title: Microsomal Metabolism of Prochiral Polychlorinated Biphenyls Results in the Enantioselective Formation of Chiral Metabolites.
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.
authors.affiliation: Department of Occupational and Environmental Health, College of Public Health, The University of Iowa , Iowa City, Iowa 52242, United States.
authors.forename: Eric
authors.identifier: 0000-0003-0653-1155
authors.initials: E
authors.lastname: Uwimana
authors.affiliation: Department of Occupational and Environmental Health, College of Public Health, The University of Iowa , Iowa City, Iowa 52242, United States.
authors.forename: Anna
authors.initials: A
authors.lastname: Maiers
authors.affiliation: Department of Occupational and Environmental Health, College of Public Health, The University of Iowa , Iowa City, Iowa 52242, United States.
authors.forename: Xueshu
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Occupational and Environmental Health, College of Public Health, The University of Iowa , Iowa City, Iowa 52242, United States.
authors.forename: Hans-Joachim
authors.identifier: 0000-0001-9163-927X
authors.initials: HJ
authors.lastname: Lehmler
mesh_terms: D000818:Animals; D006168:Guinea Pigs; D006900:Hydroxylation; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D010084:Oxidation-Reduction; D011078:Polychlorinated Biphenyls / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D013237:Stereoisomerism
chemical_list: D011078:Polychlorinated Biphenyls