Do solid-to-solid polymorphic transitions indl-norleucine proceed through nucleation?

Abstract

Disclaimer/Complaints regulationsIf you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: http://uba.uva.nl/en/contact, or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible. DL-Norleucine is a molecular crystal exhibiting two enantiotropic phase transitions. The high temperature a 4 g transition has been shown to proceed through nucleation and growth [Mnyukh et al., J. Phys. Chem. Solids, 1975, 36, 127]. We focus on the low temperature b 4 a transition in a combined computational and experimental study.The temperature dependence of the structural and energetic properties of both polymorphic forms is nearly identical. Molecular dynamics simulations and nudged elastic band calculations of the transition process itself, suggest that the transition is governed by cooperative movements of bilayers over relatively large energy barriers.

Energy barriers and mechanisms in solid–solid polymorphic transitions exhibiting cooperative motion

“…Indeed earlier molecular dynamics simulations 14 showed that the β ↔ I 2 transitions become less frequent with increasing simulation cell size. The present results which show linear isotropic scaling, triggered a reanalysis of these molecular dynamics simulations.…”

“…This is in accordance with experimental thermal stage microscopic observation where in some cases the crystal is found to "wobble" during the transition, but the cell parameters before and after the transition are again the same. 14,21 The dashed line in Fig. 5 shows the fit with only the prefactor as a free parameter and .…”

“…β↔ I 2 shifting rate obtained from MD simulations14 with different simulation cell sizes as a function of number of molecules in a bilayer. The solid and dashed lines are results of fits of eqn (2) to the data crosses (see text for details).…”

Molecular Dynamics Simulations in Drug Discovery and Pharmaceutical Development

“…Understanding the possible phase changes between different polymorphic forms of the same crystalline drugs is critical because different forms can have radically different behavior during dissolution, storage, and manufacturing. The transition between the β and α forms of DL-norleucine is a typical example of a solid-solid phase change simulated with MD [438]. It was possible to discover different transition pathways and their energy barriers and to determine that the transition proceeded by cooperative movement between the bilayers in the crystal.…”

Coordination frameworks of tetrakis[meso-(3,5-biscarboxyphenyl)]-metalloprphyrins with polynuclear metallic nodes

“…I will present advanced Molecular Dynamics (MD) simulations of two enantiotropically related polymorphic forms of DL-norleucine: α (room temperature) and β (low temperature), which are thought to transform through a martensitic mechansism by sliding along two cell axes. I will show that the mechanism of the transition occurs through a cooperative movement of bilayers via an intermediate state [1,2]. Although the layers move in a concerted fashion, the results further indicate that local fluctuations in the conformations of the aliphatic chains play a crucial role in keeping the cooperative mechanism sustainable at large length scales (see figure).…”