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

Periodic Reporting for period 2 - ULT-MAS-DNP (Dynamic Nuclear Polarization at ultra-fast sample spinning and ultra-low temperature)

Reporting period: 2018-01-01 to 2019-06-30

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 will be achieved thanks to the development of original methods and advanced instrumentation, allowing sustainable access to low sample temperatures (down to 20 K) and fast pneumatic sample spinning, under suitable microwave irradiation. We expect to improve the current sensitivity to such an extent that 4 orders of magnitude of experimental time-savings are obtained, resulting in completely new research directions.
The project is developing according to the workplan. Most of the objectives are either reached or within reach by the end of the project.

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 to conduct Dynamic Nuclear Experiment in the ultra-low temperature regime. Further progress are expected by the end of the project, especially to turn the new helium spinning system into an experiment that can be used routinely in the lab. This would enable the implementation of this setup in other research labs. Our work on natural isotopic abundance NMR applied to powdered solids and protein aggregates is currently making further progress. The same is true for the Sel-DNP approach that we have just introduced. Overall most of the results obtained within the context of this ERC project went beyond the state-of-the-art.