How to face the low intrinsic sensitivity of 2D heteronuclear NMR with fast repetition techniques: go faster to go higher!

Nuclear magnetic resonance (NMR) is one of the most widely used analytical techniques in numerous domains where molecules are objects of investigation. However, major limitations of multidimensional NMR experiments come from their low sensitivity and from the long times needed for their acquisition. In order to overcome such limitations, fast repetition NMR techniques allowed for the reduction of 2D experimental time and for the conversion of the gained time into a higher number of scans leading to a better sensitivity. Thus, fast repetition 2D heteronuclear NMR techniques have allowed new advances in NMR, especially to access infomation on low abundant nuclei, to enhance the detection of low concentrated compounds and to probe weak interactions like hydrogen bonds at natural abundance. Copyright (c) 2017 John Wiley & Sons, Ltd

1H NMR analyses of enantiomeric mixtures using chiral liquid crystals

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Nouvelles méthodologies R.M.N. en milieu liquide chiral (contribution à l'analyse stéréochimique en chimie structurale organique)

Cette thèse concerne divers développements méthodologiques et leurs applications en RMN dans les solvants cristaux liquides chiraux. Nous avons d'abord montré que les expériences comprenant des impulsions sélectives permettaient d'extraire des informations des spectres proton et carbone-13 qui étaient inaccessibles sur les spectres monodimensionnels standards. Nous avons ensuite utilisé d'autres techniques pour mesurer un maximum de couplages dipolaires pour préciser de manière non-ambiguë les configurations relatives de centres stéréogènes dans des molécules rigides. Nous avons ainsi montré que pour la DHEA, un stéroïde, une seule géométrie relative des substituants était compatible avec l'ensemble des couplages dipolaires mesurés et conduisait à un écart type entre couplages dipolaires calculés et expérimentaux correct. Cette méthode est promise à un grand avenir car elle est beaucoup moins ambiguë que les méthodes classiques utilisées en milieu isotrope. Enfin, nous avons développé cette méthode dans le cas des molécules flexibles où le problème se complique car il existe une corrélation totale entre conformation moléculaire et ordre orientationnel. Le nombre de paramètres à itérer explose rapidement, alors que le nombre de mesurables reste constant, et donc un traitement général est impossible. En prenant pour exemple le 1,2-dibromopropane, nous avons montré que le problème est gérable, à condition d'utiliser un modèle paramétrique pour calculer la valeur moyenne des paramètres d'ordre pour chaque conformation. Les paramètres à itérer, sont alors beaucoup moins nombreux et le problème peut être traité. Ainsi, nous avons montré qu'avec quatre indices de liaison et la géométrie des différents conformères obtenue par calcul ab initio, nous pouvions obtenir un excellent accord entre les couplages dipolaires calculés et expérimentaux, et déterminer sans ambiguïté la configuration relative des protons méthyléniques par rapport à la configuration du centre chiral.This thesis relates to various methodological developments and their applications in NMR in chiral liquid crystal solvents. Firstly, we have shown that experiments using selective pulses allowed us to extract information from proton and carbon-13 spectra which were inaccessible on the standard monodimensional spectra. We then used these techniques to measure a maximum of dipolar couplings in order to specify, in an unambiguous way, the relative configurations of stereogenic centres in rigid molecules. We showed that for the steroid DHEA, only one relative geometry of the substituents was compatible with all the measured dipolar couplings and led to a correct standard deviation between calculated and experimental dipolar couplings. This method is extremely promising because it is much less ambiguous than the more traditional methods used in isotropic media. Finally, we developed this method in the case of flexible molecules where the problem becomes more complicated because of the correlation between molecular conformation and orientational order. The number of parameters to be re-iterated explodes rapidly, whereas the number of measurables remain constant, and thus a general treatment is not possible. By studying for example, the 1,2-dibromopropane, we showed that the problem is manageable, under the condition of using a parametric model to calculate the average value of order parameters for each conformation. The parameters to be re-iterated, are then much fewer and the problem can be dealt with. Thus, we showed that, with four bond indices and the geometry of different conformers obtained by ab initio calculations, we could obtain an excellent agreement between the calculated and experimental dipolar couplings, and determine without ambiguity the relative configuration of the methylenic protons compared with the configuration of the chiral center.ORSAY-PARIS 11-BU Sciences (914712101) / SudocSudocFranceF

Magnetic Field Dependence of Spatial Frequency Encoding NMR

International audienceThe influence of the strength of the static magnetic field on pulse sequences based on the concept of spatial frequency encoding is addressed. The evolution of the slice selection process occurring during encoded excitation and refocusing pulses, as well as pure shift and J-edited refocusing blocks, is studied both theoretically and experimentally on a model ABX 1 H spin system. It is shown that carrying out gradient-encoded pulse sequences at higher field enhances the quality of the spin dynamics that is locally triggered in each encoded slice and results in spectra of better resolution and sensitivity

Benchtop NMR for the monitoring of bioprocesses

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Development of NMR methods at high and low field for lipid microalgae profiling

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La spectroscopie RMN de paillasse : un outil pour le suivi en ligne et non-invasif des lipides de microalgues

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Enantiomeric excess measurements in weakly oriented chiral liquid crystal solvents through 2D 1H selective refocusing experiments

International audienceIn this article, a simple and robust method is proposed for simplifying the analysis of proton spectra of molecules dissolved in weakly oriented chiral media. The NMR approach investigated is based on the use of proton selective refocusing 2D experiments (SERF) to measure proton–proton dipolar couplings from unresolved lines. This technique is applied to the case of enantiomers dissolved in chiral polypeptide liquid crystals. It is shown that an accurate determination of enantiomeric excess is possible within a short experimental time