Reactivity of free and coordinated radicals in biology and chemical carcinogenesis. II. Electron transfer from 3,4-benzopyrene to molecular oxygen and to peroxides, and interpretation of ESR signals of the intermediate radicals of oxidation.

Already a trace of oxygen mediates the one-electron transfer from 3,4-benzopyrene (benzo(a)pyrene, BP) to hydrogen peroxide or to tert. butyl hydroperoxide (ROOH), leading in this way to generation of highly reactive HO X, HO2 X or RO X and RO2 X radicals in nonpolar solvents at biological temperatures. At slightly higher concentration of O2 in solution and at moderately elevated temperature (40-60 degrees C) a stable radical pair (HO-BPO X)2 in equilibrium with its diamagnetic dimer of quinone-hydroquinone type is formed. The paradiamagnetic equilibrium of this redox system is reversibly shifted with temperature. At low temperature (up to -40 degrees C) the paramagnetism disappears. The precursor of the radical pair, which can be decomposed, applying a polar solvent, is the keto form of the hydroxy derivative (6-HO-BP) at ambient temperature. According to the study of highly resolved ESR spectra of the primary temporarily formed ion radical pair [BP+ X O-2 X] of BP oxidation in the dark, of the secondary radical pair (HO-BPO X)2 and of the coordinated unhindered phenoxy radicals of hydroxy derivatives BPO X CoIII, the mechanisms of one-electron or of hydrogen-atom transfer from radical intermediates of BP to potential biological targets is discussed.

Reactivity of free and coordinated radicals in biology and chemical carcinogenity. I. Coordinated phenoxy radicals generated by hydrogen transfer from hydroxy derivatives of 3,4-benzopyrene.

The tautomeric keto form of 6-, 7- and 8-hydroxy-3,4-benzopyrene (BP) prevails in nonpolar solvents at laboratory temperature, in contrast with the enol form of 9-HO-BP and 3-HO-BP, as it was shown according to the ESR study of H-transfer reactions initiated by tert. butyl peroxy radicals coordinated upon the hydroxy derivative of cobalt(III)-acetylacetonate [HO-Co(acac)2]. A further hydroxylation of the keto form of 6-HO-BP, mainly in the position 3, in the thermal interval 40-60 degrees C and the presence of oxygen was observed. Because of lack of steric hindrance in the neighborhood of the position 3 or 9 the primarily formed phenoxy radical after H-abstraction remains stabilized as sigma-coordinated radical on CoIII. Such a radical complex can be destroyed after addition of polar solvents (e.g. methanol). During autooxidation of BP in aerated solutions, similarly as during enzymatic oxidation, a relatively great concentration of high-stable radicals accumulates in nonpolar solvents and in the absence of peroxides. The paramagnetic species is interpreted as a radical pair of two nondissociated semiquinones. In discussion of the carcinogenic activity of oxidative products of BP, not only the enzymatically formed, but also the randomly formed radical intermediates in the first steps of autooxidation must be taken into consideration, which reactivity to biological targets is mediated with the polarity of the biological medium.