ERC DINAMIX – Real-time diffusion NMR analysis of mixtures

DINAMIX is a project led by Jean-Nicolas Dumez aiming at developing NMR methods for the analysis of out-of-equilibrium mixtures. DINAMIX has been funded by a 1.5 M€ ERC Starting Grant (n° 801774, 2019-2024).

5-year project

2019 - 2024

€ 1 499 337

ERC funds

228

person-months effort over the 5 years

8

internal team members

In order to describe, understand, and eventually control chemical reactions, scientists need to know what is happening in reaction mixtures.

Nuclear magnetic resonance (NMR) is the chemist’s most powerful tool to "see" which molecules are in a sample. However, the available options are typically a comprehensive picture on a completed reaction, and partial snapshots throughout the reaction. Using concepts derived from magnetic resonance imaging (MRI) and recent instrumentation, we are developing methods to provide a more complete picture of solution mixtures that evolve in time.

In more details

Chemical samples often come as solution mixtures. While advanced analytical methods exist for samples at equilibrium, the information on components and their interactions that may be accessed for out-of-equilibrium mixtures is much more limited. These include, for example, reaction mixtures in chemical synthesis and catalysis, as well as biochemical enzymatic reactions. The DINAMIX project aim at providing additional molecular-level information on out-of-equilibrium mixtures.

The project relies on diffusion nuclear magnetic resonance (NMR) spectroscopy, a powerful method that separates the spectra of mixtures’ components and identifies interactions, in correlation with structural insight provided by NMR observables. A spatial parallelisation is used to approach that makes it possible to acquire data in less than a second, instead of several minutes with conventional methods. This also has the potential to boost the power of hyperpolarisation methods such as dissolution dynamic nuclear polarisation (D-DNP) for mixtures analysis.

D-DNP indeed provides NMR sensitivity enhancements of up to 4 orders of magnitude, which however last only for a short time in solution. The methods developed will be used for applications in reaction monitoring in catalytic organic synthesis and biochemistry.

Project team

Jean-Nicolas DUMEZ

CNRS research

Project leader

Patrick GIRAUDEAU

Professor at the University of Nantes

Analytical chemistry

Aurélie BERNARD

Engineer

Pulse sequence and instrumentation

Hélène BONIN

Project Manager

Finances, human ressources, management and reporting

Benjamin LORANDEL

PhD student

Fast diffusion NMR for
hyperpolarization and monitoring
(2020-2023)

Achille MARCHAND

PhD student

Fast diffusion NMR method development
(2019-2022)

Célia LHOSTE

PhD Student

NMR pulse sequence developments
(2020-2023)

Rituraj MISHRA

Post-Doc

Numerical simulation and signal processing
(2019–2022)

Margherita BAZZONI

Post-Doc

Flow NMR and reaction monitoring
(2021–2023)

Past members

Corentin JACQUEMMOZ

PhD student

Spatial encoding method development
(2017-2020)

Publications

10.Ultrafast 2D NMR for the analysis of complex mixtures (link)
Célia Lhoste, Benjamin Lorandel, Clément Praud, Achille Marchand, Rituraj Mishra, Arnab Dey, Aurélie Bernard, Jean-Nicolas Dumez, Patrick Giraudeau

This review article describes ultrafast 2D NMR and its applications in the fields of monitoring, metabolomics, hyperpolarization and oriented media.

 

9. Quadratic spacing of the effective gradient area for spatially encoded diffusion NMR (link)
     Rituraj Mishra and Jean-Nicolas Dumez

We illustrate the mechanism of a frequency-swept pulse that achieves quadratic spacing of the effective gradient area in ultrafast DOSY NMR, and show that makes it possible to use fast processing methods.

8. Ultrafast 2D 1H-1H NMR spectroscopy of DNP-hyperpolarised substrates for the analysis of mixtures (link)
     Kawarpal Singh, Corentin Jacquemmoz, Patrick Giraudeau, Lucio Frydman, Jean-Nicolas Dumez

We show that TOCSY and multiple-quantum (MQ) 2D NMR spectra can be obtained for mixtures of substrates hyperpolarised by dissolution dynamic nuclear polarisation (D-DNP).

7. Optimisation of spatially encoded diffusion ordered NMR spectroscopy for the analysis of mixtures (link)
     Corentin Jacquemmoz, Rituraj Mishra, Ludmilla Guduff, Carine van Heijenoort, Jean-Nicolas Dumez

This article presents the unusual principles and implementation of the SPEN DOSY experiment, which is particularly useful for systems that evolve in time.

6. Ultrafast diffusion-based unmixing of 1H NMR spectra (link)
     Rituraj Mishra, Achille Marchand, Corentin Jacquemmoz, and Jean-Nicolas Dumez

We show that the NMR spectra of components in a mixture can be separated using 2D data acquired in less than one second, and an algorithm that is executed in just a few seconds.

5. Online reaction monitoring by single-scan 2D NMR under flow conditions (link)
    Corentin JACQUEMMOZ, François GIRAUD, Jean-Nicolas DUMEZ.

SUMMIT ERC - Online reaction monitoring by single-scan 2D NMR under flow conditions

Here we show that time series of single-scan ultrafast 2D NMR (UF2DNMR) spectra can be collected to monitor solution mixtures that circulate in a flow unit at high field.

4. Hyperpolarized NMR Metabolomics at Natural 13C Abundance (link)
    Arnab Dey, Benoît Charrier, Estelle Martineau, Catherine Deborde, Elodie Gandriau, Annick Moing, Daniel Jacob, Dmitry Eshchenko, Marc Schnell, Roberto Melzi,
    Dennis Kurzbach, Morgan Ceillier, Quentin Chappuis, Samuel F. Cousin, James G. Kempf, Sami Jannin, Jean-Nicolas Dumez and Patrick Giraudeau

This article introduces a new approach, based on hyperpolarized 13C NMR at natural abundance, that circumvents the sensitivity drawback of 13C NMR for metabolomics.

3. Frequency-swept pulses for ultrafast spatially encoded NMR
    Jean-Nicolas Dumez

This article describes the spatial encoding of relaxation, chemical shift and diffusion in a common framework and discusses directions for future developments.

2. Application and methodology of dissolution dynamic nuclear polarization in physical, chemical and biological contexts (link)
     Sami Jannin, Jean-Nicolas Dumez, Patrick Giraudeau, Dennis Kurzbach

This perspectives article highlights possible avenues for developments and applications of d-DNP in biochemical and physicochemical studies.

1. Interleaved spatial/spectral encoding in ultrafast 2D NMR spectroscopy (link)
    Bertrand Plainchont, Patrick Giraudeau, Jean-Nicolas Dumez

We analyze and further develop the strategy of using spatial/spectral pulses for spatial encoding, and introduce the concept of interleaving in excitation space, to address drawback of UF2DNMR.