Role of quinone-iron(III) interaction in NADPH-dependent enzymatic generation of hydroxyl radicals.

To study the effect of chelation of iron ions by quinones on the generation of OH radicals in biological redox systems, we have synthesized quinones that can form complexes with Fe(III) ions: 2-phenyl-4-(butylamino)naphtho[2,3-h]quinoline-7,12-dione (Qbc) and 2-phenyl-4-(octylamino)naphtho[2,3-h]quinoline-7,12-dione (Qoc). A quinone with a similar structure without chelating group was synthesized as a control sample: 2-phenyl-5-nitronaphtho[2,3-g]indole-6,11-dione (Qn). Using optical spectroscopy, we determined the stability constant of Qbc with Fe(III) [Ks = (7 +/- 1) x 10(18) M-3] and the stoichiometry of the complex Fe(Qbc)3 in chloroform solutions. One-electron reduction potentials of Qbc, Qn, and adriamycin in dimethyl sulfoxide were measured by cyclic voltammetry. In the presence of Fe(III) the one-electron reduction potentials shifted toward positive values by 0.16 and 0.1 V for Qbc and adriamycin, respectively. Using the spin trap 5,5'-dimethyl-1-pyroline N-oxide (DMPO) and EPR, it was found that Qbc in the Fe(III) complex stimulated the formation of OH radicals in the enzymatic system consisting of NADPH and NADPH-cytochrome P-450 reductase more efficiently than adriamycin and quinone Qn. This is indicated by the absence of a lag period in the spin adduct appearance for Qbc and by a significantly higher rate of the spin adduct production, as well as by a larger absolute concentration of the spin adduct obtained for Qbc in comparison with Qn in the presence of Fe(III).(ABSTRACT TRUNCATED AT 250 WORDS)