Spectroscopie RMN de Surface Exaltée par Polarisation Nucléaire Dynamique

Since its discovery in the 1950's, DNP has been a topic of significant interest in magnetic resonance. DNP is the transfer of polarization between single electrons and nuclei, driven by micro-wave irradiation. Since its renaissance at high field in the 90's, due to the introduction of gyrotrons as high-power, high-frequency microwave sources most application of this technique have been samples of biological interest in frozen solution. The long standing interest of our group in the characterization of surface species such as supported catalysts on silica lead us to apply this technique to the study of surfaces. The goal of this thesis is the development of this method, dubbed DNP Surface Enhanced NMR Spectroscopy. To that end, we first introduce new polarizing agents, soluble in organic solvents. The influence of the electron relaxation times on the DNP enhancements is demonstrated and efficient tailored polarizing agents are introduced. The optimization of the sample preparation to obtain optimal sensitivity is also discussed, as well as the interaction between the radical and the surface. These developments made it possible to apply the technique to many functionalized materials, with some examples developed in this manuscript. Finally, the issue of DNP on polarization conductors is discussed, and we show how microcrystals can be efficiently polarized using DNP.Depuis sa découverte dans les années 50, la DNP suscite un intérêt croissant en résonance magnétique. La DNP peut être définie comme le transfert d'aimantation entre des électrons célibataires et les noyaux de l'échantillon induit par irradiation micro-onde. Depuis sa renaissance à hauts champs dans les années 90, grâce à l'introduction des gyrotrons comme source micro-onde haute fréquence haute puissance, la plupart des développements et applications de la méthode concernent des échantillons d'intérêt biologique en solution solide. L'intérêt de notre groupe pour la caractérisation d'espèces de surface, tels que les catalyseurs supportés sur silice nous a conduit à appliquer la DNP à des espèces de surface. Le but de cette thèse est le développement de cette méthode nommée DNP SENS. Pour cela de nouveaux agents de polarisations sont tout d'abord introduits, avec une discussion sur l'influence des temps de relaxation électroniques sur l'efficacité DNP. L'optimisation de la préparation des échantillons pour maximiser la sensibilité RMN est discutée, ainsi que l'interaction entre les radicaux et la surface. Ces développements ont permis la caractérisation de nombreux matériaux et quelques exemples sont donnés ici. Enfin, une dernière partie se concentre sur l'application de la DNP à des conducteurs de polarisation, et montre la possibilité d'hyperpolarisés des objets de taille micrométrique

Procédé de polarisation de noyaux actifs de RMN, amplificateur de polarisation et appareil de polarisation de noyaux actifs de RMN

international Application No.: PCT/IB2014/002163International Filing Date: 30.06.2014The invention provides for a process for polarizing NMR active nuclei within an analyte of interest by dynamic nuclear polarization (DNP), said process comprising the steps of: a. providing a polarizing solution; b. contacting the analyte of interest with the polarizing solution; c. submitting the polarizing solution to DNP conditions, characterized in that it comprises the step of providing a DNP amplifying solid material dispersed or immersed in the polarizing solution, in that the DNP amplifying solid material has a real component of relative permittivity higher than that of the polarizing solution, and in that the volumetric fraction of the DNP amplifying solid material in the final mixture of polarizing solution, analyte and DNP amplifying material is in the range of 10 to 80%, preferably between 15 to 75%, most preferably between 40 to 70 %.L'invention concerne un procédé de polarisation de noyaux actifs de RMN dans un analyte d'intérêt par polarisation nucléaire dynamique (DNP), ledit procédé comprenant les étapes consistant à : a. fournir une solution de polarisation ; b. mettre l'analyte d'intérêt en contact avec la solution de polarisation ; c. soumettre la solution de polarisation à des conditions DNP, caractérisé en ce qu'il comprend l'étape consistant à fournir un matériau solide d'amplification de DNP dispersé ou immergé dans la solution de polarisation, en ce que le matériau solide d'amplification de DNP a un composant réel ayant une permittivité relative supérieure à celle de la solution de polarisation, et en ce que la fraction volumique du matériau solide d'amplification de DNP dans le mélange final de solution de polarisation, d'analyte et de matériau d'amplification de DNP se situe dans la gamme de 10 à 80 %, de préférence entre 15 à 75 %, plus préférentiellement entre 40 à 70 %

Macroscopic nuclear spin diffusion constants of rotating polycrystalline solids from first-principles simulation

A method for quantitatively calculating nuclear spin diffusion constants directly from crystal structures is introduced. This approach uses the first-principles low-order correlations in Liouville space (LCL) method to simulate spin diffusion in a box, starting from atomic geometry and including both magic-angle spinning (MAS) and powder averaging. The LCL simulations are fit to the 3D diffusion equation to extract quantitative nuclear spin diffusion constants. We demonstrate this method for the case of H-1 spin diffusion in ice and L-histidine, obtaining diffusion constants that are consistent with literature values for H-1 spin diffusion in polymers and that follow the expected trends with respect to magic-angle spinning rate and the density of nuclear spins. In addition, we show that this method can be used to model C-13 spin diffusion in diamond and therefore has the potential to provide insight into applications such as the transport of polarization in non-protonated systems. (C) 2015 Elsevier Inc. All rights reserved

Dynamic Nuclear Polarization Surface Enhanced NMR Spectroscopy

Many of the functions and applications of advanced materials result from their interfacial structures and properties. However, the difficulty in characterizing the surface structure of these materials at an atomic level can often slow their further development Solid-state NMR can probe surface structure and complement established surface science techniques, but its low sensitivity often limits its application. Many materials have low surface areas and/or low concentrations of active/surface sites. Dynamic nuclear polarization (DNP) is one Intriguing method to enhance the sensitivity of solid-state NMR experiments by several orders of magnitude. In a DNP experiment, the large polarization of unpaired electrons is transferred to surrounding nuclei, which provides a maximum theoretical DNP enhancement of similar to 658 for H-1 NMR. In this Account, we discuss the application of DPIP to enhance surface NMR signals, an approach known as DNP surface enhanced NMR spectroscopy (DNP SENS). Enabling DNP for these systems requires bringing an exogeneous radical solution into contact with surfaces without diluting the sample. We proposed the incipient wetness impregnation technique (IWI) a well-known method in materials science, to impregnate porous and particulate materials with just enough radical containing solution to fill the porous volume. IWI offers several advantages: it is extremely simple, provides a uniform wetting of the surface, and does not increase the sample volume or substantially reduce the concentration of the sample. This Account describes the basic principles behind DNP SENS through results obtained for mesoporous and nanoparticulate samples impregnated with radical solutions. We also discuss the quantification of the overall sensitivity enhancements obtained with DNP SENS and compare that with ordinary room temperature NMR spectroscopy. We then review the development of radicals and solvents that give the best possible enhancements today. With the best polarizing mixtures, DNP SENS enhances sensitivity by a factor of up to 100, which decreases acquisition time by five orders of magnitude. Such enhancement enables the detailed and expedient atomic level characterization of the surfaces of complex materials at natural isotopic abundance and opens new avenues for NMR. To illustrate these improvements, we describe the successful application of DNP SENS to characterize hybrid materials, organometallic surface species, and metal-organic frameworks

Molecular-level characterization of the structure and the surface chemistry of periodic mesoporous organosilicates using DNP-surface enhanced NMR spectroscopy

We present the molecular level characterization of a phenylpyridine-based periodicmesoporous organosilicate and its post-functionalized organometallic derivatives through the fast acquisition of high quality natural isotopic abundance 1D C-13, N-15, and Si-29 and 2D 1H-C-13 and 1H-Si-29 solid-state NMR spectra enhanced with dynamic nuclear polarization

Dynamic Nuclear Polarization NMR Spectroscopy of Microcrystalline Solids

International audienceDynamic nuclear polarization (DNP) solid-state NMR has been applied to powdered microcrystalline solids to obtain sensitivity enhancements on the order of 100. Glucose, sulfathiazole, and paracetamol were impregnated with bis-nitroxide biradical (bis-cyclohexyl-TEMPO-bisketal, bCTbK) solutions of organic solvents. The organic solvents were carefully chosen to be nonsolvents for the compounds, so that DNP-enhanced solid-state NMR spectra of the unaltered solids could be acquired. A theoretical model is presented that illustrates that for externally doped organic solids characterized by long spin-lattice relaxation times (T-1(H-1) > 200 s), H-1-H-1 spin diffusion can relay enhanced polarization over micrometer length scales yielding substantial DNP enhancements (epsilon). epsilon on the order of 60 are obtained for microcrystalline glucose and sulfathiazole at 9.4 T and with temperatures of ca. 105 K. The large gain in sensitivity enables the rapid acquisition of C-13-C-13 correlation spectra at natural isotopic abundance. It is anticipated that this will be a general method for enhancing the sensitivity of solid-state NMR experiments of organic solids

Dynamic Nuclear Polarization NMR Spectroscopy of Microcrystalline Solids

Dynamic nuclear polarization (DNP) solid-state NMR has been applied to powdered microcrystalline solids to obtain sensitivity enhancements on the order of 100. Glucose, sulfathiazole, and paracetamol were impregnated with bis-nitroxide biradical (bis-cyclohexyl-TEMPO-bisketal, bCTbK) solutions of organic solvents. The organic solvents were carefully chosen to be nonsolvents for the compounds, so that DNP-enhanced solid-state NMR spectra of the unaltered solids could be acquired. A theoretical model is presented that illustrates that for externally doped organic solids characterized by long spin-lattice relaxation times (T-1(H-1) > 200 s), H-1-H-1 spin diffusion can relay enhanced polarization over micrometer length scales yielding substantial DNP enhancements (epsilon). epsilon on the order of 60 are obtained for microcrystalline glucose and sulfathiazole at 9.4 T and with temperatures of ca. 105 K. The large gain in sensitivity enables the rapid acquisition of C-13-C-13 correlation spectra at natural isotopic abundance. It is anticipated that this will be a general method for enhancing the sensitivity of solid-state NMR experiments of organic solids

Dynamic Nuclear Polarization Enhanced NMR Spectroscopy for Pharmaceutical Formulations

Dynamic nuclear polarization (DNP) enhanced solid-state NMR spectroscopy at 9.4 T is demonstrated for the detailed atomic-level characterization of commercial pharmaceutical formulations. To enable DNP experiments without major modifications of the formulations, the gently ground tablets are impregnated with solutions of biradical polarizing agents. The organic liquid used for impregnation (here 1,1,2,2-tetrachloroethane) is chosen so that the active pharmaceutical ingredient (API) is minimally perturbed. DNP enhancements (epsilon) of between 40 and 90 at 105 K were obtained for the microparticulate API within four different commercial formulations of the over-the-counter antihistamine drug cetirizine dihydrochloride. The different formulations contain between 4.8 and 8.7 wt % API. DNP enables the rapid acquisition with natural isotopic abundances of one- and two-dimensional C-13 and N-15 solid-state NMR spectra of the formulations while preserving the microstructure of the API particles. Here this allowed immediate identification of the amorphous form of the API in the tablet. API-excipient interactions were observed in high-sensitivity H-1-N-15 correlation spectra, revealing direct contacts between povidone and the API. The API domain sizes within the formulations were determined by measuring the variation of e as a function of the polarization time and numerically modeling nuclear spin diffusion. Here we measure an API particle radius of 0.3 mu m with a single particle model, while modeling with a Weibull distribution of particle sizes suggests most particles possess radii of around 0.07 mu m

DNP enhanced NMR spectroscopy for pharmaceutical formulations

International audienceDynamic nuclear polarization (DNP) enhanced solid-state NMR spectroscopy at 9.4 T is demonstrated for the detailed atomic-level characterization of commercial pharmaceutical formulations. To enable DNP experiments without major modifications of the formulations, the gently ground tablets are impregnated with solutions of biradical polarizing agents. The organic liquid used for impregnation (here 1,1,2,2-tetrachloroethane) is chosen so that the active pharmaceutical ingredient (API) is minimally perturbed. DNP enhancements (ε) of between 40 and 90 at 105 K were obtained for the microparticulate API within four different commercial formulations of the over-the-counter antihistamine drug cetirizine dihydrochloride. The different formulations contain between 4.8 and 8.7 wt % API. DNP enables the rapid acquisition with natural isotopic abundances of one- and two-dimensional 13C and 15N solid-state NMR spectra of the formulations while preserving the microstructure of the API particles. Here this allowed immediate identification of the amorphous form of the API in the tablet. API-excipient interactions were observed in high-sensitivity 1H-15N correlation spectra, revealing direct contacts between povidone and the API. The API domain sizes within the formulations were determined by measuring the variation of ε as a function of the polarization time and numerically modeling nuclear spin diffusion. Here we measure an API particle radius of 0.3 μm with a single particle model, while modeling with a Weibull distribution of particle sizes suggests most particles possess radii of around 0.07 μm