Joost A van den Ende

F. Hoffmann-La Roche Ltd · Pharma Research & Early Development (pRED)

After years of controversy over the solid state structure of the essential amino acid L-phenylalanine, four different polymorphic forms were published recently. The common form I has symmetry P21 with four molecules in the asymmetric unit (Z = 4), similar to form III, but with a different arrangement of molecular bilayers. Form II, obtained from th...

J. Christian Sch ̈on opened the discussion of the paper by Gregory J. O. Beran: Concerning the multi-tier approach to improving the quality of the computations, where you did a careful analysis of different types of approximations, it is still very disconcerting that there appears to be no inherently systematic approach to gain an estimate of the e...

The sixth blind test of organic crystal structure prediction (CSP) methods has been held, with five target systems: a small nearly rigid molecule, a polymorphic former drug candidate, a chloride salt hydrate, a co-crystal and a bulky flexible molecule. This blind test has seen substantial growth in the number of participants, with the broad range o...

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 m...

The organisers and participants are very grateful to the crystallographers who supplied the candidate structures: Dr. Peter Horton (XXII), Dr. Brian Samas (XXIII), Prof. Bruce Foxman (XXIV), and Prof. Kraig Wheeler (XXV and XXVI). We are also grateful to Dr. Emma Sharp and colleagues at Johnson Matthey (Pharmorphix) for the polymorph screening of X...

We present a new method to calculate lattice and intermolecular interaction energies for molecular crystals from electron densities obtained within the crystalline environment: q-GRID. The electron density is partitioned over a grid, and each grid point is assigned to a specific molecule. Intermolecular interaction energies are calculated as a sum...

The solid-state phase transitions between the α, β and γ forms of dl-norleucine were studied using DSC, thermal stage polarization microscopy and solid-state NMR. Since the crystals consist of 2D hydrogen-bonded bilayers with van der Waals interactions between consecutive bilayers, the transitions occur in a layer-wise fashion with a propagating tr...

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 reclas...

dl-Norleucine is a molecular crystal exhibiting two enantiotropic phase transitions. The high temperature α ↔ γ 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 β ↔ α transition in a combined computational and experimental study. The temperature...

The properties of crystals are related to their structure and therefore they can be different for different polymorphs. For example, the pharmaceutical characteristics bioavailability and shelf life can depend on the formed polymorph and its stability. We aim to understand transitions between polymorphs that occur in the solid phase, with the ultim...

The enantiotropically related α and β polymorphs of dl-norleucine are an interesting probe for polymorphism in molecular crystals. We present the results of quantitative molecular dynamics simulations of these two polymorphs at both stable and metastable temperatures. Because of a fully flexible force field, we can judge the differences in crystal...

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 tempe...