Tailored Polarizing Hybrid Solids with Nitroxide Radicals Localized in Mesostructured Silica Walls

Hyperpolarization by dynamic nuclear polarization relies on the microwave irradiation of paramagnetic radicals dispersed in molecular glasses to enhance the nuclear magnetic resonance (NMR) signals of target molecules. However, magnetic or chemical interactions between the radicals and the target molecules can lead to attenuation of the NMR signal through paramagnetic quenching and/or radical decomposition. Here we describe polarizing materials incorporating nitroxide radicals within the walls of the solids to minimize interactions between the radicals and the solute. These materials can hyperpolarize pure pyruvic acid, a particularly important substrate of clinical interest, while nitroxide radicals cannot be used, even when incorporated in the pores of silica, because of reactions between pyruvic acid and the radicals. The properties of these materials can be engineered by tuning the composition of the wall by introducing organic functionalities.

De l'usage des protons hyperpolarisés pour augmenter la sensibilité de la RMN

Aurélien Bornet

Nuclear Magnetic Resonance (NMR) has become an inescapable technique for spectroscopic identification. Its main advantage comes from the sensitivity of NMR active nuclei embedded in a molecule to their chemical environment. NMR is also used daily in medical imaging. Magnetic Resonance Imaging (MRI) is not only remarkably versatile, but has the precious advantage of being non-invasive; moreover, the range of radiofrequency used implies that MRI deposit a limited amount of energy in tissues under investigation. Nevertheless, compared to other spectroscopic methods, NMR suffers from a relative lack of sensitivity. Indeed as the NMR transitions are low in energy, the difference of populations between the levels involved, known as polarization, is extremely low. The NMR signal, which is directly proportional to this polarization, is thus many orders of magnitude inferior to the theoretical maximum at full polarization. Dynamic Nuclear Polarization (DNP) allows one to circumvent this disadvantage by transferring the high electron spin polarization to the nuclear spins. This transfer happens via microwave irradiation under optimized conditions. The method has been constantly developed since the âfifties. A substantial breakthrough was achieved in 2003 by Golman, Ardenkjaer-Larsen and their collaborators. They proposed to dissolve a sample that has been hyperpolarized at low temperature (at about 1 K) in order to inject it into an animal, or, in fine, into a human patient, and to follow its bio-distribution and eventual metabolic conversion by MRI. This technique, called Dissolution-DNP (D-DNP), allows a signal increase on the order of 10'000, opening the way to many new experimental possibilities. Research in Dissolution-DNP was largely oriented toward the optimization of 13C polarization because of its long lifetimes. In the course of this Thesis, an alternative way that takes advantage of the proton (1H) polarization will be explored. Protons have the advantage that they can be polarized to a higher levels in a shorter time compared to 13C. Unfortunately, once ejected from the polarizer, in solution and at room temperature, the high proton magnetization will be short-lived compared to 13C. Along the chapters of this Thesis, different approaches will be proposed to maximize the advantages of 1H polarization, while minimizing its inconveniences. It is possible to use a standard NMR technique, known as Cross-Polarization (CP), to transfer the abundant magnetization of hyperpolarized protons to other nuclei like 13C, using suitable radiofrequency pulse sequences. The advantages of the 1H polarization are exploited inside the polarizer, while the interesting properties of 13C are put to use after dissolution. Still, it is also possible to observe directly the proton signal after dissolution. This can be extremely interesting, especially in the context of drug screening for pharmaceutical research. Two examples of such methods will be described. Finally, the use of hyperpolarized 1H signals after dissolution can be greatly improved if their relaxation rates could be attenuated. A first way of doing this, consisting in removing the paramagnetic species by filtration, will be explored. The use of Long-Lived States (LLS) will also be presented.

EPFL2015

Dynamic Nuclear Polarization and Other Magnetic Ideas at EPFL

Geoffrey Bodenhausen, Aurélien Bornet, Roberto Buratto, Marc Anthony Caporini, Diego Carnevale, Srinivas Chinthalapalli, Sami Jannin, Daniele Mammoli, Pascal Miéville, Jonas Milani, Angel Joaquin Perez Linde, Martial Rey, Nicola Salvi, Simone Ulzega, Shutao Wang

Although nuclear magnetic resonance (NMR) can provide a wealth of information, it often suffers from a lack of sensitivity. Dynamic Nuclear Polarization (DNP) provides a way to increase the polarization and hence the signal intensities in NMR spectra by transferring the favourable electron spin polarization of paramagnetic centres to the surrounding nuclear spins through appropriate microwave irradiation. In our group at EPFL, two complementary DNP techniques are under investigation: the combination of DNP with magic angle spinning at temperatures near 100 K ('MAS-DNP'), and the combination of DNP at 1.2 K with rapid heating followed by the transfer of the sample to a high-resolution magnet ('dissolution DNP'). Recent applications of MAS-DNP to surfaces, as well as new developments of magnetization transfer of H-1 to C-13 at 1.2 K prior to dissolution will illustrate the work performed in our group. A second part of the paper will give an overview of some 'non-enhanced' activities of our laboratory in liquid- and solid-state NMR.

Schweizerische Chemische Gesellschaft2012

Dynamic nuclear polarisation via the integrated solid effect II: experiments on naphthalene-h(8) doped with pentacene-d(14)

Tim Rolf Eichhorn

In dynamic nuclear polarisation (DNP), also called hyperpolarisation, a small amount of unpaired electron spins is added to the sample containing the nuclear spins, and the polarisation of these unpaired electron spins is transferred to the nuclear spins by means of a microwave field. Traditional DNP polarises the electron spin of stable paramagnetic centres by cooling down to low temperature and applying a strong magnetic field. Then weak continuous wave microwave fields are used to induce the polarisation transfer. Complicated cryogenic equipment and strong magnets can be avoided using short-lived photo-excited triplet states that are strongly aligned in the optical excitation process. However, a much faster transfer of the electron spin polarisation is needed and pulsed DNP methods like nuclear orientation via electron spin locking (NOVEL) and the integrated solid effect (ISE) are used. To describe the polarisation transfer with the strong microwave fields in NOVEL and ISE, the usual perturbation methods cannot be used anymore. In the previous paper, we presented a theoretical approach to calculate the polarisation transfer in ISE. In the present paper, the theory is applied to the system naphthalene-h(8) doped with pentacene-d(14) yielding the photo-excited triplet states and compared with experimental results.

Taylor & Francis2014

De l'usage des protons hyperpolarisés pour augmenter la sensibilité de la RMN

Aurélien Bornet

EPFL2015