Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Accessing long-lived nuclear singlet states between chemically equivalent spins without breaking symmetry

Nature Physics volume 8, pages 831–837 (2012)Cite this article

Subjects

Abstract

Long-lived nuclear spin states could greatly enhance the applicability of hyperpolarized nuclear magnetic resonance. Using singlet states between inequivalent spin pairs has been shown to extend the signal lifetime by more than an order of magnitude compared to the spin lattice relaxation time (T1), but they have to be prevented from evolving into other states. In the most interesting case the singlet is between chemically equivalent spins, as it can then be inherently an eigenstate. However this presents major challenges in the conversion from bulk magnetization to singlet. In the only case demonstrated so far, a reversible chemical reaction to break symmetry was required. Here we present a pulse sequence technique that interconverts between singlet spin order and bulk magnetization without breaking the symmetry of the spin system. This technique is independent of field strength and is applicable to a broad range of molecules.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: The M2S–S2M pulse sequence, all pulses are resonant with the 13C Larmor frequency.
Figure 2: Analogy between population inversion in a single spin 1/2 two-level system and population inversion in the singlet–singlet and triplet–triplet two-level system.
Figure 3: Single scan 13C spectra of DEO–13C2 acquired after the CPMG part of the M2S sequence.
Figure 4: DEO 13C signal from the M2S–τr–S2M sequence decays as a function of the waiting time τr.

Similar content being viewed by others

References

  1. Kurhanewicz, J. et al. Analysis of cancer metabolism by imaging hyperpolarized nuclei: Prospects for translation to clinical research. Neoplasia 13, 81–97 (2011).

    Article  Google Scholar 

  2. Brindle, K. M., Bohndiek, S. E., Gallagher, F. A. & Kettunen, M. I. Tumor imaging using hyperpolarized (13)C magnetic resonance. Magn. Reson. Med. 66, 505–519 (2011).

    Article  Google Scholar 

  3. Viale, A. & Aime, S. Current concepts on hyperpolarized molecules in MRI. Curr. Opin. Chem. Biol. 14, 90–96 (2010).

    Article  Google Scholar 

  4. Golman, K. et al. Silvanus Thompson Memorial Lecture Molecular imaging using hyperpolarized C-13. Br. J. Radiol. 76, S118–S127 (2003).

    Article  Google Scholar 

  5. Golman, K., in’t Zandt, R. & Thaning, M. Real-time metabolic imaging. Proc. Natl Acad. Sci. USA 103, 11270–11275 (2006).

    Article  ADS  Google Scholar 

  6. Oros, A. M. & Shah, N. J. Hyperpolarized xenon in NMR and MRI. Phys. Med. Biol. 49, R105–R153 (2004).

    Article  Google Scholar 

  7. Altes, T. A. & Salerno, M. Hyperpolarized gas MR imaging of the lung. J. Thorac. Imaging 19, 250–258 (2004).

    Article  Google Scholar 

  8. Kauczor, H. U., Surkau, R. & Roberts, T. MRI using hyperpolarized noble gases. Eur. Radiol. 8, 820–827 (1998).

    Article  Google Scholar 

  9. Abragam, A. The Principles of Nuclear Magnetism (Clarendon, 1961).

    Google Scholar 

  10. Warren, W. S., Jenista, E., Branca, R. T. & Chen, X. Increasing hyperpolarized spin lifetimes through true singlet Eigenstates. Science 323, 1711–1714 (2009).

    Article  ADS  Google Scholar 

  11. Vasos, P. R. et al. Long-lived states to sustain hyperpolarized magnetization. Proc. Natl Acad. Sci. USA 106, 18469–18473 (2009).

    Article  ADS  Google Scholar 

  12. Carravetta, M. & Levitt, M. H. Long-lived nuclear spin states in high-field solution NMR. J. Am. Chem. Soc. 126, 6228–6229 (2004).

    Article  Google Scholar 

  13. Carravetta, M., Johannessen, O. G. & Levitt, M. H. Beyond the T-1 limit: Singlet nuclear spin states in low magnetic fields. Phys. Rev. Lett. 92, 153003 (2004).

    Article  ADS  Google Scholar 

  14. Tayler, M. C. D. & Levitt, M. H. Singlet nuclear magnetic resonance of nearly-equivalent spins. Phys. Chem. Chem. Phys. 13, 5556–5560 (2011).

    Article  Google Scholar 

  15. Ahuja, P., Sarkar, R., Vasos, P. R. & Bodenhausen, G. Molecular properties determined from the relaxation of long-lived spin states. J. Chem. Phys. 127, 134112 (2007).

    Article  ADS  Google Scholar 

  16. Pileio, G., Carravetta, M. & Levitt, M. H. Storage of nuclear magnetization as long-lived singlet order in low magnetic field. Proc. Natl Acad. Sci. USA 107, 17135–17139 (2011).

    Article  ADS  Google Scholar 

  17. Sarkar, R., Vasos, P. R. & Bodenhausen, G. Singlet-state exchange NMR spectroscopy for the study of very slow dynamic processes. J. Am. Chem. Soc. 129, 328–334 (2007).

    Article  Google Scholar 

  18. Pileio, G. & Levitt, M. H. Theory of long-lived nuclear spin states in solution nuclear magnetic resonance. II. Singlet spin locking. J. Chem. Phys. 130, 214501 (2009).

    Article  ADS  Google Scholar 

  19. Pileio, G., Carravetta, M. & Levitt, M. H. Extremely low-frequency spectroscopy in low-field nuclear magnetic resonance. Phys. Rev. Lett. 103, 083002 (2009).

    Article  ADS  Google Scholar 

  20. Pileio, G., Carravetta, M., Hughes, E. & Levitt, M. H. The long-lived nuclear singlet state of 15N-nitrous oxide in solution. J. Am. Chem. Soc. 130, 12582–12583 (2008).

    Article  Google Scholar 

  21. Pileio, G. & Levitt, M. H. J-Stabilization of singlet states in the solution NMR of multiple-spin systems. J. Magn. Reson. 187, 141–145 (2007).

    Article  ADS  Google Scholar 

  22. Pileio, G., Concistre, M., Carravetta, M. & Levitt, M. H. Long-lived nuclear spin states in the solution NMR of four-spin systems. J. Magn. Reson. 182, 353–357 (2006).

    Article  ADS  Google Scholar 

  23. Carravetta, M. & Levitt, M. H. Theory of long-lived nuclear spin states in solution nuclear magnetic resonance. I. Singlet states in low magnetic field. J. Chem. Phys. 122, 214505 (2005).

    Article  ADS  Google Scholar 

  24. Jonischkeit, T. et al. Generating long-lasting 1H and 13C hyperpolarization in small molecules with parahydrogen-induced polarization. J. Chem. Phys. 124, 201109 (2006).

    Article  ADS  Google Scholar 

  25. Pople, J. A., Schneider, W. G. & Bernstein, H. J. The Analysis of Nuclear Magnetic Resonance Spectra.2. 2 Pairs of 2 Equivalent Nuclei. Can. J. Chem. 35, 1060–1072 (1957).

    Google Scholar 

  26. Bernstein, H. J., Pople, J. A. & Schneider, W. G. The analysis of nuclear magnetic resonance spectra. 1. Systems of 2 and 3 nuclei. Can. J. Chem. 35, 65–81 (1957).

    Google Scholar 

  27. McConnell, H. M. & Holm, C. H. Anisotropic relaxation and nuclear magnetic relaxation in liquids. J. Chem. Phys. 25, 1289–1289 (1956).

    Article  ADS  Google Scholar 

  28. Bloch, F. & Siegert, A. Magnetic resonance for nonrotating fields. Phys. Rev. 57, 522–527 (1940).

    Article  ADS  Google Scholar 

  29. Levitt, M. H. Composite pulses. Prog. Nucl. Magn. Reson. Spectrosc. 18, 61–122 (1986).

    Article  ADS  Google Scholar 

  30. Hogben, H. J., Krzystyniak, M., Charnock, G. T. P., Hore, P. J. & Kuprov, I. SPINACH—A software library for simulation of spin dynamics in large spin systems. J. Magn. Reson. 208, 179–194 (2011).

    Article  ADS  Google Scholar 

  31. Kuprov, I. Diagonalization-free implementation of spin relaxation theory for large spin systems. J. Magn. Reson. 209, 31–38 (2011).

    Article  ADS  Google Scholar 

  32. Kuprov, I., Wagner-Rundell, N. & Hore, P. J. Polynomially scaling spin dynamics simulation algorithm based on adaptive state-space restriction. J. Magn. Reson. 189, 241–250 (2007).

    Article  ADS  Google Scholar 

  33. Kuprov, I. Polynomially scaling spin dynamics II: Further state-space compression using Krylov subspace techniques and zero track elimination. J. Magn. Reson. 195, 45–51 (2008).

    Article  ADS  Google Scholar 

  34. Redfield, A. G. On the theory of relaxation processes. IBM J. Res. Dev. 1, 19–31 (1957).

    Article  Google Scholar 

  35. Ernst, R. R., Bodenhausen, G. & Wokaun, A. Principles of Nuclear Magnetic Resonance in One and Two Dimensions (Clarendon, 1987).

    Google Scholar 

  36. Vinogradov, E. & Grant, A. K. Long-lived states in solution NMR: Selection rules for intramolecular dipolar relaxation in low magnetic fields. J. Magn. Reson. 188, 176–182 (2007).

    Article  ADS  Google Scholar 

  37. Grant, A. K. & Vinogradov, E. Long-lived states in solution NMR: Theoretical examples in three- and four-spin systems. J. Magn. Reson. 193, 177–190 (2008).

    Article  ADS  Google Scholar 

  38. Hogben, H. J., Hore, P. J. & Kuprov, I. Multiple decoherence-free states in multi-spin systems. J. Magn. Reson. 211, 217–220 (2011).

    Article  ADS  Google Scholar 

  39. Ahuja, P., Sarkar, R., Vasos, P.R. & Bodenhausen, G. Long-lived states in multiple-spin systems. ChemPhysChem 10, 2217–2220 (2009).

    Article  Google Scholar 

  40. Kita, E. & Marai, H. Kinetics and mechanism of base hydrolysis of chromium(III) complexes with oxalates and quinolinic acid. Trans. Metal Chem. 34, 585–591 (2009).

    Article  Google Scholar 

  41. Kowalewski, J. & Maler, L. Nuclear Spin Relaxation in Liquids: Theory, Experiments, and Applications (Taylor and Francis, 2006).

    Book  Google Scholar 

  42. Tayler, M. C. D. & Levitt, M. H. Paramagnetic relaxation of nuclear singlet states. Phys. Chem. Chem. Phys. 13, 9128–9130 (2011).

    Article  Google Scholar 

  43. Mieville, P. et al. Scavenging free radicals to preserve enhancement and extend relaxation times in NMR using dynamic nuclear polarization. Angew. Chem. Int. Ed. 49, 6182–6185 (2010).

    Article  Google Scholar 

  44. Sletten, E. M. & Bertozzi, C. R. From mechanism to mouse: A tale of two bioorthogonal reactions. Acc. Chem. Res. 44, 666–676 (2011).

    Article  Google Scholar 

  45. Frisch, M. J. et al. Gaussian 09, Revision A.1. (Gaussian Inc., 2009).

  46. Deng, W., Cheeseman, J. R. & Frisch, M. J. Calculation of nuclear spin–spin coupling constants of molecules with first and second row atoms in study of basis set dependence. J. Chem. Theory Comput. 2, 1028–1037 (2006).

    Article  Google Scholar 

  47. Peralta, J. E., Barone, V., Contreras, R. H., Zaccari, D. G. & Snyder, J. P. Through-bond and through-space J(FF) spin-spin coupling in peridifluoronaphthalenes: Accurate DFT evaluation of the four contributions. J. Am. Chem. Soc. 123, 9162–9163 (2001).

    Article  Google Scholar 

  48. Sychrovsky, V., Grafenstein, J. & Cremer, D. Nuclear magnetic resonance spin–spin coupling constants from coupled perturbed density functional theory. J. Chem. Phys. 113, 3530–3547 (2000).

    Article  ADS  Google Scholar 

  49. Becke, A. D. Density-functional thermochemistry.3. The role of exact exchange. J. Chem. Phys. 98, 5648–5652 (1993).

    Article  ADS  Google Scholar 

  50. Parr, R. G. Density-Functional Theory of Atoms and Molecules (Clarendon, 1989).

    Google Scholar 

Download references

Acknowledgements

This work is funded by the National Science Foundation (grant CHE-1058727) and the NIH Training in Medical Imaging T32EB001040. We are indebted to I. Kuprov for stimulating discussions and help with the SPINACH simulation package. We thank T. Theis for stimulating discussions on DEO and constructive comments on the manuscript. We also acknowledge the Duke University NMR centre for technical assistance.

Author information

Authors and Affiliations

  1. Department of Chemistry, Duke University, Durham, North Carolina 27708, USA

    Yesu Feng & Warren S. Warren

  2. Center for Molecular and Biomolecular Imaging, Duke University, Durham, North Carolina 27708, USA

    Yesu Feng, Ryan M. Davis & Warren S. Warren

  3. Department of Biomedical Engineering, Duke University, Durham, North Carolina 27708, USA

    Ryan M. Davis

Authors
  1. Yesu Feng
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ryan M. Davis
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Warren S. Warren
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Y.F. designed research, carried out experiments, conducted theoretical simulations and wrote the paper. R.M.D. conducted the hyperpolarized MSM experiment and edited the manuscript. W.S.W. designed research and wrote the paper.

Corresponding author

Correspondence to Warren S. Warren.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Information

Supplementary Information (PDF 539 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Feng, Y., Davis, R. & Warren, W. Accessing long-lived nuclear singlet states between chemically equivalent spins without breaking symmetry. Nature Phys 8, 831–837 (2012). https://doi.org/10.1038/nphys2425

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nphys2425

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing