Stéphane Viel

Liquid state 1H high field NMR in food analysis

2012 Elsevier B.V. All rights reserved.

19F NMR: a valuable tool for studying biological events.

With the spectacular advancement of NMR techniques and the flourishing of fluorine chemistry allowing the synthesis of various fluorinated molecules, (19)F NMR represents a compelling option for studying myriad biological events ranging from the structure and function of biomolecules, enzymatic mechanisms, and metabolic pathways, through to drug screening and discovery as well as medical imaging. In this tutorial review, we aim to provide readers with a brief overview of the recent applications of (19)F NMR in various areas relating to biological and biomedical research, together with a brief introduction of specific hardware improvements permitting the practical implementation of (19)F NMR.

Enhanced diffusion-edited NMR spectroscopy of mixtures using chromatographic stationary phases

We introduce an analytical method that combines in one pot the advantages of column chromatography separation and NMR structural analysis. The separation of the NMR spectra of the components of a mixture can be achieved according to their apparent diffusion rates [James, T. L. and McDonald, G. G. (1973) J. Magn. Reson. 58, 58–61]. We show that the separation of the spectral components, corresponding to single molecular species, can be enhanced by order of magnitudes upon addition of a typical stationary phase used in HPLC. The solid phase imbibed by the mixture for analysis is an heterogeneous ensemble, so that solid-state NMR methods (high-resolution magic angle spinning) are necessary to recover high-resolution spectra. We demonstrate applications of this combination of high-resolution magic angle spinning and NMR diffusometry on test mixtures for direct (silica gel) and inverse (C18) columns. However, many common chromatographic supports available for HPLC should be readily adaptable for use with this technique.

Structurally Flexible Triethanolamine Core PAMAM Dendrimers Are Effective Nanovectors for DNA Transfection in Vitro and in Vivo to the Mouse Thymus

With the aim of developing dendrimer nanovectors with a precisely controlled architecture and flexible structure for DNA transfection, we designed PAMAM dendrimers bearing a triethanolamine (TEA) core, with branching units pointing away from the center to create void spaces, reduce steric congestion, and increase water accessibility for the benefit of DNA delivery. These dendrimers are shown to form stable nanoparticles with DNA, promote cell uptake mainly via macropinocytosis, and act as effective nanovectors for DNA transfection in vitro on epithelial and fibroblast cells and, most importantly, in vivo in the mouse thymus, an exceedingly challenging organ for immune gene therapy. Collectively, these results validate our rational design approach of structurally flexible dendrimers with a chemically defined structure as effective nanovectors for gene delivery, and demonstrate the potential of these dendrimers in intrathymus gene delivery for future applications in immune gene therapy.

Selective synthesis of (Z)-4-aryl-5-[1-(aryl)methylidene]-3-bromo-2(5H)-furanones

Abstract 4-Aryl-3-bromo-2(5 H )-furanones have been selectively synthesized in satisfactory yields by treatment of easily available 3,4-dibromo-2(5 H )-furanone either with arylboronic acids in the presence of Ag 2 O and a catalytic amount of PdCl 2 (MeCN) 2 or with aryl(trialkyl)stannanes in the presence of a catalyst precursor consisting of AsPh 3 and a Pd(II) or a Pd(0) compound. These monobromo derivatives have been then used as precursors to a variety of ( Z )-4-aryl-5-[1-(aryl)methylidene]-3-bromo-2(5 H )-furanones including the compound with the structure corresponding to that reported for naturally occurring rubrolide N. The structure and stereochemistry of these synthetic compounds have been unambiguously established by NMR techniques.

Detection of a π-π complex by diffusion-ordered spectroscopy (DOSY)

Abstract Diffusion-ordered NMR spectroscopy (DOSY) has been used in the detection of π–π complexes formed through π–π stacking interactions of a hydrophobic compound in concentrated aqueous solutions.

Quantitative Structural Constraints for Organic Powders at Natural Isotopic Abundance Using Dynamic Nuclear Polarization Solid‐State NMR Spectroscopy

A straightforward method is reported to quantitatively relate structural constraints based on (13)C-(13)C double-quantum build-up curves obtained by dynamic nuclear polarization (DNP) solid-state NMR to the crystal structure of organic powders at natural isotopic abundance. This method relies on the significant gain in NMR sensitivity provided by DNP (approximately 50-fold, lowering the experimental time from a few years to a few days), and is sensitive to the molecular conformation and crystal packing of the studied powder sample (in this case theophylline). This method allows trial crystal structures to be rapidly and effectively discriminated, and paves the way to three-dimensional structure elucidation of powders through combination with powder X-ray diffraction, crystal-structure prediction, and density functional theory computation of NMR chemical shifts.

General implementation of the ERETIC method for pulsed field gradient probe heads.

A capacitive coupling between a secondary radiofrequency (rf) channel and the gradient coil of a standard commercially available high resolution NMR spectrometer and probe head is described and used to introduce a low level exponentially damped rf signal near the frequency of the primary rf channel to serve as an external concentration standard, in analogy to the so-called ERETIC method. The stability of this inexpensive and simple to implement method, here referred to as the Pulse Into the Gradient (PIG) approach, is superb over a 14-h period and both gradient tailored water suppression and one-dimensional imaging applications are provided. Since the low level signal is introduced via the pulsed field gradient coil, the coupling is identical to that for a free induction signal and thus the method proves to be immune (within 5%) to sample ionic strength effects up to the 2M NaCl solutions explored here.

Selective Synthesis of 5,6-Disubstituted 3-Methyl-2(2H)-pyranones and 6-Substituted 3-Methyl-2(2H)-pyranones, Including Fusalanipyrone and Gibepyrone A

The 6-substituted 3-bromo-5-iodo-2(2H)-pyranones 11, prepared by iodolactonization of the corresponding 5-substituted (E)-2-bromo-2-en-4-ynoic acids 10, were used as precursors to 5,6-disubstituted 3-methyl-2(2H)-pyranones 8 and 6-substituted 3-methyl-2(2H)-pyranones 7. The synthesis of compounds 8 involved two consecutive Stille-type reactions, whereas the approach followed to prepare compounds 7 consisted of the selective reduction of the dihalogen derivatives 11 to the corresponding 6-substituted 3-bromo-2(2H)-pyranones 12, followed by a Pd/Cu-catalysed reaction with tetramethyltin. However, this synthetic approach to compounds 7 proved to be unsuitable for preparing stereoisomerically pure fusalanipyrone (7a), a natural product isolated from Fusarium solani. Nevertheless, 7a and gibepyrone A (7b), which is a natural product isolated from Gibberella fujikuroi, could be synthesized in stereoisomerically pure form by reaction sequences involving iodolactonization of easily available (2Z,6Z)- and (2Z,6E)-2,6-dimethyl-2,6-octadien-4-ynoic acids (16a) and (16b), respectively, followed by Pd-catalysed triethylammonium formate reduction of the thus obtained 6-substituted 5-iodo-3-methyl-2(2H)-pyranones 17a and 17b, respectively. (© Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)

Tandem mass spectrometry of poly(methacrylic Acid) oligomers produced by negative mode electrospray ionization.

Dissociation of small poly(methyl acrylic acid) (PMAA) anions produced by electrospray was characterized by tandem mass spectrometry. Upon collisional activation, singly, and doubly deprotonated PMAA oligomers were shown to fragment via two major reactions, dehydration and decarboxylation. The elimination of a water molecule would occur between two consecutive acid groups in a charged-remote mechanism, giving rise to cyclic anhydrides, and was shown to proceed as many times as pairs of neutral pendant groups were available. As a result, the number of dehydration steps, together with the abundance of the fragment ions produced after the release of all water molecules, revealed the polymerization degree of the molecule in the particular case of doubly charged oligomers. For singly deprotonated molecules, the exact number of MAA units could be reached from the number of carbon dioxide molecules successively eliminated from the fully dehydrated precursor ions. In contrast to dehydration, decarboxylation reactions would proceed via a charge-induced mechanism. The proposed dissociation mechanisms are consistent with results commonly reported in thermal degradation studies of poly(acrylic acid) resins and were supported by accurate mass measurements. These fragmentation rules were successfully applied to characterize a polymeric impurity detected in the tested PMAA sample.