Applied Magnetic Resonance

, Volume 48, Issue 9, pp 933–942 | Cite as

13C Dynamic Nuclear Polarization Using Derivatives of TEMPO Free Radical

  • Peter Niedbalski
  • Christopher Parish
  • Qing Wang
  • Andhika Kiswandhi
  • Lloyd Lumata
Original Paper


The nitroxide-based 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO) free radical is widely used in 13C dynamic nuclear polarization (DNP) due to its relatively low cost, commercial availability, and effectiveness as polarizing agent. While a large number of TEMPO derivatives are available commercially, so far, only few have been tested for use in 13C DNP. In this study, we have tested and evaluated the 13C hyperpolarization efficiency of eight derivatives of TEMPO free radical with different side arms in the 4-position. In general, these TEMPO derivatives were found to have slight variations in efficiency as polarizing agents for DNP of 3 M [1-13C] acetate in 1:1 v/v ethanol:water at 3.35 T and 1.2 K. X-band electron paramagnetic resonance (EPR) spectroscopy revealed no significant differences in the spectral features among these TEMPO derivatives. 2H enrichment of the ethanol:water glassing matrix resulted in further improvement of the solid-state 13C DNP signals by factor of 2 to 2.5-fold with respect to the 13C DNP signal of non-deuterated DNP samples. These results suggest an interaction between the nuclear Zeeman reservoirs and the electron dipolar system via the thermal mixing mechanism.



This work was supported in part by the US Department of Defense Grant Number W81XWH-14-1-0048 and the Robert A. Welch Foundation grant number AT-1877. All DNP experiments were performed at the Advanced Imaging Research Center (AIRC) at the University of Texas Southwestern Medical Center. The AIRC DNP facility is funded by the National Institutes of Health Grant Number 8P41-EB015908.


  1. 1.
    R.W. Darbeau, Appl. Spectrosc. Rev. 41, 401 (2006)ADSCrossRefGoogle Scholar
  2. 2.
    A. Abragam, The Principles of Nuclear Magnetism (Clarendon Press, Wotton-under-Edge, 1961)Google Scholar
  3. 3.
    J.A. Weil, J.R. Bolton, Electron Paramagnetic Resonance: Elementary Theory and Practical Applications (Wiley, New York, 2007)Google Scholar
  4. 4.
    A. Abragam, M. Goldman, Rep. Prog. Phys. 41, 395 (1978)ADSCrossRefGoogle Scholar
  5. 5.
    A.B. Barnes, G.D. Paëpe, P.C.A. van der Wel, K.-N. Hu, C.-G. Joo, V.S. Bajaj, M.L. Mak-Jurkauskas, J.R. Sirigiri, J. Herzfeld, R.J. Temkin, R.G. Griffin, Appl. Magn. Reson. 34, 237 (2008)CrossRefGoogle Scholar
  6. 6.
    J.H. Ardenkjær-Larsen, B. Fridlund, A. Gram, G. Hansson, L. Hansson, M.H. Lerche, R. Servin, M. Thaning, K. Golman, Proc. Natl. Acad. Sci. USA. 100, 10158 (2003)ADSCrossRefGoogle Scholar
  7. 7.
    K.M. Brindle, S.E. Bohndiek, F.A. Gallagher, M.I. Kettunen, Magn. Reson. Med. 66, 505 (2011)CrossRefGoogle Scholar
  8. 8.
    J. Kurhanewicz, D.B. Vigneron, K. Brindle, E.Y. Chekmenev, A. Comment, C.H. Cunningham, R.J. DeBerardinis, G.G. Green, M.O. Leach, S.S. Rajan, R.R. Rizi, B.D. Ross, W.S. Warren, C.R. Malloy, Neoplasia N. Y. N 13, 81 (2011)CrossRefGoogle Scholar
  9. 9.
    S.E. Day, M.I. Kettunen, F.A. Gallagher, D.-E. Hu, M. Lerche, J. Wolber, K. Golman, J.H. Ardenkjaer-Larsen, K.M. Brindle, Nat. Med. 13, 1382 (2007)CrossRefGoogle Scholar
  10. 10.
    M.I.K.F.A. Gallagher, M.I. Kettunen, Prog. Nucl. Magn. Reson. Spectrosc. 55, 285 (2009)CrossRefGoogle Scholar
  11. 11.
    A. Bornet, S. Jannin, J. Magn. Reson. 264, 13 (2016)ADSCrossRefGoogle Scholar
  12. 12.
    K.-N. Hu, Solid State Nucl. Magn. Reson. 40, 31 (2011)ADSCrossRefGoogle Scholar
  13. 13.
    L. Lumata, M.E. Merritt, C.R. Malloy, A.D. Sherry, Z. Kovacs, J. Phys. Chem. A 116, 5129 (2012)CrossRefGoogle Scholar
  14. 14.
    J.H. Ardenkjaer-Larsen, S. Macholl, H. Jóhannesson, Appl. Magn. Reson. 34, 509 (2008)CrossRefGoogle Scholar
  15. 15.
    H. Jóhannesson, S. Macholl, J.H. Ardenkjaer-Larsen, J. Magn. Reson. 197, 167 (2009)ADSCrossRefGoogle Scholar
  16. 16.
    J.H. Ardenkjaer-Larsen, J. Magn. Reson. 264, 3 (2016)ADSCrossRefGoogle Scholar
  17. 17.
    L. Lumata, S.J. Ratnakar, A. Jindal, M. Merritt, A. Comment, C. Malloy, A.D. Sherry, Z. Kovacs, Chem. Eur. J. 17, 10825 (2011)CrossRefGoogle Scholar
  18. 18.
    Y. Zhang, P.J. Baker, L.B. Casabianca, J. Phys. Chem. B 120, 18 (2016)CrossRefGoogle Scholar
  19. 19.
    L. Lumata, M. Merritt, C. Khemtong, S.J. Ratnakar, J. van Tol, L. Yu, L. Song, Z. Kovacs, RSC Adv. 2, 12812 (2012)CrossRefGoogle Scholar
  20. 20.
    L.L. Lumata, M.E. Merritt, C.R. Malloy, A.D. Sherry, J. van Tol, L. Song, Z. Kovacs, J. Magn. Reson. 227, 14 (2013)ADSCrossRefGoogle Scholar
  21. 21.
    L. Lumata, Z. Kovacs, A.D. Sherry, C. Malloy, S. Hill, J. van Tol, L. Yu, L. Song, M.E. Merritt, Phys. Chem. Chem. Phys. 15, 9800 (2013)CrossRefGoogle Scholar
  22. 22.
    J.W. Gordon, S.B. Fain, I.J. Rowland, Magn. Reson. Med. 68, 1949 (2012)CrossRefGoogle Scholar
  23. 23.
    A. Kiswandhi, P. Niedbalski, C. Parish, P. Kaur, A. Martins, L. Fidelino, C. Khemtong, L. Song, A.D. Sherry, L. Lumata. Phys. Chem. Chem. Phys. (2016)Google Scholar
  24. 24.
    A. Kiswandhi, B. Lama, P. Niedbalski, M. Goderya, J. Long, L. Lumata, RSC Adv. 6, 38855 (2016)CrossRefGoogle Scholar
  25. 25.
    P. Niedbalski, C. Parish, A. Kiswandhi, L. Fidelino, C. Khemtong, Z. Hayati, L. Song, A. Martins, A.D. Sherry, L. Lumata, J. Chem. Phys. 146, 014303 (2017)CrossRefGoogle Scholar
  26. 26.
    A. Bornet, R. Melzi, S. Jannin, G. Bodenhausen, Appl. Magn. Reson. 43, 107 (2012)CrossRefGoogle Scholar
  27. 27.
    D. Banerjee, D. Shimon, A. Feintuch, S. Vega, D. Goldfarb, J. Magn. Reson. 230, 212 (2013)ADSCrossRefGoogle Scholar
  28. 28.
    P. Niedbalski, C. Parish, A. Kiswandhi, L. Lumata, Magn. Reson. Chem. 54, 962 (2016)CrossRefGoogle Scholar
  29. 29.
    B. van den Brandt, F. Kurdzesau. J. Phys. Appl. Phys. 41, (2008)Google Scholar
  30. 30.
    P. Miéville, P. Ahuja, R. Sarkar, S. Jannin, P.R. Vasos, S. Gerber-Lemaire, M. Mishkovsky, A. Comment, R. Gruetter, O. Ouari, P. Tordo, G. Bodenhausen, Angew. Chem. 122, 6318 (2010)CrossRefGoogle Scholar
  31. 31.
    C. Song, K.-N. Hu, C.-G. Joo, T.M. Swager, R.G. Griffin, J. Am. Chem. Soc. 128, 11385 (2006)CrossRefGoogle Scholar
  32. 32.
    Y. Matsuki, T. Maly, O. Ouari, H. Karoui, F. LeMoigne, E. Rizzato, S. Lyubenova, J. Herzfeld, T. Prisner, P. Tordo, R.G. Griffin, Angew. Chem. 121, 5096 (2009)CrossRefGoogle Scholar
  33. 33.
    V.S. Bajaj, C.T. Farrar, M.K. Hornstein, I. Mastovsky, J. Vieregg, J. Bryant, B. Eléna, K.E. Kreischer, R.J. Temkin, R.G. Griffin, J. Magn. Reson. 160, 85 (2003)ADSCrossRefGoogle Scholar
  34. 34.
    G. Liu, M. Levien, N. Karschin, G. Parigi, C. Luchinat, M. Bennati, Nat. Chem. 9, 676 (2017)CrossRefGoogle Scholar
  35. 35.
    M. Reese, M.-T. Türke, I. Tkach, G. Parigi, C. Luchinat, T. Marquardsen, A. Tavernier, P. Höfer, F. Engelke, C. Griesinger, M. Bennati, J. Am. Chem. Soc. 131, 15086 (2009)CrossRefGoogle Scholar
  36. 36.
    H. Kobayashi, T. Ueda, K. Miyakubo, T. Eguchi, A. Tani, Phys. Chem. Chem. Phys. 10, 1263 (2008)CrossRefGoogle Scholar
  37. 37.
    G.I. Likhtenshtein, J. Yamauchi, S. Nakatsuji, A.I. Smirnov, R. Tamura, Nitroxides: applications in chemistry, biomedicine, and materials science (Wiley, New York, 2008)CrossRefGoogle Scholar
  38. 38.
    J.S. Hyde, R.A. Strangeway, T.G. Camenisch, J.J. Ratke, W. Froncisz, J. Magn. Reson. San Diego Calif. 1997 (205), 93 (2010)ADSCrossRefGoogle Scholar
  39. 39.
    A.T. Yordanov, K. Yamada, M.C. Krishna, J.B. Mitchell, E. Woller, M. Cloninger, M.W. Brechbiel, Angew. Chem. Int. Ed. 40, 2690 (2001)CrossRefGoogle Scholar
  40. 40.
    Ł. PuŁaski, G. Bartosz, J. Biochem. Biophys. Methods 33, 65 (1996)CrossRefGoogle Scholar
  41. 41.
    D.L. Marshall, M.L. Christian, G. Gryn’ova, M.L. Coote, P.J. Barker, S.J. Barker, Org. Biomol. Chem. 9, 4936 (2011)CrossRefGoogle Scholar
  42. 42.
    B. Brandt, E.I. Bunyatova, P. Hautle, J.A. Konter, Nucl. Instrum. Methods Phys. Res. Sect. Accel. Spectrom. Detect. Assoc. Equip. 526, 53 (2004)ADSCrossRefGoogle Scholar
  43. 43.
    D.A. Hall, D.C. Maus, G.J. Gerfen, S.J. Inati, L.R. Becerra, F.W. Dahlquist, R.G. Griffin, Science 276, 930 (1997)CrossRefGoogle Scholar
  44. 44.
    P. Höfer, P. Carl, G. Guthausen, T. Prisner, M. Reese, T. Carlomagno, C. Griesinger, M. Bennati, Appl. Magn. Reson. 34, 393 (2008)CrossRefGoogle Scholar
  45. 45.
    L. Friesen-Waldner, A. Chen, W. Mander, T.J. Scholl, C.A. McKenzie, J. Magn. Reson. 223, 85 (2012)ADSCrossRefGoogle Scholar
  46. 46.
    S.J. Nelson, J. Kurhanewicz, D.B. Vigneron, P.E.Z. Larson, A.L. Harzstark, M. Ferrone, M. van Criekinge, J.W. Chang, R. Bok, I. Park, G. Reed, L. Carvajal, E.J. Small, P. Munster, V.K. Weinberg, J.H. Ardenkjaer-Larsen, A.P. Chen, R.E. Hurd, L.-I. Odegardstuen, F.J. Robb, J. Tropp, J.A. Murray, Sci. Transl. Med. 5, 198ra108 (2013)CrossRefGoogle Scholar
  47. 47.
    C. Harrison, C. Yang, A. Jindal, R.J. DeBerardinis, M.A. Hooshyar, M. Merritt, A.D. Sherry, C.R. Malloy, NMR Biomed. 25, 1286 (2012)CrossRefGoogle Scholar
  48. 48.
    A. Comment, K. Uffmann, S. Jannin, F. Kurdzesau, R.B. van Heeswijk, H. Frenkel, P. Hautle, J.A. Konter, B. van den Brandt, R. Gruetter, J.J. van der Klink, Proc. Intl. Soc. Mag. Reson. Med. 15, 369 (2007)Google Scholar
  49. 49.
    K. Saito, K. Takeshita, J.-I. Ueda, T. Ozawa, J. Pharm. Sci. 92, 275 (2003)CrossRefGoogle Scholar
  50. 50.
    S.R. Burks, M.A. Makowsky, Z.A. Yaffe, C. Hoggle, P. Tsai, S. Muralidharan, M.K. Bowman, J.P.Y. Kao, G.M. Rosen, J. Org. Chem. 75, 4737 (2010)CrossRefGoogle Scholar
  51. 51.
    L. Lumata, M.E. Merritt, Z. Kovacs, Phys. Chem. Chem. Phys. 15, 7032 (2013)CrossRefGoogle Scholar
  52. 52.
    J. Heckmann, W. Meyer, E. Radtke, G. Reicherz, S. Goertz, Phys. Rev. B 74, 134418 (2006)ADSCrossRefGoogle Scholar
  53. 53.
    S.T. Goertz, Nucl. Instrum. Methods Phys. Res. Sect. Accel. Spectrom. Detect. Assoc. Equip. 526, 28 (2004)ADSCrossRefGoogle Scholar
  54. 54.
    T. Maly, G.T. Debelouchina, V.S. Bajaj, K.-N. Hu, C.-G. Joo, M.L. Mak-Jurkauskas, J.R. Sirigiri, P.C.A. van der Wel, J. Herzfeld, R.J. Temkin, R.G. Griffin, J. Chem. Phys. 128, 052211 (2008)ADSCrossRefGoogle Scholar
  55. 55.
    F. Kurdzesau, B. van den Brandt, A. Comment, P. Hautle, S. Jannin, J.J. van der Klink, J.A. Konter, J. Phys. Appl. Phys. 41, 155506 (2008)ADSCrossRefGoogle Scholar
  56. 56.
    B. Lama, J.H.P. Collins, D. Downes, A.N. Smith, J.R. Long, NMR Biomed. 29, 226 (2016)CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Austria 2017

Authors and Affiliations

  1. 1.Department of PhysicsUniversity of Texas at DallasRichardsonUSA

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