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Dynamic Nuclear Polarization at ultra-fast sample spinning and ultra-low temperature

Periodic Reporting for period 4 - ULT-MAS-DNP (Dynamic Nuclear Polarization at ultra-fast sample spinning and ultra-low temperature)

Reporting period: 2021-01-01 to 2021-06-30

The goal of the project is to develop a hyperpolarization approach called Magic Angle Spinning Dynamic Nuclear Polarization (MAS-DNP) to reach levels of sensitivity and resolution for solid-state NMR spectroscopy that have never been achieved so far.

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.
The project has mostly developed according to plans. First, we developed major pieces of instrumentation enabling the access to new experimental conditions to conduct Dynamic Nuclear Polarization (DNP) under high resolution condition (MAS, magic angle spinning). This is achieved using pressurized cold helium gas to spin and cool the sample down to cryogenic temperature while conducting in situ irradiation at the sample using suitable microwave irradiation, resulting in much higher overall sensitivity than using commercial equipment. We aim to transfer the technology developed within the core of this project to an industrial partner and to install similar systems in other research laboratories.

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 lab is currently pioneering the development of new polarizing agent for DNP and sustainable cryogenic helium sample spinning which enable conducting Dynamic Nuclear Experiment in the ultra-low temperature regime.
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.