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

Intermolecular Interactions in Crystals: via experiment and theory to industrial application. International conference, Pula 28-30 april 2013

Book of abstractThe conference will cover a number of topics in experimental and theoretical investigations on intermolecular Interactions in crystal solids and their impact on industrial applications. The event will bring together researchers from Chemical Industry, Key Universities and Research Centers of Europe. Deadline for abstract submission 15th January, 2013. The event is organized by CRS4 with support of the Ruhr University Bochum (RUB), Faculty of Chemistry within the DFG Project (German Research Foundation)2013-04-28PulaIntermolecular Interactions in Crystals: via experiment and theory to industrial applicatio

Deuterium Shifts the Equilibrium: How Heavy Water Can Influence Organic Multicomponent Crystal Formation

The use of heavy water as solvent in the reaction of oxalic acid with pyridine enables the approach to an alternative crystalline product formation compared to the analogues’ reaction in water. The thermodynamically driven molecular aggregation is heavily influenced by the shifted strength of intermolecular interactions, induced by the hydrogen/deuterium exchange

Cocrystals of Pentoxifylline: In Silico and Experimental Screening

To obtain new crystal forms with altered physicochemical properties and to get insight into the driving forces guiding cocrystallization, we performed experimental and in silico screening of pentoxifylline with 11 pharmaceutically acceptable organic acids. Neat grinding, liquid-assisted grinding, and slow solvent evaporation were used to obtain cocrystals of pentoxifylline. The free energy of experimental and hypothetical crystal structures have been calculated using the FlexCryst program. Three cocrystals of pentoxifylline with aspirin, salicylic acid, and benzoic acid in a 1:1 molar ratio have been obtained and characterized by physical methods. The experimental and in silico results were found to match very well. Strong correlation between melting points of pentoxifylline cocrystals and coformers has been detected. A significant decrease in solubility of pentoxifylline cocrystals as compared to pure pentoxifylline was observed

IL10 promoter haplotypes may contribute to altered cytokine expression and systemic inflammation in celiac disease.

Celiac disease (CD) is an autoimmune/inflammatory condition triggered by dietary gluten intake in genetically predisposed individuals. Though associations with MHC class II HLA-DQ2 or -DQ8 are the primary and necessary genetic predisposition for CD, >97% of genetically predisposed individuals never develop CD. Cytokines were measured in the serum of CD patients and controls. Possible associations with IL10 promoter variants were investigated. Cytokine expression from PBMCs was monitored in response to gluten exposure, or CD3/TCR complex stimulation in the absence or presence of recombinant IL-10. Serum cytokines varied between patients with CD at the time of diagnosis, after dietary elimination of gluten, and healthy controls. Serum IL-17A reflected disease activity. Reduced IL-10 serum levels and altered IL-10 expression by PBMCs coincided with IL10 promoter haplotypes that encode for "low" IL-10 expression (ATA). Increased prevalence of ATA IL10 promoter haplotypes and subsequently reduced IL-10 expression may be an immunological cofactor in individuals genetically predisposed for the development of CD. Resulting cytokine imbalances may be utilized as disease biomarkers in CD

Investigation of Water Structure in Nafion Membranes by Infrared Spectroscopy and Molecular Dynamics Simulation.

The structure and interactions of water species in hydrated Na\ufb01on membranes as a function of water content were investigated on the basis of medium-infrared spectral analysis and molecular dynamics (MD) simulations. The spectral decomposition of the FT-IR data in the stretching OH region was performed on different levels of hydration of the sulfate functional groups (\u3bbH2O/RSO3- = 2-22). Quantum mechanical calculations of two model systems [per\ufb02uoroethanesulfonic acid/(H2O)6 cluster] and a [per\ufb02uorobutanesulfonic acid/(H2O)6 crystal] were carried out in order to account for the band assignments of Na\ufb01on in the stretching OH region (2500-4000 cm-1). Our \ufb01ndings indicated that the secondary structure of water species in Na\ufb01on can be accurately explained in terms of our reactive force \ufb01eld for water. The distinction between \u201csurface\u201d and \u201cbulk\u201d water contributions in Na\ufb01on membrane pores is proposed along with a quantitative estimate of the different types of OH groups present in the system. The average pore size was calculated and supported by the spectral results

Cocrystals of Pentoxifylline: In Silico and Experimental Screening

To obtain new crystal forms with altered physicochemical properties and to get insight into the driving forces guiding cocrystallization, we performed experimental and in silico screening of pentoxifylline with 11 pharmaceutically acceptable organic acids. Neat grinding, liquid-assisted grinding, and slow solvent evaporation were used to obtain cocrystals of pentoxifylline. The free energy of experimental and hypothetical crystal structures have been calculated using the <i>FlexCryst</i> program. Three cocrystals of pentoxifylline with aspirin, salicylic acid, and benzoic acid in a 1:1 molar ratio have been obtained and characterized by physical methods. The experimental and in silico results were found to match very well. Strong correlation between melting points of pentoxifylline cocrystals and coformers has been detected. A significant decrease in solubility of pentoxifylline cocrystals as compared to pure pentoxifylline was observed

Latin America’s new regional architecture : a cooperative or segmented regional governance complex?

In Latin America the repercussions of the proliferation and overlapping of regional organizations are discussed widely. This article examines the opposing views on this process. Some authors postulate that an exhaustion of integration in Latin America will end up in segmented regionalism and hemispheric disintegration. Others endorse a variable geometry of integration that facilitates intraregional cooperation and minimizes the risk of veto players and zero-sum politics. The article takes Latin America as a vantage point to analyse the topic of interacting and overlapping regional organizations from a more general perspective. It asks about the conditions under which the proliferation and overlapping of regional organizations might have positive or negative effects (on regional integration and cooperation). Additionally, it advocates broadening the analytical focus and replacing the analytical concepts of regional integration and cooperation with the analytical concept of regional governance. Regional governance more adequately captures and integrates different patterns of regional cooperation and different regional projects that result in overlapping regional organizations. Instead of looking at the proliferation of regional organizations from a perspective of fragmentation, this article contends that the focus should be redirected to analysing how different regional organizations interact. Regional interaction patterns can vary between synergistic, cooperative, conflictive, or segmented regional governance (complexes). In an initial application of this analytical scheme, the article summarizes the changing regional cooperation patterns in South America since 1990. In the conclusions it outlines some preliminary ideas for a future research agenda on regional governance (complexes)