Solid-State Forms of β-Resorcylic Acid: How Exhaustive Should a Polymorph Screen Be?

An extensive experimental screen, coupled with a computational study, revealed seven new solid-state forms of β-resorcylic acid. The known, stable polymorph II° shows a reversible phase transformation to the new, kinetically stable, probably disordered high temperature form I. The study provides a consistent picture of the solid-state of β-resorcylic acid

Towards crystal structure prediction of complex organic compounds - a report on the fifth blind test

Following on from the success of the previous crystal structure prediction blind tests (CSP1999, CSP2001, CSP2004 and CSP2007), a fifth such collaborative project (CSP2010) was organized at the Cambridge Crystallographic Data Centre. A range of methodologies was used by the participating groups in order to evaluate the ability of the current computational methods to predict the crystal structures of the six organic molecules chosen as targets for this blind test. The first four targets, two rigid molecules, one semi-flexible molecule and a 1: 1 salt, matched the criteria for the targets from CSP2007, while the last two targets belonged to two new challenging categories - a larger, much more flexible molecule and a hydrate with more than one polymorph. Each group submitted three predictions for each target it attempted. There was at least one successful prediction for each target, and two groups were able to successfully predict the structure of the large flexible molecule as their first place submission. The results show that while not as many groups successfully predicted the structures of the three smallest molecules as in CSP2007, there is now evidence that methodologies such as dispersion-corrected density functional theory (DFT-D) are able to reliably do so. The results also highlight the many challenges posed by more complex systems and show that there are still issues to be overcome

Molecular Conformations and Relative Stabilities Can Be as Demanding of Electronic Structure Method as Intermolecular Calculations

We have performed a variety of high-level electronic structure calculations on two moderately sized organic molecules and found considerable sensitivity of the intramolecular potential energy surface to the method employed. The gas-phase structure of tyrosine-glycine varies qualitatively between B3LYP and MP2 optimizations, producing different close contacts between the tyrosine ring and the glycine moiety. The relative energies of the 2-(acetylamino)benzamide conformations found in its two polymorphs can vary by over 20 kJ mol(-1) between MP2 and B3LYP calculations, using the same basis set. It is shown by a novel analysis that the intramolecular equivalent of basis set superposition error competes with the errors in the intramolecular dispersion in causing this sensitivity

Successful prediction of a model pharmaceutical in the fifth blind test of crystal structure prediction

The range of target structures in the fifth international blind test of crystal structure prediction was extended to include a highly flexible molecule, (benzyl-(4-(4-methyl-5-(p-tolylsulfonyl)-1,3-thiazol-2-yl)phenyl)carbamate, as a challenge representative of modern pharmaceuticals. Two of the groups participating in the blind test independently predicted the correct structure. The methods they used are described and contrasted, and the implications of the capability to tackle molecules of this complexity are discussed