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Synthesis, structure elucidation, and determination of polyhalogenated N-methylpyrroles (PMPs) in blue mussels

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Abstract

Polyhalogenated N-methylpyrroles (PMPs) are halogenated natural products (HNPs) recently detected in seagrass, blue mussels, and other marine organisms. In this study, we synthesized 2,3,4,5-tetrachloro-N-methylpyrrole (Cl4-MP), 2,3,4,5-tetrabrominated-N-methylpyrrole (Br4-MP, aka TBMP), and mixed tetrahalogenated (Cl and Br) N-methylpyrrole congeners. Use of one- and two-dimensional 1H and 13C NMR verified the structures of isolated/enriched 3,4-dibromo-2,5-dichloro-N-methylpyrrole (3,4-Br2-2,5-Cl2-MP), 2,3,4-tribromo-5-chloro-N-methylpyrrole (2,3,4-Br3-5-Cl-MP), and 3-bromo-2,4,5-trichloro-N-methylpyrrole (3-Br-2,4,5-Cl3-MP). GC/EI-MS and GC/ECNI-MS mass spectra of the five PMPs were studied with regard to fragmentation pattern and individual responses which were strongly affected by the presence (or absence) of Br in α-position(s). Quantitative solutions of the synthesized standards were used to determine the elution order of isomers and to quantify PMPs in selected blue mussel samples (Mytilus sp.) from the European Atlantic coast (Spain, France), the North Sea (the Netherlands, Germany) and Baltic Sea (Germany). PMPs were detected in all samples and the concentrations ranged between 0.6 and 52 μg/kg lipids with Br4-MP being the most abundant representative of this substance class.

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References

  • Barón E, Hauler C, Gallistl C, Gimenez J, Gauffier P, Castillo JJ, Fernandez-Maldonado C, de Stephanis R, Vetter W, Eljarrat E, Barcelo D (2015) Halogenated natural products in dolphins: brain-blubber distribution and comparison with halogenated flame retardants. Environ Sci Technol 49:9073–9083

    Article  Google Scholar 

  • Barrow RA, Capon RJ (1993) Brominated pyrrole carboxylic acids from an Australian marine sponge, Axinella sp. Nat Prod Lett 1:243–250

    Article  CAS  Google Scholar 

  • Buser HR (1986) Selective detection of brominated aromatic compounds using gas chromatography/negative chemical ionization mass spectrometry. Anal Chem 58:2913–2919

    Article  CAS  Google Scholar 

  • Cordell GA (1975) 2-Halopyrroles. Synthesis and Chemistry. J Org Chem 40:3161–3169

    Article  CAS  Google Scholar 

  • Dang TT, Ahmad R, Dang TT, Reinke H, Langer P (2008) Regioselective Suzuki cross-coupling reactions of 2,3,4,5-tetrabromo-1-methylpyrrole. Tetrahedron Lett 49:1698–1700

    Article  CAS  Google Scholar 

  • Franssen MCR (1994) Halogenation and oxidation reactions with haloperoxidases. Biocatalysis 10:87–111

    Article  CAS  Google Scholar 

  • Gaul S, Bendig P, Olbrich D, Rosenfelder N, Ruff P, Gaus C, Mueller JF, Vetter W (2011) Identification of the natural product 2,3,4,5-tetrabromo-1-methylpyrrole in Pacific biota, passive samplers and seagrass from Queensland, Australia. Mar Pollut Bull 62:2463–2468

    Article  CAS  Google Scholar 

  • Gilow HM, Burton DE (1981) Bromination and chlorination of pyrrole and some reactive 1-substituted pyrroles. J Org Chem 46:2221–2225

    Article  CAS  Google Scholar 

  • Gribble GW (2010) Naturally occurring organohalogen compounds—a comprehensive update. Springer, Vienna

  • Gribble GW (2012) Occurrence of halogenated alkaloids. In: Knölker H-J (ed) The Alkaloids. Academic Press, London, p 1–165

  • Gribble GW, Knölker HJ (eds) (2012) Occurrence of halogenated alkaloids. Elsevier, London

    Google Scholar 

  • Gribble GW, Blank DH, Jasinski JP (1999) Synthesis and identification of two halogenated bipyrroles present in seabird eggs. Chem Comm 21:2195–2196

    Article  Google Scholar 

  • Haraguchi K, Hisamichi Y, Endo T (2006) Bioaccumulation of naturally occurring mixed halogenated dimethylbipyrroles in whale and dolphin products on the Japanese market. Arch Environ Contam Toxicol 51:135–141

    Article  CAS  Google Scholar 

  • Haraguchi K, Hisamichi Y, Kotaki Y, Kato Y, Endo T (2009) Halogenated bipyrroles and methoxylated tetrabromodiphenyl ethers in tiger shark (Galeocerdo cuvier) from the southern coast of Japan. Environ Sci Technol 43:2288–2294

    Article  CAS  Google Scholar 

  • Hauler C, Vetter W (2015) A non-targeted gas chromatography/electron capture negative ionization mass spectrometry selected ion monitoring screening method for polyhalogenated compounds in environmental samples. Rapid Commun Mass Spectrom 29:619–628

    Article  CAS  Google Scholar 

  • Hauler C, Martin R, Knölker H-J, Gaus C, Mueller JF, Vetter W (2013) Discovery and widespread occurrence of polyhalogenated 1,1′-dimethyl-2,2′-bipyrroles (PDBPs) in marine biota. Environ Pollut 178:329–335

    Article  CAS  Google Scholar 

  • Hauler C, Rimkus G, Risacher C, Knölker H-J, Vetter W (2014) Concentrations of halogenated natural products versus PCB 153 in bivalves from the North and Baltic Seas. Sci Total Environ 490C:994–1001

    Article  Google Scholar 

  • Herrera-Rodriguez LN, Khan F, Robins KT, Meyer HP (2011) Perspectives on biotechnological halogenation: part I: halogenated products and enzymatic halogenation. Chim Oggi 29:31–33

    CAS  Google Scholar 

  • Hoh E, Lehotay SJ, Mastovska K, Ngo HL, Vetter W, Pangallo KC, Reddy CM (2009a) Capabilities of direct sample introduction-comprehensive two-dimensional gas chromatography-time-of-flight mass spectrometry to analyze organic chemicals of interest in fish oils. Environ Sci Technol 43:3240–3247

    Article  CAS  Google Scholar 

  • Hoh E, Lehotay SJ, Pangallo KC, Mastovska K, Ngo HL, Reddy CM, Vetter W (2009b) Simultaneous quantitation of multiple classes of organohalogen compounds in fish oils with direct sample introduction comprehensive two-dimensional gas chromatography and time-of-flight mass spectrometry. J Agric Food Chem 57:2653–2660

    Article  CAS  Google Scholar 

  • Hoh E, Dodder NG, Lehotay SJ, Pangallo KC, Reddy CM, Maruya KA (2012) Nontargeted comprehensive two-dimensional gas chromatography/time-of-flight mass spectrometry method and software for inventorying persistent and bioaccumulative contaminants in marine environments. Environ Sci Technol 46:8001–8008

    Article  CAS  Google Scholar 

  • Huang Y, Qingyu O, Weile Y (1990) Characteristics of flame ionization detection for the quantitative analysis of complex organic mixtures. Anal Chem 62:2063–2064

    Article  CAS  Google Scholar 

  • Kumar A, Borgen M, Aluwihare LI, Fenical W (2017) Ozone-activated halogenation of mono- ad dimethylpyrrole in seawater. Environ Sci Technol 51:589–595

    Article  CAS  Google Scholar 

  • Martin R, Jäger A, Knölker HJ (2011) Transition metals in organic synthesis, part 97: silver-catalyzed synthesis of hexahalogenated 2,2′-bipyrroles. Synlett:2795–2798

  • Pangallo K, Nelson RK, Teuten EL, Pedler BE, Reddy CM (2008) Expanding the range of halogenated 1′-methyl-1,2′-bipyrroles (MBPs) using GC/ECNI-MS and GC*GC/TOF-MS. Chemosphere 71:1557–1565

    Article  CAS  Google Scholar 

  • Risacher C (2012) Master thesis, TU Dresden

  • Risacher C, Hauler C, Vetter W, Knölker HJ (2017) Manuscript in preparation

  • Shaul NJ, Dodder NG, Aluwihare LI, Mackintosh SA, Maruya KA, Chivers SJ, Danil K, Weller DW, Hoh E (2015) Nontargeted biomonitoring of halogenated organic compounds in two ecotypes of bottlenose dolphins (Tursiops truncatus) from the southern California bight. Environ Sci Technol 49:1328–1338

    Article  CAS  Google Scholar 

  • Stapleton HM, Dodder NG, Kucklick JR, Reddy CM, Schantz MM, Becker PR, Gulland F, Porter BJ, Wise SA (2006) Determination of HBCD, PBDEs and MeO-BDEs in California sea lions (Zalophus californianus) stranded between 1993 and 2003. Mar Pollut Bull 52:522–531

    Article  CAS  Google Scholar 

  • Steinwandter H, Schlüter H (1977) Beiträge zur Verwendung von Kieselgel in der Pesticidanalytik I. Eine einfache Multimatrixmethode zur Bestimmung von Chlorkohlenwasserstoff-Pesticiden und polychlorierten Biphenylen. Z. Anal. Chem 286:90–94

    CAS  Google Scholar 

  • Teuten EL, Pedler BE, Hangsterfer AN, Reddy CM (2006a) Identification of highly brominated analogues of Q1 in marine mammals. Environ Pollut 144:336–344

    Article  CAS  Google Scholar 

  • Teuten EL, Saint-Louis R, Pedler BE, Xu L, Pelletier E, Reddy CM (2006b) Expanding the range of brominated Q1 analogues. Mar Poll Bull 52:578–582

    Article  CAS  Google Scholar 

  • Thurnhofer S, Vetter W (2005) A gas chromatography/electron ionization-mass spectrometry-selected ion monitoring method for determining the fatty acid pattern in food after formation of fatty acid methyl esters. J Agric Food Chem 53:8896–8903

    Article  CAS  Google Scholar 

  • Tittlemier SA, Simon M, Jarman WM, Elliott JE, Norstrom RJ (1999) Identification of a novel C10H6N2Br4Cl2 heterocyclic compound in seabird eggs. A bioaccumulating marine natural product? Environ Sci Technol 33:26–33

    Article  CAS  Google Scholar 

  • Tittlemier SA, Fisk AT, Hobson KA, Norstrom RJ (2001) Examination of the bioaccumulation of halogenated dimethyl bipyrroles in an Arctic marine food web using stable nitrogen isotope analysis. Environ Pollut 116:85–93

    Article  Google Scholar 

  • Tittlemier S, Borrell A, Duffe J, Duignan PJ, Fair P, Hall A, Hoekstra P, Kovacs KM, Krahn MM, Lebeuf M, Lydersen C, Muir D, O’Hara T, Olsson M, Pranschke J, Ross P, Siebert U, Stern G, Tanabe S, Norstrom R (2002) Global distribution of halogenated dimethyl bipyrroles in marine mammal blubber. Arch Environ Contam Toxicol 43:244–255

    Article  CAS  Google Scholar 

  • Vetter W (2001) A GC/ECNI-MS method for the identification of lipophilic anthropogenic and natural brominated compounds in marine samples. Anal Chem 73:4951–4957

    Article  CAS  Google Scholar 

  • Vetter W (2006) Marine halogenated natural products of environmental and food relevance. Rev Environ Contam Toxicol 188:1-57

    CAS  Google Scholar 

  • Vetter W (2012) Polyhalogenated alkaloids in environmental and food samples. In: Knölker H-J (ed) The Alkaloids. London, p 211–276

  • Vetter W, Luckas B (1995) Synthesis, isolation, and chromatography of perdeuterated α-1,2,3,4,5,6-hexachlorocyclohexane. J High Resolut Chromatogr 18:643–646

    Article  CAS  Google Scholar 

  • Vetter W, Wu J (2003) Non-polar halogenated natural products bioaccumulated in marine samples. II Brominated and mixed halogenated compounds. Chemosphere 52:423–431

    Article  CAS  Google Scholar 

  • Vetter W, Jun W, Althoff G (2003) Non-polar halogenated natural products bioaccumulated in marine samples. I. 2,3,3′,4,4′,5,5′-heptachloro-1′-methyl-1,2′-bipyrrole (Q1). Chemosphere 52:415–422

    Article  CAS  Google Scholar 

  • Vetter W, Gaul S, Olbrich D, Gaus C (2007) Monobromo and higher brominated congeners of the marine halogenated natural product 2,3,3′,4,4′,5,5′-heptachloro-1′-methyl-1,2′-bipyrrole (Q1). Chemosphere 66:2011–2018

    Article  CAS  Google Scholar 

  • Weichbrodt M, Vetter W, Luckas B (2000) Microwave-assisted extraction and accelerated solvent extraction with ethyl acetate-cyclohexane before determination of organochlorines in fish tissue by gas chromatography with electron-capture detection. J AOAC Int 83:1334–1343

    CAS  Google Scholar 

  • Wu J, Vetter W, Gribble GW, Schneekloth JS Jr, Blank DH, Görls H (2002) Structure and synthesis of the natural heptachloro-1′-methyl-1,2′-bipyrrole (Q1). Angew Chem 41:1740–1743

    Article  CAS  Google Scholar 

  • Zoller W, Schäfer W, Class T, Ballschmiter K (1985) Quantitation of polychlorodibenzodioxin and polychlorobiphenyl standards by gas-chromatography-flame ionization detection. Fresenius Z Anal Chem 321:247–251

    Article  CAS  Google Scholar 

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Correspondence to Walter Vetter.

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Hauler, C., Vetter, W. Synthesis, structure elucidation, and determination of polyhalogenated N-methylpyrroles (PMPs) in blue mussels. Environ Sci Pollut Res 24, 26029–26039 (2017). https://doi.org/10.1007/s11356-017-0229-2

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