Visualisation of enantiomers via insertion of a BIRD module in X-H correlation experiments in chiral liquid crystal solvent.

Several 13C-1H NMR techniques are derived simplifying the visualisation of enantiomers in chiral ordering solvents. They proceed through various heteronuclear 2D experiments where a bilinear rotation decoupling sequence (BIRD) is inserted in the middle of the t1 evolution period. In this way, the small couplings are refocused while the large couplings are preserved. The methods allow extracting precise values of one-bond carbon-proton residual dipolar couplings for each enantiomer out of unresolved proton-coupled 13C or carbon-coupled 1H spectra. Illustrative examples are analysed and discussed using various pulse sequences.

Lipid composition and structure of commercial parenteral emulsions.

In order to study the influence of the phospholipid/triacylglycerol (PL/TG) ratio of parenteral emulsions on the distribution and the physico-chemical properties of their fat particles, commercial 10, 20 or 30% fat formulas were fractionated by centrifugation into an upper lipid cake (resuspended in aqueous glycerol) and a subnatant or mesophase, from which a PL-rich subfraction (d = 1.010-1.030 g/l) was purified by density gradient ultracentrifugation. Chemical and 31P-NMR analyses of these fractions indicated that at least two types of fat particles coexist in parenteral emulsions: (i) TG-rich particles (mean diameter: 330, 400, 470 nm in the 10, 20, 30% emulsion) which contain practically all the TG and esterified phytosterols of native emulsions, but only a fraction of their PL, unesterified cholesterol and phytosterols, and other minor lipids; (ii) PL-bilayer particles or liposomes (mean diameter: 80-100 nm) which are constituted with the remaining PL and relatively very small amounts of TG and other lipids. The higher the oil content of the emulsion, the lower the amount of these PL-rich particles, which represent the major particle population of the mesophase. Indeed, minute amounts of TG-rich particles (probably the smallest ones) are also present in the mesophase, even in the PL-rich subfraction which contains the bulk of liposomal PL. Since the PL-rich particles of the infused emulsion generate lipoprotein X-like particles, only the large TG-rich particles can be considered as true chylomicron counterparts.

In vitro adrenal cortex lesions characterization by NMR spectroscopy.

Percentage of lipid content of 22 adrenal cortex lesions and their water proton longitudinal relaxation time were measured in vitro at 60 MHz. Although water relaxation times obtained on benign and malignant samples overlap each other, measurements of the percentage of lipids performed on the same tissues allow us to distinguish the two pathologies. The specific tool of characterization should be possible to obtain through in vivo spectroscopic imaging techniques.

Automatic NMR field-frequency lock-pulsed phase locked loop approach.

A self-contained deuterium frequency-field lock scheme for a high-resolution NMR spectrometer is described. It is based on phase locked loop techniques in which the free induction decay signal behaves as a voltage-controlled oscillator. By pulsing the spins at an offset frequency of a few hundred hertz and using a digital phase-frequency discriminator this method not only eliminates the usual phase, rf power, offset adjustments needed in conventional lock systems but also possesses the automatic pull-in characteristics that dispense with the use of field sweeps to locate the NMR line prior to closure of the lock loop.

[Unidimensional imaging. A simple method for evaluating the efficacy of a contrast agent in magnetic resonance imaging. Application of new nitroxides]. / L'imagerie unidimensionnelle. Une méthode simple pour évaluer l'efficacité d'un agent de contraste en imagerie par résonance magnétique. Application à de nouveaux nitroxydes.

We present an experimental set-up of one-dimension imaging which permits on a conventional NMR spectrometer, to measure the difference in relaxation time T1 of two organ samples, one normal and the other injected with a contrast agent. Using that technique and M.R.I. two new nitroxides reveal a substantial contrast effect for kidneys and heart.

[Biodistribution of new polynitroxides using electron paramagnetic resonance]. / Biodistribution de nouveaux polynitroxydes par résonance paramagnétique électronique.

The most important paramagnetic contrast agents used in Nuclear Magnetic Resonance Imaging are limited to a few metal complexes such Gd-DTPA or stable free radicals such as nitroxides simply functionalized. We studied the biodistribution of new polynitroxides agents by Electronic Paramagnetic Resonance in Sprague Dawley rats. Three of the six different polynitroxides agents studied, showed an interesting and selective localisation in the lungs, heart and liver.

Diastereomeric Shape Recognition Using NMR Spectroscopy in a Chiral Liquid Crystalline Solvent.

Unambiguous assignment of the resonances of different diastereomers in a nonracemic mixture is possible with (1)H-decoupled (2)H NMR spectroscopy in a chiral liquid crystalline solvent. This is demonstrated with, for example, the alpha,alpha'-dideuterated diol shown in the picture. Even diastereomers with centers of chirality up to nine bonds apart can be discriminated.

Improvements to selective refocusing phased (SERFph) experiments.

Selective refocusing experiments are very powerful for extracting proton-proton couplings one by one. However we demonstrate in the present work that various spectral artefacts are produced by the initial sequence and we show that the combined addition of a refocusing pi pulse and a zero-quantum filter greatly improves the experimental sensitivity, and moreover leads to observation of pure absorption lineshapes in the resulting phased 2D spectrum. These developments are applied to the differentiation of enantiomers dissolved in a chiral liquid crystal.

Investigation of the enantioselectivity of three polypeptide liquid-crystalline solvents using NMR spectroscopy.

The enantioselective potentialities of three polypeptide liquid-crystalline solutions made of poly-gamma-benzyl-L-glutamate (PBLG), poly-gamma-ethyl-L-glutamate (PELG) or poly-epsilon-carbobenzyloxy-L-lysine (PCBLL) are investigated and compared using proton, carbon-13 and deuterium NMR spectroscopy. From a practical point of view, we propose an efficient alternative to the PBLG system, which is essential when this chiral homopolymer fails in distinguishing between enantiomers or enantiotopic elements. From a theoretical point of view, this study provides new information on the role of the lateral side chain of the polypeptide in the mechanisms of enantiodiscrimination. The various experimental results reported show the extraordinary adaptability of this methodology, and so enlighten the very large potential of NMR in chiral liquid crystals in the field of enantiomeric and enantiotopic analysis.

NMR experimental evidence of the differentiation of enantiotopic directions in C(s) and C(2v) molecules using partially oriented, chiral media.

We report new and explicit experimental evidence of the differentiation of (1)H-(1)H, (13)C-(1)H, and (13)C-(2)H enantiotopic directions in prochiral molecules with C(s) and C(2v)symmetry dissolved in a chiral liquid-crystalline phase using (13)C and (2)H-[(1)H] NMR spectroscopy at the natural abundance level. The case of endo-bicyclo[2.2.2]oct-5-ene-2,3-dicarboxylic anhydride, bicyclo[2.2.1]hepta-2,5-diene, and ethyl alcohol oriented in organic solutions of poly-gamma-benzyl-L-glutamate (PBLG) or poly-epsilon-carbobenzyloxy-L-lysine (PCBLL) is investigated and discussed. Next, we describe the first NMR differentiation of enantiotopic directions in a C(2v) molecule with no prostereogenic carbon using malononitrile as a model. The various results presented in this work experimentally validate our recent theoretical arguments which predict that NMR spectra of nonplanar C(s) and C(2v) compounds embedded in a chiral oriented solvent should differ from those recorded in nonchiral oriented media, because their effective molecular symmetry point group (interacting molecule) is different from their molecular point group (isolated molecule). In addition, the differentiation of enantiotopic directions in C(2v) molecules exhibiting no prostereogenic tetrahedral center illustrates for the first time an old stereochemical hypothesis which speculates that "for molecules of the type CXXYY. the two X groups as well as the Y groups are equivalent and cannot be distinguished in chiral or achiral circumstances. However, the relationships between X and Y groups are not all equivalent. The four X-Y relationships may be ordered into two enantiotopic sets of two equivalent relationships" (Mislow, K.; Raban, M. Top. Stereochem. 1967, 1, 1) and validate the stereogenicity concepts proposed more recently by Fujita (Fujita, S. J. Am. Chem. Soc. 1990, 112, 3390).

[Demonstration by spectroscopy NMR at 1,5 Tesla of changes in lipid/water ratio in pathology of the adrenal cortex]. / Mise en évidence par spectroscopie RMN à 1,5 Tesla des changements de la proportion lipides/eau en pathologie du cortex surrénalien.

By NMR proton spectrometry with a main field of approximately 1.5 Tesla the authors have studied on pieces obtained at surgery changes of the lipid/water ratio in the cortex of diseased adrenal glands. On the basis of 58 samples taken from 20 different glands they show that this ratio is comparable in hyperplasias and adenomas but quite significantly reduced in carcinomas. They are therefore of the opinion that this ratio might serve as a malignancy index in spectroscopic imaging of patients bearing tumors of the adrenal cortex.

Cleavage of L-leucine-containing dipeptides by Clostridium butyricum.

The ability of Clostridium butyricum cultures to hydrolyze three L-leucine-containing dipeptides (Leu-Leu, Leu-Gly and Gly-Leu) in a synthetic minimal medium is demonstrated by using gas chromatography coupled with mass spectrometry. The 13C nuclear magnetic resonance and a labeled dipeptide L-[1-13C]Leu-Gly were used to confirm this activity.