Microsomal Metabolism of Prochiral Polychlorinated Biphenyls Results in the Enantioselective Formation of Chiral Metabolites

Eric Uwimana; Anna Maiers; Xueshu Li; Hans-Joachim Lehmler

doi:10.1021/acs.est.6b05387

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Microsomal Metabolism of Prochiral Polychlorinated Biphenyls Results in the Enantioselective Formation of Chiral Metabolites

Journal article

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Microsomal Metabolism of Prochiral Polychlorinated Biphenyls Results in the Enantioselective Formation of Chiral Metabolites

Eric Uwimana, Anna Maiers, Xueshu Li and Hans-Joachim Lehmler

Environmental science & technology, Vol.51(3), pp.1820-1829

02/07/2017

DOI: 10.1021/acs.est.6b05387

PMCID: PMC5300040

PMID: 28038482

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Abstract

Polychlorinated biphenyl (PCB) congeners with multiple ortho chlorine substituents and their metabolites exist as stable rotational isomers, or atropisomers, that are nonsuperimposable mirror images of each other. Additionally, the oxidation of certain axially prochiral PCBs, such as 2,2',4,6'-tetrachlorobiphenyl (PCB 51) and 2,2',4,5,6'-pentachlorobiphenyl (PCB 102), in the meta position of the symmetrically substituted phenyl ring is expected to form axially chiral hydroxylated metabolites (OH-PCBs); however, the formation of chiral OH-PCBs from prochiral PCBs has not been demonstrated experimentally. Here, we investigate if the oxidation of PCB 51 and PCB 102 by different microsomal preparations results in the formation of chiral OH-PCBs. Gas chromatographic analysis revealed that PCB 51 and PCB 102 were metabolized to 2,2',4,6'-tetrachlorobiphenyl-3'-ol (OH-PCB 51) and 2,2',4,5,6'-pentachlorobiphenyl-3'-ol (OH-PCB 102), respectively, by liver microsomes from male rats pretreated with different inducers; untreated male monkeys, guinea pigs, rabbits, and hamsters; and female dogs. The formation of both metabolites was inducer- and species-dependent. Both OH-PCB 51 and OH-PCB 102 were chiral and formed enantioselectively by all microsomal preparations investigated. These findings demonstrate that axially chiral PCB metabolites are formed from axially prochiral PCB congeners, a fact that should be considered when studying the environmental fate, transport, and toxicity of OH-PCBs.

Animals

Guinea Pigs

Polychlorinated Biphenyls - chemistry

Hydroxylation

Oxidation-Reduction

Stereoisomerism

Microsomes, Liver - metabolism

Rats

Male

Polychlorinated Biphenyls - metabolism

ISRP Project 3 2015-2020

ISRP Project 5 2015-2020

Synthesis Core

Details

Title: Subtitle: Microsomal Metabolism of Prochiral Polychlorinated Biphenyls Results in the Enantioselective Formation of Chiral Metabolites
Creators: Eric Uwimana - Department of Occupational and Environmental Health, College of Public Health, The University of Iowa , Iowa City, Iowa 52242, United States
Anna Maiers - Department of Occupational and Environmental Health, College of Public Health, The University of Iowa , Iowa City, Iowa 52242, United States
Xueshu Li - Department of Occupational and Environmental Health, College of Public Health, The University of Iowa , Iowa City, Iowa 52242, United States
Hans-Joachim Lehmler - Department of Occupational and Environmental Health, College of Public Health, The University of Iowa , Iowa City, Iowa 52242, United States
Resource Type: Journal article
Publication Details: Environmental science & technology, Vol.51(3), pp.1820-1829
DOI: 10.1021/acs.est.6b05387
PMID: 28038482
PMCID: PMC5300040
NLM abbreviation: Environ Sci Technol
ISSN: 0013-936X
eISSN: 1520-5851
Publisher: United States
Grant note: P42 ES013661 / NIEHS NIH HHS
Language: English
Date published: 02/07/2017
Academic Unit: Occupational and Environmental Health; Iowa Neuroscience Institute; Iowa Superfund Research Program
Record Identifier: 9984065387402771

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