3,4\u27,5-Trichlorobiphenyl-4-yl 2,2,2-trichloroethyl sulfate

Crystals of the title compound, C14H8Cl6O4S, are twinned by inversion, with unequal components [0.85 (3):0.15 (3)]. The asymmetric unit contains two independent molecules that are related by a pseudo-inversion center. The Car-O [1.393 (9) and 1.397 (9) Å] and ester S-O bond lengths [1.600 (5) and 1.590 (5) Å] of both molecules are comparable to the structurally related 2,3,5,5-trichlorobiphenyl-4-yl 2,2,2-trichloroethyl sulfate. The dihedral angles between the benzene rings in the two molecules are 37.8 (2) and 35.0 (2)°

Metabolism of 2,2',3,3',6,6'-hexachlorobiphenyl (PCB 136) atropisomers in tissue slices from phenobarbital or dexamethasone-induced rats is sex-dependent.

1. Chiral polychlorinated biphenyls (PCBs) such as PCB 136 enantioselectively sensitize the ryanodine receptor (RyR). In light of recent evidence that PCBs cause developmental neurotoxicity via RyR-dependent mechanisms, this suggests that enantioselective PCB metabolism may influence the developmental neurotoxicity of chiral PCBs. However, enantioselective disposition of PCBs has not been fully characterized. 2. The effect of sex and cytochrome P450 (P450) enzyme induction on the enantioselective metabolism of PCB 136 was studied using liver tissue slices prepared from naïve control (CTL), phenobarbital (PB; CYP2B inducer) or dexamethasone (DEX; CYP3A inducer) pretreated adult Sprague-Dawley rats. PCB 136 metabolism was also examined in hippocampal slices derived from untreated rat pups. 3. In liver tissue slices, hydroxylated PCB (OH-PCB) profiles depended on sex and inducer pretreatment, and OH-PCB levels followed the rank orders male > female and PB > DEX > CTL. In contrast, the enantiomeric enrichment of PCB 136 and its metabolites was independent of sex and inducer pretreatment. Only small amounts of PCB 136 partitioned into hippocampal tissue slices and no OH-PCB metabolites were detected. 4. Our results suggest that enantioselective metabolism, sex and induction status of P450 enzymes in the liver may modulate the neurotoxic outcomes of developmental exposure to chiral PCBs

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

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)°

Interactions of the Stereoisomers of α-Hydroxytamoxifen with Human Hydroxysteroid Sulfotransferase SULT2A1 and Rat Hydroxysteroid Sulfotransferase STa

ABSTRACT Tamoxifen (TAM) is a nonsteroidal antiestrogenic drug that is widely used for the treatment of estrogen receptor-dependent breast cancer. An increased risk of endometrial cancer in some patients treated with TAM has been linked to the metabolic formation of α-hydroxytamoxifen (α-OHTAM) and its subsequent sulfation. α-OHTAM has been found to be a substrate for rat and human hydroxysteroid sulfotransferases (STa and SULT2A1, respectively). Since stereochemistry plays an important role in the interactions of hydroxysteroid sulfotransferases with their substrates, we have now investigated the interactions of each of the stereoisomers of α-OHTAM with highly purified recombinant STa and SULT2A1. Methods for preparation of the enantiomers of E-and Z-α-OHTAM were developed. When each of the four enantiomers was examined with rat STa, E-(+)-α-OHTAM was the only substrate for the enzyme, while E-(-)-α- OHTAM, Z-(+)-α-OHTAM, and Z-(-)-α-OHTAM were inhibitors of the sulfation of E- (+)-α-OHTAM catalyzed by STa. The dissociation constants for the α-OHTAM enantiomers indicated that they bound to STa with similar affinity, but only the E-(+)-enantiomer was a substrate. In contrast to the results obtained with rat hydroxysteroid sulfotransferase STa, all enantiomers of α-OHTAM were substrates for the human SULT2A1. Moreover, k cat /K m values with SULT2A1 were higher with the Z-enantiomers than with the E-enantiomers. As a result of the potential for interconversion of the E and Z geometric isomers upon metabolism, the sulfation of the Z-isomers may be of greater concern in human tissues than has been previously assumed