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Absolute configuration of 2,2',3,3',6-pentachlorinatedbiphenyl (PCB 84) atropisomers.

ABSTRACT: Nineteen polychlorinated biphenyl (PCB) congeners, such as 2,2',3,3',6-pentachlorobiphenyl (PCB 84), display axial chirality because they form stable rotational isomers, or atropisomers, that are non-superimposable mirror images of each other. Although chiral PCBs undergo atropselective biotransformation and atropselectively alter biological processes, the absolute structure of only a few PCB atropisomers has been determined experimentally. To help close this knowledge gap, pure PCB 84 atropisomers were obtained by semi-preparative liquid chromatography with two serially connected Nucleodex ?-PM columns. The absolute configuration of both atropisomers was determined by X-ray single-crystal diffraction. The PCB 84 atropisomer eluting first and second on the Nucleodex ?-PM column correspond to (aR)-(-)-PCB 84 and (aS)-(+)-PCB 84, respectively. Enantioselective gas chromatographic analysis with the ?-cyclodextrin-based CP-Chirasil-Dex CB gas chromatography column showed the same elution order as the Nucleodex ?-PM column. Based on earlier reports, the atropisomers eluting first and second on the BGB-172 gas chromatography column are (aR)-(-)-PCB 84 and (aS)-(+)-PCB 84, respectively. An inversion of the elution order is observed on the Cyclosil-B gas chromatography and Cellulose-3 liquid chromatography columns. These results advance the interpretation of environmental and human biomonitoring as well as toxicological studies.

SUBMITTER: Li X

PROVIDER: S-EPMC5823790 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Absolute configuration of 2,2',3,3',6-pentachlorinatedbiphenyl (PCB 84) atropisomers.

Li Xueshu X Parkin Sean R SR Lehmler Hans-Joachim HJ

Environmental science and pollution research international 20170523 17

Nineteen polychlorinated biphenyl (PCB) congeners, such as 2,2',3,3',6-pentachlorobiphenyl (PCB 84), display axial chirality because they form stable rotational isomers, or atropisomers, that are non-superimposable mirror images of each other. Although chiral PCBs undergo atropselective biotransformation and atropselectively alter biological processes, the absolute structure of only a few PCB atropisomers has been determined experimentally. To help close this knowledge gap, pure PCB 84 atropisom ...[more]

PMID: 28537024

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Project description:Developmental exposure to multiple ortho-substituted polychlorinated biphenyls (PCBs) causes adverse neurodevelopmental outcomes in laboratory animals and humans by mechanisms involving the sensitization of Ryanodine receptors (RyRs). In the case of PCB 136, the sensitization of RyR is enantiospecific, with only (-)-PCB 136 being active. However, the role of enantioselective metabolism in the developmental neurotoxicity of PCB 136 is poorly understood. The present study employed hepatic microsomes from phenobarbital (PB)-, dexamethasone (DEX)- and corn oil (VEH)-treated male Sprague-Dawley rats to investigate the hypothesis that PCB 136 atropisomers are enantioselectively metabolized by P450 enzymes to potentially neurotoxic, hydroxylated PCB 136 metabolites. The results demonstrated the time- and isoform-dependent formation of three metabolites, with 5-OH-PCB 136 (2,2',3,3',6,6'-hexachlorobiphenyl-5-ol) being the major metabolite. The formation of 5-OH-PCB 136 increased with the activity of P450 2B enzymes in the microsomal preparation, which is consistent with PCB 136 metabolism by rat P450 2B1. The minor metabolite 4-OH-PCB 136 (2,2',3,3',6,6'-hexachlorobiphenyl-4-ol) was produced by a currently unidentified P450 enzyme. An enantiomeric enrichment of (-)-PCB 136 was observed in microsomal incubations due to the preferential metabolism of (+)-PCB 136 to the corresponding 5-OH-PCB 136 atropisomer. 4-OH-PCB 136 displayed an enrichment of the atropisomer formed from (-)-PCB 136; however, the enrichment of this metabolite atropisomer did not affect the enantiomeric enrichment of the parent PCB because 4-OH-PCB 136 is only a minor metabolite. Although the formation of 5- and 4-OH-PCB 136 atropisomers increased with time, the enantioselective formation of the OH-PCB metabolites resulted in constant enantiomeric enrichment, especially at later incubation times. These observations not only demonstrate that the chiral signatures of PCBs and their metabolites in wildlife and humans are due to metabolism by P450 enzymes but also suggest that the enantioselective formation of neurotoxic PCB 136 metabolites, such as 4-OH-PCB 136, may play a role in the developmental neurotoxicity of PCBs.

Dataset Information

Absolute configuration of 2,2',3,3',6-pentachlorinatedbiphenyl (PCB 84) atropisomers.

Publications

Absolute configuration of 2,2',3,3',6-pentachlorinatedbiphenyl (PCB 84) atropisomers.

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