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Nitroxides as metabolic and EPR imaging probes in biological model systems

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Abstract

Nitroxides are unusually stable free radicals and sensitive “reporters” of the chemico-physical environment which surround them. The term “reporter group” was used to indicate this property, later the term spin label or spin probe was preferred. The facile synthesis and the multiplicity of compounds which have been coupled to the nitroxide moiety has allowed the development of a number of applications. Nitroxides have been used to study molecular mobility of proteins and lipids in membranes, enzyme active sites, DNA synthesis, and measure of electrical potential, pH, temperature as well as oxygen gradients across membranes; more recently, as contrast agents in magnetic resonance imaging and electron paramagnetic resonance imaging (EPRI). Aim of this work is to review and comment on the use of various nitroxides as metabolic probes, and in EPRI in studies of biomedical interest.

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References

  1. D. Johnson, M. Rogers, and G. Trappe, J.Chem.Soc. 1093 (1956).

  2. A.K. Hoffman and A.T. Henderson, J. Am. Chem. Soc. 83, 4671 (1961).

    Article  Google Scholar 

  3. E.G. Rozantsev and L.A. Krinitzkaya, Tetrahedron 21 491 (1965).

    Article  CAS  Google Scholar 

  4. E. Burr and D.E. Koshland, Proc. Nat. Acad. Sci. USA 52, 1017 (1964).

    Article  CAS  Google Scholar 

  5. E.G. Rozantsev, Free Nitroxyl Radicals, Plenum Press, New York, London, 1970.

    Google Scholar 

  6. G.T. Likhtenstein, Spin Labeling, Nauka, Moscow, 1974.

    Google Scholar 

  7. G.I. Likhtenstein and R.I. Zhdanov, Biomacromolecules in Spin Labeling, Nauka, Moscow, 1988.

    Google Scholar 

  8. E.G. Rozantsev and R.I. Zhdanov, Nitroxyl Radicals Synthesis, Chemistry and Applications, Nauka, Moscow, 1987,

    Google Scholar 

  9. G.I. Likhtenstein and R.I. Zhdanov, Biomacromolecules in Spin Labeling, Nauka, Moscow, 1988.

    Google Scholar 

  10. L.J. Berliner and J. Reuben (Eds.), Biological Magnetic Resonance, Vol. 8, Plenum Press, New York, 1989.

    Google Scholar 

  11. S. Morris, G. Sosnovsky, B. Hui, C.O. Huber, N.U.M. Rao, and H.M. Swartz, J. Pharmaceutical Sciences 80, 149 (1991).

    Article  CAS  Google Scholar 

  12. L.J. Berliner and J. Reuben (Eds.), Biological Magnetic Resonance, lVol. 13, EMR of Paramagnetic Molecules, Plenum Press, New York, 1993.

  13. A. Iannone and A. Tomasi, Acta Phamaceutica Jugoslavica 41, 277 (1991).

    CAS  Google Scholar 

  14. M. Calvin, H.H. Wang, G. Entine, D. Gill, P. Ferruti, N.A. Harpold, and M.P. Klein, Proc. Natl. Acad. Sci. 63 1 (1969).

    Article  CAS  Google Scholar 

  15. A. Stier and I. Reitz, Xenobiotica, 1, 499 (1971).

    Article  CAS  Google Scholar 

  16. G.M. Rosen, E.J. Rauckman, and K.W. Hank, Tox. Letters, 1 71 (1977).

    Article  CAS  Google Scholar 

  17. J.F.W. Keana, S. Pou, and G.M. Rosen, Mag. Res. Med. 5, 525 (1987).

    Article  CAS  Google Scholar 

  18. A. Iannone, A. Bini, H.M. Swartz, A. Tomasi, and V. Vannini, Biochem. Pharmacol. 38, 2581 (1989).

    Article  CAS  Google Scholar 

  19. A. Iannone, A. Tomasi, V. Vannini, and H.M. Swartz, Biochim. Biophys. Acta 1034, 285 (1990).

    CAS  Google Scholar 

  20. H. Utsumi, A Shimakura, M. Ashigawi, and A. Hamada, J. Biochem. 105, 239 (1989).

    CAS  Google Scholar 

  21. N. Furukawa, H. Nakamura, M. Sato, and Y. Suzuki, Biochem. Pharmacol. 36, 1291 (1987).

    Article  CAS  Google Scholar 

  22. J.S. Wood and B.A. Fowler, Biochem. Pharmacol. 33, 571 (1985).

    Article  Google Scholar 

  23. A.T. Quintanilha and L. Packer, Proc. Natl. Acad. Sci. USA 74, 570 (1977).

    Article  CAS  Google Scholar 

  24. R.J. Mehlhorn and L. Packer, Can. J. Chem. 60, 1452 (1982).

    Article  CAS  Google Scholar 

  25. D.O. Nettleton, P.D.I.I. Morse, W. Dobrucki, H.M. Swartz, and N.J.F. Dodd, Biochim. Biophys. Acta 944, 315 (1988).

    Article  CAS  Google Scholar 

  26. A.T. Quintanilha, L. Packer, Proc. Natl. Acad. Sci. USA 74, 570 (1977).

    Article  CAS  Google Scholar 

  27. K. Chen, P.D.I.I. Morse and H.M. Swartz, Biochim. Biophys. Acta 943, 477 (1988).

    Article  CAS  Google Scholar 

  28. A. Iannone, A. Tomasi, V. Vannini, and H.M. Swartz, Biochim. Biophys. Acta 1034, 290 (1990).

    CAS  Google Scholar 

  29. T. Yoshida, T. Oguro, S. Numazeva, and Y. Kuroiwa, Biochem. Biophys. Res. Commun. 145, 50 (1987).

    Article  Google Scholar 

  30. J. Kaplan, P.G. Canonico, and W.J. Caspary, Proc. Natl. Acad. Sci. USA, 70, 66 (1973).

    Article  CAS  Google Scholar 

  31. K.Y. Chen and M.G. McLaughlin, Biochim. Biophys. Acta. 845, 189 (1985).

    Article  CAS  Google Scholar 

  32. K. Chen and H.M. Swartz, Biochim. Biophys. Acta 970, 270 (1988).

    Article  CAS  Google Scholar 

  33. M. Sentjurc, S. Pecar, K. Chen, M. Wu, and H. Swartz, Biochimica et Biophysica Acta 1073, 329 (1991).

    CAS  Google Scholar 

  34. H.P. Hu, G. Sosnovsky, S.W. Li, N.U.M. Rao, P.D.I.I. Morse, and H.M. Swartz, Biochimica et Biophysica Acta 1014, 211 (1989).

    CAS  Google Scholar 

  35. G. Sosnovsky, M. Poenie, N.U.M. Rao, S.W. Li, and H.M. Swartz, J. Org. Chem. 54, 3667 (1989).

    Article  CAS  Google Scholar 

  36. H.C. Chan, R.L. Magin, and H.M. Swartz, Magn. Reson. Med. 8, 160 (1988).

    Article  CAS  Google Scholar 

  37. H.M. Swartz, M. Sentjurc, and I.I.P.D. Morse, Biochim. Biophys. Acta. 888, 82 (1986).

    Article  CAS  Google Scholar 

  38. A. Iannone, H. Huping, A. Tomasi, V. Vannini, and H.M. Swartz, Biochim. Biophys. Acta 991, 90 (1989).

    CAS  Google Scholar 

  39. U.G. Eriksson, T.N. Tozer, G. Sosnovsky, J. Lukszo, and R.C. Brash, J. Pharmac. Sci. 75, 334 (1986).

    Article  CAS  Google Scholar 

  40. G.P. Pessina, L. Ciccoli, M.P. Picchi, F. Laschi, and G. Fanetti, Zeitschrift für Naturforschung C-A Journal of Biosciences 44, 824 (1989).

    CAS  Google Scholar 

  41. M. Minetti and G. Scorza, Biochimica et Biophysica Acta 1074, 112 (1991).

    CAS  Google Scholar 

  42. M. Kveder, S. Pecar, M. Nemec, and M. Schara,Acta Pharmaceutica Jugoslavica41 (1991).

  43. R.C. Brasch, Radiology 147, 781 (1983).

    CAS  Google Scholar 

  44. L.K. Griffeth, G.M. Rosen, E.J. Rauckman, and B.P. Drayer, Invest. Radiol. 19, 553 (1984).

    Article  CAS  Google Scholar 

  45. U.G. Eriksson, G. Shuhmann, R.C. Brasch, and T.N. Tozer, J. Pharmaceutical Sciences 77, 97 (1988).

    Article  CAS  Google Scholar 

  46. M.G. Wikstrom, M.E. Moseley, D.L. White, J.W. Dupon, J.L. Winkelhake, J. Kopplin, and R.C. Brasch, Investigative Radiology 24, 609 (1989).

    Article  CAS  Google Scholar 

  47. K.U. Schallreuter, M.R. Pittelkow, and J.M. Wood, J. Invest. Dermatol. 87, 728 (1986).

    Article  CAS  Google Scholar 

  48. K.U. Schallreuter, and J.M. Wood, Biochim. Biophys. Res. Commun. 136, 630 (1986).

    Article  CAS  Google Scholar 

  49. K.U. Schallreuter and J.M. Wood, J. Biochim. Biophys. Acta 967, 103 (1988).

    CAS  Google Scholar 

  50. K.U. Schallreuter and J.M. Wood, Free Rad. Biol. Med. 6, 519 (1989).

    Article  CAS  Google Scholar 

  51. K.U. Schallreuter and J.M. Wood, Biochim. Biophys. Acta 967, 103 (1988).

    CAS  Google Scholar 

  52. K.U. Schallreuter, M.R. Pittelkow, and J.M. Wood, Journal of Investigative Dermatology 95, 241 (1990).

    Article  CAS  Google Scholar 

  53. J. Fuchs and K.U. Schallreuter, J. Invest. Dermatol. 91, 92 (1988).

    Article  CAS  Google Scholar 

  54. J. Fuchs, R.J. Mehlhorn, L. Packer, J. Invest. Dermatol. 93, 633 (1989).

    Article  CAS  Google Scholar 

  55. N.P. Konovalova, R.F. Diatchkovskaya, G.V. Kukushkina, L.M. Volkova, V.N. Varfolomeev, L.S. Dombrovsky, and A.B. Shapiro, Neoplasma 35, 185 (1988).

    CAS  Google Scholar 

  56. G.M. Rosen, H.J. Halpern, L.A. Brunstig, D.P. Spencer, K.E. Strauss, M.K. Bowman, and A. Wechsler, Proc. Natl. Acad. Sci. USA 85, 7772 (1988).

    Article  CAS  Google Scholar 

  57. L.J. Berliner, and X. Wan, Magn. Reson. Med. 9, 430 (1989).

    Article  CAS  Google Scholar 

  58. S. Ishida, H. Kumashiro, N. Tsuchihashi, T. Ogata, M. Ono, H. Kamada, and E. Yoshida, Phys. Med. Biol. 34, 1317 (1989).

    Article  CAS  Google Scholar 

  59. M. Ferrari, S. Colacicchi, G. Gualtieri, M.T. Santini, and A. Sotgiu, Biochemical and Biophysical Research Communications 166, 168 (1990).

    Article  CAS  Google Scholar 

  60. S.I. Ishida, S. Matsumoto, H. Yokoyama, N. Mori, H. Kumashiro, N. Tsuchihashi, T. Ogata, M. Yamada, M. Ono, T. Kitajima, H. Kamada, and E. Yoshida, Masn. Reson. Imag. 10, 109 (1992).

    Article  CAS  Google Scholar 

  61. K. Takeshita, H. Utsumi, A. Hamada, Biochem. Biophys. Res. Comm. 177, 874 (1991).

    Article  CAS  Google Scholar 

  62. V. Gabrijelcic, M. Sentjurc, and M. Schara, Periodicum Biologorum 93, 245 (1991).

    Google Scholar 

  63. J. Fuchs, N. Groth, T. Herrling, R. Milbradt, G. Zimmer, and L. Packer, Journal of Investigative Dermatology 98, 713 (1992).

    Article  CAS  Google Scholar 

  64. S. Colacicchi, M. Ferrari, and A. Sotgiu, Int. J. Biochem. 24, 205 (1992).

    Article  CAS  Google Scholar 

  65. M. Alecci, S. Della Penna, A. Sotgiu, L. Testa, and I. Vanucci, Rev. Sci. Instrum. 63, (1993), in press.

  66. V. Quaresima, M. Alecci, M. Ferrari, and A. Sotgiu, Biochem. Biophys. Res. Comm. 183 829 (1992).

    Article  CAS  Google Scholar 

  67. H.F. Bennett, R.D. Brown, III, J.F.W. Keana, S.H. Koening, and H.M. Swartz, Magn. Res. Med. 14, 40 (1990).

    Article  CAS  Google Scholar 

  68. M. Ferrari, S. Colacicchi, G. Gualtieri, M.T. Santini, and A. Sotgiu, Biochem. Biophys. Res. Comm. 166, 168 (1990).

    Article  CAS  Google Scholar 

  69. S. Colacicchi, P.L. Indovina, F. Momo, and A. Sotgiu, J. Phys. E: Sci. Instrum. 21, 910 (1988).

    Article  Google Scholar 

  70. X. Wang, J. Liu, I. Yokoi, M. Kohno, and A. Mori, Free Rad. Biol. Med. 12, 121 (1981).

    Article  Google Scholar 

  71. H. Utsumi, E. Muto, S. Masuda, and A. Hamada, Biochem. Biophys. 172, 1342 (1990).

    Article  CAS  Google Scholar 

  72. M.J. Povich. Anal. Chem. 47, 346 (1975).

    Article  CAS  Google Scholar 

  73. M.J. Povich, J. Phys. Chem. 79, 1106 (1975).

    Article  CAS  Google Scholar 

  74. J.M. Backer, V.G. Budker, S.I. Eremenko, and Yu.N. Molin, Biochim. Biophys, Acta 460, 152 (1977).

    Article  CAS  Google Scholar 

  75. D.A. Windram and W.Z. Plachy, Biochim. Biophys. Acta 600, 655 (1980).

    Article  Google Scholar 

  76. Y. Deguchi, J. Chem. Phys. 32, 1584 (1960).

    Article  CAS  Google Scholar 

  77. K.H. Hausser, Naturwissenschaften 47, 251 (1960).

    Article  CAS  Google Scholar 

  78. M. Tinkham and M.W.P. Strandberg, Phys. Rev. 97, 937 (1955).

    Article  CAS  Google Scholar 

  79. M. Tinkham and M.W.P. Strandberg, Phys. Rev. 97, 951 (1955).

    Article  CAS  Google Scholar 

  80. C.C. Felix, J.S. Hyde, T. Sarna, and R.C. Sealy, J. Am. Chem. Soc. 100, 3922 (1978).

    Article  CAS  Google Scholar 

  81. H.M. Swartz, and M.A. Pals, in J. Miguel, H. Weber, and A. Quintanilha (Eds.), Handbook of Biomedicine of Free Radicals and Antioxidants CRC Press, Boca Raton, Florida, U.S.A., 1989, p. 141.

    Google Scholar 

  82. J.F. Glockner, H.M. Swartz, and M.A. Pals, J. Cell. Physiol 140, 505 (1989).

    Article  CAS  Google Scholar 

  83. T. Prelesnik, F. Demsar, M. Nemec, S. Pecar, and M. Shara, Period. Biol. 88, 185 (1986).

    CAS  Google Scholar 

  84. C.-S. Lai, L.E. Hopwood, J.S. Hyde, and S. Lukiewicz, Proc. Natl. Acad. Sci. U.S.A. 79, 1166 (1982).

    Article  CAS  Google Scholar 

  85. W.K. Subczynski, and J.S. Hyde, Biochim. Biophys. Acta 643, 283 (1981).

    Article  CAS  Google Scholar 

  86. S. Belkin, R.J. Mehlhorn, and L. Packer, Arch. Biochem. Biophys. 252, 487 (1987).

    Article  CAS  Google Scholar 

  87. Strzalka, T. Walczak, T. Sarna, and H.M. Swartz, Arch. Biochem. Biophys. 281, 312 (1990).

    Article  CAS  Google Scholar 

  88. W.K. Subczynski, E. Markowska, and J. Sielewiesiuk, Biochim. et Biophys. Acta 1068, 68 (1991).

    Article  CAS  Google Scholar 

  89. J.S. Hyde and W.K. Subczynski in L.J. Berliner and J. Reuben (Eds.), Biological Magnetic Resonance. Vol. 8, Plenum Press, New York and London, 1989, p. 399.

    Google Scholar 

  90. K. Takeshita, H. Utsumi, and A. Hamada, Biochemistry and Molecular Biology International 29, 17 (1993),

    CAS  Google Scholar 

  91. H.C. Chan, J.F. Glockner, and H.M. Swartz, Biochimica et Biophysica Acta 1014, 141 (1989).

    CAS  Google Scholar 

  92. J.F. Glockner, H.-C. Chan, and H.M. Swartz, Magn. Reson. Med. 20, 123 (1991).

    Article  CAS  Google Scholar 

  93. W.L. Hubbell, W. Froncisz, and J.S. Hyde, Rev. Sci. Instrum. 58, 1879 (1987).

    Article  Google Scholar 

  94. J.J. Jiang, J.F. Bank, W.W. Zhao, and C.P. Scholes, Biochemistry 31, 1331 (1992).

    Article  CAS  Google Scholar 

  95. W. Froncisz, C.-S. Lai, and J.S. Hyde, Proc. Acad. Natl. Sci. USA 82, 411 (1985).

    Article  CAS  Google Scholar 

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  1. Istituto di Patologia generale, Universitá degli Studi di Modena, via Campi 287, 41100, Modena, Italy

    A. Iannone & A. Tomasi

  2. Dipartimento di Scienze e Tecnologie Biomediche, Universitd dell’Aquila, 67100, Collemaggio, L’Aquila, Italy

    V. Quaresima & M. Ferrari

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  1. A. Iannone
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Iannone, A., Tomasi, A., Quaresima, V. et al. Nitroxides as metabolic and EPR imaging probes in biological model systems. Res Chem Intermed 19, 715–731 (1993). https://doi.org/10.1163/156856793X00343

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