Nuclear magnetic resonance (NMR) spectroscopy is a key tool for characterizing complex solid systems, such as functionalized materials, pharmaceutical formulations or viral assemblies. Despite its wide range of applications, this spectroscopy suffers from an intrinsic low sensitivity. Dynamic nuclear polarization (DNP) has recently emerged as an essential tool for significantly increasing the sensitivity of solid-state NMR spectroscopy under magic angle spinning, enabling advanced analyses to be carried out in reasonable experimental times. DNP is based on a polarization transfer from electron spins to neighboring nuclear spins. The electron source is usually exogenous, and is introduced into the system under study in the form of free radicals, known as polarizing agents.
This thesis focused on the development of new formulations for DNP at high magnetic fields and/or high temperatures. The main contribution was the development of new polarizing agents, for efficient DNP at high magnetic fields and high spinning frequencies In particular, we focused on new families of water-soluble binitroxides, derived from the TinyPols radicals introduced in 2020. We have shown that the addition of protonated chains to the biradical structure significantly enhances their DNP performance, and explained this effect through the joint analysis of Electron Paramagnetic Resonance (EPR) data and Molecular Dynamics simulations. In particular, we have shown that deuterated glycerol molecules present in the polarization matrix are mainly located in the second solvation layer of the nitroxide radical, limiting access to protonated water molecules and restricting spin diffusion pathways. Extensive spin dynamics simulations on a large number of spin ensemble representing the DNP matrix were carried out to confirm these observations and the decisive role of protonated chains in hyperpolarization transfer. DNP enhancement factors as high as ~200 were measured with one of the best TinyPol derivatives, dubbed M-TinyPol-(OH)4, in a 0.7 mm probe; with a MAS frequency of 60 kHz, at 18.8 T and 100 K. This is nearly a factor 2 larger than the enhancements obtained with the previous best performing dinitroxides. The performance of this radical has been carefully compared with other gold standard polarizing agents.
In parallel, we studied the effect of temperature on the DNP enhancement factor of the HyTEK2, a hybrid biradical introduced in 2018 composed of a nitroxide and a 1,3-Bis(diphenylene)-2-phenylallyl (BDPA) unit, in ortho-terphenyl (OTP). Numerical simulations were implemented to interpret the experimental NMR and EPR data. In particular, the importance of the relaxation times of both radical moieties has been highlighted.
The results obtained in this PhD thesis pave the way for the development of new DNP formulations suitable for high-field and/or high-temperature hyperpolarized solid-state NMR.
Gratuit
Disciplines