Joost van den Ende

Report on the sixth blind test of organic crystal structure prediction methods

The results of the sixth blind test of organic crystal structure prediction methods are presented and discussed, highlighting progress for salts, hydrates and bulky flexible molecules, as well as on-going challenges.

The effect of temperature and velocity on superlubricity

We study the effects of temperature and sliding velocity on superlubricity in numerical simulations of the Frenkel-Kontorova model. We show that resonant excitations of the phonons in an incommensurate sliding body lead to an effective friction and to thermal equilibrium with energy distributed over the internal degrees of freedom. For finite temperature, the effective friction can be described well in terms of a viscous damping force, with a damping coefficient that emerges naturally from the microscopic dynamics. This damping coefficient is a non-monotonic function of the sliding velocity which peaks around resonant velocities and increases with temperature. At low velocities, it remains finite and nonzero, indicating the preservation of superlubricity in the zero-velocity limit. Finally, we propose experimental systems in which our results could be verified.

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

Understanding solid–solid polymorphic transitions within molecular crystals on the molecular scale is a challenging task. It is, however, crucial for the understanding of transitions that are thought to occur through cooperative motion, which offer an interesting perspective for future applications. In this paper, we study the energy barriers and mechanisms involved in the β → α DL-norleucine transition at the molecular scale by applying different computational techniques. We conclude that the mechanism of the transition is a cooperative movement of bilayers through an intermediate state. The results 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. We have characterized the intermediate state.

Solvent and additive interactions as determinants in the nucleation pathway: general discussion

Sarah Price opened a general discussion of the paper by Sven Schroeder: I have been generating the thermodynamically plausible crystal structures of organic molecules for many years, and back in 2004 we did a crystal structure prediction (CSP) study on imidazole1 and found that it was relatively straightforward. Following your paper, we have reclassified the low energy structures according to the tilt within the hydrogen-bonded chain and the relative direction of the chains. Although the observed structure was the global minimum, two other structures with a displacement of otherwise identical layers are very close in energy. Do you think that if imidazole had crystallised in one of these alternative structures it would be distinguishable by NEXAFS? This would be a very sensitive test of whether NEXAFS combined with CSP could be used in characterising crystal structures.

Understanding the polymorphic phase transitions of linear amino acids using in situ characterisation

Polymorphism is a common phenomenon for molecular crystals. Here we aim to understand the mechanisms involved in transitions between polymorphic forms in the solid state. Ultimately, the understanding will allow for the control of polymorphic forms by promoting or inhibiting transitions, which is important for prolonging the shelf life of polymorphic forms of active pharmaceutical ingredients (API). The established classification of phase transitions cannot explain several phenomena in molecular systems, such as cooperative motion1. This mechanism has been inferred to explain thermosalient behaviour2. I will present the in-situ characterisation of the reversible α-β and α-γ phase transitions of DL-norleucine (NLE) and the α-β transition of DL-methionine (MET). Although all polymorphs involved have been reported in the literature, little is known about the transition between the structures. I will show that the transition behaviour in these linear amino acids can be explained by cooperative motion. NLE is an amino acid with three known polymorphic forms, which consist of zwitterionic H-bonded bilayers. The three monoclinic structures differ in the stacking of the bilayers (β↔α, α↔γ) and in the conformation of the molecules (α↔γ)3. MET has two known polymorphic forms (β&α) with different bilayer stacking and different conformations. We studied the transitions using complementary in situ techniques (DSC, SCXRD, solid-state NMR, polarisation microscopy) to get a full picture of the phase transitions. Especially solid-state NMR proved to be a powerful technique, due to its sensitivity to changes in the environment of atoms. The α-γ phase transition of NLE behaves as a typical first order phase transition with the nucleation and growth mechanism. The α-β phase transition of NLE is difficult to observe and occurs very irregularly. It shows coexistence and a large dependence on crystal quality and defect density that suggests cooperative motion.5 This is in agreement with molecular dynamics simulations.6 The α-β transition of MET shows intermediate behaviour and is consistent with kinetic hindrance. 1.Brandel et al, Chem. Mat. 27,6360-6373 (2015). 2.Naumov et al, Chem. Rev. 115,12440-12490 (2015). 3.Coles et al, Cryst. Growth & Des. 9,4610-4612 (2009). 4.Görbitz et al, Acta Cryst E. 70,337-340 (2014), Acta Cryst E. 71,o398-o399 (2015). 5.Smets et al, Cryst. Growth Des. 15,5157-5167 (2015). 6.Van den Ende, Smets, et al, Faraday Discuss. 179,421-436 (2015).