Molecular Dynamics of Gd(III) Complexes in Aqueous Solution by HF EPR

  • Alain Borel
  • Lothar Helm
  • André E. Merbach
Part of the Biological Magnetic Resonance book series (BIMR, volume 22)


The study of electron spin relaxation in aqueous Gd(III) complexes is the source of new insights into the physics and chemistry of magnetic resonance imaging (MRI) contrast agents. The coupling of the seven unpaired electrons of the Gd(III) ion with the surrounding water protons observed in MRI is the basis of the contrast agent effectiveness. Therefore, understanding the behavior of the electron spin system can provide valuable information for the development of new compounds. The availability of high frequency electron paramagnetic resonance (HF EPR) spectrometers is vital for complete relaxation studies, and played an important role in improving our knowledge of Gd(III) electron spin relaxation in the last few years. Variable temperature HF EPR has been an invaluable tool to improve our understanding of the underlying relaxation mechanisms.

Key words

relaxation MRI gadolinium zero-field splitting rotational diffusion 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Abernathy, S. M., Miller, J. C., Lohr, L. L. and Sharp, R. R., 1998, Nuclear magnetic resonance-paramagnetic relaxation enhancements: Influence of spatial quantization of the electron spin when the zero-field splitting energy is larger than the Zeeman energy. J. Chem. Phys. 109: 4035–4046.CrossRefGoogle Scholar
  2. Abernathy, S. M. and Sharp, R. R., 1997, Spin dynamics calculations of electron and nuclear spin relaxation times in paramagnetic solutions. J. Chem. Phys. 106: 9032–9043.Google Scholar
  3. Abragam, A., 1961, The Principles of Nuclear Magnetism. Clarendon Press, Oxford. Abragam, A. and Bleaney, B., 1970, Electron Paramagnetic Resonance of Transition Ions. Oxford University Press, Oxford.Google Scholar
  4. Aime, S., Barge, A., Borel, A., Botta, M., Chemerisov, S., Merbach, A. E., Müller, U. and Pubanz, D., 1997a, A Multinuclear NMR Study on the Structure and Dynamics of Lanthanide(III) Complexes of the Poly(amino carboxylate) EGTA¢ in Aqueous Solution. Inorg. Chem. 36: 5104–5112.CrossRefGoogle Scholar
  5. Aime, S., Botta, M., Fasano, M., Marques, M. P. M., Geraldes, C., Pubanz, D. and Merbach, A. E., 1997b, Conformational and Coordination Equilibria on DOTA Complexes of Lanthanide Metal Ions in Aqueous Solution Studied by ‘H-NMR Spectroscopy. lnorg. Chem. 36: 2059–2068.CrossRefGoogle Scholar
  6. Alexander, S., Luz, Z., Naor, Y. and Poupko, R., 1977, Magnetic resonance lineshape in the presence of slow motion. Application of the asymptotic method, and the strong collision limit. Mol. Phys. 33: 1119–1130.CrossRefGoogle Scholar
  7. Atsarkin, V. A., Demidov, V. V. and Vasneva, G. A., 1995, Electron-spin-lattice relaxation in GdBa2Cu3Ox 6 `. Phys. Rev. B 52: 1290–1296.CrossRefGoogle Scholar
  8. Atsarkin, V. A., Demidov, V. V., Vasneva, G. A., Odintsov, B. M., Belford, R. L., Radüchel, B. and Clarkson, R. B., 2001, Direct Measurement of Fast Electron Spin-Lattice Relaxation: Method and Application to Nitroxide Radical Solutions and Gd3+ Contrast Agents. J. Phys. Chem. 105: 9323–9327.CrossRefGoogle Scholar
  9. Bauer, H. 1991, Wahrscheinlichkeitstheorie. de Gruyter, Berlin.Google Scholar
  10. Benetis, N., Kowalewski, J., Nordenskiöld, L., Wennerström, H. and Westlund, P., 1983a, Dipole-dipole nuclear spin relaxation. A cross correlation correction to the Solomon-Bloembergen equation for T2. Mol. Phys. 50: 515–530.CrossRefGoogle Scholar
  11. Benetis, N., Kowalewski, J., Nordenskiöld, L., Wennerström, H. and Westlund, P., 1983b, Nuclear spin relaxation in paramagnetic systems. The slow motion problem for electron spin relaxation. Mol. Phys. 48: 329–346.CrossRefGoogle Scholar
  12. Benetis, N., Kowalewski, J., Nordenskiöld, L., Wennerström, H. and Westlund, P., 1984, Nuclear Spin Relaxation in Paramagnetic Systems (S=1) in the Slow-Motion Regime for the Electron Spin. II. The Dipolar T2 and the Role of Scalar Interaction. J. Magn. Reson. 58: 261–281.Google Scholar
  13. Binsch, G., 1968, Direct method for calculating high-resolution nuclear magnetic resonance spectra. Mol. Phys. 15: 469–478.CrossRefGoogle Scholar
  14. Bloembergen, N., 1957, Proton Relaxation Times in Paramagnetic Solutions. J. Chem. Phys. 27: 572–573.CrossRefGoogle Scholar
  15. Bloembergen, N. and Morgan, L. 0., 1961, Proton Relaxation Times in Paramagnetic Solutions. Effects of Electron Spin Relaxation. J. Chem. Phys. 34: 842–850.Google Scholar
  16. Borel, A., Helm, L. and Merbach, A. E., 2001, Molecular Dynamics Simulations of MRIRelevant Gd(III) Chelates: Direct Access to Outer-Sphere Relaxivity. Chem. Eur. J. 7: 600–610.PubMedCrossRefGoogle Scholar
  17. Borel, A., Helm, L., Merbach, A. E., Atsarkin, V. A., Demidov, V. V., Odintsov, B. M., Belford, R. L. and Clarkson, R. B., 2002a, Tie in four Gd3+ Chelates: LODEPR Measurements and Models for Electron Spin Relaxation. J. Phys. Chem. A 106: 6229–6231.Google Scholar
  18. Borel, A., Toth, E., Helm, L. and Merbach, A. E., 2000, EPR on aqueous Gd3+ complexes and a new analysis method considering both line. Phys. Chem. Chem. Phys. 2: 1311 1317.Google Scholar
  19. Borel, A., Yerly, F., Helm, L. and Merbach, A. E., 2002b, Multiexponential Electronic Spin Relaxation and Redfield’s Limit in Gd(III) Complexes in Solution: Consequences for 17011H NMR and EPR Simultaneous Analysis. J. Am. Chem. Soc. 124: 2042–2048.PubMedCrossRefGoogle Scholar
  20. Buckmaster, H. A., Chatterjee, R. and Shing, Y. H., 1972, Application of tensor operators in the analysis of EPR and ENDOR [electron nuclear double resonance] spectra. Phys. Status Solidi (a) 13: 9–50.CrossRefGoogle Scholar
  21. Caravan, P., Ellison, J. J., Mcmurry, T. J. and Lauffer, R. B., 1999a, Gadolinium(III) chelates as MRI contrast agents: Structure, dynamics, and applications. Chem. Rev. 99: 2293–2352.PubMedCrossRefGoogle Scholar
  22. Caravan, P., Toth, E., Rockenbauer, A. and Merbach, A. E., 1999b, Nuclear and Electronic Relaxation of Eue+(aq): An Extremely Labile Aqua Ion. J. Am. Chem. Soc. 121: 10403–10409.CrossRefGoogle Scholar
  23. Clarkson, R. B., Smimov, A. I., Smirnova, T. I., Kang, H., Belford, R. L., Earle, K. and Freed, J. H., 1998, Multi-frequency EPR determination of zero field splitting of high spin. Mol. Phys. 95: 1325–1332.CrossRefGoogle Scholar
  24. Connolly, M. L., 1983, Analytical molecular surface calculation. J. Appl. Cryst. 16: 548–558.CrossRefGoogle Scholar
  25. Cossy, C., Helm, L., Powell, D. H. and Merbach, A. E., 1995, A change in coordination number from nine to eight along the lanthanide(III) aqua ion series in solution: A neutron diffraction study. New J. Chem. 19: 27–35.Google Scholar
  26. Curl, R. F. J., 1965, Relation between electron spin rotation coupling constants and g-tensor components. Mol. Phys. 9: 585–597.CrossRefGoogle Scholar
  27. Dunand, F. A., T6th, E., Hollister, R. and Merbach, A. E., 2001, Lipari-Szabo approach as a tool for the analysis of macromolecular gadolinium(III)-based MRI contrast agents illustrated by the [Gd(EGTA-BA-(CH2)12)]nn+ polymer. J. Biol. Inorg. Chem. 6: 247–255.PubMedCrossRefGoogle Scholar
  28. Fraenkel, G. K., 1965, Static and Dynamic Frequency Shifts in Electron Spin Resonance Spectra. J. Chem. Phys. 42: 4275–7298.CrossRefGoogle Scholar
  29. Fraenkel, G. K., 1967, Line widths and frequency shifts in electron spin resonance spectra. J. Chem. Phys. 71: 139–171.CrossRefGoogle Scholar
  30. Freed, J. H., 1978, Dynamic effect of pair correlation functions on spin relaxation by translational diffusion in liquids. II. Finite jumps and independent T1 processes. J. Chem. Phys. 69: 4034–4037.CrossRefGoogle Scholar
  31. Gonzalez, G., Powell, D. H., Tissieres, V. and Merbach, A. E., 1994, Water-exchange, electronic relaxation, and rotational dynamics of the MRI contrast agent [Gd(DTPABMA)(H2O)] in aqueous solution: a variable pressure, temperature, and magnetic field oxygen-17 NMR study. J. Phys. Chem. 98: 53–59.CrossRefGoogle Scholar
  32. Handbook of Chemistry and Physics,1986, 67`h edition edition. CRC Press, Boca Raton. Hengrasmee, S. and Probst, M. M., 1991, A Study of Hydrated Rare Earth Ions. Z Naturforsch 46a: 117–121.Google Scholar
  33. Hudson, A. and Lewis, J. W., 1970, Electron Spin Relaxation of 8S Ions in Solution. Trans. Faraday Society 66: 1297–1301.CrossRefGoogle Scholar
  34. Hutchinson, C. A. J. and Wong, E., 1958, Paramagnetic Resonance in Rare Earth Trichlorides. J. Chem. Phys. 29: 754–760.CrossRefGoogle Scholar
  35. Hwang, L. and Freed, J. H., 1975, Dynamic effects of pair correlation functions on spin relaxation by translational diffusion in liquids. J. Chem. Phys. 63: 4017–4025.Google Scholar
  36. Kannan, D., 1979, An introduction to stochastic processes. Elsevier North Holland, New York.Google Scholar
  37. Kowalewski, J., Nordenskiöld, L., Benetis, N. and Westlund, P., 1985, Theory of Nuclear Spin Relaxation in Paramagnetic Systems in Solution. Prog. in NMR Spectroscopy 17: 141–185.Google Scholar
  38. Kurisaki, T., Yamaguchi, T. and Wakita, H., 1993, Effect of temperature on the structure of hydrated lanthanide(III) ions in crystals and in solution. J. Alloys and Compounds 192: 293–295.CrossRefGoogle Scholar
  39. Lebedev, Y. S., 1990, Modern Pulsed and Continuous-Wave Electron Spin Resonance ed L Kevan and M K Bowman (New York: Wiley) pp 365–404. In Modern Pulsed and Continuous-Wave Electron Spin Resonance (ed. L. Kevan and M. K. Bowman ). Wiley, New York.Google Scholar
  40. MATLAB. (2000). The MathWorks Inc.Google Scholar
  41. Merbach, A. E. and Toth, É. 2001, The Chemistry of Contrast Agents in Medical Magnetic Resonance Imaging, 1’ edition. John Wiley Sons, Chichester.Google Scholar
  42. Micskei, K., Powell, D. H. Helm, L., Brticher, E. and Merbach, A. E., 1993, Water Exchange on Gd(H2O)83+ and Gd(Pdta)(H2O)2- in Aqueous Solution–A Variable-Pressure, -Temperature and–Magnetic Field 0–17 NMR Study. Magn. Reson. Chem. 31: 1011–1020.Google Scholar
  43. Nilsson, T. and Kowalewski, J., 2000, Low-field theory of nuclear spin relaxation in paramagnetic low-symmetry complexes for electron spin systems of S = 1, 3/2, 2, 5/2, 3 and 7/2. Mol. Phys. 98: 1617–1638.CrossRefGoogle Scholar
  44. Nyberg, G., 1967, Spin-rotational relaxation in solution E.S.R. Mol. Phys. 12: 69–81. Poupko, R., Baram, A. and Luz, Z., 1974, Dynamic frequency shift in the ESR spectra of transition metal ions. Mol. Phys. 27: 1345–1357.Google Scholar
  45. Powell, D. H., Merbach, A. E., Gonzalez, G., Brticher, E., Micskei, K., Ottaviani, M. F., Köhler, K., Von Zelewsky, A., Grinberg, O. Y. and Lebedev, Y. S., 1993, Magneticfield-dependent electronic relaxation of gadolinium(3+) in aqueous solutions of the complexes [Gd(H2O)8]3+, [Gd(propane-1,3-diamine-N,N,N’,N’-tetraacetate)(H2O)2r, and Gd(N,N’-bis[(N-methylcarbamoyl)methyl]-3-azapentane-1,5-diamine-3,N,N’triacetate)(H20)] of interest in magnetic-resonance imaging. Hely. Chim. Acta 76: 2129–2146.CrossRefGoogle Scholar
  46. Powell, D. H., Ni Dhubhghaill, O. M., Pubanz, D., Helm, L., Lebedev, Y. S., Schlaepfer, W. and Merbach, A. E., 1996, Structural and dynamic parameters obtained from O17 NMR, EPR, and NMRD studies of monomeric and dimeric Gd3+ complexes of interest in magnetic resonance imaging–an integrated and theoretically self consistent approach. J. Am. Chem. Soc. 118: 9333–9346.CrossRefGoogle Scholar
  47. Rast, S., Belorizky, E., Fries, P. H. and Travers, J. P., 2001a, Mechanisms of the intermolecular nuclear magnetic relaxation dispersion of the (CH3)4N+ protons in Gd3+ heavy-water solutions. Interrest for the theory of magnetic resonance imaging. J. Phys. Chem. B 105: 1978–1983.CrossRefGoogle Scholar
  48. Rast, S., Borel, A., Helm, L., Belorizky, E., Fries, P. H. and Merbach, A. E., 2001b, EPR Spectroscopy of MRI-related Gd(III) Complexes: Simultaneous analysis of Multiple Frequency and Temperature Spectra, Including Static and Transient Crystal Field Effects. J. Am. Chem. Soc. 123: 2637–2644.PubMedCrossRefGoogle Scholar
  49. Rast, S., Fries, P. H. and Belorizky, E., 1999, Theoretical study of electronic relaxation processes in hydrated Gd3+ complexes in solutions. J. Chim. Phys. 96: 1543–1550.Google Scholar
  50. Rast, S., Fries, P. H. and Belorizky, E., 2000, Static zero field splitting effects on the electronic relaxation of paramagnetic metal ion complexes in solution. J. Chem. Phys. 113: 8724–8735.Google Scholar
  51. Rast, S., Fries, P. H., Belorizky, E., Borel, A., Helm, L. and Merbach, A. E., 2001c, A general approach to the electronic spin relaxation of Gd(III) complexes in solutions. Monte Carlo simulations beyond the Redfield limit. J. Chem. Phys. 115: 7554–7563.Google Scholar
  52. Redfield, A. G., 1965, The Theory of Relaxation Processes. In Advan. Magn. Resonance (ed. J. S. Waugh ), pp. 1–32. Academic Press Inc, Ney York.Google Scholar
  53. Reuben, J., 1971, Electron spin relaxation in aqueous solutions of Gadolinium(III). Aquo, Cacodylate, and Bovin Serum Albumine Complexes. J. Phys. Chem. 75: 3164–3167.CrossRefGoogle Scholar
  54. Rubinstein, M., Baram, A. and Luz, Z., 1971, Electronic and Nuclear Relaxation in Solutions of Transition Metal Ions with Spin S=3/2 and 5/2. Mol. Phys. 20: 67–60.CrossRefGoogle Scholar
  55. Schafer, O. and Daul, C., 1997, Modeling of the hydration sphere of gadolinium(III) ion using density functional theory. J. Quant. Chem. 61: 541–546.CrossRefGoogle Scholar
  56. Smirnova, T. I., Smirnov, A. I., Belford, R. L. and Clarkson, R. B., 1998, Lipid Magnetic Resonance Imaging Contrast Agent Interactions: A Spin-Labeling and a Multifrequency EPR Study. J. Am. Chem. Soc. 120: 5060–5072.Google Scholar
  57. Smith, M. R., Shing, Y. H., Chatterjee, R. and Buckmaster, H. A., 1977, Ethyl sulfate host lattice effects in the EPR spectra of gadolinium(3+) ions. II. J. Magn. Reson. 36: 351–363.Google Scholar
  58. Strandberg, E. and Westlund, P., 1996, 1H NMRD profile and ESR lineshape calculation for an isotropic electron spin system with S = 7/2. A generalized modified SolomonBloembergen-Morgan theory for nonextreme-narrowing conditions. J. Magn. Reson. A 122: 179–191.Google Scholar
  59. Strandberg, E. and Westlund, P., 1999, Paramagnetic proton nuclear spin relaxation theory of low-symmetry complexes for electron spin quantum number S = 5/2. J. Magn. Reson. 137: 333–344.Google Scholar
  60. Struis, R. P. W. J., De Bleijser, J, and Leyte, J. C., 1987, An NMR contribution to the interpretation of the dynamial behavior of water molecules as a function of the magnesium chloride concentration at 25°C. J. Phys. Chem. 91: 6309–6315.CrossRefGoogle Scholar
  61. Swift, T. J. and Connick, R. E., 1962, NMR-Relaxation Mechanisms of 170 in Aqueous Solutions of Paramagnetic Cations and the Lifetime of Water Molecules in the First Coordination Sphere. J. Chem. Phys. 37: 307–320.CrossRefGoogle Scholar
  62. Vigouroux, C., Bardet, M., Belorizky, E. and Fries, P. H., 1998, Nuclear and electronic relaxation in lanthanide solutions: (CH3)4N+/Gd3+ repulsive ion pair in D2O. Chem. Phys. Lett. 286: 93–100.CrossRefGoogle Scholar
  63. Vigouroux, C., Belorizky, E. and Fries, P. H., 1999, NMR approach of the electronic properties of the hydrated trivalent rare. Eur. Phys. J. D 5: 243–255.Google Scholar
  64. Yerly, F. (2001). VISUALISEUR. EPFL, Lausanne.Google Scholar

Copyright information

© Springer Science+Business Media New York 2004

Authors and Affiliations

  • Alain Borel
    • 1
  • Lothar Helm
    • 1
  • André E. Merbach
    • 1
  1. 1.Institute of Molecular and Biological ChemistrySwiss Federal Institute of Technology - Lausanne, EPFL — BCHLausanneSwitzerland

Personalised recommendations