Synthesis, structure and conformation of partially-modified retro- and retro-inverso psi[NHCH(CF3)]Gly peptides

Partially modified retro- (PMR) and retro-inverso (PMRI) psi[NHCH(CF(3))]Gly peptides, a conceptually new class of peptidomimetics, have been synthesized in wide structural diversity and variable length by aza-Michael reaction of enantiomerically pure alpha-amino esters and peptides with enantiomerically and geometrically pure N-4,4,4-trifluorocrotonoyl-oxazolidin-2-ones. The factors underlying the observed moderate to good diastereocontrol have been investigated. The conformations of model PMR-psi[NHCH(CF(3))]Gly tripeptides have been studied in solution by (1)H NMR spectroscopy supported by MD calculations, as well as in the solid-state by X-ray diffraction. Remarkable stability of turn-like conformations, comparable to that of parent malonyl-based retropeptides, was evidenced, as a likely consequence of two main factors: 1) severe torsional restrictions about sp(3) bonds in the [CO-CH(2)-CH(CF(3))-NH-CH(R)-CO] module, which is biased by the stereoelectronically demanding CF(3) group and the R side chain; 2) formation of nine-membered intramolecularly hydrogen-bonded rings, which have been clearly detected both in CHCl(3) solution and in some crystal structures. The former factor seems to be more important, as turn-like conformations were found in the solid-state even in the absence of intramolecular hydrogen bonding. The relative configuration of the -C*H(CF(3))NHC*H(R)- stereogenic centers has a major effect on the stability of the turn-like conformation, which seems to require a syn stereochemistry. X-ray diffraction and ab initio computational studies showed that the [-CH(CF(3))NH-] group can be seen as a sort of hybrid between a peptide bond mimic and a proteolytic transition state analogue, as it combines some of the properties of a peptidyl -CONH- group (low NH basicity, CH(CF(3))-NH-CH backbone angle close to 120 degrees, C-CF(3) bond substantially isopolar with the C=O) with some others of the tetrahedral intermediate [-C(OX)(O(-))NH-] involved in the protease-mediated hydrolysis reaction of a peptide bond (high electron density on the CF(3) group, tetrahedral backbone carbon).     

The Contribution of the ESRF to Biomedical Science: From Nano to Humans

Abstract

“2D or not 2D, that is the question” —An Anonymous Surface Scientist     

A note on medieval microfabrication: the visualization of a prayer nut by synchrotron‐based computer X‐ray tomography

One of the most fascinating objects in the Rijksmuseum (Amsterdam, The Netherlands) is an early 16th century prayer nut. This spherical wooden object measures 4 cm in diameter and consists of two hemispheres connected with a small hinge so that it can be opened. The interior of the nut holds wood carvings with scenes from the life of Christ. These miniature reliefs show an incredible degree of finish with carving details well beyond the millimetre scale. In the present paper it is shown how synchrotron‐based computer X‐ray tomography revealed the structure and fabrication method of the bead. The central part of the relief was cut from a single piece of wood, rather than assembled from multiple components, underlining the extraordinary manual dexterity of its maker. In addition, a piece of fibrous material contained in the inner structure of the bead is revealed. This may have served as a carrier for an odorous compound, which would be in line with the religious function of the prayer nut.     

The CRESST dark matter search

We discuss the short-and long-term perspectives of the CRESST (Cryogenic Rare Event Search using Superconducting Thermometers) project and present the current status of the experiment and new results concerning detector development. In the search for elementary particle dark matter, CRESST is presently the most advanced deep underground, low-background, cryogenic facility. The basic technique involved is to search for WIMPs (Weakly Interacting Massive Particles) by the measurement of nonthermal phonons, as created by WIMP-induced nuclear recoils. Combined with our newly developed method for the simultaneous measurement of scintillation light, strong background discrimination is possible, resulting in a substantial increase in WIMP detection sensitivity. This will allow a test of the reported positive evidence for a WIMP signal by the DAMA Collaboration in the near future. In the long term, the present CRESST setup permits the installation of a detector mass up to 100 kg. In contrast to other projects, CRESST technology allows the employment of a large variety of detection materials. This offers a powerful tool in establishing a WIMP signal and in investigating WIMP properties in the event of a positive signal.     

Characterization of a sCMOS‐based high‐resolution imaging system

The detection system is a key part of any imaging station. Here the performance of the novel sCMOS‐based detection system installed at the ID17 biomedical beamline of the European Synchrotron Radiation Facility and dedicated to high‐resolution computed‐tomography imaging is analysed. The system consists of an X‐ray–visible‐light converter, a visible‐light optics and a PCO.Edge5.5 sCMOS detector. Measurements of the optical characteristics, the linearity of the system, the detection lag, the modulation transfer function, the normalized power spectrum, the detective quantum efficiency and the photon transfer curve are presented and discussed. The study was carried out at two different X‐ray energies (35 and 50 keV) using both 2× and 1× optical magnification systems. The final pixel size resulted in 3.1 and 6.2 µm, respectively. The measured characteristic parameters of the PCO.Edge5.5 are in good agreement with the manufacturer specifications. Fast imaging can be achieved using this detection system, but at the price of unavoidable losses in terms of image quality. The way in which the X‐ray beam inhomogeneity limited some of the performances of the system is also discussed.     

Advances in synchrotron hard X-ray based imaging

Modern synchrotron radiation (SR) sources have dramatically fostered the use of SR-based X-ray imaging. The relevant information such as density, chemical composition, chemical states, structure, and crystallographic perfection is mapped in two, or, increasingly, in three dimensions. The development of nano-science requires pushing spatial resolution down towards the nanoscale.The present article describes a selection of hard X-ray imaging and microanalysis techniques that emerged over the last few years, by taking advantage of the flux and coherence of the SR beams, as well as exploiting the advances in X-ray optics and detectors, and the increased possibilities of computers (memory, speed). Examples are given to illustrate the opportunities associated with the use of these techniques, and a number of recent references are provided. To cite this article: J. Baruchel et al., C. R. Physique 9 (2008).     

Visualization of pigment distributions in paintings using synchrotron K-edge imaging

X-ray radiography plays an important role in the study of artworks and archaeological artifacts. The internal structure of objects provides information on genesis, authenticity, painting technique, material condition and conservation history. Transmission radiography, however, does not provide information on the exact elemental composition of objects and heavy metal layers can shadow or obscure the ones including lighter elements. This paper presents the first application of synchrotron-based K-edge absorption imaging applied to paintings. Using highly monochromatic radiation, K-edge imaging is used to obtain elemental distribution images over large areas. Such elemental maps visualize the distribution of an individual pigment throughout the paint stratigraphy. This provides color information on hidden paint layers, which is of great relevance to art historians and painting conservators. The main advantage is the quick data acquisition time and the sensitivity to elements throughout the entire paint stratigraphy. The examination of a test painting is shown and further instrumental developments are discussed. PACS 07.85.Qe; 07.05.Pj     

Comparison of in vitro breast cancer visibility in analyser‐based computed tomography with histopathology,mammography, computed tomography and magnetic resonance imaging

High‐resolution analyser‐based X‐ray imaging computed tomography (HR ABI‐CT) findings on in vitro human breast cancer are compared with histopathology, mammography, computed tomography (CT) and magnetic resonance imaging. The HR ABI‐CT images provided significantly better low‐contrast visibility compared with the standard radiological images. Fine cancer structures indistinguishable and superimposed in mammograms were seen, and could be matched with the histopathological results. The mean glandular dose was less than 1 mGy in mammography and 12–13 mGy in CT and ABI‐CT. The excellent visibility of in vitro breast cancer suggests that HR ABI‐CT may have a valuable role in the future as an adjunct or even alternative to current breast diagnostics, when radiation dose is further decreased, and compact synchrotron radiation sources become available.     

Amplification of the phase contrast signal at very high x-ray energies

X-ray phase contrast imaging is increasingly being used in several fields, both at synchrotron facilities and with laboratory sources, due to its increased sensitivity compared to conventional x-ray methods. One important problem is the development of methods to make it suitable for use at very high x-ray energies, needed in many applications. We show how the edge illumination concept, which stands at the basis of the coded-aperture method, allows achieving hyperintense phase signals at energies close to 100 keV, by showing images of both weak phase objects and highly absorbing fossils with a high iron content.     

I?N  S  N?I – Darstellung und Struktur

I? N ? S ? N? I, Preparation and Reactivity I? N ? S ? N? I is prepared form IN[Si(CH₃)₃]₂ by reaction with SF₄. It is a shock sensitive yellow powder, that appears in brown crystals after recrystallisation from CH₂Cl₂. The crystal structure reveals a syn-anti conformation for the molecule. Due to I … N contacts a layer lattice is formed.