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1. Oxidation of benzo[a]pyrene (BP) by I2 in the presence of AgClO4 in benzene generates the BP.+ ClO4- · AgI complex. This same method was used to produce radical cations from 6-FBP, 6-ClBP, 6-BrBP and 6-CH3BP. 2. Reaction of the BP,6-FBP,6-ClBP and 6-BrBP radical cation perchlorates with H2O produced BP 1,6-, 3,6- and 6,12- dione, whereas 6-CH3BP.+ClO4- · AgI yielded 6-CH2OHBP. 3. When BP.+ClO4- · AgI and 6-FBP.+ClO4- · AgI were reacted with NaOAc in H2O/CH3CN (9:1), 6-OAcBP was formed, in addition to the quinones. In the case of 6-CIBP.+ClO4- · AgI, a small amount of 1-OAc-6-ClBP and 3-OAc-6-ClBP was formed in, addition to the diones, whereas for 6-BrBP and 6-CH3BP the reaction products were BP diones and 6-CH2OHBP respectively. 4. These results confirm the localization of charge in the BP.+ at C-6, followed by C-1 and C-3. 5. The reaction of BP with NOBF4 in CH2Cl2 produced BP.+ BF4-, radical cation free of complexation with inorganic salts. 6. Reaction of BP.+BF4- with DNA produced the depurinating adducts BP-6-C8Gua, BP-6-C8dGua and BP-6-N7Gua.

Radial cations of benzopyrene (BP) and 6-substituted derivatives were synthesized by two methods: reaction of the hydrocarbon with I2 and AgClO4 in benzene, and reaction of the hydrocarbon with NOBF4 in CH3CN/CH2Cl2.Both the radical cation perchlorates and tetrafluoroborates were stable for prolonged periods of time when stored under argon at subzero temperatures.The radical cations were reacted with nucleophiles of various strengths, namely H2O, AcO(1-) and F(1-), as a means of best characterizing these intermediates, as well as determining their chemical properties.Reaction of BP, 6-FBP, 6-ClBP, and 6-BrBP radical cation perchlorates with H2O produced BP 1,6-, 3,6-, and 6,12-dione, whereas the radical cation derived from 6-CH3BP yielded 6-CH2OHBP.When BP(.1+)ClO4(1-) and 6-FBP(.1+)ClO4(1-) were reacted with NaOAc in H2O/CH3CN (9:1), 6-OAcBP was formed, in addition to the quinones. 6-ClBP(.1+)ClO4(1-) formed a small amount of 1-OAc-6-ClBP and 3-OAc-6-ClBP, in addition to the diones, whereas for 6-BrBP(.1+)ClO4(1-) and 6-CH3BP(.1+)ClO4(1-) the reaction products were BP diones and 6-CH2OHBP, respectively.Reactions conducted under anhydrous conditions, using tetramethylammonium acetate in CH3CN, gave similar results, except that no quinones were formed.These results confirm the reactivity of nucleophiles at the postions of high charge localization in the BP(.1+), i.e.C-6, followed by C-1 and C-3.

various environmental chemical are metabolised to chemically reactive sulfuric acid esters, which may covalently bind to cellular macromoleculaes and induce mutations and tumours. This activation pathway is usually not taken into account in external xenobiotic-metabolising systems used in short-term tests. We therefore analysed the abilities of cytosols from mammalian cell lines to activate benzylic alcohols (1-hydroxymethylpyrene and 9-hydroxymethylanthracene) to mutagens detectable in Salmonella typhimurium TA98. No activation was observed in cell lines which are commonly used in mutagenicity and cell transformation assays, and only low activities were found in epithelial cell lines in culture. We have therefore constructed Chineses hamster V79-derived cell lines which stably express a heterologous sulfotransferase, rat hydroxysteroid sulfotransferase a. Cytosol of these cells effectively activated 1-hydroxymethylpyrene and 9-hydroxymethylanthracene to mutagens detected in S. pyphimurium. The hepatocarcinogen 6-hydroxymethylbenzopyrene induced gene mutations in sulfotransferase-expressing V79-derived cells, whereas it elicited only marginal effects in sulfotransferase-deficient control cells. The new cell lines may allow the detection of novel classes of mutagens, since some externally generated reactive sulfuric acid esters may not readily penetrate target cells due to their short life span and their ionization. - Keywords: Benzylic alcohols; Bioactivation; Sulfotransferase; Sulfuric acid esters; V79 cells

Radical cations of benzopyrene (BP) and 6-substituted derivatives were generated by one-electron oxidation with 2 equiv of Mn(OAc)3*2H2O.Some of the properties of these radical cations were investigated by nucleophilic trapping with acetate ion.BP produced predominantly 6-OAcBP and small amounts of BP 1,6-, 3,6-, and 6,12-dione. 6-FBP yielded 6-OAcBP, a mixture of 1,6-(OAc)2BP and 3,6-(OAc)2BP, and BP diones.In the case of 6-ClBP and 6-BrBP the major products obtained were a mixture of the 1-OAc and 3-OAc derivatives, and BP diones, while substantial starting material remained unreacted. 6-CH3BP afforded mostly 6-OAcCH2BP, a mixture of 1-OAc and 3-OAc derivatives of 6-CH3BP, and a mixture of 1-OAc and 3-OAc derivatives of 6-OAcCH2BP.These results indicate that nucleophilic substitution of BP-radical-cation and 6-FBP-radical-cation occurs exclusively at C-6.For 6-ClBP-radical-cation and 6-BrBP-radical-cation substitution at C-1 and C-3, which are the positions of second highest charge density in their radical cations after C-6, complete successfully for nucleophilic substitution.For 6-CH3BP-radical-cation charge localization at C-6 activates the methyl group rendering it the most reactive toward nucleophilic attack.Competitive acetoxylation of 6-CH3BP-radical-cation also occurs to a minor extent at C-1 and C-3.These mechanistic studies have been useful in clarifying some aspects of the metabolism of BP and its halogeno derivatives by cytochrome P-450 and peroxidases.Furthermore, this chemistry can provide some guidance in understanding the mechanism of tumor initiation by these compounds.

The EPR spectrum of 6-methylbenzopyrene (6-CH3-BaP) in thallium(III)tris(trifluoroacetate)-trifluoroacetic acid (TTFA/TFA) solutions has been analyzed in terms of the 6-CH3-BaP cation radical with the aid of the ENDOR spectrum.Benzopyren (BaP) in TTFA/TFA gives an EPR and ENDOR spectra which are assigned and analyzed as the 6-(trifluoroacetoxy)benzopyrene cation radical.The EPR of several other 6-substituted BaP's have been investigated in both H2SO4 and TTFA/TFA solutions.Reactions of 6-CH3-BaP and 6-F-BaP in H2SO4 were observed.The EPR spectrum of 6-CH3-BaP(+.) changes over a period of an hour into the spectrum identical with that of 6-CH2OH-BaP(+.).Similarly, the EPR spectrum of 6-F-BaP(+.) in H2SO4 changes to one identical with 6-OH-BaP(+.).These observations are discussed in terms of their possible significance to the metabolic reactions of these compounds.