Pyrimidine Nucleobases as Versatile and Multidentate Ligands for Heavy Metal Ions. Significance of Metal Binding to the C(5) Sites of Uracil and Cytosine

  • F. Zamora
  • P. Amo-Ochoa
  • B. Lippert
Part of the NATO ASI Series book series (ASEN2, volume 26)


The N(7) positions of the purine nucleobases guanine and adenine are frequently the principal binding sites for heavy metal ions in double-stranded nucleic acids [1]. These sites are located in the major groove of DNA and therefore are well accessible. For example, the antitumor agent Cisplatin preferentially coordinates to these positions [2, 3]. With denatured nucleic acids, single-stranded oligonucleotides and isolated nucleobases, many more metal binding patterns exist [4]. On the other hand, metal binding to non- purine sites can also occur in paired nucleic acids, examples being Hg(II) (C(5) of uracil or cytosine [5]; N(3) of thymine [6]) or Pb(II) (N(3) of cytosine and 0(4) of uracil) [7]. Even Pt(II), under certain circumstances, can switch from guanine-N(7) to cytosine-N(3)


Metal Binding PyrimIdine NucleoSIde Linkage IsomerizatIon Metal Entity Pyrimidine Nucleobases 
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.
    Martin, R.B. (1996) Dichotomy of Metal Ion Binding to Nl and N7 of Purines, Metal Ions Biol. Syst., 32, 61–89.Google Scholar
  2. 2.
    Lippett, B. (1989) Platinum Nucleobase Chemistry, Prog. Inorg. Chem. 37, 1–97.CrossRefGoogle Scholar
  3. 3.
    Reedijk, J. (1996) Improved Understanding in Platinum Antitumor Chemistry, J. Chem. Soc., Chem. Comm. 801–806.Google Scholar
  4. 4.
    (a) Lusty, J.R. (1990) Handbook of Nucleobase Complexes, Vol. I, CRC Press, Boca Raton, (b) Lusty, J.R., Wearden, P., and Moreno, V. (1992) Handbook of Nucleobase Complexes, Vol. II, CRC Press, Boca Raton.Google Scholar
  5. 5.
    Dale, R.M.K., Martin, E., Livingston, D.C., and Ward, DC. (1975) Direct Covalent Mercunation of Nucleotides and Polynucleotides, Biochemistry, 14, 2447–2457.CrossRefGoogle Scholar
  6. 6.
    Fnφystein, N. A., and Sletten, E. (1994) Interaction of Hg(II) with the DNA Dodecarmer (GCGAATTCGCG), a 1H-and 15N-NMR Study, J. Am. Chem. Soc, 116, 3240–3250.CrossRefGoogle Scholar
  7. 7.
    Brown, R.S., Hingerty, B.E., Dewan, J.C, and Klug, A. (1983) Pb(II)-catalysed cleavage of the sugar-phosphate backbone of yeast tRNAphe-implications for lead toxicity and self-splicing RNA, Nature, 303, 543–546.CrossRefGoogle Scholar
  8. 8.
    (a) Comess, K.M., Costetlo, C.E., and Lippard, S.J. (1990) Identification and Characterization of a Novel Linkage Isomerization in the Reaction of trans-Diamminedichloroplatinum(II) with 5′-d(TCTACGCGTTCT), Biochemistry, 29, 2102–2110. (b) Dalbies, R., Payet, D., and Leng, M. (1994) DNA double helix promotes a linkage isomerization reaction in trans-diamminedichloroplatinum(II)-modified DNA, Proc. Natl. Acad. Sci. USA, 91, 8147-8151.CrossRefGoogle Scholar
  9. 9.
    Bergstrom, D.E., Ruth, J.L., and Warwick, P. (1981) C5-Substituted Pyrimidine Nucleosides. 3. Reaction of Allylic Chlorides, Alcohols, and Acetates with Pyrimidine Nucleoside Derived Organopalladium Intermediates, J. Org. Chem., 46, 1432–1441.CrossRefGoogle Scholar
  10. 10.
    De Clercq, E. (1985) in Approaches to Antiviral Agents, M.R. Harnden ed., VCH, Great Britain.Google Scholar
  11. 11.
    Robertson, M.P., and Miller, S.L. (1995) Prebiotic Synthesis of 5-Substituted Uracils-a Bridge between the RNA World and the DNA-Protein World, Science, 268, 702–705.CrossRefGoogle Scholar
  12. 12.
    Mansy, S., and Tobias, R.S. (1975) Nature of the Reaction between Mercury(II) and Undine or Thymidine. Vibrational Spectroscopy Studies on Binding to N(3), C(4)=O, and C(5) of the Uracil Base, Inorg. Chem. 14, 287.Google Scholar
  13. 13.
    (c) Wrocynski, P., Kujawa, A., and Skulski, L. (1985) Iodo-and Chlorodemercuration of 5, 5′-Mercunbisuracils, Chem. Heterocl. Comp. 21, 323–325. (b) Skulski, L., Kujawa, A., and Kujaba, T. M. (1987) Halodemercuration Reactions of the 1, 3-Dimethyluracil and 1-Methyuracil 5-Substituted Mercunals, Bull. Pol. Acad. Sci. Chem., 35, 499-505.Google Scholar
  14. 14.
    Schöllhorn, H., Thewalt, U., and Lippert, B. (1986) Pt(III) Coordination through C5 of 1-Methyluracil: The First Example of a Pt-Nucleobase Complex Containing a Pt-C Bond, J. Chem. Soc., Chem. Comm., 258–260.Google Scholar
  15. 15.
    Toma, P.H., Dalla Riva Toma, J.M., and Bergstrom, D.E. (1993) Structure of 5-Chloromercuno-2-deoxyuridine, Acta Crystallogr. C49, 2047–2049.Google Scholar
  16. 16.
    Höpp, M., Erxleben, A., Rombeck, I., and Lippert, B. (19%) The Uracil C(5) Position as a Metal Binding Site: Solution and X-ray Crystal Structure Studies of PtII and HgII Compounds, Inorg. Chem, 35, 397–403.CrossRefGoogle Scholar
  17. 17.
    Zamora, F., Sabat, M., and Lippert, B. (1996) (l, 3-Dimethyl-5-yl)mercury(II): Preparative, Structural and NMR Spectroscopic Studies of an Analogue of CH3Hg(II). Inorg. Chem., in press.Google Scholar
  18. 18.
    Micklitz, W., Lippert, B., Lianza, F., and Albinati, A. (1994) Simultaneous binding of soft and hard metals to a pyrimidine nucleobase: preparation and X-ray structure of [(en)Pd(1-MeT)2Na2](NO3)2H2O (l-MeT= 1-methylthymine anion), Inorg. Chim. Acta, 111, 5–10.CrossRefGoogle Scholar
  19. 19.
    (a) Prizant, L., Rivest, R., and Beauchamp, A.L. (1981) Complexes of methylmercury(II) with 1-methylcytosine and crystal structure of n-(l-methylcytosinato-N3, N4)bis(methylmercury(II)) nitrate, Can. J. Chem. 59, 2290–2297. (b) Guay, F., and Beauchamp, A.L. (1982) Role of the Carbonyl Groups in the N3-coordinated Thymine Ring. Crystal Structure of (1-Methylthyminato) methylmercury(II) Hemihydrate and its Mixed Compound with Sodium Nitrate, Inorg. Chim. Acta 66, 57-63.CrossRefGoogle Scholar
  20. 20.
    Schöllhorn, H., Thewalt, U., and Lippert, B. (1989) Metal-Stabilized Rare Tauto-mers of Nucleobases. 2. 2-Oxo-4-hydroxo Form of Uracil: Crystal Structures and Solution Behavior of Two Platinum(II) Complexes Containing Iminol Tautomers of 1-Methyluracil, J. Am. Chem. Soc., 111, 7213–7221.CrossRefGoogle Scholar
  21. 21.
    Krizanovic, O., Sabat, M., Beyerle-Pfnür, R., and Lippert, B. (1993) Metal-Modified Nucleobase Pairs: Mixed Adenine, Thymine Complexes of trans-a2Pt (a= NH3, CH3NH2) with Watson-Crick and Hoogsteen Orientations of the Bases, J. Am. Chem. Soc, 115, 5538–5548.CrossRefGoogle Scholar
  22. 22.
    Schöllhorn, H., Thewalt, U., and Lippert, B. (1984) 1-Methyluracil (Hmeu) as a Tetradentate Ligand: Crystal Structure of trans-(NH3)2Pt(meu)2Ag2(NO3)(H2O)H2O, J. Chem. Soc., Chem. Comm., 769–770.Google Scholar
  23. 23.
    Guay, F., and Beauchamp, A.L. (1985) Preparation, Infrared Spectra, and Crystal Structure of Two Modifications of the (thymidinato-N3)methylmercury(II), Can. J. Chem. 63, 3456–3463.CrossRefGoogle Scholar
  24. 24.
    Canty, S., and Tobias, R.S. (1980) Synthesis and Structure of Methylmercury(II) Complexes of 9-Methylguanine, including the X-Ray Stuctural Analysis of (9-Methylguanine)methylmercury(II) Nitrate. J. Chem. Soc, Dalton Trans. 1693–1697.Google Scholar
  25. 25.
    (a) Zhang, S., and Shepherd, R.E. (1989)η2-1, 3-Dimethyluracil Complexes of Pentaammineruthenium(II) and Pentaammineosmium(II). Inorg. Chim. Acta, 163, 237–243. (b) Zhang, S., Holl, L.A., and Shepherd, R.E. (1990) η2 Coordination of RuII (hedta) at C-5-C-6 Bonds of Cytidine and Undine. Inorg. Chem., 29, 1012-1022. (c) Shepherd, R.E., Zhang, S., Lin, F.-T., and Kortes, R.A. (1992) Influence of 5-Substituent of Uracils and Undines on η2 Coordination of RuII (hedta) at C-5-C-6 Bonds. Inorg. Chem., 31, 1457-1462.CrossRefGoogle Scholar
  26. 26.
    Mealli, C., Pichierri, F., Randaccio, L., Zangrando, E., Krumm, M., Holthennch, D., and Lippert, B. (1995) Theoretical Aspects of the Heteronuclear Dimers with the T over Square Structural Motif. Synthesis and Structure of a Heteronuclear Platinum and Palladium Complex with 1-Methylcytosinato Bridging Ligands, Inorg. Chem., 34, 3418–3424.CrossRefGoogle Scholar
  27. 27.
    Krumm, M., Zangrando, E., Randaccio, L., Menzer, S., and Lippert, B. (1993) Strong Metal-Metal Bonds between of trans-(amine)2Pt and-Pd in Heteronuclear Complexes of Cytosine Nucleobases: Preparation, X-ray Structures, and NMR Spectroscopy, Inorg. Chem., 32, 700–712.CrossRefGoogle Scholar
  28. 28.
    Fusch, G., Fusch, E.C., Erxleben, A., Hüttermann, J., Scholl, H., and Lippert, B. (1996) Heteronuclear μ-1-methylcytosinato, N3, N4 complexes containing very short Pt→Cu dative bonds, Inorg. Chim. Acta, in press.Google Scholar
  29. 29.
    Krumm, M., Zangrando, E., Randaccio, L., Menzer, S., Danzmann, A., Holthenrich, D., and Lippert, B. (1993) Mixed Platinum(II)-Mercury(II) Cytosine Nucleobase Complexes with Metal-Metal Bonds, Inorg. Chem., 32, 2183–2189.CrossRefGoogle Scholar
  30. 30.
    Holthenrich, D., Krumm, M., Zangrando, E., Pichierri, F., Randaccio, L., and Lippert, B. (1995) Cytosine Nucleobase as a Tridentate Ligand: Metal Binding to N(3), N(4) and O(4) in trans-(NH2Me)2Pt(dmcyt)2Ag2][NO3]2(dmcyt= 1, 5-dimethylcytosinate), J. Chem. Soc, Dalton Trans. 3275–3279.Google Scholar
  31. 31.
    Amo-Ochoa, P., Freisinger, E., and Lippert, B., to be published.Google Scholar
  32. 32.
    Rauter, H., Hillgeris, E.C., Erxleben, A., and Lippert, B. (1994) [enPt(uracilate)]4 4+: A Metal Analogue of Calix[4]arene. Similarities and Differences with Classical Calix[4]arenes, J. Am. Chem. Soc, 116, 616–624.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 1997

Authors and Affiliations

  • F. Zamora
    • 1
    • 2
  • P. Amo-Ochoa
    • 1
    • 2
  • B. Lippert
    • 1
  1. 1.Fachbereich ChemieUniversität DortmundDortmundGermany
  2. 2.Departamento de Química InorgánicaUniversidad Autónoma de MadridMadridSpain

Personalised recommendations