Biphenyl-4-yl 2,2,2-trichloro­ethyl sulfate

The mol­ecular structure of the title compound, C14H11Cl3O4S, displays a biphenyl dihedral angle of 4.9 (2)° between the benzene rings, which is significantly smaller than the calculated dihedral angle of 41.2° of biphenyl derivatives without ortho substituents. The CAr—O bond length of 1.432 (4) Å is comparable with other sulfuric acid biphenyl-4-yl ester 2,2,2-trichloro­ether ester derivatives without electronegative substituents in the sulfated phenyl ring

Suppression of Peroxisomal Enzyme Activities and Cytochrome P450 4A Isozyme Expression by Congeneric Polybrominated and Polychlorinated Biphenyls

The purpose of this study was to determine the effects of PCBs and PBBs on peroxisome proliferator-activated receptor-α-(PPARα-) associated enzyme activities or protein levels. Male Sprague-Dawley rats were administered a single IP injection (150 μ mol/kg) of either 3,3′,4,4′-tetrabromobiphenyl, 3,3′,4,4′-tetrachlorobiphenyl, 3,3′,5,5′-tetrabromobiphenyl, 2′,3,3′,4,5-pentachlorobiphenyl, 3,3′,4,4′,5-pentachlorobiphenyl, 2,2′,3,3′,5,5′-hexachlorobiphenyl, or 3,3′,4,4′,5,5′-hexabromobiphenyl in corn oil (10 ml/kg). One week later, the activities of catalase, peroxisomal fatty acyl-CoA oxidase, and peroxisomal beta-oxidation as well as cytochrome P450 4A (CYP4A) protein content were determined in subcellular liver fractions. None of the peroxisomal enzyme activities were significantly increased by any of the halogenated biphenyl congeners tested. Except for minor (approx. 25%) increases in the total CYP4A content following treatment with 2,2′,3,3′,5,5′-hexachlorobiphenyl and 3,3′,5,5′-tetrabromobiphenyl, CYP4A protein contents were not increased by any treatment. The two Ah receptor agonists, 3,3′,4,4′-tetrabromobiphenyl and 3,3′,4,4′,5-pentachlorobiphenyl, significantly diminished the liver content of CYP4A proteins and activities of the peroxisomal enzymes studied. Since a range of congeners with different biologic and toxicologic activities were selected for this study, it may be concluded that the polyhalogenated biphenyls do not induce peroxisome proliferation in the male rat, but rather certain members of this class of compounds down regulate peroxisome-associated enzymes. Since PCBs and PBBs do not increase enzyme activities and expression of proteins associated with PPARα, these agents are therefore exerting their carcinogenic and promoting activities by some other mechanism

In Vitro Inhibition of Human Hepatic and cDNA-Expressed Sulfotransferase Activity with 3-Hydroxybenzo[a]pyrene by Polychlorobiphenylols

Sulfonation is a major phase II biotransformation reaction. In this study, we found that several polychlorobiphenylols (OH-PCBs) inhibited the sulfonation of 3-hydroxybenzo[a]pyrene (3-OH-BaP) by human liver cytosol and some cDNA-expressed sulfotransferases. At concentrations > 0.15 μM, 3-OH-BaP inhibited its own sulfonation in cytosol fractions that were genotyped for SULT1A1 variants, as well as with expressed SULT1A1*1, SULT1A1*2, and SULT1E1, but not with SULT1A3 or SULT1B1. The inhibition fit a two-substrate kinetic model. We examined the effects of OH-PCBs on the sulfonation of 0.1 or 1.0 μM 3-OH-BaP, noninhibitory and inhibitory substrate concentrations, respectively. At the lower 3-OH-BaP concentration, OH-PCBs with a 3-chloro-4-hydroxy substitution pattern were more potent inhibitors of cytosolic sulfotransferase activity [with concentrations that produced 50% inhibition (IC(50)) between 0.33 and 1.1 μM] than were OH-PCBs with a 3,5-dichloro-4-hydroxy substitution pattern, which had IC(50) values from 1.3 to 6.7 μM. We found similar results with expressed SULT1A1*1 and SULT1A1*2. The OH-PCBs were considerably less potent inhibitors when assay tubes contained 1.0 μM 3-OH-BaP. The inhibition mechanism was noncompetitive, and our results suggested that the OH-PCBs competed with 3-OH-BaP at an inhibitory site on the enzyme. The OH-PCBs tested inhibited sulfonation of 3-OH-BaP by SULT1E1, but the order of inhibitory potency was different than for SULT1A1. SULT1E1 inhibitory potency correlated with the dihedral angle of the OH-PCBs. The OH-PCBs tested were generally poor inhibitors of SULT1A3- and SULT1B1-dependent activity with 3-OH-BaP. These findings demonstrate an interaction between potentially toxic hydroxylated metabolites of PCBs and polycyclic aromatic hydrocarbons, which could result in reduced clearance by sulfonation

3′,4′-Dichloro­biphenyl-4-yl 2,2,2-trichloro­ethyl sulfate

The four independent mol­ecules in the asymmetric unit of the title compound, C14H9Cl5O4S, are related by pseudo-inversion centres. The mol­ecules have Caromatic—O bond lengths ranging from 1.426 (10) to 1.449 (9) Å and biphenyl-4-yl sulfate ester bond lengths ranging from 1.563 (6) to 1.586 (6) Å, which is comparable to structurally related sulfuric acid diesters. The dihedral angles between the benzene rings range from 22.5 (4) to 29.1 (4)° and are significantly smaller than the calculated dihedral angle of 41.2°

4′-Chloro­biphenyl-3-yl 2,2,2-trichloro­ethyl sulfate

The title compound, C14H10Cl4O4S, is a 2,2,2-trichloro­ethyl-protected precursor of 4′-chloro­biphenyl-3-yl sulfate, a sulfuric acid ester of 4′-chloro­biphenyl-3-ol. The Caromatic—O and O—S bond lengths of the Caromatic—O—S unit are comparable to those in structurally analogous biphenyl-4-yl 2,2,2-trichloro­ethyl sulfates with no electro­negative chlorine substituent in the benzene ring with the sulfate ester group. The dihedral angle between the aromatic rings is 27.47 (6)°

1,3,5-Trichloro-2-methoxy­benzene

The meth­oxy group of the title compound, C7H5Cl3O, is rotated out of the plane of the aromatic ring system, with a dihedral angle of 84.11 (13)°, due to the two bulky ortho-chloro substituents

4′-Chloro­biphenyl-4-yl 2,2,2-trichloro­ethyl sulfate

The title compound, C14H10Cl4O4S, is an inter­mediate in the synthesis of the PCB sulfate monoester of 4′-chloro-biphenyl-4-ol. Both the sulfate monoester and 4′-chloro-biphenyl-4-ol are metabolites of PCB 3 (4-chloro­biphen­yl). There are two mol­ecules with different conformations in the asymmetric unit. The solid state dihedral angles between the benzene rings are 18.52 (10) and 41.84 (16)° in the two mol­ecules, whereas the dihedral angles between the least-squares plane of the sulfated benzene ring and O—S (Ar—C—O—S) are 66.2 (3) and 89.3 (3)°. The crystal was an inversion twin with a refined component fraction of 0.44 (7)

Dietary Fat Interacts with PCBs to Induce Changes in Lipid Metabolism in Mice Deficient in Low-Density Lipoprotein Receptor

There is evidence that dietary fat can modify the cytotoxicity of polychlorinated biphenyls (PCBs) and that coplanar PCBs can induce inflammatory processes critical in the pathology of vascular diseases. To test the hypothesis that the interaction of PCBs with dietary fat is dependent on the type of fat, low-density lipoprotein receptor–deficient (LDL-R(−/−)) mice were fed diets enriched with either olive oil or corn oil for 4 weeks. Half of the animals from each group were injected with PCB-77. Vascular cell adhesion molecule-1 (VCAM-1) expression in aortic arches was non-detectable in the olive-oil–fed mice but was highly expressed in the presence of PCB-77. PCB treatment increased liver neutral lipids and decreased serum fatty acid levels only in mice fed the corn-oil–enriched diet. PCB treatment increased mRNA expression of genes involved in inflammation, apoptosis, and oxidative stress in all mice. Upon PCB treatment, mice in both olive- and corn-oil–diet groups showed induction of genes involved in fatty acid degradation but with up-regulation of different key enzymes. Genes involved in fatty acid synthesis were reduced only upon PCB treatment in corn-oil–fed mice, whereas lipid transport/export genes were altered in olive-oil–fed mice. These data suggest that dietary fat can modify changes in lipid metabolism induced by PCBs in serum and tissues. These findings have implications for understanding the interactions of nutrients with environmental contaminants on the pathology of inflammatory diseases such as atherosclerosis

Education and Decision Making at the Time of Triptan Prescribing: Patient Expectations vs Actual Practice

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106941/1/head12308.pd