Periodic Reporting for period 4 - ULT-MAS-DNP (Dynamic Nuclear Polarization at ultra-fast sample spinning and ultra-low temperature)
Periodo di rendicontazione: 2021-01-01 al 2021-06-30
Application fields range from material sciences to bio-inspired/targeted chemistry.
These goals were achieved thanks to the development of original methods (SelDNP, MAS-DNP simulations), new DNP polarizing agents (AsymPol family) and advanced instrumentation (Closed-cycle cryogenic He spinning).
The experimental setup developed within the context of this ERC grant enables conducting solid-state NMR combined with sustainable helium sample spinning at ultra-low temperature (down to 30 K) under microwave irradiation.
Second, we also made significant progress (both theoretically and experimentally) in the in depth understanding of the hyper-polarization transfer at stake during dynamic nuclear polarization, which led us to the design of improved polarizing agent molecules. The latter molecules belong to a class of paramagnetic dopants and are used as source of polarization in DNP experiments. Thanks to the in situ microwave irradiation, the electron polarization is transferred to the surrounding nuclei, boosting the sensitivity of NMR experiments by several orders of magnitude.
The improvement in sensitivity were used to conduct new NMR experiments, out of reach using conventional NMR. We notably showed that structural information (e.g. internuclei distances) can be extracted from data recorded on organic nano-assemblies and more generally powdered solids, without requiring the use of isotopic enrichment. This approach was also extended to the study of protein aggregates (involved in Huntington diseases), paving the way to NMR studies on patient or animal-derived materials.
We have also demonstrated a new approach, called Sel-DNP, to selectively detect hyperpolarize protein binding sites using high resolution DNP-enhanced NMR. This method relies on the combined use of functionalized ligand and difference spectroscopy and yield resolved multidimensional NMR spectra of selected parts of a biomolecular assembly. In our first work, we showed that this could be used on a carbohydrate binding protein to locate and assign the binding site without previous knowledge of the system.
Our experimental setup (quasi unique in the world) is not only very efficient but has become very robust and can be operated on a routine basis.
We are now seeking to make our new polarizing agents commercially available and are discussing with industrial partners how to make our technology accessible to other laboratories in the world.