Ring Oxidation Products Research Articles

Revealing the intrinsic mechanism of the influence of different rings and oxidized structures on the room temperature phosphorescence

In this work, we used density functional theory (DFT) and time-dependent density functional theory (TD-DFT) methods to study the mechanism of pure organic room temperature phosphorescence emission. The effects on the electronic structure and photochemical properties of thiophene and diketone derivatives with different cyclic and oxidized structures. The result suggests that varying ring configurations and oxidation products significantly influence the photochemical characteristics of thiophene and diketone derivatives. The complex experiences conformational distortion along with the oxidation product, which causes notable alterations in the energy gap and charge density of its frontier molecular orbitals. An oxidation process significantly distorts the molecular structure of the compound, leading to excited singlet and excited triplet states structural similarities. With energy gaps dropping from 0.22 eV to 0.05 eV and spin–orbit coupling constants rising from 0.42 cm−1 to 57.48 cm−1, the excited singlet and excited triplet states share structures and charge distributions that increase the energy level channels appropriate for intersystem crossing. Therefore, this work can provide theoretical support for the design and structural optimization of highly efficient pure organic phosphorescent materials.

Oxidation of 3’-methoxyflavone, 4’-methoxyflavone, and 3’,4’-dimethoxyflavone and their derivatives having 5,7-dihydroxyl moieties by human cytochromes P450 1B1 and 2A13

Oxidation of 3’-methoxyflavone, 4’-methoxyflavone, and 3’,4’-dimethoxyflavone and their derivatives containing 5,7-dihydroxyl groups by human cytochrome P450 (P450 or CYP) 1B1 and 2A13 was determined using LC-MS/MS systems. 3’-Methoxyflavone and 4’-methoxyflavone were mainly O-demethylated to form 3’-hydroxyflavone and 4’-hydroxyflavone, respectively, and then 3’,4’-dihydroxyflavone at higher rates with CYP1B1 than with CYP2A13. 4’-Methoxy-5,7-dihydroxyflavone (acacetin) was found to be demethylated by CYP1B1 and 2A13 to form 4’,5,7-trihydroxyflavone (apigenin) at rates of 0.098−1 and 0.42 min−1, respectively. 3’-Methoxy-5,7-dihydroxyflavone was also demethylated by both P450s, with CYP2A13 being more active. 3’,4’-Dimethoxyflavone was a good substrate for CYP1B1 but not for CYP2A13 and was found to be mainly O-demethylated to form 3’,4’-dihydroxyflavone (at a rate of 4.2 min−1) and also several ring-oxygenated products having m/z 299 fragments. Molecular docking analysis supported the proper orientation for formation of these products by CYP1B1. Our present results showed that 3’- and 4’-methoxyflavone can be oxidised to their O-demethylated products and, to a lesser extent, to ring oxidation products by both P450s 1B1 and 2A13 and that 3’,4’-dimethoxyflavone is a good substrate for CYP1B1 in forming both O-demethylated and ring-oxidation products. Introduction of a 57diOHF moiety into these methoxylated flavonoids caused decreased in oxidation by CYP1B1 and 2A13.

Preference for O-demethylation reactions in the oxidation of 2′-, 3′-, and 4′-methoxyflavones by human cytochrome P450 enzymes

2′-, 3′-, and 4′-Methoxyflavones (MeFs) were incubated with nine forms of recombinant human cytochrome P450 (P450 or CYP) enzymes in the presence of an NADPH-generating system and the products formed were analyzed with LC-MS/MS methods.CYP1B1.1 and 1B1.3 were highly active in demethylating 4′MeF to form 4′-hydroxyflavone (rate of 5.0 nmol/min/nmol P450) and further to 3′,4′-dihydroxyflavone (rates of 2.1 and 0.66 nmol/min/nmol P450, respectively). 3′MeF was found to be oxidized by P450s to m/z 239 (M-14) products (presumably 3′-hydroxyflavone) and then to 3′,4′-dihydroxyflavone. P450s also catalyzed oxidation of 2′MeF to m/z 239 (M-14) and m/z 255 (M-14, M-14 + 16) products, presumably mono- and di-hydroxylated products, respectively.At least two types of ring oxidation products having m/z 269 fragments were formed, although at slower rates than the formation of mono- and di-hydroxylated products, on incubation of these MeFs with P450s; one type was products oxidized at the C-ring, having m/z 121 fragments, and the other one was the products oxidized at the A-ring (having m/z 137 fragments).Molecular docking analysis indicated the preference of interaction of O-methoxy moiety of methoxyflavones in the active site of CYP1A2.These results suggest that 2′-, 3′-, and 4′-methoxyflavones are principally demethylated by human P450s to form mono- and di-hydroxyflavones and that direct oxidation occurs in these MeFs to form mono-hydroxylated products, oxidized at the A- or B-ring of MeF.

Transformation of alkylbenzenes in an oxidizing medium on H-ZSM-5 catalyst under supercritical conditions

Reactions of the substituted benzenes toluene, p-xylene, fluorobenzene, phenol, cumene and styrene with nitrous oxide as an oxidant on H-ZSM-5 catalyst under supercritical conditions at 345–420°C and 70–150 atm were studied. It is shown that the products of disproportionation, isomerization and condensation that do not contain oxygen form predominantly. Only in the oxidation of toluene does the selectivity to the oxidation product (cresols) reach 35%. The yield of corresponding phenols in the oxidation of alkyl-, hydroxy- and fluorobenzenes is negligible. The double bond conjugated with the π-system of benzene rings (styrene), as well as the presence of branched alkyl substituents (in cumene) and hydroxyl-group (in phenol) hinder the formation of benzene ring oxidation products.

Mechanisms of Degradation of the Natural High-Potency Sweetener (2R,4R)-Monatin in Mock Beverage Solutions

The sodium, potassium, or mixed sodium/potassium salt of the naturally occurring high-potency sweetener (2R,4R)-monatin, also known by the common name arruva, degrades over time in model beverage solutions in the presence of light. By use of UHPLC, LC-MS/MS, and peroxide assays, it has been demonstrated that degradation is accelerated by UV/visible light and the presence of trace metal ions. Data are presented that are consistent with a role for singlet oxygen (¹O₂), free radicals, and peroxides (both H₂O₂ and organic peroxides) in monatin oxidation. Separation of degradation products by UHPLC/HPLC or LC-MS/MS provided evidence for the formation of hydroxylated and peroxide species formed on the indole ring (mass increases 16 and 32, respectively) as well as multiple ring and side-chain oxidation and scission products. Model oxidation systems using the photosensitizer Rose Bengal as a source of ¹O₂ support the proposed photodegradation pathways.

Identification of potential biomarkers of exposure to di(isononyl)cyclohexane-1,2-dicarboxylate (DINCH), an alternative for phthalate plasticizers

Di(isononyl)cyclohexane-1,2-dicarboxylate (DINCH) is used as an alternative for some phthalate plasticizers. In rats, DINCH mostly eliminates in feces as cyclohexane-1,2-dicarboxylic acid (CHDA), mono isononyl ester (MINCH) or in urine as CHDA. However, CHDA is not a specific biomarker of DINCH and measuring MINCH in feces is impractical. To identify additional potential biomarkers, we administered DINCH (500 mg/kg body weight) in a single subcutaneous (SC) or oral dose to four adult female Sprague-Dawley rats. We collected 24-h urine samples before dosing (to be used as controls) and 24-h and 48-h after dosing, and serum at necropsy after 48 h. We positively identified and accurately quantified CHDA and cyclohexane-1,2-dicarboxylic [corrected] acid, mono hydroxyisononyl ester (MHNCH) using authentic standards. Moreover, we tentatively identified MINCH and 12 oxidative metabolites, including 4 cyclohexane ring oxidation products, based on their mass spectrometric-fragmentation patterns. CHDA and MHNCH levels were higher in the urine collected 24 h after oral than SC administration. By contrast, 48-h after dosing, CHDA urinary levels were similar regardless of the exposure route. We detected all but two of the urine metabolites also in serum. Levels of CHDA and MHNCH in serum were lower than in the two post-dose urine collections. Our results suggest that several urinary oxidative metabolites, specifically CHDA, mono oxoisononyl ester and MHNCH may be used as specific biomarkers of DINCH exposure in humans.

ChemInform Abstract: Reaction Network and Kinetics for the Catalytic Oxidation of Toluene Over V2O5.

Abstract The oxidation of three methyl-diphenylmethane isomers and of bibenzyl, benzyl alcohol, and benzaldehyde, which are intermediates in the catalytic oxidation of toluene over V2O5, has been studied to elucidate the reaction network and relative importance of various reactions. Selectivity dependences reveal that the network is composed mainly of three parallel reaction routes: (1) sidechain oxidation with consecutive reactions, (2) oxidative coupling with both parallel and consecutive reactions, and (3) carbon oxide formation. Coupling products are not negligible, with an initial selectivity of 29% (400°C). Anthraquinone is produced mainly from o-methyl-diphenylmethane through o-methyl-diphenylmethanone. Initial ring oxidation products were not found with the conditions and catalyst used. Selectivity depencences suggested product lumping and a simplified network. Kinetic analysis of this reaction network indicates that higher temperatures favor route 2 over route 1. The same initial intermediates for route 1 of side-chain oxidation and for route 2 of oxidative coupling are suggested.

Styrene Metabolism, Genotoxicity, and Potential Carcinogenicity

This report reviews styrene biotransformation, including minor metabolic routes, and relates metabolism to the genotoxic effects and possible styrene-related carcinogenicity. Styrene is shown to require metabolic activation in order to become notably genotoxic and styrene 7,8-oxide is shown to contribute quantitatively by far the most (in humans more than 95%) to the genotoxicity of styrene, while minor ring oxidation products are also shown to contribute to local toxicities, especially in the respiratory system. Individual susceptibility depending on metabolism polymorphisms and individual DNA repair capacity as well as the dependence of the nonlinearity of the dose-response relationships in the species in question and the consequences for risk evaluation are analyzd.

Effect of pH on the Inorganic Species Involved in a Chlorine Dioxide Reaction System

The effects of pH on the inorganic products formed during the reaction of chlorine dioxide with an etherified lignin model compound have been studied. Analyses of the inorganic species produced during the reaction at pH 8 revealed that 2 mol of chlorite are liberated for every 1 mol of oxidized nonphenolic lignin model compound formed, consistent with two consecutive one-electron-transfer processes. In contrast, the low-pH reactions produced mostly ring oxidation products and chlorinated organic material, accompanied by increased levels of hypochlorous acid. The transient hypochlorous acid rapidly reacted with chlorite to generate chloride ions, with a maximum chloride formation at pH 4. Chlorate formation was shown to increase with increasing reaction pH. These results are in contrast to those previously reported for reactions with wood pulps and are explained on the basis of the slow reaction kinetics of nonphenolic lignin moieties as compared to phenolic ones, thereby enabling hypochlorous acid to react with chlorine dioxide to produce chlorate.

Oxidation of aromatic hydrocarbons with oxygen in a radiofrequency plasma

The reactions of three aromatic hydrocarbons, benzene, toluene, and styrene, with oxygen in a radiofrequency (r∫) plasma were investigated. Benzene was oxidized to yield phenol as a single volatile organic product. Similarly, toluene gave the ring oxidation products, cresols, as well as considerable amounts of methyl oxidation products, consisting mainly of benzaldehyde and benzyl alcohol. In contrast, the oxidation of styrene took place predominantly on the olefinic double bond to produce styrene oxide On basis of the products and effects of reaction variables, r∫ power and flow rates of hydrocarbons and oxygen, on the reaction rate, the oxidation mechanism was discussed, particularly focusing on the intermediate species responsible for the formation of major products.

Aromatic ring oxidation of vanillyl and veratryl alcohols by Lentinus edodes: possible artifacts in the lignin peroxidase and veratryl alcohol oxidase assays

The degradation pathway of vanillyl and veratryl alcohol by Lentinus edodes extracellular enzymes was studied. In both cases several products of side chain oxidation and aromatic ring cleavage were isolated and characterized. We have observed that the products from veratryl alcohol degradation by Lentinus edodes are quite different from those isolated from incubations with other white-rot fungi which have veraraldehyde as the major product, in fact, this compound is not produced as final metabolite in L. edodes incubations. This behaviour could explain the apparent absence of lignin peroxidase and veratryl alcohol oxidase activities in L. edodes cultures, since such activities are usually measured by monitoring veratraldehyde formation during the veratryl alcohol oxidation; thus, it is suggested that additional assay methods should be developed, with preferably direct observation of aromatic ring oxidation products.

Reaction of benzotriazole ultraviolet light absorbers with free radicals

The photolysis of benzotriazole ultraviolet light absorber additives (Bz-UVAs) in acrylic/melamine clearcoats suggests that Bz-UVAs are destroyed by clearcoat-driven photooxidation chemistry. Tinuvin 900 is converted to parent benzotriazole and phenol ring oxidation products. Bz-UVAs are not destroyed by photolysis in acrylic/melamine clearcoats in the absence of oxygen. Solution photolysis experiments reveal that Bz-UVAs are not attacked by free radicals generated by thermal decomposition of azoisobutyronitrile (AIBN) or cumene hydroperoxide (CHP) in ethanol or cyclohexane. Bz-UVAs are also not attacked by free radicals generated by photolytic decompostion of AIBN or CHP in cyclohexane. Bz-UVAs, however, are destroyed when AIBN or CHP are photolytically decomposed in ethanol. Photolysis without oxygen leads to Bz-UVA phenol ring solvent and initiator adducts. Photolysis with oxygen leads to cleavage to form free benzotriazole and to destruction of the phenol ring. It is suggested that an excited state of the non-planar Bz-UVA form may be susceptible to free radical attack. Detailed liquid chromatography tandem mass spectrometry (LC/MS/MS) product analysis results are reported in a companion paper.

Isolation and characterization of a fluorene-degrading bacterium: identification of ring oxidation and ring fission products.

An Arthrobacter sp. strain, F101, able to use fluorene as the sole source of carbon and energy, was isolated from sludge from an oil refinery wastewater treatment plant. During growth in the presence of fluorene, four major metabolites were detected and isolated by thin-layer chromatography and high-performance liquid chromatography. 9-Fluorenol, 9H-fluoren-9-one, and 3,4-dihydrocoumarin were identified by UV spectra, mass spectrometry, and 300-MHz proton nuclear magnetic resonance. The fourth metabolite has been characterized, but precise identification was not possible. Since strain F101 is not able to grow with fluorenone, two different pathways of fluorene biodegradation are suggested: one supports cell growth and produces 3,4-dihydrocoumarin as an intermediate and probably the unidentified metabolite, and the other produces 9-fluorenol and 9H-fluoren-9-one and appears to be a dead-end route.

One-electron oxidation of nickel porphyrins: effect of structure and medium on formation of nickel(III) porphyrin or nickel(II) porphyrin .pi.-radical cation

The oxidation of several nickel(II) porphyrins by various radicals has been studied by pulse radiolysis in different media (Cl{sub 2}{sup {sm bullet}{minus}} and Br{sub 2}{sup {sm bullet}{minus}} in aqueous systems, Br atoms in organic solvents, and peroxyl radicals in organic and aqueous/organic systems). Photochemical oxidation was also examined in some cases. The absorption spectrum of the oxidation product was monitored within several microseconds after the pulse. Two types of differential spectra were observed, a broad absorption at 640-700 nm ascribed to the {pi}-radical cation, or a sharp absorption at 560-580 nm ascribed to nickel(III) porphyrin. Ni{sup II}TPP (tetraphenylporphyrin) in several organic solvents, protic and aprotic, was oxidized to Ni{sup III}TPP. The addition of 10% water as cosolvent or 0.1 M of electrolyte changed the route of oxidation to give the radical cation Ni{sup II}TPP{sup {sm bullet}+}. On the other hand, Ni{sup II}TSPP (tetrakis(4-sulfonatophenyl)porphyrin), which has four negative charges, was oxidized on the porphyrin ligand by all the radicals examined, in water and in several organic solvents. Ni{sup II}bis(N-methyl-4-pyridyl)diphenylporphyrin, with a charge of +2, and Ni{sup II} tris(4-sulfonatophenyl)(N-methyl-4-pyridyl)porphyrin, with an overall charge of {minus}2, were oxidized on the ligand in aqueous solution but on the metal in organic solvents. These andmore » other results led to the conclusion that most radicals react with Ni{sup II}P by an inner-sphere mechanism to bind onto the metal and give the Ni{sup III}P form. However, when the porphyrin is sufficiently charged to repel the axially bound anion, and/or when the medium enhances the separation of this anion from the metal, the result is oxidation of the porphyrin {pi}-system. In all cases, however, the one-electron-oxidation products, whether Ni{sup II}P{sup {sm bullet}+} or Ni{sup III}P, decay to yield two-electron ring oxidation products.« less

Reaction network and kinetics for the catalytic oxidation of toluene over V 2O 5

The oxidation of three methyl-diphenylmethane isomers and of bibenzyl, benzyl alcohol, and benzaldehyde, which are intermediates in the catalytic oxidation of toluene over V 2O 5, has been studied to elucidate the reaction network and relative importance of various reactions. Selectivity dependences reveal that the network is composed mainly of three parallel reaction routes: (1) sidechain oxidation with consecutive reactions, (2) oxidative coupling with both parallel and consecutive reactions, and (3) carbon oxide formation. Coupling products are not negligible, with an initial selectivity of 29% (400°C). Anthraquinone is produced mainly from o-methyl-diphenylmethane through o-methyl-diphenylmethanone. Initial ring oxidation products were not found with the conditions and catalyst used. Selectivity depencences suggested product lumping and a simplified network. Kinetic analysis of this reaction network indicates that higher temperatures favor route 2 over route 1. The same initial intermediates for route 1 of side-chain oxidation and for route 2 of oxidative coupling are suggested.

Aryl-alcohol oxidase and lignin peroxidase from the white-rot fungus Bjerkandera adusta

Both aryl-alcohol oxidase (AAO) and lignin peroxidase (LiP) have been purified from ligninolytic cultures of the white-rot fungus Bjerkandera adusta. In contrast, the well-studied lignin peroxidase producing white-rot fungus Phanerochaete chrysosporium does not produce AAO. The reactivity of these enzymes in the oxidation of 3,4-dimethoxybenzyl alcohol (veratryl alcohol) and the related lignin model compounds 3,4-dimethoxyphenyl acetic acid (homoveratric acid) and 1-(3,4-dimethoxyphenyl)-2-phenylethanol (α-benzyl veratryl alcohol), a β-1 model, was investigated. In the AAO-catalyzed oxidation of veratryl alcohol, veratraldehyde is isolated as the sole product. Both homoveratric acid and α-benzyl veratryl alcohol are not substrates for the AAO. In contrast, in the oxidation of veratryl alcohol by both the LiP from B. adusta and the LiP from P. chrysosporium veratraldehyde is isolated as the major product. In addition, however, several minor products (three quinones and three ring-opened products), all resulting from one-electron oxidation of the aromatic ring, could be detected. Veratraldehyde is also the major product in the oxidation of both homoveratric acid and α-benzyl veratryl alcohol by the LiPs from both fungi. Monitoring veratraldehyde formation in the veratryl alcohol oxidation is a widely used assay method for LiP activity. However, the presence of AAO or other enzymes oxidizing veratryl alcohol via direct side-chain oxidation might lead to erroneous results, thus it is suggested that additional assay methods should be developed, with preferably direct observation of aromatic ring oxidation products.

Electrochemical amide oxidations in the presence of monomethoxylated phenyl rings. An unexpected relationship between the chemoselectivity of the oxidation and the location of the methoxy substituent

The chemoselectivity of electrochemical amide oxidations in the presence of monomethoxylated phenyl rings was examined. Oxidation of (3-methoxyphenyl)acylpyrrolidine led to exclusive formation of the desired amide oxidation products, while oxidation of the 4-methoxyphenyl isomer led to exclusive formation of aromatic ring oxidation products.

Pyrene degradation by a Mycobacterium sp.: identification of ring oxidation and ring fission products.

The degradation of pyrene, a polycyclic aromatic hydrocarbon containing four aromatic rings, by pure cultures of a Mycobacterium sp. was studied. Over 60% of [14C]pyrene was mineralized to CO2 after 96 h of incubation at 24 degrees C. High-pressure liquid chromatography analyses showed the presence of one major and at least six other metabolites that accounted for 95% of the total organic-extractable 14C-labeled residues. Analyses by UV, infrared, mass, and nuclear magnetic resonance spectrometry and gas chromatography identified both pyrene cis- and trans-4,5-dihydrodiols and pyrenol as initial microbial ring-oxidation products of pyrene. The major metabolite, 4-phenanthroic acid, and 4-hydroxyperinaphthenone and cinnamic and phthalic acids were identified as ring fission products. 18O2 studies showed that the formation of cis- and trans-4,5-dihydrodiols were catalyzed by dioxygenase and monooxygenase enzymes, respectively. This is the first report of the chemical pathway for the microbial catabolism of pyrene.

Metabolism and DNA binding of 1-nitro[14C]pyrene by isolated rabbit tracheal epithelial cells

The metabolism of 1-nitro[14C]pyrene (1-NP) and the binding of its reactive intermediates to DNA and protein was examined in rabbit tracheal epithelial cells. The tracheal cells isolated by two protease digestion methods had normal cellular morphology and viability. The digestion method which demonstrated the highest rate of 1-NP metabolism and DNA binding used a 1 h incubation of the tracheas with 1% protease at 37 degrees C. Metabolites from the incubation medium and cell lysates were extracted, analyzed and quantitated by h.p.l.c. The majority of the metabolites produced by tracheal cells were EA:AC extractable and were released to the surrounding incubation medium. The predominant metabolites identified and quantified in the medium were the ring oxidation products, a 1-NP-diol, 1-NP phenols (6- or 8-OH-1-NP), 10-OH-1-NP and 3-OH-1-NP. Major metabolites formed by nitroreduction were NAAP and 1-AMP. The metabolites retained by tracheal cells were qualitatively identical to those identified in the medium but were present at one-seventh to one-tenth of the amounts. The rate of both 1-NP metabolism and DNA binding was very high. After 4 h, 62% of the 1-NP was metabolized and 198 DNA adducts/10(6) nucleotides were formed. The rate of [14C]1-NP-DNA adducts formation was highest at 30 min of incubation (124 adducts/10(6) nucleotides/h). These high rates of metabolism and DNA binding are consistent with the possibility that tracheal cells may be a particular target tissue for tumor induction by nitrosubstituted polycyclic aromatic hydrocarbons associated with diesel and other combustion emission particles. The preponderance of highly mutagenic 1-NP phenols as metabolites suggest that ring oxidation as well as nitroreduction may result in intermediates which form DNA adducts.

DNA adducts formed by ring-oxidation of the carcinogen 2-naphthylamine with prostaglandin H synthase in vitro and in the dog urothelium in vivo.

The presence of relatively high levels of prostaglandin H synthase (PHS) in the dog urinary bladder and its ability to mediate the activation of carcinogenic arylamines to DNA-bound products in vitro suggests the involvement of this enzyme in arylamine-induced bladder carcinogenesis. Since the PHS-dependent metabolism of 2-naphthylamine (2-NA) had been shown to yield both ring- and N-oxidation products in vitro, we compared the reactivity of 3H-labeled N-hydroxy-2-naphthylamine (N-OH-2-NA), 2-nitrosonaphthalene, and 2-amino-1-naphthol (2-AN) toward DNA and protein. In the PHS-incubation system, all three derivatives bound at high levels to protein, but only N-OH-2-NA and 2-AN bound appreciably to DNA. Though ring-oxidation has usually been considered a detoxification pathway, the covalent binding of [3H]2-AN to DNA was found to occur readily under aerobic conditions and was enhanced at acidic pH. At pH 5 in air, the reactivity of [3H]2-AN with nucleic acids and protein was in the order: serum albumin greater than tRNA greater than poly G greater than poly C greater than DNA greater than poly A greater than rRNA greater than poly U. Enzymatic hydrolysis of DNA reacted with [3H]2-AN and subsequent analysis by h.p.l.c. indicated the presence of several carcinogen-nucleoside adducts. The major product was characterized as N4-(deoxyguanosin-N2-yl)-2-amino-1,4-naphthoquinoneimine; and two minor products were tentatively identified as N4-(deoxyadenosin-N6-yl)-2-amino-1,4-naphthoquinoneimine and a deoxyguanosin-N2-yl adduct of a naphthoquinoneimine dimer. These adducts accounted for approximately 60% of the total DNA binding obtained by incubation of [3H]2-NA with PHS in vitro and for approximately 20% of the [3H]2-NA bound to dog urothelial DNA in vivo. The remaining adducts were identical to those previously reported as products of the reaction of N-OH-2-NA with DNA. These results suggest that a minor proportion of the DNA adducts found in vivo may be formed by PHS-activation of 2-NA in the target tissue. Furthermore, the reactivity of 2-AN with cellular nucleophiles, presumably through formation of 2-imino-1-naphthoquinone or a protonated 4-naphthocarbenium ion, indicates that ring-oxidation products of arylamines and of other carcinogenic aryl compounds should be evaluated as proximate carcinogenic metabolites.