Role of Cationization and Multimers Formation for Diastereomers Differentiation by Ion Mobility-Mass Spectrometry

Stereochemistry plays an important role in biochemistry, particularly in therapeutic applications. Indeed, enantiomers have different biological activities, which can have important consequences. Many analytical techniques have been developed in order to allow the identification and the separation of stereoisomers. Here, we focused our work on the study of small diastereomers using the coupling of traveling wave ion mobility and mass spectrometry (TWIMS-MS) as a new alternative for stereochemistry study. In order to optimize the separation, the formation of adducts between diastereomers (M) and different alkali cations (X) was carried out. Thus, monomers [M + X]⁺ and multimers [2M + X]⁺ and [3M + X]⁺ ions have been studied from both experimental and theoretical viewpoints. Moreover, it has been shown that the study of the multimer [2Y + M + Li]⁺ ion, in which Y is an auxiliary diastereomeric ligand, allows the diastereomers separation. The combination of cationization, multimers ions formation, and IM-MS is a novel and powerful approach for the diastereomers identification. Thus, by this technique, diastereomers can be identified although they present very close conformations in gaseous phase. This work presents the first TWIMS-MS separation of diastereomers, which present very close collision cross section thanks to the formation of multimers and the use of an auxiliary diastereomeric ligand.

Étude d'une ligne de jets impactant une paroi concave par PIV stéréoscopiqueStudy of a row of jets impinging a concave wall by stereoscopic PIV

The aerodynamic study of a row of axisymmetric jets impinging a concave wall is carried out from velocity measurements obtained by the standard and stereoscopic Particle Image Velocimetry. The principle and the specific aspects of the stereoscopic PIV set up, a recent technique of three-dimensional velocimetry, are explained. After a statistical data processing, the three-dimensional structure and the characteristics of multiple jets impinging a concave wall are described with the mean velocity fields and the turbulent values in several planes of the flow. To cite this article: V. Gilard, L.-E. Brizzi, C. R. Mecanique 334 (2006).     

Preparation of non-racemic single-stereocentre α-aminonitriles and a study of their fate in Bruylants reactions

A number of chiral carboxamide dehydration methods were investigated for the preparation of four representative enantiomerically enriched α-aminonitriles possessing only one stereogenic centre; best results were observed using Burgess' salt (yield up to 87%, er up to 92/8) or the trifluoroacetic anhydride-triethylamine combination (yield up to 98%, er up to 86/14). Two of the aminonitriles thus obtained were subjected to Bruylants reactions with a methyl Grignard reagent to furnish the corresponding tertiary amines; these products, along with any unreacted starting materials, were obtained essentially in racemic form. In accord with the accepted mechanism for this reaction, a magnesium species is implicated in the formation of an iminium, the common intermediate for both chemical transformation and racemization processes.     

On the fundamental state for a Schrödinger operator with magnetic field in a domain with corners

We show that the Neumann realization for the Schrödinger operator with a constant magnetic field in a sector has at least one eigenvalue below the essential spectrum, when the angle is sufficiently small. We establish the complete asymptotics of the lowest eigenvalue as the angle tends to 0. This study is applied to the analysis of the bottom of the spectrum in the semi-classical case for domains with edges. To cite this article: V. Bonnaillie, C. R. Acad. Sci. Paris, Ser. I 336 (2003).     

Direct alkylation of heteroaryls using potassium alkyl- and alkoxymethyltrifluoroborates

A direct alkylation of various heteroaryls using stoichiometric potassium alkyl- and alkoxymethyltrifluoroborates has been developed. This method leads to the synthesis of complex substituted heterocycles, which have been obtained with yields up to 89%.     

(R)-3,5-diCF3-SYNPHOS and (R)-p-CF3-SYNPHOS, electron-poor diphosphines for efficient room temperature Rh-catalyzed asymmetric conjugate addition of arylboronic acids

Two new atropisomeric electron-poor chiral diphosphine ligand analogues of SYNPHOS were prepared, and their electronic properties are described. These two ligands afforded high performance for the Rh-catalyzed asymmetric 1,4-addition of arylboronic acids to α,β-unsaturated carbonyl compounds at room temperature.     

Optimization of micro‐HPLC peak focusing for the detection and quantification of low hepcidin concentrations

Micro‐high‐performance liquid chromatography is a miniaturized, economic and ecological chromatographic system allowing the use of reduced size chromatographic columns. Coupled with electrospray ionization tandem mass spectrometry, this technique can be used to detect and quantify low concentrations of peptides. In this study, hepcidin was used as the model compound and analysed using octadecylsilica stationary phase by means of a gradient elution mode at a flow rate of 4 μL/min. Several parameters were studied to optimize peak focusing. Using the methodology of experimental design, the mobile‐phase gradient conditions and the sample composition were optimized in order to maximize the sensitivity and minimize retention time. Stability of the target peptide in solution was also demonstrated.     

Free volume holes diffusion to describe physical aging in poly(mehtyl methacrylate)/silica nanocomposites

The spontaneous thermodynamically driven densification, the so-called physical aging, of glassy poly(mehtyl methacrylate) (PMMA) and its nanocomposites with silica has been described by means of the free volume holes diffusion model. This mechanism is able to account for the partial decoupling between physical aging and segmental dynamics of PMMA in nancomposites. The former has been found to be accelerated in PMMA/silica nanocomposites in comparison to "bulk" PMMA, whereas no difference between the segmental dynamics of bulk PMMA and that of the same polymer in nanocomposites has been observed. Thus, the rate of physical aging also depends on the amount of interface polymer/nanoparticles, where free volume holes disappear after diffusing through the polymer matrix. The free volume holes diffusion model is able to nicely capture the phenomenology of the physical aging process with a structure dependent diffusion coefficient.     

A diverted total synthesis of mycolactone analogues: an insight into Buruli ulcer toxins

Mycolactones are complex macrolides responsible for a severe necrotizing skin disease called Buruli ulcer. Deciphering their functional interactions is of fundamental importance for the understanding, and ultimately, the control of this devastating mycobacterial infection. We report herein a diverted total synthesis approach of mycolactones analogues and provide the first insights into their structure-activity relationship based on cytopathic assays on L929 fibroblasts. The lowest concentration inducing a cytopathic effect was determined for selected analogues, allowing a clear picture to emerge by comparison with the natural toxins.