Jonas Nyman

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.

Static and lattice vibrational energy differences between polymorphs

A computational study of 1061 experimentally determined crystal structures of 508 polymorphic organic molecules has been performed with state-of-the-art lattice energy minimisation methods, using a hybrid method that combines density functional theory intramolecular energies with an anisotropic atom–atom intermolecular model. Rigid molecule lattice dynamical calculations have also been performed to estimate the vibrational contributions to lattice free energies. Distributions of the differences in lattice energy, free energy, zero point energy, entropy and heat capacity between polymorphs are presented. Polymorphic lattice energy differences are typically very small: over half of polymorph pairs are separated by less than 2 kJ mol−1 and lattice energy differences exceed 7.2 kJ mol−1 in only 5% of cases. Unsurprisingly, vibrational contributions to polymorph free energy differences at ambient conditions are dominated by entropy differences. The distribution of vibrational energy differences is narrower than lattice energy differences, rarely exceeding 2 kJ mol−1. However, these relatively small vibrational free energy contributions are large enough to cause a re-ranking of polymorph stability below, or at, room temperature in 9% of the polymorph pairs.

Pellet formation of zygomycetes and immobilization of yeast

Pelleted growth provides many advantages for filamentous fungi, including decreased broth viscosity, improved aeration, stirring, and heat transfer. Thus, the factors influencing the probability of pellet formation of Rhizopus sp. in a defined medium was investigated using a multifactorial experimental design. Temperature, agitation intensity, Ca(2+)-concentration, pH, and solid cellulose particles, each had a significant effect on pelletization. Tween 80, spore concentration, and liquid volume were not found to have a significant effect. All of the effects were additive; no interactions were significant. The results were used to create a simple defined medium inducing pelletization, which was used for immobilization of a flocculating strain of Saccharomyces cerevisiae in the zygomycetes pellets. A flor-forming S. cerevisiae strain was also immobilized, while a non-flocculating strain colonized the pellets but was not immobilized. No adverse effects were detected as a result of the close proximity between the filamentous fungus and the yeast, which potentially allows for co-fermentation with S. cerevisiae immobilized in pellets of zygomycetes.

Clathrate Structure Determination by Combining Crystal Structure Prediction with Computational and Experimental 129Xe NMR Spectroscopy

Abstract An approach is presented for the structure determination of clathrates using NMR spectroscopy of enclathrated xenon to select from a set of predicted crystal structures. Crystal structure prediction methods have been used to generate an ensemble of putative structures of o‐ and m‐fluorophenol, whose previously unknown clathrate structures have been studied by 129Xe NMR spectroscopy. The high sensitivity of the 129Xe chemical shift tensor to the chemical environment and shape of the crystalline cavity makes it ideal as a probe for porous materials. The experimental powder NMR spectra can be used to directly confirm or reject hypothetical crystal structures generated by computational prediction, whose chemical shift tensors have been simulated using density functional theory. For each fluorophenol isomer one predicted crystal structure was found, whose measured and computed chemical shift tensors agree within experimental and computational error margins and these are thus proposed as the true fluorophenol xenon clathrate structures.

A novel chimaeric flocculation protein enhances flocculation in Saccharomyces cerevisiae

Yeast flocculation is the reversible formation of multicellular complexes mediated by lectin-like cell wall proteins binding to neighbouring cells. Strong flocculation can improve the inhibitor tolerance and fermentation performance of yeast cells in second generation bioethanol production. The strength of flocculation increases with the size of the flocculation protein and is strain dependent. However, the large number of internal repeats in the sequence of FLO1 from Saccharomyces cerevisiae S288c makes it difficult to recombinantly express the gene to its full length. In the search for novel flocculation genes resulting in strong flocculation, we discovered a DNA sequence, FLONF, that gives NewFlo phenotype flocculation in S. cerevisiae CEN.PK 113-7D. The nucleotide sequence of the internal repeats of FLONF differed from those of FLO1. We hypothesized that a chimaeric flocculation gene made up of a FLO1 variant derived from S. cerevisiae S288c and additional repeats from FLONF from S. cerevisiae CCUG 53310 would be more stable and easier to amplify by PCR. The constructed gene, FLOw, had 22 internal repeats compared to 18 in FLO1. Expression of FLOw in otherwise non-flocculating strains led to strong flocculation. Despite the length of the gene, the cassette containing FLOw could be easily amplified and transformed into yeast strains of different genetic background, leading to strong flocculation in all cases tested. The developed gene can be used as a self-immobilization technique or to obtain rapidly sedimenting cells for application in e.g. sequential batches without need for centrifugation.

Structure searching methods: general discussion

HAL is a multi-disciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L’archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d’enseignement et de recherche français ou étrangers, des laboratoires publics ou privés. Structure searching methods: general discussion Matthew Addicoat, Claire Adjiman, Mihails Arhangelskis, Gregory Beran, Gerit Brandenburg, Doris Braun, Virginia Burger, Asbjoern Burow, Chris Collins, Andrew Cooper, et al.

Predicting Porous Molecular Crystals and Clathrates

The last decade has seen dramatic improvements in the theories and computer algorithms underlying computational Crystal Structure Predictions [1]. It is now possible to reliably obtain the most likely crystal structures of at least simple molecules starting from nothing more than a drawing of the molecule. We can now go even further and look for rare and exotic kinds of crystals such as porous molecular crystals, clathrates and inclusion compounds among our predictions and calculate their physical properties [2], paving the way for the “science of hypothetical materials”. In our poster, we present results on the prediction of fluorophenol xenon clathrates. We have performed crystal structure predictions by global lattice energy searches on oand m-fluorophenol. The predicted structures have then been analyzed for porosity and their likelihood of being clathrates. From the several thousands of predicted structures, we select a few likely candidates according to an empirical rule based on the guest to host volume ratio [3]. Results from solid state xenon-129 NMR indicate that we have successfully determined the crystal structures of both oand m-fluorophenol xenon clathrates and we suggest that Crystal Structure Prediction in combination with xenon-129 NMR is a powerful method for determining the structures of clathrates in general.