Gas chromatographic separation of methoxylated polychlorinated biphenyl atropisomers

Abstract

Several polychlorinated biphenyls (PCBs) and their hydroxylated metabolites display axial chirality. Here we describe an enantioselective, gas chromatographic separation of methylated derivatives of hydroxylated (OH-)PCB atropisomers (MeO-PCB) using a chemically bonded β-cyclodextrin column (Chirasil-Dex). The atropisomers of several MeO-PCBs could be separated on this column with resolutions ranging from 0.42-0.87 under isothermal or temperature-programmed conditions. In addition, the enantiomeric fraction of OH-PCB 136 metabolites was determined in male and female rats treated with racemic PCB 136. The methylated derivatives of two OH-PCB 136 metabolites showed an enantiomeric enrichment in liver tissue, whereas PCB 136 itself was near racemic.

Chiral polychlorinated biphenyls: absorption, metabolism and excretion—a review

“…The availability of small quantities of pure PCB atropisomers allowed the determination of the optical rotation (i.e., (+)- vs. (−)-enantiomer) (Haglund 1996b); the elution order on different enantioselective gas chromatography columns (Haglund and Wiberg 1996) and the absolute configuration (i.e., R - vs. S -enantiomer) of some, but not all C-PCBs (Toda et al 2012). Moreover, the metabolites of C-PCBs are also chiral due to the hindered rotation around the central C-C bond (Nezel et al 1997), and—as with the parent compounds—can be separated into their atropisomers using liquid chromatography (Pham-Tuan et al 2005, Zhai et al 2013) or gas chromatography (Kania-Korwel et al 2011, Kania-Korwel et al 2008c). The absolute configuration of several C-PCB metabolites has been determined using a combination of experimental and computational techniques (Pham-Tuan et al 2005).…”

Chirality as an Environmental Forensics Tool

“…While the exact isomers of these metabolites are unknown, at least some of the many unidentified OH-PCBs in previous studies [7,283] could have been formed from biotransformation of chiral parents, perhaps also in nonracemic proportions. This was demonstrated recently, as rats exposed to racemic PCB 136 in vivo formed 3-OH-PCB 136 and 3-OH-PCB-150 in nonracemic proportions [6]. The latter OH-PCB is a 1,2-chlorine shift product of PCB 136 and is also chiral.…”

“…Only one enantiomer of each compound is depicted further react to form glutathione conjugates, which in turn can undergo a series of reactions through the mercapturic acid pathway [41] to form methylthio-PCBs and then PCB methyl sulfones (MeSO 2 -PCBs). As with the parent compounds, PCB metabolites can also be atropisomeric [6,7,42], such as the OH-PCBs [6] and the MeSO 2 -PCB end products (Figure 4.4). Of the 837 possible MeSO 2 -PCBs, 456 are chiral, with 170 environmentally stable due to tri-or tetra-ortho substitution [42].…”

“…The latter OH-PCB is a 1,2-chlorine shift product of PCB 136 and is also chiral. Those authors have synthesized a number of authentic OH-PCB congeners corresponding to chiral PCB Phase I metabolites [6] to enable further studies on stereoselectivity of chiral PCB metabolism. It is not yet clear if the OH-PCBs are formed or degraded enantioselectively, and other factors affecting CYP-mediated enzymatic degradation of PCBs (e.g.…”

“…A number of the organochlorine (OC) pesticides are also chiral: the technical dichlorodiphenyltrichloroethane (DDT) component o,p 0 -DDT and its anaerobic metabolite o,p 0 -DDD; a-hexachlorocyclohexane (a-HCH), the only chiral isomer of technical HCH; many of the cyclodienes in the chlordane class, including major components cis-and trans-chlordane and heptachlor, minor components such as MC-5, MC-6, MC-7, and U82, and degradates such as oxychlordane and heptachlor epoxide; and most of the possible chlorobornane congeners of toxaphene [3]. Many emerging POPs are also chiral, such as pyrethroid insecticides, hexabromocyclododecane (HBCDD), other brominated flame retardants such as polybrominated biphenyls (PBBs) [4] and some ethers [5], and PCB metabolites such as hydroxylated [6] and methylsulfonyl PCBs [7]. Surprisingly, the chirality of pollutants has received relatively limited attention, despite the significantly different toxicity that enantiomers may have compared to each other and to the racemate, and the insights that enantiomer analysis can bring to understanding processes affecting pollutants in the environment.…”