Halide Effects in the Hydrolysis Reactions of (±)-7β,8α-Dihydroxy-9α,10α-epoxy-7,8,9,10-tetrahydrobenzo- [<i>a</i>]pyrene

Lin, Bin; Doan, Lanxuan; Yagi, Haruhiko; Jerina, Donald M.; Whalen, Dale L.

doi:10.1021/tx9701743

Cited by 10 publications

(29 citation statements)

References 24 publications

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“…Analysis of DNA from BaPtreated animals and from humans exposed to BaP indicates that the major adduct is produced by reaction with the (7R,8S,9S,10R)-enantiomer of BPDE (9,16). Hydrolysis of anti-BPDE produces predominantly transanti-BaP-tetraol (57). Taken together, these results indicate that trans-anti-BaP-tetraol should be the major isomer detected in urine, and our results are consistent with this conclusion.…”

Section: Discussionsupporting

confidence: 89%

Determination of r-7,t-8,9,c-10-Tetrahydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene in Human Urine by Gas Chromatography/Negative Ion Chemical Ionization/Mass Spectrometry

Simpson

Christiani

et al. 2000

Chem. Res. Toxicol.

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r-7,t-8,9,c-10-Tetrahydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene (trans-anti-BaP-tetraol) is the major hydrolysis product of r-7, t-8-dihydroxy-t-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (anti-BPDE), the principal ultimate carcinogen of the environmental pollutant benzo[a]pyrene (BaP). As part of a program to establish activation/detoxification profiles of urinary metabolites of BaP in humans, we developed a method for quantifying trans-anti-BaP-tetraol. Urine was collected from three groups of individuals exposed to BaP: psoriasis patients treated with a coal tar-containing ointment, steel workers, and smokers. [(2)H(12)]-trans-anti-BaP-tetraol was added to the urine as an internal standard. The urine was treated with beta-glucuronidase and sulfatase, and then the BaP-tetraols were enriched by reverse-phase and phenylboronic acid solid-phase extraction. The resulting fraction was treated with sodium hydride and methylmethane sulfonate to convert BaP-tetraols to the corresponding tetramethyl ethers (BaP-TME). The mixture was purified by normal-phase HPLC and analyzed by gas chromatography/negative ion chemical ionization/mass spectrometry with selected ion monitoring. [(13)CH(3)](4)-trans-anti-BaP-TME was used as an external standard. Ions at m/z 376, 380, and 388 were monitored for quantitation of trans-anti-BaP-TME, [(13)CH(3)](4)-trans-anti-BaP-TME, and [(2)H(12)]-trans-anti-BaP-TME, respectively. The instrumental detection limit was approximately 1 fmol of trans-anti-BaP-TME. trans-anti-BaP-tetraol (as trans-anti-BaP-TME) was detected in 20 of 20 individuals receiving coal tar therapy (mean, 16 fmol/mL of urine), 13 of 13 exposed steel workers (mean, 4.1 fmol/mL of urine), and nine of 21 cigarette smokers (mean, 0.5 fmol/mL of urine). The means in these groups were significantly different (P < 0.0001). The urine of steel workers was also analyzed for cis-anti-BaP-tetraol and cys-syn-BaP-tetraol, but neither was found. The results of this study provide a quantitative method for determination of parts per trillion levels of trans-anti-BaP-tetraol in human urine. Ultimately, this method can be employed as part of a phenotyping approach for assessing BaP metabolites in human urine.

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Section: Discussionsupporting

confidence: 89%

Determination of r-7,t-8,9,c-10-Tetrahydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene in Human Urine by Gas Chromatography/Negative Ion Chemical Ionization/Mass Spectrometry

Simpson

Christiani

et al. 2000

Chem. Res. Toxicol.

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“…If the rate of ring-opening depended only on a H + , the data from all three acids would be the same. Although the rate of epoxide ring-opening is most strongly influenced by the protonation of the epoxide by H 3 O + , the rate of the reaction is also influenced by general acids (such as HSO 4 − ) donating a hydrogen to the epoxide oxygen − and is increased by the presence of stronger nucleophiles than water, such as NO 3 − or SO 4 2− . ,− For solutions consisting of H 2 SO 4 and sodium sulfate (or any other sulfate salt), all three must be considered.…”

Section: Resultsmentioning

confidence: 99%

Kinetics and Products of the Acid-Catalyzed Ring-Opening of Atmospherically Relevant Butyl Epoxy Alcohols

2010

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Epoxydiols are produced in the gas phase from the photo-oxidation of isoprene in the absence of significant mixing ratios of nitrogen oxides (NO x ). The reactive uptake of these compounds onto acidic aerosols has been shown to produce secondary organic aerosol (SOA). To better characterize the fate of isoprene epoxydiols in the aerosol phase, the kinetics and products of the acid-catalyzed ring-opening reactions of four hydroxy-substituted epoxides were studied by nuclear magnetic resonance (NMR) techniques. Polyols and sulfate esters are observed from the ring-opening of the epoxides in solutions of H2SO4/Na2SO4. Likewise, polyols and nitrate esters are produced in solutions of HNO3/NaNO3. In sulfuric acid, the rate of acid-catalyzed ring-opening is dependent on hydronium ion activity, sulfate ion, and bisulfate. The rates are much slower than the nonhydroxylated equivalent epoxides; however, the hydroxyl groups make them much more water-soluble. A model was constructed with the major channels for epoxydiol loss (i.e., aerosol-phase ring-opening, gas-phase oxidation, and deposition). In the atmosphere, SOA formation from epoxydiols will depend on a number of variables (e.g., pH and aerosol water content) with the yield of ring-opening products varying from less than 1% to greater than 50%.

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“…At pH < ∼7 in 10:90 dioxane−water, 1 reacts with H + to form a triol carbocation 2 , which reacts with water to form trans 9,10- and cis 9,10-tetrols 3 and 4 in a 94:6 ratio. In this reaction, epoxide ring opening is rate-limiting, and carbocation 2 has a sufficient lifetime in water solutions to react with external nucleophiles such as azide and halide , ions.…”

Section: Introductionmentioning

confidence: 99%

“…It has also been observed that the covalent adducts from reaction of 5 with deoxyadenosine and with DNA have mostly cis 9,10-stereochemistry, whereas the covalent adducts from the reaction of diol epoxide 1 with DNA in the absence of chloride ion have mostly trans 9,10-stereochemistry. ,, There are significant cellular concentrations of chloride ion (∼10 mM), and therefore, chlorohydrin 5 may be formed from the reaction of diol epoxide 1 in vivo; thus, 5 may play a role in chemical carcinogenesis . At [Cl - ] = 10 mM, it can be calculated that ∼10% of carbocation 2 is trapped by chloride ion in water solution to form 5 …”

Section: Introductionmentioning

confidence: 99%

Chloride Ion Catalyzed Conformational Inversion of Carbocation Intermediates in the Hydrolysis of a Benzo[a]pyrene 7,8-Diol 9,10-Epoxide

et al. 2002

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A highly efficient procedure for converting 7beta,8alpha-dihydroxy-9alpha,10alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (1) to its trans-9,10-chlorohydrin (5) with excellent yield and purity by the reaction of anhydrous HCl in THF has been developed. The rate of reaction of 5 has been determined as a function of sodium chloride concentration in 1:1 dioxane-water solutions. A large common ion rate depression for the reaction of the chlorohydrin was observed, and the rate data are fit to a mechanism in which all of the tetrol products are formed by the reaction of water with the C-10 carbocation intermediate. Yet, the cis/trans ratio of tetrols from the reaction of the carbocation intermediate from the hydrolysis of chlorohydrin 5 is different than the cis/trans tetrol ratio from the acid-catalyzed hydrolysis of diol epoxide 1, which hydrolyzes via a carbocation with the same connectivity as that formed in the hydrolysis of 5. To rationalize these results, it is proposed that the S(N)1 reaction of chlorohydrin 5 yields a different distribution of carbocation conformations than that formed from the reaction of 1 with H(+). The energy barrier for the inversion of these carbocation conformations must be large relative to the energy barriers for the reaction of each carbocation conformation with water. In solutions containing sufficient concentrations of chloride ion, however, a lower energy pathway via a halohydrin exists for the interconversion of the carbocation conformations. Thus, chloride ion catalyzes the interconversion of these two carbocation conformations.

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Halide Effects in the Hydrolysis Reactions of (±)-7β,8α-Dihydroxy-9α,10α-epoxy-7,8,9,10-tetrahydrobenzo- [a]pyrene

Cited by 10 publications

References 24 publications

Determination of r-7,t-8,9,c-10-Tetrahydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene in Human Urine by Gas Chromatography/Negative Ion Chemical Ionization/Mass Spectrometry

Determination of r-7,t-8,9,c-10-Tetrahydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene in Human Urine by Gas Chromatography/Negative Ion Chemical Ionization/Mass Spectrometry

Kinetics and Products of the Acid-Catalyzed Ring-Opening of Atmospherically Relevant Butyl Epoxy Alcohols

Chloride Ion Catalyzed Conformational Inversion of Carbocation Intermediates in the Hydrolysis of a Benzo[a]pyrene 7,8-Diol 9,10-Epoxide

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