Photosensitization by anticancer agents--10. ortho-semiquinone and superoxide radicals produced during anthrapyrazole-sensitized oxidation of catechols.
Photosensitized oxidation of catechol, 3,4-dihydroxybenzoic acid (DHBA), 3,4-dihydroxy-dihydrocinnamic acid (DHCA), and 3,4-dihydroxy-phenylalanine (DOPA) by novel anticancer agents, anthrapyrazoles (AP), has been studied employing EPR and the spin trapping technique. The formation of o-semiquinone radicals, the one-electron oxidation products of the catechols, stabilized in the form of zinc ion complexes, has been demonstrated. Rate constants for the disproportionation of the semiquinone radical/Zn2+ complexes in (DMSO)/acetate buffer (pH 4.5, 1:1 vol/vol; 100 mM Zn2+) mixture have been determined to be 0.35 x 10(4), 14 x 10(4), 8.8 x 10(4) and 3 x 10(4) M-1 s-1 for catechol, DHBA, DHCA and DOPA respectively. The presence of oxygen enhanced rather than inhibited the photogeneration of the o-semiquinone radicals and facilitated their EPR detection. The EPR spectrum of the superoxide radical adduct with the spin trap 5,5-dimethyl-1-pyrroline-N-oxide was observed for the first time during photosensitized oxidation of the catechols in acidic aqueous solutions and in DMSO/acetate buffer mixture.
Reszka
K
K
Laboratory of Molecular Biophysics, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709.
Lown
J W
JW
Chignell
C F
CF
D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic / Q000737:chemistry / Q000494:pharmacology*; D016227:Benzoquinones / Q000737:chemistry / Q000528:radiation effects; D002396:Catechols / Q000737:chemistry / Q000528:radiation effects*; D004578:Electron Spin Resonance Spectroscopy; D005609:Free Radicals; D007700:Kinetics; D010084:Oxidation-Reduction; D010777:Photochemistry; D011838:Radiation-Sensitizing Agents / Q000737:chemistry / Q000494:pharmacology; D013481:Superoxides / Q000737:chemistry / Q000528:radiation effects
D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic; D016227:Benzoquinones; D002396:Catechols; D005609:Free Radicals; D011838:Radiation-Sensitizing Agents; D013481:Superoxides; C025232:semiquinone radicals; C055925:anthrapyrazole