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Prediction and Measurement of Redox Properties of Drugs and Biomolecules

  • Peter Wardman
Part of the NATO ASI Series book series (NSSA, volume 198)

Abstract

Selective activation of drugs via redox processes is now firmly established, both at the clinical level with the widespread use of drugs such as metronidazole or chlorpromazine, and at the experimental stage with the search, for example, for hypoxic-specific chemotherapeutic agents active against solid tumours. Ionizing radiation by definition initiates redox processes, so the study of radiation-drug interactions has much to learn from, and contribute to, research with redox-active drugs not involving radiation. Quantitative measures of ease of reduction or of oxidation, of both drugs and biomolecules, are central to our understanding of molecular mechanisms and the search for new drugs. This paper outlines the basis for such measurements, emphasising the value of applying experience from wider fields to provide a framework for reliable prediction of redox properties. Since conventional measures of redox processes involving the transfer of two or more electrons are widely available in electrochemistry and bioenergetics, the redox couples discussed here are restricted to those involving only one electron, with a free radical as reductant or oxidant. Such radicals are increasingly recognised to be obligate intermediates in the activation of many drugs.

Keywords

Reduction Potential Redox Property Pulse Radiolysis Phenoxyl Radical Substituent Constant 
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.

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References

  1. 1.
    P. Wardman, J. Phys. Chem. Ref. Data, 18:1637–1755 (1989).CrossRefGoogle Scholar
  2. 2.
    P. Wardman, Free Rad. Res. Comms. (In press) (1989).Google Scholar
  3. 3.
    P. Wardman, Curr. Topics Radiat. Res. Quart. 11:347–398 (1977).Google Scholar
  4. 4.
    A. Breccia, G. Berrilli, and S. Roffia, Int. J. Radiat. Biol. 36:85–89 (1979).CrossRefGoogle Scholar
  5. 5.
    P. O’Neill, Anal Proc. 282–283 (1980).Google Scholar
  6. 6.
    P. Zuman, Substituent Effects in Organic Polarography, Plenum Press, New York (1967).Google Scholar
  7. 7.
    D.D. Perrin, B. Dempsey and E.P. Serjeant, pKa Prediction for Organic Acids and Bases, Chapman and Hall, London (1981).Google Scholar
  8. 8.
    P. Wardman, in: Advanced Topics on Radiosensitizers of Hypoxic Cells, A. Breccia, C. Rimondi and G.E. Adams, eds. NATO Advanced Study Institute Series A: Life Sciences, Plenum Press, New York, 43:49–75 (1982).CrossRefGoogle Scholar
  9. 9.
    P. Wardman, in Cheraotherapeutic Strategy, D.I. Edwards and D.R. Hiscock, eds. Macmillian, London, 173–192 (1983).Google Scholar
  10. 10.
    B.G. White, Proc. 10th British Weed Control Conf., 997–1007 (1970).Google Scholar
  11. 11.
    J. Lind, X. Shen, T.E. Eriksen and G. Merényi, J. Amer. Chem. Soc. (In press) (1990).Google Scholar
  12. 12.
    P. Neta, M.G. Simic, M.Z. Hoffman, J. Phys. Chem. 80:2018–2023 (1976).CrossRefGoogle Scholar
  13. 13.
    P. Wardman, Int. J. Radiat. Biol. 28:585–588 (1975).CrossRefGoogle Scholar
  14. 14.
    W.R. Wilson, R.F. Anderson and W.A. Denny, J. Med. Chem. 32:23–30 (1989).PubMedCrossRefGoogle Scholar
  15. 15.
    W.A. Denny, B.F. Cain, G.J. Atwell, A. Panthananickal, and A. Leo, J. Med. Chem. 25:276–315 (1982).PubMedCrossRefGoogle Scholar
  16. 16.
    J. Chodkowski and W. Kiwak, Roczniki Chem. 47:157–171 (1973).Google Scholar
  17. 17.
    E.G. Janzen, Acc. Chem. Res. 2:279–288 (1969).CrossRefGoogle Scholar
  18. 18.
    D. Meisel and P. Neta, J. Am. Chem. Soc. 97:5198–5203 (1975).CrossRefGoogle Scholar
  19. 19.
    D. Meisel, Chem. Phys. Lett. 34:263–266 (1975).CrossRefGoogle Scholar
  20. 20.
    P. Wardman and E.D. Clarke, Biophys. Res. Commun. 69:942–949 (1976).CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1990

Authors and Affiliations

  • Peter Wardman
    • 1
  1. 1.Gray Laboratory of the Cancer Research CampaignMount Vernon HospitalMiddx.UK

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