Theoretical and electrochemical study of the mechanism of anthraquinone-mediated one-electron reduction of oxygen: the involvement of adducts of dioxygen species to anthraquinones

Abstract

Anthraquinone derivatives, which are an important class of anticancer drugs, possess the ability to mediate the transfer of one electron to molecular oxygen to form the superoxide anion radical, which results in their undesirable peroxidating and, further, cardiotoxic properties. In this paper one-electron reduction of dioxygen–anthraquinone systems was studied using electrochemical and theoretical methods. Cyclic voltammetry (CV) experiments performed on dimethyl sulfoxide and dimethylformamide solutions of selected anthraquinones suggest that anthraquinones bearing hydroxy groups or their semiquinones interact remarkably with molecular oxygen; this is manifested as a shift of anthraquinone-reduction potential towards more positive values in the presence of oxygen. This phenomenon can be explained by the assumption that anthraquinone reduction is accompanied with oxygen addition to form hydroperoxide anion radicals, which can be formed by anthraquinones possessing proton-donor (e.g. hydroxy) groups only; the calculated (using the ab initio, DFT and semiempirical PM3 methods, with 1-hydroxynaphthoquinone and model anthraquinone derivatives as model compounds) enthalpies of this process are greater than those of anthraquinone reduction alone.

References

1. J. W. Lown, Chem. Soc. Rev., 1993, 165.
2. J. W. Lown, in Reactive Oxygen Species in Chemistry, Biology, and Medicine, ed. A. Quintanilha, Plenum Press, New York, 1988, pp. 167–185.
3. J. W. Lown, Anthracycline and anthracenedione-based anticancer drugs, Elsevier, Amsterdam, 1988.
4. J. H. Doroshow and K. J. A. Davies, J. Biol. Chem., 1986, 261, 3068.
5. K. J. A. Davies and J. H. Doroshow, J. Biol. Chem., 1986, 261, 3060.
6. E. G. Mimaugh, M. A. Trush and T. M. Gram, Biochem. Pharmacol., 1981, 30, 2797.
7. J. Tarasiuk, A. Garnier-Suillerot and E. Borowski, Biochem. Pharmacol., 1989, 38, 2285.
8. A. Tempczyk, J. Tarasiuk, T. Ossowski and E. Borowski, Anti-Cancer Drug Design, 1988, 2, 371.
9. J. Tarasiuk, A. Liwo, S. Wojtkowiak, M. Dzieduszycka, A. Tempczyk, A. Garnier-Suillerot, S. Martelli and E. Borowski, Anti-Cancer Drug Design, 1991, 6, 399.
10. D. Jeziorek, D. Dyl, A. Liwo, W. Woźnicki, A. Tempczyk and E. Borowski, AntiCancer Drug Design, 1992, 7, 451.
11. D. Jeziorek, D. Dyl, A. Liwo, W. Woźnicki, A. Tempczyk and E. Borowski, Anti-Cancer Drug Design, 1993, 8, 223.
12. D. Jeziorek, D. Dyl, A. Liwo, T. Ossowski and W. Woźnicki, Anti-Cancer Drug Design, 1994, 9, 435.
13. N. R. Bachur, S. R. Gordon and M. V. Gee, Cancer Res., 1978, 38, 1745.
14. E. A. Lissi, M. Encinas, E. Lemp and M. A. Rubio, Chem. Rev., 1993, 93, 699.
15. A. Carmichel, M. M. Mossoba and P. Riesz, FEBS Lett., 1983, 164, 401.
16. J. L. Zweier, J. Biol. Chem., 1983, 259, 6056.
17. L. Gianni, J. L. Zweier, A. Levy and C. E. Myers, J. Biol. Chem., 1985, 260, 6820.
18. M. S. Kharasch and B. S. Joshi, J. Org. Chem., 1957, 22, 1439.
19. M. J. Thomas and C. S. Foote, Photochem. Photobiol., 1978, 27, 683.
20. F. Jensen and C. S. Foote, Photochem. Photobiol., 1987, 46, 325.
21. R. L. Clough, B. G. Yee and C. S. Foote, J. Am Chem. Soc., 1979, 101, 683.
22. P. Dowd, S. W. Ham and S. J. Geib, J. Am. Chem. Soc., 1991, 113, 7734.
23. D. T. Sawyer and E. J. Nanni, in Oxygen and oxy-radicals in chemistry and biology, ed. M. A. J. Rodgers and E. L. Powers, Academic Press, New York, 1982, pp. 15–44.
24. D. J. Schiffrin, in Electrochemistry, ed. D. Pletcher, The Chemical Society, Burlington House, London, 1983, vol. 8, ch. 4.
25. H. Weiss, T. Friedrich, G. Hofhaus and D. Preis, Eur. J. of Biochem., 1991, 197, 563.
26. D. D. Perrin and W. L. F. Armari, Purification of Laboratory Chemicals, Pergamon Press, New York, 1988.
27. J. G. Hanna, in Treatise on Analytical Chemistry, ed. I M Kolthoff and P. J. Elving, Wiley, New York, 1983, Part I, vol. 3., pp. 557–559, and references therein.
28. D. K. Gosser, Jr, Cyclic Voltammetry. Simulation and Analysis of Reaction Mechanisms, VCH Publishers, New York 1993.
29. Z. Galus, Fundamentals of Electrochemical Analysis, Ellis Horwood, New York, PWN, Warsaw, 1994, pp. 294–295.
30. R. L. Audri, A. O. Allen and B. H. Bielski, FEBS Lett., 1981, 135, 265.
31. M. W. Schmidt, K. K. Baldridge, J. A. Boatz, S. T. Elbert, M. S. Gordon, J. J. Jensen, S. Koseki, N. Matsunaga, K. A. Nguyen, S. Su, T. L. Windus, M. Dupuis and J. A. Montgomery, J. Comput. Chem., 1993, 14, 1347.
32. J. Andzelm, in Density Functional Methods in Chemistry, ed. J. K. Labanowski and J. W. Andzelm, Springer, New York, 1993, pp. 155–174.
33. J. J. P. Stewart, J. Comput.-Aided Mol. Design, 1990, 4, 1.
34. J. J. P. Stewart, MOPAC 93.00 Manual. Fujitsu Limited, Tokyo, Japan, 1993.
35. N. E. Heimer, J. T. Swanson and J. J. P. Stewart, QCPE program QCPM 085, modified by Kapsomenos G. QCPE Catalogue, 1991, 23, 41.
36. J. J. Gajewski and K. E. Gilbert, PCMODEL ver. 4.0, Serena Software, Box 3076, Bloomington 1991, Indiana, USA.
37. W. Adam and B. Nestler, J. Am. Chem. Soc., 1993, 115, 5041.
38. K. Fukuhara, Y. Hara and N. Miyata, J. Chem. Soc., Chem. Commun., 1994, 955.
39. A. Klamt and G. Schüürmann, J. Chem. Soc., Perkin Trans. 2, 1993, 799.