Publications (17)58.35 Total impact
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Article: Dechlorane plus mono adducts in a Lake Ontario (Canada) food web and biotransformation by lake trout (Salvelinus namaycush) liver microsomes.
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ABSTRACT: Compounds related to the high production volume flame retardant Dechlorane Plus (DP), were measured in a Lake Ontario food web located downstream of a DP manufacturing plant. These compounds, 1,3- and 1,5-DP-mono-adducts (DPMA), are positional isomers and are thought to arise from the incomplete reaction of DP or impurities in the DP starting material during its manufacture. The 1,3-DPMA isomer was measured (0.12 - 199 ng g(-1) lipid weight) in all trophic levels (TLs) while 1,5-DPMA was measured only sporadically in the food web and not detectable in the apex predator, lake trout (Salvelinus namaycush). Concentrations of DPMA isomers when detected in Lake Ontario biota were greater than that of total DP for all TLs. The prevalence of 1,3-DPMA in the food web, and especially in lake trout, may be due to obstruction of the existing carbon double bond to enzyme attack rendering it less readily metabolized. To examine this hypothesis, biotransformation kinetic experiments using in vitro lake trout liver microsomal exposures were performed. Zero-order depletion rate constants for 1,3- and 1,5-DPMA were 92.2 and 134.6 pmole h(-1) , respectively, with corresponding half-lives of 2.03 ± 0.14 h (1,3-DPMA) and 1.39 ± 0.09 h (1,5-DPMA). Further, the 1,5-isomer was depleted to a greater extent than 1,3-DPMA. Specific biotransformation products were not identified. These data support the hypothesis that 1,5-DPMA is more readily metabolized than 1,3-DPMA by lake trout. This study also shows that the concentrations of these isomers, which we speculate might be unintended impurities/by-products in some technical DP formulations, exceed that of the intended product in biota. Environ. Toxicol. Chem. © 2013 SETAC.Environmental Toxicology and Chemistry 02/2013; · 2.81 Impact Factor -
Article: Preparation and X-ray structural characterization of further stereoisomers of 1,2,5,6,9,10-hexabromocyclododecane.
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ABSTRACT: Technical 1,2,5,6,9,10-hexabromocyclododecane (HBCD) consists largely of three diastereomers (α-, β-, and γ-HBCD) produced by the trans addition of bromine to cis,trans,trans-cyclododeca-1,5,9-triene (CDT). However, another seven diastereomers are theoretically possible and may be produced by trans addition of bromine across the double bonds of the other three isomers of 1,5,9-CDT. There are indications that small amounts of the minor HBCD isomers may be present in commercial HBCD mixtures or in products containing this brominated flame retardant (BFR). Such minor components may indeed derive from traces of other 1,5,9-CDTs in the cis, trans, trans starting material, however their formation may also be possible through isomerizations during the processing of this BFR or by bioisomerization subsequent to its release into the environment. Two of the seven additional diastereomers (δ- and ε-HBCD) were synthesized previously from trans,trans,trans-CDT. We now report the preparation of the remaining five diastereomers, ζ-, η-, and θ-HBCD from cis,cis,trans-CDT and ι- and κ-HBCD from cis,cis,cis-CDT, and their characterization by (1)H NMR spectroscopy and X-ray crystallography. The availability of these further diastereomers of HBCDshould aid in determining if the minor isomers are present in commercial samples of this BFR, in products containing HBCDs, or in environmental samples. We have also carried out an X-ray crystal structure determination on ε-HBCD, so that crystal structures are now available for all 10 HBCD diastereomers.Chemosphere 07/2011; 84(7):900-7. · 3.21 Impact Factor -
Article: Perfluorooctane sulfonate (PFOS) precursors can be metabolized enantioselectively: principle for a new PFOS source tracking tool.
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ABSTRACT: Perfluorooctane sulfonate (PFOS) is the most prominent perfluoroalkyl substance found in the serum of humans and wildlife, yet the major routes by which exposure occurs are not clear. An important issue facing both the scientific and chemical regulatory communities is the extent to which PFOS concentrations in biota are attributable to direct exposure versus metabolism of PFOS-precursors (higher molecular weight derivatives that can be biotransformed to PFOS). Given that certain branched PFOS-precursors are chiral, we hypothesized that nonracemic proportions of PFOS isomers in biological samples could be used as a marker of significant exposure to PFOS-precursors. In this proof-of-principle study we examined the enantiomer-specific biotransformation of a high-purity model PFOS-precursor isomer: C(6)F(13)C*F(CF(3))SO(2)N(H)CH(2)(C(6)H(4))OCH(3) (named 1m-PreFOS hereafter, and whereby * indicates the chiral carbon center). A method for the enantiospecific separation of a compound with a long perfluoroalkyl chain and a chiral center was developed and applied to evaluate the enantioselectivity of 1m-PreFOS biotransformation in human liver microsomes. Gradient elution in reversed-phase mode on a Chiralpak IC column permitted the near-baseline separation of the two enantiomers (E1 and E2, nomenclature based on retention order) in 65 min. Microsome incubations demonstrated that E1 and E2 were metabolized at significantly different rates; k(E1) = 6.5(+/-0.3) x 10(-2) min(-1) (half-life = 10.6 min) and k(E2) = 5.2(+/-0.3) x 10(-2) min(-1) (half-life = 13.3 min), respectively. These results suggest that tracking of PFOS exposure sources by enantiomeric fractionation is feasible, and that new analytical methods for the enantioselective analysis of PFOS isomers in human and environmental samples should be developed.Environmental Science and Technology 11/2009; 43(21):8283-9. · 5.23 Impact Factor -
Article: Branched perfluorooctane sulfonate isomer quantification and characterization in blood serum samples by HPLC/ESI-MS(/MS).
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ABSTRACT: Perfluorooctane sulfonate (PFOS) is a global contaminant and is currently among the most prominent contaminants in human blood and wildlife samples. Although "total PFOS" (SigmaPFOS) analytical methods continue to be the most commonly used for quantification, recent analytical method developments have made it possible to resolve the various isomers of PFOS by HPLC-MS/MS. Characterized technical PFOS standards (i.e., containing a mixture of PFOS isomers) are now available that enable isomer specific quantification of PFOS, however the advantages of such an analysis have notyet been examined systematically. Herein, PFOS isomers have been individually quantified for the first time in real samples and the results are compared to a traditional SigmaPFOS method; the influence of analytical standards and isomer specific electrospray and MS/ MS behavior were also investigated. The two human serum standard reference materials chosen for analysis contained dramaticallydifferent PFOS isomer profiles (approximately 30-50% total branched isomers) emphasizing that isomer patterns should not be ignored and may provide useful information on exposure sources (i.e., direct exposure to PFOS vs indirect exposure from PFOS-precursors). Depending on the sample and the particular MS/MS transition chosen for SigmaPFOS analysis (i.e., 499-->80 or 499-->99), SigmaPFOS concentrations may be over- or underestimated compared to the isomer specific analysis. Differences in the extent of in-source fragmentation and MS/MS dissociation contributed to the systematic analytical bias. It was also shown that SigmaPFOS data are prone to interlaboratory variation due to various choices of PFOS standards and instrumental conditions used. In the future, for either SigmaPFOS or isomer specific PFOS analyses, we suggest that accuracy can be maximized and interlaboratory discrepancies minimized by using a common chemically pure technical PFOS standard characterized by 19F NMR.Environmental Science and Technology 10/2009; 43(20):7902-8. · 5.23 Impact Factor -
Article: Structural characterization and thermal stabilities of the isomers of the brominated flame retardant 1,2,5,6-tetrabromocyclooctane (TBCO).
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ABSTRACT: 1,2,5,6-Tetrabromocyclooctane (TBCO) is a commercial brominated flame retardant that is employed mainly as an additive in textiles, paints and plastics. Very little is known about its presence or behavior in the environment or its analysis. TBCO can exist as two diastereomers, the stereochemistries of which have not been previously reported. We have named the first eluting isomer, under HPLC conditions, as alpha-TBCO (alpha-TBCO) and the later eluting isomer as beta-TBCO (beta-TBCO) when using an Acquity UPLC BEH C(18) column with methanol/acetonitrile/water as the mobile phase. The structural elucidation of these two isomers was accomplished by 1H NMR spectroscopy, GC/MS, LC/MS and X-ray structure determinations. alpha-TBCO is (1R,2R,5S,6S)-1,2,5,6-tetrabromocyclooctane and beta-TBCO is rac-(1R,2R,5R,6R)-1,2,5,6-tetrabromocyclooctane. As with some other brominated cycloaliphatic compounds, TBCO is thermally labile and the isomers easily interconvert. A thermal equilibrium mixture of alpha- and beta-TBCO consists of approximately 15% and 85% of these isomers, respectively. Separation of the two diastereomers, with minimal thermal interconversion between them, is achievable by careful selection of GC-capillary column length and injector temperature. LC/MS analyses of TBCO also presents an analytical challenge due to poor resolution of the isomers on chromatographic stationary phases, and weak intensity of molecular ions (or major fragment ions) when using LC-ESI/MS. Only bromide ions were seen in the mass spectra. APCI and APPI also failed to produce the molecular ion with sufficient intensity for identification.Chemosphere 02/2009; 74(11):1538-43. · 3.21 Impact Factor -
Article: Structure characterization and thermal stabilities of the isomers of the brominated flame retardant 1,2-dibromo-4-(1,2-dibromoethyl)cyclohexane.
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ABSTRACT: 1,2-Dibromo-4-(1,2-dibromoethyl)cyclohexane (TBECH) is used primarily as an additive flame retardant. 1H NMR spectroscopy and an X-ray structure determination have revealed that a technical mixture consists largely of two (of the four possible) diastereomers, rac-(1R,2R)-1,2-dibromo-(4S)-4-((1S)-1,2-dibromoethyl)cyclohexane (alpha-TBECH) and rac-(1R,2R)-1,2-dibromo-(4S)-4-((1R)-1,2-dibromoethyl)cyclohexane (beta-TBECH), in a mole ratio of approximately 1:1. The two other possible isomers, gamma- and delta-TBECH, were not detected in a technical mixture. The TBECH isomers are thermally sensitive and can easily interconvert at temperatures of 125 degrees C. A thermal equilibrium mixture of alpha-, beta-, gamma- and delta-TBECH consists of approximately 33%, 33%, 17% and 17% of these isomers, respectively. Separation of all four TBECH diastereomers, with minimal thermal interconversion of the isomers, was achieved by careful selection of GC-capillary column length and injector temperature. Although technical TBECH does not contain the gamma- and delta-isomers, they may still be relevant environmental contaminants since manufacturing processes utilize thermal processes which may induce their formation.Chemosphere 08/2008; 72(8):1163-70. · 3.21 Impact Factor -
Article: Identification of the minor components of Great Lakes DE-71 technical mix by means of 1H NMR and GC/MS.
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ABSTRACT: The production of technical penta-BDE products such as Great Lakes DE-71 is not a clean process but, instead, gives complex mixtures of various BDE congeners. This study reports the verification of the structures of many of the BDE congeners in Great Lakes DE-71 using (1)H NMR and/or GC/MS. In total, 24 BDE congeners, including nine (tetra-BDEs 42, 48, 51, and 91; penta-BDEs 102, 104, and 119; hexa-BDEs 149 and 155) which had not been reported previously, were identified in this technical mix by (1)H NMR. The quantification of these congeners was realized by two independent methods: (1)H NMR spectroscopy in combination with HRGC/LRMS and isotopic dilution and HRGC/HRMS analysis. The values obtained compare well between methods, and with data produced in earlier studies.Chemosphere 05/2008; 73(1 Suppl):S39-43. · 3.21 Impact Factor -
Article: Separation and fluorine nuclear magnetic resonance spectroscopic (19F NMR) analysis of individual branched isomers present in technical perfluorooctanesulfonic acid (PFOS).
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ABSTRACT: The production of perfluoroalkylsulfonate (PFOS) derivatives from linear alkyl precursors using electrochemical fluorination is not a clean process but, instead, gives complex mixtures. This study reports the isolation and (19)F NMR characterization of eleven perfluorooctanesulfonate isomers from a commercial mixture. This allowed the quantification of the individual CF(3) branched isomers that predominate in technical PFOS.Chemosphere 05/2008; 73(1 Suppl):S53-9. · 3.21 Impact Factor -
Article: Structure-dependent inhibition of bladder and pancreatic cancer cell growth by 2-substituted glycyrrhetinic and ursolic acid derivatives.
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ABSTRACT: Derivatives of oleanolic acid, ursolic acid and glycyrrhetinic acid substituted with electron-withdrawing groups at the 2-position in the A-ring which also contains a 1-en-3-one structure are potent inhibitors of cancer cell growth. In this study, we have compared the effects of several 2-substituted analogs of triterpenoid acid methyl esters derived from ursolic and glycyrrhetinic acid on proliferation of KU7 and 253JB-V bladder and Panc-1 and Panc-28 pancreatic cancer cells. The results show that the 2-cyano and 2-trifluoromethyl derivatives were the most active compounds. The glycyrrhetinic acid derivatives with the rearranged C-ring containing the 9(11)-en-12-one structure were generally more active than the corresponding 12-en-11-one isomers. However, differences in growth inhibitory IC(50) values were highly variable and dependent on the 2-substituent (CN vs CF(3)) and cancer cell context.Bioorganic & medicinal chemistry letters 05/2008; 18(8):2633-9. · 2.65 Impact Factor -
Article: Some issues relating to the use of perfluorooctanesulfonate (PFOS) samples as reference standards.
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ABSTRACT: Samples of potassium perfluorooctanesulfonate (PFOSK) from three suppliers were analyzed by LC-ESI-MS/MS for purity and by LC-ESI-MS for the percentage of linear isomer present. Our data indicated that the purity ranged from 80% to 98% and the percentages of linear isomer from 67% to 79%. The proportion of branched isomers present in the samples was also estimated using (19)F NMR. These results agreed quite closely with those found by LC-ESI-MS indicating that there is essentially no difference in overall SIM response factor for the branched isomers vs. that of the linear isomer. Several further observations relevant to the use of standards when analyzing for PFOS were encountered during this study. It appears unlikely that matrix effects attributable to the cation (sodium or potassium) present in PFOSNa or PFOSK internal standards is an issue. In seeking potential matrix effects, it was found that the chromatography was improved substantially when the standard was injected as a solution in 80:20 methanol/water rather than 100% methanol. Notably, in concert with the improvement in chromatography, an increase of about 10% in response was observed. In some closely related studies, when (18)O(2) mass-labeled perfluorohexanesulfonate was used as an internal standard, the actual and theoretical concentration ratios matched closely those for related native sulfonates as long as they did not co-elute. However, when they did co-elute, the peak intensities of the native species were enhanced by about 5%, while those of the labeled compound were suppressed by a similar amount. If this effect were not taken into account, the concentration of the native would be inflated by 10%.Chemosphere 02/2008; 70(4):616-25. · 3.21 Impact Factor -
Article: Synthesis of the two minor isomers, delta- and epsilon-1,2,5,6,9,10-hexabromocyclododecane, present in commercial hexabromocyclododecane.
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ABSTRACT: Hexabromocyclododecane (HBCD) is prepared commercially by bromination of cis,trans,trans-cyclododecatriene (ctt-CDT) and widely used as a flame retardant, particularly in polystyrene foams. Commercial HBCD consists largely of three diastereomers, alpha-, beta-, and gamma-HBCD, the structures of which have been known for many years. Recently, the presence in the mixture of small amounts of two minor diastereomers, delta- and epsilon-HBCD, has been reported. Bearing in mind the manner in which commercial HBCD is generated, it was anticipated that these components are probably formed by bromination of trans,trans,trans-cyclododecatriene (ttt-CDT), a common contaminant in commercial ctt-CDT. Indeed, when a sample of ttt-CDT was brominated it gave two products, the NMR spectra and LC/MS and GC/MS behaviour of which confirmed that they are identical to the minor components, delta- and epsilon-HBCD, present in commercial HBCD.Chemosphere 07/2007; 68(5):887-92. · 3.21 Impact Factor -
Article: Structure-dependent activity of glycyrrhetinic acid derivatives as peroxisome proliferator-activated receptor {gamma} agonists in colon cancer cells.
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ABSTRACT: Glycyrrhizin, a pentacyclic triterpene glycoside, is the major phytochemical in licorice. This compound and its hydrolysis product glycyrrhetinic acid have been associated with the multiple therapeutic properties of licorice extracts. We have investigated the effects of 2-cyano substituted analogues of glycyrrhetinic acid on their cytotoxicities and activity as selective peroxisome proliferator-activated receptor gamma (PPARgamma) agonists. Methyl 2-cyano-3,11-dioxo-18beta-olean-1,12-dien-30-oate (beta-CDODA-Me) and methyl 2-cyano-3,11-dioxo-18alpha-olean-1,12-dien-30-oate (alpha-CDODA-Me) were more cytotoxic to colon cancer cells than their des-cyano analogues and introduction of the 2-cyano group into the pentacyclic ring system was necessary for the PPARgamma agonist activity of alpha-CDODA-Me and beta-CDODA-Me isomers. However, in mammalian two-hybrid assays, both compounds differentially induced interactions of PPARgamma with coactivators, suggesting that these isomers, which differ only in the stereochemistry at C18 which affects conformation of the E-ring, are selective receptor modulators. This selectivity in colon cancer cells was shown for the induction of two proapoptotic proteins, namely caveolin-1 and the tumor-suppressor gene Krüppel-like factor-4 (KLF-4). beta-CDODA-Me but not alpha-CDODA-Me induced caveolin-1 in SW480 colon cancer cells, whereas caveolin-1 was induced by both compounds in HT-29 and HCT-15 colon cancer cells. The CDODA-Me isomers induced KLF-4 mRNA levels in HT-29 and SW480 cells but had minimal effects on KLF-4 expression in HCT-15 cells. These induced responses were inhibited by cotreatment with a PPARgamma antagonist. This shows for the first time that PPARgamma agonists derived from glycyrrhetinic acid induced cell-dependent caveolin-1 and KLF-4 expression through receptor-dependent pathways.Molecular Cancer Therapeutics 06/2007; 6(5):1588-98. · 5.23 Impact Factor -
Article: Nuclear magnetic resonance spectral characterization and semi-empirical calculations of conformations of alpha- and gamma-1,2,5,6,9,10-hexabromocyclododecane.
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ABSTRACT: The full 1H and 13C NMR spectral characterization of alpha- and gamma-1,2,5,6,9,10-hexabromocyclododecane (HBCD) is reported in this paper. The use of various NMR experiments, an analysis of the magnitude of the NMR chemical shifts and coupling constants, and computer modeling has enabled the visualization of the three-dimensional structures for both the alpha- and gamma-diastereomers. This information may provide insight into the different behavior of the alpha- and gamma-HBCD diastereomers in the environment.Chemosphere 05/2007; 67(9):1684-94. · 3.21 Impact Factor -
Article: Mass spectral studies of native and mass-labeled perfluorooctanesulfonamides.
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ABSTRACT: This work examines the mass spectra of several environmentally relevant amides, perfluorooctanesulfonamide (FOSA), NMeFOSA, NEtFOSA, and NMe(2)FOSA, under electron ionization conditions. A previous mass spectral study of FOSA and NEtFOSA led the authors to propose possible structures for some of the fragment ions and fragmentation pathways that might explain their formation. In the present communication, further fragment ions are identified for these two compounds and alternative fragmentation pathways proposed. Mass spectral analyses of NMeFOSA and NMe(2)FOSA and of mass-labeled NMeFOSA and NEtFOSA reinforce our conclusions about potential fragmentation pathways for these amides and the fragment ions expected. The mass spectral data presented here will help chemists to identify signals found in a gas chromatographic/mass spectrometric (GC/MS) analysis that stem from these perfluoroalkylsulfonamides.Rapid Communications in Mass Spectrometry 02/2007; 21(6):929-36. · 2.79 Impact Factor -
Article: Analysis of perfluoroalkyl anion fragmentation pathways for perfluoroalkyl carboxylates and sulfonates during liquid chromatography/tandem mass spectrometry: evidence for fluorine migration prior to secondary and tertiary fragmentation.
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ABSTRACT: It is known that under liquid chromatography/electrospray tandem mass spectrometry (LC/ES-MS/MS) conditions, the perfluorocarboxylate anion [R(F)CO(2)](-) first loses CO(2) to give a perfluoroalkyl anion R(F)(-), [(M-H)-CO(2)](-), which can subsequently fragment to give inter alia lower mass carbanions. It has been suggested in a previous study that such secondary fragmentation involves cleavage of C(n)F(2n) segments. Our study of the LC/ES-MS/MS of a series of (13)C-labeled perfluoroalkyl carboxylic acids (PFCAs) indicates that fragmentation of the R(F)(-) anion does not involve simple 'unzipping' of a primary perfluoroalkyl anion of the type F(3)C(CF(2))(x)CF(2)(-). For example, we have discovered that the secondary transition for the mass-labeled PFOA, perfluoro-1,2,3,4-(13)C(4)-octanoic acid (MPFOA), gives two signals of equal intensity at m/z 169 and 172. We propose a mechanism of fragmentation that involves rapid fluorine shifts, after the initial decarboxylation, which generate a series of new anions prior to secondary and tertiary fragmentation.Rapid Communications in Mass Spectrometry 02/2007; 21(23):3803-14. · 2.79 Impact Factor -
Article: Structure-dependent Ah receptor agonist activities of chlorinated biphenylenes.
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ABSTRACT: Polychlorinated biphenylenes (PCBP) have been identified as combustion by-products that bind the aryl hydrocarbon receptor (AhR) and exhibit 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-like activity. This study investigates the Ah-responsiveness of 2,3,6,7-tetrachlorobiphenylene (2,3,6,7-CBP), 2,3,6-CBP, 2,3-CBP and 2-CBP in breast cancer cells. MCF-7 or ZR-75 cells were treated with different concentrations (1-100 nM) of the compounds alone to determine their activity as inducers of CYP1A1 protein expression or luciferase activity in cells transfected with a construct (pDRE(3)) containing three tandem dioxin responsive elements (DREs) linked to a luciferase reporter gene. In both assays, the order of potency was 2,3,6,7-CBP>2,3,6-CBP>2,3-CBP approximately 2-CBP, and 2,3,6,7-CBP and TCDD were equipotent. Similar results were also observed in an antiestrogenic assay in MCF-7 cells, confirming the high AhR agonist activity of 2,3,6,7-CBP in breast cancer cells.Toxicology in Vitro 10/2006; 20(7):1234-7. · 2.78 Impact Factor -
Article: Synthesis of the two minor isomers, δ- and ε-1,2,5,6,9,10-hexabromocyclododecane, present in commercial hexabromocyclododecane
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ABSTRACT: Hexabromocyclododecane (HBCD) is prepared commercially by bromination of cis,trans,trans-cyclododecatriene (ctt-CDT) and widely used as a flame retardant, particularly in polystyrene foams. Commercial HBCD consists largely of three diastereomers, α-, β-, and γ-HBCD, the structures of which have been known for many years. Recently, the presence in the mixture of small amounts of two minor diastereomers, δ- and ε-HBCD, has been reported. Bearing in mind the manner in which commercial HBCD is generated, it was anticipated that these components are probably formed by bromination of trans,trans,trans-cyclododecatriene (ttt-CDT), a common contaminant in commercial ctt-CDT. Indeed, when a sample of ttt-CDT was brominated it gave two products, the NMR spectra and LC/MS and GC/MS behaviour of which confirmed that they are identical to the minor components, δ- and ε-HBCD, present in commercial HBCD.Chemosphere 68(5):887-892. · 3.21 Impact Factor
Top co-authors
Top Journals
Institutions
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2006–2008
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Texas A&M University
- Department of Veterinary Physiology & Pharmacology
College Station, TX, USA
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2007
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Texas A&M University System Health Science Center
- Institute of Biosciences and Technology
Bryan, TX, USA
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