Description

NMR is a cornerstone technique in many scientific fields, ranging from chemistry to medicine, biology and physics because of its ability to address a wide range of problems in systems as diverse as polymers, proteins, superconductors, metal oxides, small organic molecules, supramolecular assemblies, animals and humans. This spectroscopy suffers however from one key weakness, weak NMR signals. This prevents NMR being used for characterization in many of the most exciting areas of modern science, in particular the study of surfaces and materials, or of large proteins. Thus, for years, methods to surpass this limitation in sensitivity have been actively investigated. Dynamic Nuclear Polarization (DNP) in combination with Magic Angle Spinning (MAS) solid-state NMR spectroscopy (DNP MAS ssNMR) has recently emerged as a powerful tool to enhance the NMR signals of solid samples. It has been shown that DNP experiments that achieve even a fraction of the theoretical maximum signal enhancement (658 for 1H, 2617 for 13C) allow major breakthroughs in the detailed characterization of previously inaccessible systems. For instance, structural studies of materials (hybrid silica, MOF, metal oxides, polymers, pharmaceutical formulation), or biomolecules have established the astonishing abilities of this technique. In the past 5 years, the optimization of the structural and magnetic properties of the polarizing agents (PAs) has significantly contributed to the increase of the signal enhancement at 9 T and to the success of the technique. The two partners of the project have provided an input in the field by developing more efficient polarizing agents (AMUPol and TEKPol), establishing new methodologies for DNP ssNMR (DNP SENS) and demonstrating the high value of DNP ssNMR for the detailed characterization of various samples. AMUPol and TEKPol, commercially available for 18 months, are currently the most efficient polarizing agents and are used now by the ssNMR/DNP community. However, ssNMR/DNP still faces some important disadvantages, such as the requirement of a glassy matrix, non-optimal signal enhancement and a poor spectral resolution due to the low temperature of the experiments (ca 100 K). Moreover, at high field (18 T), the gain in sensitivity is dramatically reduced in regards with experiments performed at 9T. With AMUPol, the DNP signal enhancements drop from 200-250 at 9T (400 MHz, 100 K) to 30-40 at 18 T (800 MHz, 100 K) in model systems (proline or urea sample). This translates typically in DNP factor of roughly 10 at 18T on protein samples. Recent experiments suggest that our understanding of the polarizing processes at high fields (18T) needs to be re-examined. Therefore, there is a clear challenge to get a better understanding of DNP at high field and to develop new polarizing agents efficient at 18 T and or at higher temperatures. The proposed project will lead to the development of new polarizing agents and new methodologies that will make clearly beneficial the use of DNP at high field (18 T) and/or at higher temperature (above 200 K). Our initiatives will bring advances with efficient polarizing agents, a better understanding of the polarizing processes, and in the developments of ssNMR for the structural studies on challenging samples. The work will cover from the design and synthesis of new radicals, to EPR investigations at high field (with G. Jeschke, ETH), DFT calculations and ssNMR DNP experiments at 9, 14 and 18 T and at various temperatures (9 and 18 T DNP systems available in partner 2). To meet these challenges, new families of polarizing agents will be introduced, such as strongly dipolar coupled dinitroxides, heterobiradicals, new narrow line radicals with pseudo-isotropic g values, new radicals for Overhauser Effect. Finally, these polarizing agents (PAs) will be exploited to record high-resolution high-temperature DNP enhanced NMR spectra on biological samples.

Membres de l'équipe