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.
Similar content being viewed by others
References
D. Johnson, M. Rogers, and G. Trappe, J.Chem.Soc. 1093 (1956).
A.K. Hoffman and A.T. Henderson, J. Am. Chem. Soc. 83, 4671 (1961).
E.G. Rozantsev and L.A. Krinitzkaya, Tetrahedron 21 491 (1965).
E. Burr and D.E. Koshland, Proc. Nat. Acad. Sci. USA 52, 1017 (1964).
E.G. Rozantsev, Free Nitroxyl Radicals, Plenum Press, New York, London, 1970.
G.T. Likhtenstein, Spin Labeling, Nauka, Moscow, 1974.
G.I. Likhtenstein and R.I. Zhdanov, Biomacromolecules in Spin Labeling, Nauka, Moscow, 1988.
E.G. Rozantsev and R.I. Zhdanov, Nitroxyl Radicals Synthesis, Chemistry and Applications, Nauka, Moscow, 1987,
G.I. Likhtenstein and R.I. Zhdanov, Biomacromolecules in Spin Labeling, Nauka, Moscow, 1988.
L.J. Berliner and J. Reuben (Eds.), Biological Magnetic Resonance, Vol. 8, Plenum Press, New York, 1989.
S. Morris, G. Sosnovsky, B. Hui, C.O. Huber, N.U.M. Rao, and H.M. Swartz, J. Pharmaceutical Sciences 80, 149 (1991).
L.J. Berliner and J. Reuben (Eds.), Biological Magnetic Resonance, lVol. 13, EMR of Paramagnetic Molecules, Plenum Press, New York, 1993.
A. Iannone and A. Tomasi, Acta Phamaceutica Jugoslavica 41, 277 (1991).
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).
A. Stier and I. Reitz, Xenobiotica, 1, 499 (1971).
G.M. Rosen, E.J. Rauckman, and K.W. Hank, Tox. Letters, 1 71 (1977).
J.F.W. Keana, S. Pou, and G.M. Rosen, Mag. Res. Med. 5, 525 (1987).
A. Iannone, A. Bini, H.M. Swartz, A. Tomasi, and V. Vannini, Biochem. Pharmacol. 38, 2581 (1989).
A. Iannone, A. Tomasi, V. Vannini, and H.M. Swartz, Biochim. Biophys. Acta 1034, 285 (1990).
H. Utsumi, A Shimakura, M. Ashigawi, and A. Hamada, J. Biochem. 105, 239 (1989).
N. Furukawa, H. Nakamura, M. Sato, and Y. Suzuki, Biochem. Pharmacol. 36, 1291 (1987).
J.S. Wood and B.A. Fowler, Biochem. Pharmacol. 33, 571 (1985).
A.T. Quintanilha and L. Packer, Proc. Natl. Acad. Sci. USA 74, 570 (1977).
R.J. Mehlhorn and L. Packer, Can. J. Chem. 60, 1452 (1982).
D.O. Nettleton, P.D.I.I. Morse, W. Dobrucki, H.M. Swartz, and N.J.F. Dodd, Biochim. Biophys. Acta 944, 315 (1988).
A.T. Quintanilha, L. Packer, Proc. Natl. Acad. Sci. USA 74, 570 (1977).
K. Chen, P.D.I.I. Morse and H.M. Swartz, Biochim. Biophys. Acta 943, 477 (1988).
A. Iannone, A. Tomasi, V. Vannini, and H.M. Swartz, Biochim. Biophys. Acta 1034, 290 (1990).
T. Yoshida, T. Oguro, S. Numazeva, and Y. Kuroiwa, Biochem. Biophys. Res. Commun. 145, 50 (1987).
J. Kaplan, P.G. Canonico, and W.J. Caspary, Proc. Natl. Acad. Sci. USA, 70, 66 (1973).
K.Y. Chen and M.G. McLaughlin, Biochim. Biophys. Acta. 845, 189 (1985).
K. Chen and H.M. Swartz, Biochim. Biophys. Acta 970, 270 (1988).
M. Sentjurc, S. Pecar, K. Chen, M. Wu, and H. Swartz, Biochimica et Biophysica Acta 1073, 329 (1991).
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).
G. Sosnovsky, M. Poenie, N.U.M. Rao, S.W. Li, and H.M. Swartz, J. Org. Chem. 54, 3667 (1989).
H.C. Chan, R.L. Magin, and H.M. Swartz, Magn. Reson. Med. 8, 160 (1988).
H.M. Swartz, M. Sentjurc, and I.I.P.D. Morse, Biochim. Biophys. Acta. 888, 82 (1986).
A. Iannone, H. Huping, A. Tomasi, V. Vannini, and H.M. Swartz, Biochim. Biophys. Acta 991, 90 (1989).
U.G. Eriksson, T.N. Tozer, G. Sosnovsky, J. Lukszo, and R.C. Brash, J. Pharmac. Sci. 75, 334 (1986).
G.P. Pessina, L. Ciccoli, M.P. Picchi, F. Laschi, and G. Fanetti, Zeitschrift für Naturforschung C-A Journal of Biosciences 44, 824 (1989).
M. Minetti and G. Scorza, Biochimica et Biophysica Acta 1074, 112 (1991).
M. Kveder, S. Pecar, M. Nemec, and M. Schara,Acta Pharmaceutica Jugoslavica41 (1991).
R.C. Brasch, Radiology 147, 781 (1983).
L.K. Griffeth, G.M. Rosen, E.J. Rauckman, and B.P. Drayer, Invest. Radiol. 19, 553 (1984).
U.G. Eriksson, G. Shuhmann, R.C. Brasch, and T.N. Tozer, J. Pharmaceutical Sciences 77, 97 (1988).
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).
K.U. Schallreuter, M.R. Pittelkow, and J.M. Wood, J. Invest. Dermatol. 87, 728 (1986).
K.U. Schallreuter, and J.M. Wood, Biochim. Biophys. Res. Commun. 136, 630 (1986).
K.U. Schallreuter and J.M. Wood, J. Biochim. Biophys. Acta 967, 103 (1988).
K.U. Schallreuter and J.M. Wood, Free Rad. Biol. Med. 6, 519 (1989).
K.U. Schallreuter and J.M. Wood, Biochim. Biophys. Acta 967, 103 (1988).
K.U. Schallreuter, M.R. Pittelkow, and J.M. Wood, Journal of Investigative Dermatology 95, 241 (1990).
J. Fuchs and K.U. Schallreuter, J. Invest. Dermatol. 91, 92 (1988).
J. Fuchs, R.J. Mehlhorn, L. Packer, J. Invest. Dermatol. 93, 633 (1989).
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).
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).
L.J. Berliner, and X. Wan, Magn. Reson. Med. 9, 430 (1989).
S. Ishida, H. Kumashiro, N. Tsuchihashi, T. Ogata, M. Ono, H. Kamada, and E. Yoshida, Phys. Med. Biol. 34, 1317 (1989).
M. Ferrari, S. Colacicchi, G. Gualtieri, M.T. Santini, and A. Sotgiu, Biochemical and Biophysical Research Communications 166, 168 (1990).
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).
K. Takeshita, H. Utsumi, A. Hamada, Biochem. Biophys. Res. Comm. 177, 874 (1991).
V. Gabrijelcic, M. Sentjurc, and M. Schara, Periodicum Biologorum 93, 245 (1991).
J. Fuchs, N. Groth, T. Herrling, R. Milbradt, G. Zimmer, and L. Packer, Journal of Investigative Dermatology 98, 713 (1992).
S. Colacicchi, M. Ferrari, and A. Sotgiu, Int. J. Biochem. 24, 205 (1992).
M. Alecci, S. Della Penna, A. Sotgiu, L. Testa, and I. Vanucci, Rev. Sci. Instrum. 63, (1993), in press.
V. Quaresima, M. Alecci, M. Ferrari, and A. Sotgiu, Biochem. Biophys. Res. Comm. 183 829 (1992).
H.F. Bennett, R.D. Brown, III, J.F.W. Keana, S.H. Koening, and H.M. Swartz, Magn. Res. Med. 14, 40 (1990).
M. Ferrari, S. Colacicchi, G. Gualtieri, M.T. Santini, and A. Sotgiu, Biochem. Biophys. Res. Comm. 166, 168 (1990).
S. Colacicchi, P.L. Indovina, F. Momo, and A. Sotgiu, J. Phys. E: Sci. Instrum. 21, 910 (1988).
X. Wang, J. Liu, I. Yokoi, M. Kohno, and A. Mori, Free Rad. Biol. Med. 12, 121 (1981).
H. Utsumi, E. Muto, S. Masuda, and A. Hamada, Biochem. Biophys. 172, 1342 (1990).
M.J. Povich. Anal. Chem. 47, 346 (1975).
M.J. Povich, J. Phys. Chem. 79, 1106 (1975).
J.M. Backer, V.G. Budker, S.I. Eremenko, and Yu.N. Molin, Biochim. Biophys, Acta 460, 152 (1977).
D.A. Windram and W.Z. Plachy, Biochim. Biophys. Acta 600, 655 (1980).
Y. Deguchi, J. Chem. Phys. 32, 1584 (1960).
K.H. Hausser, Naturwissenschaften 47, 251 (1960).
M. Tinkham and M.W.P. Strandberg, Phys. Rev. 97, 937 (1955).
M. Tinkham and M.W.P. Strandberg, Phys. Rev. 97, 951 (1955).
C.C. Felix, J.S. Hyde, T. Sarna, and R.C. Sealy, J. Am. Chem. Soc. 100, 3922 (1978).
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.
J.F. Glockner, H.M. Swartz, and M.A. Pals, J. Cell. Physiol 140, 505 (1989).
T. Prelesnik, F. Demsar, M. Nemec, S. Pecar, and M. Shara, Period. Biol. 88, 185 (1986).
C.-S. Lai, L.E. Hopwood, J.S. Hyde, and S. Lukiewicz, Proc. Natl. Acad. Sci. U.S.A. 79, 1166 (1982).
W.K. Subczynski, and J.S. Hyde, Biochim. Biophys. Acta 643, 283 (1981).
S. Belkin, R.J. Mehlhorn, and L. Packer, Arch. Biochem. Biophys. 252, 487 (1987).
Strzalka, T. Walczak, T. Sarna, and H.M. Swartz, Arch. Biochem. Biophys. 281, 312 (1990).
W.K. Subczynski, E. Markowska, and J. Sielewiesiuk, Biochim. et Biophys. Acta 1068, 68 (1991).
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.
K. Takeshita, H. Utsumi, and A. Hamada, Biochemistry and Molecular Biology International 29, 17 (1993),
H.C. Chan, J.F. Glockner, and H.M. Swartz, Biochimica et Biophysica Acta 1014, 141 (1989).
J.F. Glockner, H.-C. Chan, and H.M. Swartz, Magn. Reson. Med. 20, 123 (1991).
W.L. Hubbell, W. Froncisz, and J.S. Hyde, Rev. Sci. Instrum. 58, 1879 (1987).
J.J. Jiang, J.F. Bank, W.W. Zhao, and C.P. Scholes, Biochemistry 31, 1331 (1992).
W. Froncisz, C.-S. Lai, and J.S. Hyde, Proc. Acad. Natl. Sci. USA 82, 411 (1985).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
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
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1163/156856793X00343