Chlorination Increases the Persistence of Semiquinone Free Radicals Derived from Polychlorinated Biphenyl Hydroquinones and Quinones

Abstract

Polychlorinated biphenyls (PCBs) comprise a group of persistent organic pollutants that differ significantly in their physicochemical properties, their persistence, and their biological activities. They can be metabolized via hydroxylated and dihydroxylated metabolites to PCB quinone intermediates. We have recently demonstrated that both dihydroxy PCBs and PCB quinones can form semiquinone radicals (SQ •− ) in vitro. These semiquinone radicals are reactive intermediates that have been implicated in the toxicity of lower chlorinated PCB congeners. Here we describe the synthesis of selected PCB metabolites with differing degrees of chlorination on the oxygenated phenyl ring, e.g. 4,4′-dichloro-biphenyl-2,5-diol, 3,6,4′-trichloro-biphenyl-2,5-diol, 3,4,6,-trichlorobiphenyl-2,5-diol and their corresponding quinones. In addition two chlorinated orthohydroquinones were prepared, 6-chloro-biphenyl-3,4-diol and 6,4′-dichloro-biphenyl-3,4-diol. These PCB (hydro-)quinones readily react with oxygen or via comproportionation to yield the corresponding semiquinone free radicals, as detected by electron paramagnetic resonance spectroscopy (EPR alias ESR). The greater the number of chlorines on the (hydro-)quinone (oxygenated) ring, the higher the steady-state level of the resulting semiquinone radical at near neutral pH.

Quinobis(imidazolylidene): Synthesis and Study of an Electron‐Configurable Bis(N‐Heterocyclic Carbene) and Its Bimetallic Complexes

“…Although all attempts to characterize the electrochemical properties of 1 by CV resulted in rapid decomposition, reaction of 1 with a stoichiometric quantity of CoCp 2 in THF afforded a compound that exhibited a sharp, isotropic EPR signal at g = 2.008 (Figure 6 A). [105] This value is consistent with those of other semiquinone radical anionic species [106,107] and the signal for 1 À matched a simulated isotropic spectrum centered at g = 2.008 (Figure 6 B). The absence of hyperfine coupling indicated that the spin density was localized primarily on the quinone moiety and leads us to suggest that reduction of the QBI linker in complexes 2-5 could increase the overall electron-donating ability of 1 without significantly altering the electronic topology of the NHC sites.…”

Nonenzymatic displacement of chlorine and formation of free radicals upon the reaction of glutathione with PCB quinones

“…We have previously shown that the greater the number of chlorines on the oxygenated ring, the more persistent the resulting semiquinone radical (26). Chlorines on the quinone ring should increase the overall electrophilic character of the quinone ring and thereby increase the ease of Michael addition of nucleophiles such as glutathione.…”

“…However, for 2,5-dichloro-1,4-benzoquinone these potentials are more positive, ϩ470 and ϩ620 mV (16); for 2,3,5,6-tetrachloro-1,4-benzoquinone (chloranil) these potentials increase to ϩ650 and ϩ726 mV. Semiquinone radicals having a higher degree of chlorination are more persistent (26); thus, production of O 2…”

“…DMPO was from Dojindo Laboratories. The PCB hydroquinones and quinones were synthesized as described (5,26). All EPR and oxygen consumption experiments were carried out in 100 mM phosphate buffer (pH 7.4) containing 250 M DETAPAC.…”

Polychlorinated biphenyl quinone induces endothelial barrier dysregulation by setting the cross talk between VE-cadherin, focal adhesion, and MAPK signaling

“…PCB29-pQ was synthesized and characterized as previously described (59). Stock solution (50 mM) of PCB29-pQ was prepared in dimethyl sulfoxide (DMSO) before use.…”