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

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

doi:10.1021/ja020436+

Cited by 10 publications

(12 citation statements)

References 23 publications

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“…They are also involved in modulation of cell cycle, apoptosis, cell adhesion, and cell motility . In addition, chloride ions catalyze the formation of cis adducts in the binding of BPDE to nucleic acids, and this may provide a link between CLIC1 and the effect of BPDE. , …”

Section: Resultsmentioning

confidence: 99%

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Proteomic Analysis of Cellular Responses to Different Concentrations of anti-Benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide in Human Amniotic Epithelial FL Cells

2007

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Benzo(a)pyrene is an ubiquitous environmental carcinogen produced during incomplete combustion of organic substances, and anti-benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide (BPDE), is the most carcinogenic form of its ultimate metabolites. The goal of this study was to examine the response of human amniotic epithelial FL cells to increasing concentrations of BPDE and to find potential biomarkers involved in this cellular response. Human amniotic epithelial FL cells were incubated with 0.005, 0.05, and 0.5 microM BPDE to obtain protein extracts which were resolved by two-dimensional electrophoresis (2-DE) and visualized by silver staining. More than 60 protein spots significantly changed after BPDE exposure. Among these, 2 spots were detected only in the exposed group, and 36 spots were up-regulated, while 27 spots were down-regulated. These altered spots were excised from the gels and analyzed by matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF-MS). The analysis led to the identification of 46 proteins affected by BPDE. These proteins were involved in regulation of transcription, cell cycle, cell proliferation, transport, signal transduction, metabolism, and so forth. However, no single protein changed in a dose-dependent manner in all three concentrations. Therefore, the changes of proteomic profiles cannot be considered as only an amplification of low-dose response in the case of high-dose exposure and the cellular responses to different doses of DNA damaging agent may be quite different. These results will aid our understanding of the mechanism of BPDE-induced cell response and provide the possibility of the establishment of potential biomarkers.

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Section: Resultsmentioning

confidence: 99%

“…44 In addition, chloride ions catalyze the formation of cis adducts in the binding of BPDE to nucleic acids, and this may provide a link between CLIC1 and the effect of BPDE. 45,46 2. 14-3-3 Protein.…”

Section: Resultsmentioning

confidence: 99%

Proteomic Analysis of Cellular Responses to Different Concentrations of anti-Benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide in Human Amniotic Epithelial FL Cells

2007

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“…From the observation that the reaction of trans chlorohydrin 8 shows a marked common ion rate depression upon reaction in solutions containing chloride ion, it was concluded that tetrol products from its hydrolysis also result from reaction of carbocation 5 with water . The observation that diol epoxide and trans -chlorohydrin hydrolyze to cis and trans tetrols in different ratios was rationalized by mechanisms in which each reacts via different distributions of two conformations of carbocation 5 , with an energy barrier separating the two conformations that is greater than the energy barrier for reaction of each carbocation conformation with solvent …”

Section: Introductionmentioning

confidence: 99%

“…However, a later study showed that both cis - and trans -chlorohydrins are formed from the reactions of aryl epoxides with this reagent, and in some cases where the aryl group greatly stabilizes charge at the benzylic position, cis -chlorohydrin may even be the major product . The reaction of DE - 2 with HCl in anhydrous THF, a reagent that might also be expected to form both cis - and trans -chlorohydrins, cleanly yields the trans -chlorohydrin 8 …”

Section: Introductionmentioning

confidence: 99%

Synthesis and Hydrolysis of a cis-Chlorohydrin Derived from a Benzo[a]pyrene 7,8-Diol 9,10-Epoxide

et al. 2004

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(+/-)-7beta,8alpha-Dihydroxy-9beta,10beta-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (DE-1) undergoes reaction with anhydrous HCl in dioxane to yield predominantly ( approximately 94%) a single chlorohydrin. This chlorohydrin was assigned structure 9, in which the chloro goup at C-10 is located cis to the C-9 hydroxyl group, on the basis of its (1)H NMR spectrum. This result is in contrast to the reaction of a diastereomeric benzo[a]pyrene 7,8-diol 9,10-epoxide (DE-2) with HCl, which yields only trans-chlorohydrin 8. The hydrolysis of cis-chlorohydrin 9 in 10:90 dioxane-water solutions yields the same ratio of tetrols ( approximately 89% cis/11% trans) as that formed by acid-catalyzed hydrolysis of DE-1. This result again contrasts with the hydrolysis of trans-chlorohydrin 8, which undergoes hydrolysis to give tetrols in a ratio different from that from acid-catalyzed hydrolysis of DE-2. A marked common ion rate depression in the hydrolysis of cis-chlorohydrin 9 is observed, which shows that hydrolysis proceeds via an intermediate carbocation that has a sufficient lifetime to be trapped by external chloride ion. The observation that DE-1 reacts with HCl to give mainly the cis-chlorohydrin is rationalized by quantum chemical calculations that suggest that the cis-chlorohydrin is more stable than the epimeric trans-chlorohydrin.

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“…Conformational factors affecting the stereochemistry of attack of solvent may be primarily responsible for these observations ( , ). Conformational factors also play important roles in determining the cis/trans tetrol ratios from acid-catalyzed hydrolyses of benzo[ a ]pyrene 7,8-diol 9,10-epoxides ( , ).…”

Section: Introductionmentioning

confidence: 99%

Transition State Effects in the Acid-Catalyzed Hydrolysis of 5-Methoxyacenaphthylene 1,2-Oxide: Implications for the Mechanism of Acid-Catalyzed Hydrolysis of Cyclopenta[cd]pyrene 3,4-Oxide

Zhao

Whalen

2006

Chem. Res. Toxicol.

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5-Methoxyacenaphthylene 1,2-oxide (5) was synthesized by the reaction of 5-methoxyacenaphthylene with dimethyldioxirane. The rates and products from the acid-catalyzed and pH-independent reactions of 5 in 50:50 dioxane/water have been determined. The half-life of the pH-independent reaction of this very reactive epoxide in 50:50 dioxane/water is only 22 s. Acid-catalyzed hydrolysis of 5 in 50:50 dioxane/water yields 62% of cis diol 6, 37% of trans diol 7, and approximately 1% of 5-methoxy-1,2-dihydroacenaphthylen-1-one (8). The pH-independent reaction of 5 yields mostly ketone 8 (94%), along with minor amounts of cis and trans diols. The relative stabilities of cis and trans diols 6 and 7 were determined by treating either cis or trans diol with perchloric acid in water solutions and following the approach to an equilibrium cis/trans diol mixture as a function of time. At equilibrium, the ratio of cis and trans diols is 19:81, which establishes that trans diol 7 is more stable than cis diol 6. The acid-catalyzed hydrolysis of epoxide 5 therefore yields the less stable cis diol as the major product. It is concluded that transition state effects therefore selectively stabilize the transition state for attack of water on the intermediate carbocation leading to the less stable cis diol. These results suggest that transition state effects are also responsible for formation of the major cis diol in the acid-catalyzed hydrolysis of cyclopenta[cd]pyrene 3,4-oxide, which has a cyclopenta-fused ring similar to that in 5.

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

Cited by 10 publications

References 23 publications

Proteomic Analysis of Cellular Responses to Different Concentrations of anti-Benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide in Human Amniotic Epithelial FL Cells

Proteomic Analysis of Cellular Responses to Different Concentrations of anti-Benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide in Human Amniotic Epithelial FL Cells

Synthesis and Hydrolysis of a cis-Chlorohydrin Derived from a Benzo[a]pyrene 7,8-Diol 9,10-Epoxide

Transition State Effects in the Acid-Catalyzed Hydrolysis of 5-Methoxyacenaphthylene 1,2-Oxide: Implications for the Mechanism of Acid-Catalyzed Hydrolysis of Cyclopenta[cd]pyrene 3,4-Oxide

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