Anne Routledge

Dietary intake estimate for perfluorooctanesulphonic acid (PFOS) and other perfluorocompounds (PFCs) in UK retail foods following determination using standard addition LC–MS/MS

The analysis of 252 food samples (UK-produced and imported) purchased from a variety of retail outlets in the UK was undertaken for the presence of perfluorooctanesulphonic acid (PFOS), perfluorooctanoic acid (PFOA) and nine other perfluorocompounds (PFCs). A limit of quantification (LOQ) of 1 µg/kg was achieved for all target analytes, in all samples. Standard addition was used for quantification of PFC levels. All 11 of the targeted PFCs were detected in 75 individual food items. In 70% of the samples, including all meat other than offal, none of the analytes were present above the LOD. The highest levels found were 59 µg/kg perfluorooctanesulphonic acid (PFOS) and 63 µg/kg total PFCs (ΣPFCs) in an eel sample, and 40 µg/kg PFOS (62 µg/kg ΣPFCs) in a whitebait sample. The highest level in an offal sample was 10 µg/kg, in a wild roe deer liver. There were six samples with ΣPFCs >15 µg/kg (fish, shellfish, crustaceans), a further seven samples with ΣPFCs ranging 11–15 µg/kg (including a liver), nine with ΣPFCs ranging 6–10 µg/kg (fish and livers), 31 with ΣPFCs in the range 2–5 µg/kg (including kidneys, popcorn and processed peas) and a further 22 with ΣPFCs close to the LOD of 1 µg/kg (including eggs and potatoes). These concentrations indicate that UK consumers are being exposed to a low level of PFC contamination from food. The estimated upper bound dietary intake of 10 ng/kg bodyweight (bw)/day of PFOS for average adult consumers is well below the 0.15 µg (150 ng)/kg bw tolerable daily intake (TDI) set by the European Food Safety Authority. The lower bound adult dietary intake estimate of 1 ng/kg bw/day is similar to estimates undertaken and reported in countries such as Canada, Germany and Spain.

Synthesis of 2-Oxindole Derivatives via the Intramolecular Heck Reaction on Solid Support

Abstract Solid phase intramolecular Heck coupling allows the synthesis of 2-oxindoles. Additional diversity is introduced into the molecule by reductive alkylation prior to the Heck cyclisation and also by conjugate addition of a variety of nucleophiles onto the cyclised product prior to cleavage.

Cyclisation of dienes using phosphorus-centred radicals to form organophosphorus adducts

Abstract Reaction of various dienes with phosphites or related phosphorus hydrides, under free radical cyclisation conditions, affords cyclic organophosphorus adducts. This quick, mild and technically clean approach affords 5- and 6-ring carbocycles and heterocycles in good to excellent yield.

Staphyloferrin A as siderophore-component in fluoroquinolone-based Trojan horse antibiotics

A series of fluoroquinolone conjugates was synthesised by linking the carboxylic acid functionality of the carboxylate-type siderophore staphyloferrin A and its derivatives to the piperazinyl nitrogen of ciprofloxacin and norfloxacin via amide bond formation. Four siderophore-drug conjugates were screened against a panel of bacteria associated with infection in humans. Whilst no activity was found against ciprofloxacin- or norfloxacin-resistant bacteria, one of the conjugates retained antibacterial activity against fluoroquinolone-susceptible strains although the structure of its lysine-based siderophore component differs from that of the natural siderophore staphyloferrin A. In contrast, three ornithine-based siderophore conjugates showed significantly reduced activity against strains that are susceptible to their respective parent fluoroquinolones, regardless of the type of fluoroquinolone attached or chirality at the ornithine Cα-atom. The loss of potency observed for the (R)- and (S)-ornithine-based ciprofloxacin conjugates correlates with their reduced inhibitory activity against the target enzyme DNA gyrase.

Synthesis of citrate-ciprofloxacin conjugates.

Two regioisomeric citrate-functionalized ciprofloxacin conjugates have been synthesized and their antimicrobial activities against a panel of clinically-relevant bacteria have been determined. Cellular uptake mechanisms were investigated using wild-type and ompF deletion strains of Escherichia coli K-12.

Mass spectral studies towards more reliable measurement of perfluorooctanesulfonic acid and other perfluorinated chemicals (PFCs) in food matrices using liquid chromatography/tandem mass spectrometry

Liquid chromatography/mass spectrometry (LC/MS) experiments are described, leading to a reliable method for the measurement of perfluorooctanesulfonic acid (PFOS) and other perfluorinated chemicals (PFCs) in foods. Separations were performed on new fluorinated stationary phases, RP Octyl (-C(8)F(17)) or propyl-perfluorobenzene (-C(3)H(6)-C(6)F(5)), to ensure resolution of PFOS and interfering taurohydroxycholate isomers. Aqueous ammonium formate (5 mM) and methanol were used as the mobile phases. The mass spectrometer was operated in negative electrospray ionisation mode, recording two transitions for each analyte and one for each internal standard. The purities of the analytical standards for the eleven target perfluoro analytes (C(7) to C(12) carboxylic acids, C(4), C(6) and C(8) sulfonic acids, and octanesulfonamide (PFOSA)) were found to be in close agreement with the supplied values; the lowest purity was 91%. Five candidate internal standards were investigated, (13)C(4)-PFOS, (13)C(4)-perfluorooctanoic acid, (13)C(2)-perfluorodecanoic acid, D(9)-n-ethylperfluorooctanesulfonamidoethanol (D(9)-n-Et-FOSE) and D(3)-n-methylperfluorooctanesulfonamide (D(3)-n-Me-FOSA); the purities were all >98%. The use of tetrahydro-PFOS generated backgrounds (>1 microg/kg) for perfluoroheptanoic acid and perfluorobutanesulfonic acid. Similarly D(9)-n-Et-FOSE was unacceptable and D(3)-n-Me-FOSA was volatile, leaving no clear candidate for normalisation of the measurement of PFOSA. Severe matrix-induced suppression and enhancement effects influenced ionisation, making external calibration and quantification problematic. This was addressed by a parallel standard addition and matrix-matching approach, comparing ionisation in methanol, in procedural blanks and in food-based extracts. The limits of detection (LODs) of 0.001-0.01 microg/kg in solvent and 0.01-1 microg/kg in foods demonstrate that this method is suitable for the determination of PFCs in all food to the required 1 microg/kg reporting level.

SYNTHESIS OF MONO- AND DIMANNOSIDE PHOSPHORAMIDITE DERIVATIVES FOR SOLID-PHASE CONJUGATION TO OLIGONUCLEOTIDES

Abstract Mannose and dimannose derivatives have been prepared with an anomerically-linked hydrophobic spacer, and converted to phosphoramidite derivatives suitable for conjugation to oligoribodeoxynucleotides on a DNA/RNA synthesizer. Synthesis of a monomannoside-linked 15-mer oligoribodeoxynucleotide is reported.

New fluoride-labile linkers for solid-phase organic synthesis

Abstract Silyl-linkers 2 and 3 are shown to be useful linkers for solid-phase synthesis. They can be cleaved by fluoridolysis under basic (TBAF) or neutral (CsF) conditions. Methods for the synthesis, loading and release are described.

A photolabile ‘traceless’ linker for solid-phase organic synthesis

Abstract A photolabile linker based on a thiohydroxamic acid has been shown to be an efficient ‘traceless’ linker, revealing an aliphatic CH bond on photolysis at 350 nm. Methods for the synthesis, loading and photolytic cleavage of the linker are described.

The glycosidic precursor of (Z)-5-ethylidene-2(5H)-furanone in Halocarpus biformis juvenile foliage

A new glycosidic lactone, (5R,6R)-5-(1-hydroxyethyl)-2(5H)-furanone beta-D-glucopyranoside, has been identified as the principal precursor of (Z)-5-ethylidene-2(5H)-furanone in juvenile foliage of the New Zealand tree Halocarpus biformis. Three related lactone glycosides were isolated in smaller amounts, together with the known phenolic glycosides pyroside, arbutin and picein. The principal lactone glycoside underwent facile elimination of glucose, in neutral or basic conditions, to yield (Z)-5-ethylidene-2(5H)-furanone and its E-isomer. This lactone glycoside was also detected in foliage of H. bidwillii and H. kirkii.