Emmanuel Wenger

Helical Oligomers of Thiazole‐Based γ‐Amino Acids: Synthesis and Structural Studies

9-Helix: 4-Amino(methyl)-1,3-thiazole-5-carboxylic acids (ATCs) were synthesized as new γ-amino acid building blocks. The structures of various ATC oligomers were analyzed in solution by CD and NMR spectroscopy and in the solid state by X-ray crystallography. The ATC sequences adopted a well-defined 9-helix structure in the solid state and in aprotic and protic organic solvents as well as in aqueous solution.

Diffraction studies under in situ electric field using a large-area hybrid pixel XPAD detector

A new experimental approach to perform in situ electric field diffraction on single crystals using an on-then-off pump–probe mode in situ (i.e. the field-switching method) with a synchrotron or a laboratory X-ray source is presented. Taking advantage of the fast readout of the XPAD hybrid pixel two-dimensional detector and its programmable functionalities, the operation mode of the detector has been customized to significantly increase the efficiency of the method. The very weak electric field-induced structural response of a piezoelectric crystal can be accurately measured. This allows the piezoelectric tensor to be precisely obtained from Δθ shifts while the structural variations can be modelled using a full set of ΔI/I data. The experimental method and methodology are detailed and tested as a case study on pure piezoelectric compounds belonging to the α-quartz family (SiO2 and GaAsO4 single crystals). Using the two scan modes developed, it is demonstrated that tiny Bragg angle shifts can be measured as well as small field-induced Bragg intensity variations (<1%). The relevance of measurements performed with an X-ray laboratory source is demonstrated: partial data sets collected at synchrotrons can be completed, but more interestingly, a large part of the study can now be realized in the laboratory (medium to strong intensity reflections) in a comparable data collection time.

Robust helix formation in a new family of oligoureas based on a constrained bicyclic building block.

BAC for more: a constrained bicyclic building block with urea linkages is an efficient combination for the formation of a highly rigid helical system. This type of bicyclic amino carbamoyl (BAC) foldamer was studied both in solution and in the solid state. A robust H-bond (dotted line) network was found between the carbonyl oxygen atoms (red) and the amino groups (dark blue) within the helix.

Anharmonicity and isomorphic phase transition: a multi-temperature X-ray single-crystal and powder diffraction study of 1-(2′-aminophenyl)-2-methyl-4-nitroimidazole

Multi-temperature single-crystal and powder diffraction experiments on 1-(2′-aminophenyl)-2-methyl-4-nitroimidazole show that this crystal undergoes an isomorphic phase transition with the coexistence of two phase domains over a wide temperature range. The anharmonic approach was the only way to model the resulting disorder.

Cyclic α,β-Tetrapeptoids: Sequence-Dependent Cyclization and Conformational Preference

The presence of at least one N-Cα branched side chain is crucial for successful cyclization of α,β-tetrapeptoids. The ctct amide sequence revealed in the crystal structure of the 14-membered cyclotetrapeptoid 8 is also the most populated conformation in solution and is reminiscent of the predominant amide arrangement of the 12-membered cyclic tetrapeptides (CTPs).

Mixed Oligoureas Based on Constrained Bicyclic and Acyclic β‐Amino Acids Derivatives: On the Significance of the Subunit Configuration for Folding

The combination of a non-functionalized constrained bicyclo[2.2.2]octane motif along with urea linkages allowed the formation of a highly rigid 2.5(12/14) helical system both in solution and the solid state. In this work, we aimed at developing stable and functionalized systems as promising materials for biological applications in investigating the impact of this constrained motif and its configuration on homo and heterochiral mixed-oligourea helix formation. Di-, tetra-, hexa-, and octa-oligoureas alternating the highly constrained bicyclic motif of (R) or (S) configuration with acyclic (S)-β(3)-amino acid derivatives were constructed. Circular dichroism (CD), NMR experiments, and the X-ray crystal structure of the octamer unequivocally proved that the alternating heterochiral R/S sequences form a stable left-handed 2.5-helix in contrast to the mixed (S/S)-oligoureas, which did not adopt any defined secondary structure. We observed that the (-)-synclinal conformation around the C(α)-C(β) bond of the acyclic residues, although sterically less favorable than the (+)-synclinal conformation, was imposed by the (R)-bicyclic amino carbamoyl (BAC) residue. This highlighted the strong ability of the BAC residue to drive helical folding in heterochiral compounds. The role of the stereochemistry of the BAC unit was assessed and a model was proposed to explain the misfolding of the S/S sequences.

Asymmetric synthesis of β2-tryptophan analogues via Friedel-Crafts alkylation of indoles with a chiral nitroacrylate.

The asymmetric Friedel-Crafts alkylation of various indoles with a chiral nitroacrylate provides optically active β-tryptophan analogues after reduction of the nitro group and removal of the chiral auxiliary. This reaction generally occurs in good yield and high diastereoselectivity (up to 90:10).

Click synthesis of symmetric bis-triazol ligands and full characterisation of their copper(II)-complexes

Eight novel ligands were prepared from a known symmetric diaza-18-crown-6 (cyclic ligand) and two commercial N,N′-dimethyl-alkyl diamines (acyclic ligands) via the Cu(I)-catalyzed Huisgen dipolar cycloaddition. All C2-symmetric isolated ligands readily formed stable crystalline 1 : 1-copper(II) complexes with cupric perchlorate. Their structural, electrochemical and physico-chemical properties were fully investigated with the help of X-ray diffraction, cyclic voltammetry, FT-IR, UV-visible, and electron paramagnetic resonance (EPR) spectroscopies. Planar – or nearly planar – arrangement of the two N3-triazole nitrogens and the two tertiary amine pivot nitrogens was found in one single four-coordinated species, in four five-coordinated species, and three six-coordinated species, with one or two solvent molecule(s), or two oxygen atoms of the crown ether, occupying the axial position(s) in the solid sate. The electron-donating or electron-withdrawing effect of the N1-substituent on the triazol was found to influence the Cu(II)/Cu(I) redox potential of all studied complexes in DMF. The EPR-spectrum of cyclic complexes in frozen DMF at 100 K exhibited two mononuclear species, one of them likely promoting the formation of dinuclear species as a minor component, whereas most acyclic complex spectra were quite similar.

Comparison of CCD, CMOS and Hybrid Pixel x-ray detectors: detection principle and data quality

We compare, from a crystallographic point of view, the data quality obtained using laboratory x-ray diffractometers equipped with a Molybdenum micro-source using different detector types: CCD, CMOS and XPAD hybrid pixel. First we give an overview of the working principle of these different detector types with a focus on their principal differences and their impact on the data quality. Then, using the example of an organic crystal, a comparison between the detector systems concerning the raw data statistics, the refinement agreement factors, the deformation electron density maps, and the residual density after multipolar refinement is presented. It is found that the data quality obtained with the XPAD detector is the best, even though the detection efficiency at the Mo energy (17.5 keV) is only 37% due to the Si-sensor layer thickness of 300 μm. Finally, we discuss the latest x-ray detector developments with an emphasis on the sensor material, where replacing Si by another material such as GaAs would yield detection efficiencies close to 100%, up to energies of 40 keV for hybrid pixel detectors.

Betulin Phosphonates; Synthesis, Structure, and Cytotoxic Activity

Betulin derivatives are a widely studied group of compounds of natural origin due to their wide spectrum of biological activities. This paper describes new betulin derivatives, containing a phosphonate group. The allyl-vinyl isomerization and synthesis of acetylenic derivatives have been reported. Structural identification of products as E and Z isomers has been carried out using 1H-, 13C-, 31P-NMR, and crystallographic analysis. The crystal structure in the orthorhombic space group and analysis of crystal packing contacts for 29-diethoxyphosphoryl-28-cyclopropylpropynoyloxy-lup-20E(29)-en-3β-ol 8a are reported. All new compounds were tested in vitro for their antiproliferative activity against human T47D (breast cancer), SNB-19 (glioblastoma), and C32 (melanoma) cell lines.