Searching for stereoisomerism in crystallographic databases: algorithm, analysis and chiral curiosities.

The automated identification of chiral centres in molecular residues is a non-trivial task. Current tools that allow the user to analyze crystallographic data entries do not identify chiral centres in some of the more complex ring structures, or lack the possibility to determine and compare the chirality of multiple structures. This article presents an approach to identify asymmetric C atoms, which is based on the atomic walk count algorithm presented by Rücker & Rücker [(1993), J. Chem. Inf. Comput. Sci. 33, 683-695]. The algorithm, which we implemented in a computer program named ChiChi, is able to compare isomeric residues based on the chiral centres that were identified. This allows for discrimination between enantiomers, diastereomers and constitutional isomers that are present in crystallographic databases. ChiChi was used to process 254 354 organic entries from the Cambridge Structural Database (CSD). A thorough analysis of stereoisomerism in the CSD is presented accompanied by a collection of chiral curiosities that illustrate the strength and versatility of this approach.

Health status in Europe: comparison of 24 urban areas to the corresponding 10 countries (EURO-URHIS 2).

Background: : In Europe, over 70% of the population live in urban areas (UAs). Most international comparative health research is done using national level data, as reliable and comparable urban data are often unavailable or difficult to access. This study aims to investigate whether population health is different in UAs compared with their corresponding countries. : Routinely available health-related data were collected by the EURO-URHIS 2 project, for 10 European countries and for 24 UAs within those countries. National and UA level data for 11 health indicators were compared through the calculation of relative difference, and geographical patterns within Europe were investigated using the Mann Whitney U test. Linear regression modelling was used to adjust for population density, gross domestic product and urbanicity. : In general, the urban population in Eastern Europe is less healthy than the Western European urban population. However, people in Eastern Europe have significantly better broad health outcomes in UAs as compared with the corresponding country as a whole, whereas people in Western Europe have generally worse broader health outcomes in UAs. : For most European countries and UAs that were investigated, the national level health status data does not correspond with the health status at UA level. In order to identify health problems in UAs and to provide information for local health policy, health monitoring and international benchmarking should also be conducted at the local level.

Contribution of smoking to socioeconomic inequalities in mortality: a study of 14 European countries, 1990-2004.

BACKGROUND: Smoking contributes to socioeconomic inequalities in mortality, but the extent to which this contribution has changed over time and driven widening or narrowing inequalities in total mortality remains unknown. We studied socioeconomic inequalities in smoking-attributable mortality and their contribution to inequalities in total mortality in 1990-1994 and 2000-2004 in 14 European countries. METHODS: We collected, harmonised and standardised population-wide data on all-cause and lung-cancer mortality by age, gender, educational and occupational level in 14 European populations in 1990-1994 and 2000-2004. Smoking-attributable mortality was indirectly estimated using the Preston-Glei-Wilmoth method. RESULTS: In 2000-2004, smoking-attributable mortality was higher in lower socioeconomic groups in all countries among men, and in all countries except Spain, Italy and Slovenia, among women, and the contribution of smoking to socioeconomic inequalities in mortality varied between 19% and 55% among men, and between -1% and 56% among women. Since 1990-1994, absolute inequalities in smoking-attributable mortality and the contribution of smoking to inequalities in total mortality have decreased in most countries among men, but increased among women. CONCLUSIONS: In many European countries, smoking has become less important as a determinant of socioeconomic inequalities in mortality among men, but not among women. Inequalities in smoking remain one of the most important entry points for reducing inequalities in mortality.

Inequalities in tuberculosis mortality: long-term trends in 11 European countries.

SETTING: Previous studies in many countries have shown that mortality due to tuberculosis (TB) is higher among people of lower socio-economic status. OBJECTIVE: To assess the magnitude and direction of trends in educational inequalities in TB mortality in 11 European countries. DESIGN: Data on TB mortality between 1980 and 2011 were collected among persons aged 35-79 years. Age-standardised mortality rates by educational level were calculated. Inequalities were estimated using the relative and slope indices of inequality. RESULTS: In the first decade of the twenty-first century, educational inequalities in TB mortality occurred in all countries in this study. The largest absolute inequalities were observed in Lithuania, and the smallest in Denmark. In most countries, relative inequalities have remained stable since the 1980s or 1990s, while absolute inequalities remained stable or went down. In Lithuania and Estonia, however, absolute inequalities increased substantially. CONCLUSION: The reduction in absolute inequalities in TB mortality, as seen in many European countries, is a major achievement; however, inequalities persist and are still a major cause for concern in the twenty-first century. Interventions aimed at preventing TB disease and reducing TB case fatality in lower socio-economic groups should be intensified, especially in the Baltic countries.

Population-based mammography screening below age 50: balancing radiation-induced vs prevented breast cancer deaths.

INTRODUCTION: Exposure to ionizing radiation at mammography screening may cause breast cancer. Because the radiation risk increases with lower exposure age, advancing the lower age limit may affect the balance between screening benefits and risks. The present study explores the benefit-risk ratio of screening before age 50. METHODS: The benefits of biennial mammography screening, starting at various ages between 40 and 50, and continuing up to age 74 were examined using micro-simulation. In contrast with previous studies that commonly used excess relative risk models, we assessed the radiation risks using the latest BEIR-VII excess absolute rate exposure-risk model. RESULTS: The estimated radiation risk is lower than previously assessed. At a mean glandular dose of 1.3 mGy per view that was recently measured in the Netherlands, biennial mammography screening between age 50 and 74 was predicted to induce 1.6 breast cancer deaths per 100,000 women aged 0-100 (range 1.3-6.3 extra deaths at a glandular dose of 1-5 mGy per view), against 1121 avoided deaths in this population. Advancing the lower age limit for screening to include women aged 40-74 was predicted to induce 3.7 breast cancer deaths per 100,000 women aged 0-100 (range 2.9-14.4) at biennial screening, but would also prevent 1302 deaths. CONCLUSION: The benefits of mammography screening between age 40 and 74 were predicted to outweigh the radiation risks.

The hydration/dehydration behavior of aspartame revisited.

Aspartame, l-aspartyl-l-phenylalanine methyl ester, has two hydrates (IA and IB), a hemi-hydrate (IIA) and an anhydrate (IIB). The hydration/dehydration behavior of aspartame was investigated using hot-humidity stage X-ray powder diffraction (XRPD) and molecular mechanics modeling in combination with differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). The results of this study are compared to earlier studies on aspartame as described in literature. It is shown that earlier transition studies were hampered by incomplete conversions and wrong assignment of the forms. The combination of the techniques applied in this study now shows consistent results for aspartame and yields a clear conversion scheme for the hydration/dehydration behavior of the four forms.

"Clickphine": a novel and highly versatile P,N ligand class via click chemistry.

[Structure: see text] A novel P,N-type ligand family (ClickPhine) is disclosed that is easily accessible using the Cu(I)-catalyzed azide-alkyne "click" cycloaddition. A diverse set of ligands was made in just three steps from readily available starting materials to give several homogeneous and a heterogeneous catalyst. Preliminary experiments show the efficacy of these ligands in the Pd-catalyzed allylic alkylation reaction.

Remarkable features in lattice-parameter ratios of crystals. I. Orthorhombic, tetragonal and hexagonal crystals.

The investigation of the lattice-parameter ratios of tetrahedral and hexagonal-rhombohedral inorganic compounds, as reported by Constant & Shlichta [(2003), Acta Cryst. A59, 281-282], has been extended to the structural data found for organic and metal-organic compounds (CSD), for bio-macromolecular crystals (PDB) and for inorganic materials (ICSD). In this first part of the series, the frequency distribution of orthorhombic, tetragonal and hexagonal crystals is presented. The results obtained confirm the existence of sharp peaks as a function of the ratios of lattice parameters and reveal additional exponential components, decaying for large and small values of these ratios. Practically all the important peaks occur at ratios which correspond to lattices having metric tensors with rational entries, the so-called integral lattices. The exponential component is interpreted as expressing a general statistical distribution which is valid for the generic crystal lattices, i.e. those normally considered. The exponential fraction dominates the peaked component in the organic and metal-organic cases, is less important for bio-macromolecular crystals and is much less important than the sharp peaks for inorganic crystals. Remarkable is the crystallographic relevance of the isometric hexagonal lattice, characterized by the axial ratio c/a = 1 and first observed in the molecular form of a protein. In the frequency distribution of 12 117 inorganic hexagonal crystals, the highest peak of 937 crystals occurs for c = a. In the hexagonal case of the bio-macromolecules the most important peak of 422 crystals is observed near the ideal h.c.p. (hexagonal closed packing) ratio of (8/3)(1/2).

Remarkable features in lattice-parameter ratios of crystals. II. Monoclinic and triclinic crystals.

The frequency distributions of monoclinic crystals as a function of the lattice-parameter ratios resemble the corresponding ones of orthorhombic crystals: an exponential component, with more or less pronounced sharp peaks, with in general the most important peak at the ratio value 1. In addition, the distribution as a function of the monoclinic angle beta has a sharp peak at 90 degrees and decreases sensibly at larger angles. Similar behavior is observed for the three triclinic angular parameters alpha, beta and gamma, with characteristic differences between the organic and metal-organic, bio-macromolecular and inorganic crystals, respectively. The general behavior observed for the hexagonal, tetragonal, orthorhombic, monoclinic and triclinic crystals {in the first part of this series [de Gelder & Janner (2005). Acta Cryst. B61, 287-295] and in the present case} is summarized and commented. The data involved represent 366 800 crystals, with lattice parameters taken from the Cambridge Structural Database, CSD (294 400 entries), the Protein Data Bank, PDB (18 800 entries), and the Inorganic Crystal Structure Database, ICSD (53 600 entries). A new general structural principle is suggested.

Method for the computational comparison of crystal structures.

A new method for assessing the similarity of crystal structures is described. A similarity measure is important in classification and clustering problems in which the crystal structures are the source of information. Classification is particularly important for the understanding of properties of crystals, while clustering can be used as a data reduction step in polymorph prediction. The method described uses a radial distribution function that combines atomic coordinates with partial atomic charges. The descriptor is validated using experimental data from a classification study of clathrate structures of cephalosporins and data from a polymorph prediction run. In both cases, excellent results were obtained.

Powder pattern indexing using the weighted crosscorrelation and genetic algorithms.

X-ray diffraction is a powerful technique for investigating the structure of crystals and crystalline powders. Unfortunately, for powders, the first step in the structure elucidation process, retrieving the unit cell parameters (indexing), is still very critical. In the present article, an improved approach to powder pattern indexing is presented. The proposed method matches peak positions from experimental X-ray powder patterns with peak positions from trial cells using a recently published method for pattern comparison (weighted crosscorrelation). Trial cells are optimized with Genetic Algorithms. Patterns are not pretreated to remove any existing zero point shift, as this is determined during optimization. Another improvement is the peak assignment procedure. This assignment is needed for determining the similarity between lines from trial cells and experiment. It no longer allows calculated peaks to be assigned twice to different experimental peaks, which is beneficial for the indexing process. The procedure proves to be robust with respect to false peaks and accidental or systematic absensences of reflections, and is successfully applied to powder patterns originating from orthorhombic, monoclinic, and triclinic compounds measured with synchrotron as well as with conventional laboratory X-ray diffractometers.

beta -Helical polymers from isocyanopeptides.

Polymerization of isocyanopeptides results in the formation of high molecular mass polymers that fold in a proteinlike fashion to give helical strands in which the peptide chains are arranged in beta-sheets. The beta-helical polymers retain their structure in water and unfold in a cooperative process at elevated temperatures. The peptide architecture in these polymers is a different form of the beta-helix motif found in proteins. Unlike their natural counterparts, which contain arrays of large beta-sheets stacked in a helical fashion, the isocyanopeptide polymers have a central helical core that acts as a director for the beta-sheet-like arrangement of the peptide side arms. The helical structure of these isocyanopeptide polymers has the potential to be controlled through tailoring of the side branches and the hydrogen-bonding network present in the beta-sheets.

Lamellar organic thin films through self-assembly and molecular recognition.

Molecular clips possessing U-shaped cavities have been functionalized on their convex side with long aliphatic tails. These molecules form dimers which self-assemble into malleable lamellar thin films. Upon addition of a guest (methyl 3,5-dihydroxybenzoate), a 1:1 host-guest complex is formed, which prohibits clip dimerization. As a result, the lamellar structure of the material is lost. Complexation of 3,5-dihydroxybenzoic acid in the clip results in host-guest complexes which dimerize by hydrogen bonding interactions between the carboxylic acid functions of the bound guests. This dimerization restores the lamellar type architecture of the material.

Molecular clips based on propanediurea: exceptionally high binding affinities for resorcinol guests.

A series of new receptor molecules derived from 2,4,6,8-tetraazabicyclo[3.3.1]nonane-3,7-dione (propanediurea) is described. These molecules possess a cavity which is defined by two nearly parallel aromatic side walls positioned on top of a bis-urea framework. The resulting "U-shaped" clip molecules are ideal hosts for the complexation of flat aromatic guest molecules. The affinity of these new propanediurea based molecular clips for dihydroxybenzene derivatives is exceptionally high, with association constants up to K(a) = 2 400 000 L mol(-)(1). Comparison of the binding mechanism of a variety of clip and half clip hosts, in conjunction with NMR, IR, and X-ray studies, has enabled the reason for this high binding to be elucidated. It is shown that subtle sub-angstrom changes in the geometry of the clip molecules have a great impact on their binding properties.

Steric control over arene coordination to beta-diiminate rhodium(I) fragments

The bulky ligands L(X)- (L(X) = (2,6-C6H3X2)NC(Me)CHC(Me)N(2,6-C6H3X2), X =Cl, Me) can be used to generate fluxional mononuclear arene complexes [L(X)Rh(eta4-arene)] (arene = benzene, toluene, m-xylene, mesitylene), which for X = Me disproportionate to fluxional dinuclear complexes [[L(Me)Rh]2(anti-mu-arene)]. For both mononuclear and dinuclear complexes, steric interactions do not stop the fluxionality but govern the preferred orientation of the methyl-substituted arenes, thus allowing indirect determination of the static NMR parameters. For the mu-arene complexes, two distinct types of fluxionality are proposed on the basis of calculations: ring rotation and metal shift. In the solid state, the toluene complex has an eta4(1,2,3,4):eta4(3,4,5,6)-bridged structure; the NMR analysis indicates that the benzene and m-xylene complexes have similar structures. The mesitylene complex, however, has an unprecedented eta3(1,2,3):eta3(3,4,5)-bridged structure, which is proposed to correspond to the transition state for arene rotation in the other cases. Steric factors are thought to be responsible for this reversal of stabilities.

2-rhodaoxetanes: their formation of oxidation of [RhI(ethene)]+ and their reactivity upon protonation.

New cationic, pentacoordinate complexes [(TPA)Rh1(ethene)]+, [1a]+, and [(MeTPA)Rh1(ethene)]+, [1b]+, have been prepared (TPA = N,N,N-tri(2-pyridylmethyl)amine, MeTPA = N-[(6-methyl-2-pyridyl)-methyl]-N,N-di(2-pyridylmethyl)amine). Complex [1a]+ is selectively converted by aqueous HCl to [(TPA)RhIII-(ethyl)Cl]+, [2a]+. The same reaction with [1b]+ results in the [(MeTPA)RhIII-(ethyl)Cl]+ isomers [2b]+ and [2c]+. Treatment of [1a]+ and [1b]+ with aqueous H2O2 results in a selective oxygenation to the unsubstituted 2-rho-da(III)oxetanes (1-oxa-2-rhoda(III)cyclo-butanes) [(TPA)RhIII(kappa2-C,O-2-oxyethyl)]+, [3a]+, and [(MeTPA)RhIII(kappa2-C,O-2-oxyethyl)]+, [3b]+. The reactivity of 2-rhodaoxetanes [3a]+ and [3b]+ is dominated by the nucleophilic character of their 2-oxyethyl oxygen. Reaction of [3a]+ and [3b]+ with the non-coordinating acid HBAr(f)4 results in the dicationic protonated 2-rhodaoxetanes [(TPA)RhIII(kappa2-2-hydroxyethyl)]2+, [4a]2+, and [(MeTPA)RhIII(kappa2-2-hydroxyethyl)]2+, [4b]2+. These eliminate acetaldehyde at room temperature, probably via a coordinatively unsaturated kappa1-2-hydroxyethyl complex. In acetonitrile, complex [4a]2+ is stabilised as [(TPA)-RhIII(kappa1-2-hydroxyethyl)(MeCN)]2+, [5a]2+, whereas the MeTPA analogue [4b]2+ continues to eliminate acetaldehyde. Reaction of [3a]+ with NH4Cl and Mel results in the coordinatively saturated complexes [(TPA)RhIII(kappa1-2-hydroxyethyl)(Cl)]+, [6a]+, and [(TPA)-RhIII(kappa1-2-methoxyethyl)(I)+, [7a]+, respectively. Reaction of [3a]+ with NH4+ in MeCN results in formation of the dicationic metallacyclic amide [(TPA)-RhIII [kappa2-O,C-2-(acetylamino)ethyl]]2+, [9]2+, via the intermediates [4a]2+, [5a]2+ and the metallacyclic iminoester [(TPA)RhIII[kappa2-N,C-2-(acetimidoyloxy)ethyl]]2+, [8]2+. The observed overall conversion of the [Rh(I)(ethene)] complex [1a]+ to the metallacyclic amide [9]2+ via 2-rhodaoxetane [3a]+, provides a new route for the amidation of a [RhI(ethene)] fragment.