195Pt NMR-Fourier Spectroscopy in the Analysis of the Mechanism of the Cytostatic Activity of Platinum Complexes

  • V. E. Stefanov
  • A. A. Tulub
Part of the NATO Science Series book series (NAII, volume 76)


Interaction of platinum complexes with two model targets (polynucleotides of different length and GTP-tubulin) was analyzed by means of 195Pt NMR-Fourier spectroscopy. Slow hydrolysis of cis-dichlorodiamineplatinum (complex I) is followed by rapid binding of the released aqua-form cis-[Pt(NH3)2ClH2O]+ (complex II) with polynucleotides, two signals being recorded at 5 = -1841 and -2304 ppm. Unlike the aqua-form, the monohydroxo-form, cis -[Pt(NH3)2OHCT (complex III), interacts with polynucleotides very slowly. The signal at 6 = -2304 ppm is shifted downfield (5 = -2450 ppm). An agreement between the resonance at 8 = -2450 ppm and that of the tetracoordinated complex of Pt(II) is supported by the resonance of cis-[Pt(NH3)4]2+ in the same spectral region (δ = -2470 ppm). Cyclization of monofunctional adducts of cis- [Pt(NH3)2(N)Cl]+ (IV) into bifunctional adducts is slower than monofunctional binding of the aqua-form (II). Removing cloride ligands with AgNO3 yields cis-[Pt(NH3)2(N)H2O]2+ (complex V), which immediately forms a chelate giving rise to a resonance at δ = -2450 ppm. l95Pt NMR- Fourier spectroscopy analysis of interaction of cis-dichlorodiamineplatinum with tubulin bound GTP showed that originally observed resonance in NMR 195Pt spectra at -2060ppm decreases giving rise to a resonance at -2030ppm, which corresponds to the bidentate coordination of the platinum complex. Mechanisms of action of platinum complexes on the intercellular molecular targets and nature of cytostatic effects of platinum are discussed on the basis of the obtained 195Pt NMR -spectroscopy data.


Platinum Complex Cytostatic Activity Bidentante Coordination Slow Hydrolysis Rapid Binding 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. [1]
    Rosenberg B., van Camp L., Krigas T. (1965). Nature 205, 698.CrossRefGoogle Scholar
  2. [2]
    S. Neidle and M. Waring, editors (1993). Molecular Aspects of Anticancer Drug-DNA interactions. McMillan Press Ltd., London, 169–212.Google Scholar
  3. [3]
    Raynaud F., Boxall F.E., Kelland L.R.(1997). Clin. Cancer Res. 3, 2063.Google Scholar
  4. [4]
    Giandomenico CM., Abrams M.J., Murrer B.A., Vollano J.F., Rheinheimer M.I. (1995) Inorg. Chem. 34, 1015.CrossRefGoogle Scholar
  5. [5]
    Galanski M., Keppler B.K. (1996). Inorg. Chem. 35, 1709.CrossRefGoogle Scholar
  6. [6]
    Wong E., Giandomenico C.M. (1999) Chem.Rev. 99, 2451.CrossRefGoogle Scholar
  7. [7]
    Jamieson E.R., Lippard S.J. (1999) Chem. Rev. 99, 2467.CrossRefGoogle Scholar
  8. [8]
    Reedijk J. (1999) Chem. Rev. 99, 2499.CrossRefGoogle Scholar
  9. [9]
    Mclntoch D.P., Cooke R.J., McLachlan A.J., Daley-Yaks P.T., Rowland M. J. (1997) Pharm. Sci. 86, 1478.CrossRefGoogle Scholar
  10. [10]
    Stefanov V.E., Tulub A.A., Kutin A.A. (1999) International J.Biological Macromolecules, 26, 161CrossRefGoogle Scholar
  11. [11]
    Andreu J.M., Gorbunoff M.J., Medrano F.J., Rossi M., Timasheff S.N. (1991) Biochemistry. 31,: 8080.Google Scholar
  12. [12]
    Medrano F.J., Andreu J.M., Gorbunoff M.J., Timasheff S.N. (1991) Biochemistry. 31, 3770CrossRefGoogle Scholar
  13. [13]
    Wong E., Giandomenico CM. (1999) Chem.Rev. 99, 2451CrossRefGoogle Scholar
  14. [14]
    Neidle S., Snook CF., Murrer B.A., Barnard F.J. (1995) Acta Cryst. 51, 822.CrossRefGoogle Scholar
  15. [15]
    Stefanov V.E., Tulub A.A., Kutin A.A. (2001) International J.Biological Macromolecules, 28, 191CrossRefGoogle Scholar
  16. [16]
    Sherman S.E., Gibson D., Wang A.H., Lippard S.J. (1988) J. Am. Chem. Soc. 110, 7368CrossRefGoogle Scholar
  17. [17]
    Appleton T.G., Bamham K.J., Hall J.R., Mathieson M.T. (1991) Inorg. Chem. 30, 2751CrossRefGoogle Scholar
  18. [18]
    Appleton T.G., Bamham K.J., Byriel K.A., Hall J.R., Kennard C.H.L.. Mathieson M.T., Penman K.G. (1995) Inorg. Chem. 34, 6040CrossRefGoogle Scholar
  19. [19]
    Watabe M., Kobayashi T., Kawahashi T., Hino A., Watanabe T., Mikami T., Matsumoto T., Suzuki M. (1999) J. Inorg. Biochem. 73, 1CrossRefGoogle Scholar
  20. [20]
    Bancroft D.P., Lepre CA., Lippard S.J. (1990) J. Am. Chem. Soc. 112, 6860CrossRefGoogle Scholar
  21. [21]
    Lin Z., Hall M.B. (1991) Inorg. Chem. 30, 646CrossRefGoogle Scholar
  22. [22]
    Barnham K.J., Djuran M.I., Murdoch P.S., Ranford J.D., Sadler P.J. (1996) Inorg. Chem. 35, 1065CrossRefGoogle Scholar
  23. [23]
    Talman E.G, Bruning W., Reedijk J., Spek AL., Veldman N. (1997) Inorg. Chem. 36, 854CrossRefGoogle Scholar
  24. [24]
    Matsunami J., Urata H., Matsumoto K. (1995) Inorg. Chem. 34, 202CrossRefGoogle Scholar
  25. [25]
    O’Halloran T.V., Lippard S.J. (1989) Inorg. Chem. 28, 1289CrossRefGoogle Scholar
  26. [26]
    Kemp W. (1986) NMR in Chemistry. London: McMillan.Google Scholar
  27. [27]
    Bovey F.A., Mirau P.A. (1996) NMR of Polymers. San Diego. Acad. PressGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2002

Authors and Affiliations

  • V. E. Stefanov
    • 1
  • A. A. Tulub
    • 1
  1. 1.Department of BiochemistrySt.Petersburg State UniversitySt.PetersburgRussia

Personalised recommendations