concomitantly occurred with a transition from a kinetically favored metastable structure (fcc-like) to the thermodynamically stable structure (hcp-like) [5]. Here, we present our new results on simple organic molecules.

[1] “Polymorph selection: Challenges for the future?”, N. Blagden and R. J. Davey, Crystal Growth and Design 3, 873 (2003). [2] “Dense Liquid Precursor for the Nucleation of Ordered Solid Phases from Solution.”, P. G. Vekilov, Crystal Growth and Design 4, 671 (2004). [3] “Ritonavir: An Extraordinary Example of Conformational Polymorphism.”, J. Bauer, S. Spanton, R. Henry, J. Quick, W. Dziki, W. Porter, and J. Morris, Pharmaceutical Research 18, 859 (2001). [4] “Crystal Engineering: from Structure to Function.”, M. D. Hollingsworth, Science 295, 2410 (2002). [5] ‘Reorganization and growth of metastable ?-N2 critical nuclei into stable ?-N2 crystals.', J.-M. Leyssale, J. Delhommelle and C. Millot, Journal of the American Chemical Society 126, 12286 (2004). [6] “Prediction of absolute crystal-nucleation rate in hard-sphere colloids.”, S. Auer and D. Frenkel, Nature 409, 1020 (2001).