d-DNP | HMRLab

What is d-DNP ?

Dissolution Dynamic Nuclear Polarization (d-DNP) is a hyperpolarization technique which aims at increasing the sensitivity by several orders of magnitude for liquid state Nuclear Magnetic Resonance (NMR) and Magnetic Resonance Imaging (MRI).It consists of transferring the strong polarization of unpaired electron spins (from radicals) to nuclear spins under microwave irradiation at cryogenic temperatures (typ. 1-4 Kelvin) and at high magnetic field (typ. 5-7 T). The frozen hyperpolarized sample is subsequently rapidly dissolved into solution to be transferred in an NMR or MRI instrument for measurement.

How does it work ?

1 - A stable radical (typ. Trityl, TEMPOL) is added to the sample which is frozen at ~1 K.

2 - Microwaves irradiation is applied to transfer polarization from electrons to nuclei.

3 - The hyperpolarized sample gets rapidly dissolved with a hot and pressurized solvent.

4 - It gets transferred via a transfer line for being injected into the NMR/MRI system for detection within minutes (before relaxation decays the polarization).

For which application ?

d-DNP makes the undetectable detectable, allows tracking of fast kinetics, and powers breakthroughs in many fields, amongst which…

Metabolic Imaging & Biomedicine

· Tracking in vivo hyperpolarized [¹³C] metabolite probes in cancer studies. [1–4]

· Real-time monitoring of enzymatic activity. [5, 6]

Chemistry & Catalysis

· Studying fast reactions and catalysis at millisecond-second timescales. [7–9]

· Observing intermediates that normally fall below the NMR detection limit. [10]

Materials Science

· Gaining insights into battery electrolytes degradation. [11]

Biochemistry & Metabolomics

· Characterizing low-concentration metabolites in native biological samples. [12–14]

· Monitoring protein-ligand binding. [15–18]

d-DNP training

More d-DNP training online course in this youtube channel : http://www.youtube.com/@samijannin2161

References:

1. Ardenkjær-Larsen JH, Fridlund B, Gram A, Hansson G, Hansson L, Lerche MH, Servin R, Thaning M, Golman K (2003) Increase in signal-to-noise ratio of > 10,000 times in liquid-state NMR. Proc Natl Acad Sci USA 100:10158–10163. https://doi.org/10.1073/pnas.1733835100

2. Qin H, Tang S, Riselli AM, Bok RA, Delos Santos R, Van Criekinge M, Gordon JW, Aggarwal R, Chen R, Goddard G, Zhang CT, Chen A, Reed G, Ruscitto DM, Slater J, Sriram R, Larson PEZ, Vigneron DB, Kurhanewicz J (2022) Clinical translation of hyperpolarized 13 C pyruvate and urea MRI for simultaneous metabolic and perfusion imaging. Magnetic Resonance in Med 87:138–149. https://doi.org/10.1002/mrm.28965

3. Witney TH, Kettunen MI, Hu D, Gallagher FA, Bohndiek SE, Napolitano R, Brindle KM (2010) Detecting treatment response in a model of human breast adenocarcinoma using hyperpolarised [1-13C]pyruvate and [1,4-13C2]fumarate. Br J Cancer 103:1400–1406. https://doi.org/10.1038/sj.bjc.6605945

4. Gallagher FA, Woitek R, McLean MA, Gill AB, Manzano Garcia R, Provenzano E, Riemer F, Kaggie J, Chhabra A, Ursprung S, Grist JT, Daniels CJ, Zaccagna F, Laurent M-C, Locke M, Hilborne S, Frary A, Torheim T, Boursnell C, Schiller A, Patterson I, Slough R, Carmo B, Kane J, Biggs H, Harrison E, Deen SS, Patterson A, Lanz T, Kingsbury Z, Ross M, Basu B, Baird R, Lomas DJ, Sala E, Wason J, Rueda OM, Chin S-F, Wilkinson IB, Graves MJ, Abraham JE, Gilbert FJ, Caldas C, Brindle KM (2020) Imaging breast cancer using hyperpolarized carbon-13 MRI. Proc Natl Acad Sci USA 117:2092–2098. https://doi.org/10.1073/pnas.1913841117

5. Dos Santos K, Bertho G, Caradeuc C, Baud V, Montagne A, Abergel D, Giraud N, Baudin M (2023) A Toolbox For Glutamine Use In Dissolution Dynamic Nuclear Polarization: From Enzymatic Reaction Monitoring To The Study Of Cellular Metabolic Pathways And Imaging. ChemPhysChem e202300151. https://doi.org/10.1002/cphc.202300151

6. Soussi-Therond M, Guarin D, Razanahoera A, Zhang Y, Baudin M, Miclet E, Giraud N, Abergel D (2024) Simultaneous Observation of the Anomerization and Reaction Rates of Enzymatic Dehydrogenation of Glucose-6-Phosphate by Dissolution DNP. J Am Chem Soc. https://doi.org/10.1021/jacs.4c12904

7. Fukazawa J, Mochizuki Y, Kanai S, Miura N, Negoro M, Kagawa A (2024) Real-Time Monitoring of Hydrolysis Reactions of Pyrophosphates with Dissolution Dynamic Nuclear Polarization. J Phys Chem Lett 7288–7294. https://doi.org/10.1021/acs.jpclett.4c01456

8. Kim Y, Chen C-H, Hilty C (2018) Direct observation of Ru-alkylidene forming into ethylene in ring-closing metathesis from hyperpolarized 1 H NMR. Chem Commun 54:4333–4336. https://doi.org/10.1039/C7CC08135A

9. Zhang G, Schilling F, Glaser SJ, Hilty C (2016) Reaction monitoring using hyperpolarized NMR with scaling of heteronuclear couplings by optimal tracking.

Journal of Magnetic Resonance 272:123–128. https://doi.org/10.1016/j.jmr.2016.09.006

10. Kim J, Kim Y, Luu QS, Kim J, Qi C, Hilty C, Lee Y (2020) Indirect detection of intermediate in decarboxylation reaction of phenylglyoxylic acid by hyperpolarized 13 C NMR. Chem Commun 56:15000–15003. https://doi.org/10.1039/D0CC06331B

11. Gioiosa C, Pokochueva EV, Dieterich J, Tolchard J, Bocquelet C, Ennachet MA, Le N, Veyre L, Montarnal D, Lesage A, Laage S, Pondaven S, Jannin S (2025) Hyperpolarized13 C NMR by Dissolution DNP Enables Snapshot Detection of Degradation Products in Lithium-Ion Battery Electrolytes. J Am Chem Soc 147:19039–19051. https://doi.org/10.1021/jacs.5c03773

12. Dey A, Charrier B, Lemaitre K, Ribay V, Eshchenko D, Schnell M, Melzi R, Stern Q, Cousin SF, Kempf JG, Jannin S, Dumez J-N, Giraudeau P (2022) Fine optimization of a dissolution dynamic nuclear polarization experimental setting for 13 C NMR of metabolic samples. Magn Reson 3:183–202. https://doi.org/10.5194/mr-3-183-2022

13. Ribay V, Dey A, Charrier B, Praud C, Mandral J, Dumez J-N, Letertre MPM, Giraudeau P (2023) Hyperpolarized 13C NMR Spectroscopy of Urine Samples at Natural Abundance by Quantitative Dissolution Dynamic Nuclear Polarization. Angew Chem Int Ed e202302110. https://doi.org/10.1002/anie.202302110

14. Dey A, Charrier B, Martineau E, Deborde C, Gandriau E, Moing A, Jacob D, Eshchenko D, Schnell M, Melzi R, Kurzbach D, Ceillier M, Chappuis Q, Cousin SF, Kempf JG, Jannin S, Dumez J-N, Giraudeau P (2020) Hyperpolarized NMR Metabolomics at Natural 13 C Abundance. Anal Chem 92:14867–14871. https://doi.org/10.1021/acs.analchem.0c03510

15. Kim Y, Hilty C (2015) Affinity Screening Using Competitive Binding with Fluorine‐19 Hyperpolarized Ligands. Angew Chem Int Ed 54:4941–4944. https://doi.org/10.1002/anie.201411424

16. Kim Y, Liu M, Hilty C (2016) Parallelized Ligand Screening Using Dissolution Dynamic Nuclear Polarization. Anal Chem 88:11178–11183. https://doi.org/10.1021/acs.analchem.6b03382

17. Stern Q, Milani J, Vuichoud B, Bornet A, Gossert AD, Bodenhausen G, Jannin S (2015) Hyperpolarized Water to Study Protein–Ligand Interactions. J Phys Chem Lett 6:1674–1678. https://doi.org/10.1021/acs.jpclett.5b00403

18. Cala O, Bocquelet C, Gioiosa C, Torres F, Cousin SF, Guibert S, Ceillier M, Busse V, Decker F, Kempf JG, Elliott SJ, Stern Q, Bornet A, Jannin S (2025) Micromolar Concentration Affinity Study on a Benchtop NMR Spectrometer with Secondary13 C Labeled Hyperpolarized Ligands. ACS Omega 10:3332–3337. https://doi.org/10.1021/acsomega.4c05101

19. Jannin S, Dumez J-N, Giraudeau P, Kurzbach D (2019) Application and methodology of dissolution dynamic nuclear polarization in physical, chemical and biological contexts. Journal of Magnetic Resonance 305:41–50. https://doi.org/10.1016/j.jmr.2019.06.001

20. Jähnig F, Kwiatkowski G, Ernst M (2016) Conceptual and instrumental progress in dissolution DNP. Journal of Magnetic Resonance 264:22–29. https://doi.org/10.1016/j.jmr.2015.12.024

21. Köckenberger W (2014) Dissolution Dynamic Nuclear Polarization. In: Harris RK, Wasylishen RL (eds) eMagRes. John Wiley & Sons, Ltd, Chichester, UK, pp 161–170

22. Plainchont B, Berruyer P, Dumez J-N, Jannin S, Giraudeau P (2018) Dynamic Nuclear Polarization Opens New Perspectives for NMR Spectroscopy in Analytical Chemistry. Anal Chem 90:3639–3650. https://doi.org/10.1021/acs.analchem.7b05236

23. Wang ZJ, Ohliger MA, Larson PEZ, Gordon JW, Bok RA, Slater J, Villanueva-Meyer JE, Hess CP, Kurhanewicz J, Vigneron DB (2019) Hyperpolarized 13 C MRI: State of the Art and Future Directions. Radiology 291:273–284. https://doi.org/10.1148/radiol.2019182391

24. Ribay V, Praud C, Letertre MPM, Dumez J-N, Giraudeau P (2023) Hyperpolarized NMR metabolomics. Current Opinion in Chemical Biology 74:102307. https://doi.org/10.1016/j.cbpa.2023.102307

25. Ardenkjaer-Larsen JH (2016) On the present and future of dissolution-DNP. Journal of Magnetic Resonance 264:3–12. https://doi.org/10.1016/j.jmr.2016.01.015

26. Elliott SJ, Stern Q, Ceillier M, El Daraï T, Cousin SF, Cala O, Jannin S (2021) Practical dissolution dynamic nuclear polarization. Progress in Nuclear Magnetic Resonance Spectroscopy 126–127:59–100. https://doi.org/10.1016/j.pnmrs.2021.04.002