The ecotoxicology of marine tributyltin (TBT) hotspots: A review.

Tributyltin (TBT) was widely used as a highly efficient biocide in antifouling paints for ship and boat hulls. Eventually, TBT containing paints became globally banned when TBT was found to cause widespread contamination and non-target adverse effects in sensitive species, with induced pseudohermaphroditism in female neogastropods (imposex) being the best-known example. In this review, we address the history and the status of knowledge regarding TBT pollution and marine TBT hotspots, with a special emphasis on the Norwegian coastline. The review also presents a brief update on knowledge of TBT toxicity in various marine species and humans, highlighting the current understanding of toxicity mechanisms relevant for causing endocrine disruption in marine species. Despite observations of reduced TBT sediment concentrations in many marine sediments over the recent decades, contaminant hotspots are still prevalent worldwide. Consequently, efforts to monitor TBT levels and assessment of potential effects in sentinel species being potentially susceptible to TBT in these locations are still highly warranted.

Synthesis of macrolones with central piperazine ring in the linker and its influence on antibacterial activity.

Three macrolides, clarithromycin, azithromycin and 11-O-Me-azithromycin have been selected for the construction of a series of new macrolone derivatives. Quinolone-linker intermediates are prepared by Sonogashira-type C(6)-alkynylation of 6-iodoquinolone precursors. The final macrolones, differing by macrolide moiety and substituents at the position N-1 of the quinolone or by the presence of an ethyl ester or free acid on the quinolone unit attached via a linker. The linker comprises of a central piperazine ring bonded to the 4″-O position of cladinose by 3-carbon ester or ether functionality. Modifications of the linker did not improve antibacterial properties compared to the previously reported macrolone compounds. Linker flexibility seems to play an important role for potency against macrolide resistant respiratory pathogens.

Accumulation of polychlorinated dibenzo-p-dioxins and furans in Atlantic cod (Gadus morhua)--cage experiments in a Norwegian Fjord.

Polychlorinated dibenzo-p-dioxins (PCDD) and polychlorinated dibenzofurans (PCDF) have been discharged to the Frierfjord (Eastern Norway) for 50 yr. The discharges, dominated by PCDF, were highest in the early 1970s and subsequently reduced 3-4 orders ofmagnitude to 1-2 g toxic equivalents (TEQ)/yr in 1992-2002. Atlantic cod (Gadus morhua) and semipermeable membrane devices (SPMD) were placed in cages for 6 wk in the Frierfjord and at two locations in the adjacent Langesundsfjord. The objective was to clarify the importance of PCDD/PCDF accumulation from the water directly compared to important food items. Little accumulation of PCDD and a significant accumulation of PCDF were observed in the SPMD. Accumulation of PCDF was observed in fish at Kastebukta, closest to the original source, but not at the other two stations. The PCDF concentrations detected in caged fish at Kastebukta were low compared to concentrations found in locally caught fish. Data indicate that it would take 4-55 yr to reach the PCDF-levels observed in locally caught cod if they were exposed only through water. Our results indicate that accumulation of PCDF/PCDD from prey is more important than accumulation from water.

Petroleum oil and mercury pollution from shipwrecks in Norwegian coastal waters.

Worldwide there are tens of thousands of sunken shipwrecks lying on the coastal seabed. These potentially polluting wrecks (PPW) are estimated to hold 3-25milliont of oil. Other hazardous cargo in PPW includes ordnance, chemicals and radioactive waste. Here, we present and discuss studies on mercury (Hg) and oil pollution in coastal marine sediment caused by two of the >2100 documented PPW in Norwegian marine waters. The German World War II (WWII) submarine (U-864) lies at about 150m below the sea surface, near the Norwegian North Sea island of Fedje. The submarine is estimated to have been carrying 67t of elemental Hg, some of which has leaked on to surrounding sediment. The total Hg concentration in bottom surface sediment within a 200m radius of the wreckage decreases from 100g/kgd.w. at the wreckage hotspot to about 1mg/kgd.w. at 100m from the hotspot. The second wreck is a German WWII cargo ship (Nordvard), that lies at a depth of ca. 30m near the Norwegian harbor of Moss. Oil leakage from Nordvard has contaminated the bottom coastal sediment with polycyclic aromatic hydrocarbons (PAH). The findings from this study provide useful insight to coastal administration authorities involved in assessing and remediating wreck-borne pollution from any of the tens of thousands of sunken shipwrecks.

Polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs) in the Grenlandfjords (Norway)--disposition, levels, and effects.

Polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs) are regarded as highly toxic. Their lipophilicity and persistence also render them subject to bioaccumulation. The Grenlandfjords (southern Norway) have long been polluted by PCDD/Fs through the magnesium production at Herøya (1951-2002). Therefore, extensive environmental monitoring was performed in the area, and the project "Dioxins in the Grenlandfjords--DIG" was launched to study abiotic mass balances, biotic processes and ecological risk. This article describes some results from DIG on the dispositions of PCDD/Fs in the food web and biological effects. Furthermore, data from the Norwegian monitoring of the Grenlandfjords are described. Differences in cod liver PCDD/F levels were found between stations, with the highest concentrations in the inner fjord (the Frierfjord), closest to the pollution source. Furthermore, considerable decreases in the concentrations followed the large discharge reductions (1975 and 1990). Contrary to earlier food web studies on other organochlorines, it was found that the concentrations of PCDD/Fs decline with higher trophic level. Higher chlorinated congeners also constituted a lower percentage of sigmaPCDD/Fs higher in the food chain. The results indicated a limited bioaccumulation of PCDD/Fs, especially of higher chlorinated congeners, likely due to reduced membrane permeability (high molecular size), and possibly slow transport through intestinal aqueous phases. Hepatic cod 7-ethoxyresorufin O-deethylase (EROD) activities differed between the Frierfjord and the Eidangerfjord, showing the different PCDD/F exposure in the two fjords. Furthermore, seasonal variations in cytochrome P-450 (CYP) 1A activity were shown, with different responses between genders. The differences were likely linked to the reproductive cycle of the fish.

Effects of increased sea water concentrations of CO2 on growth of the bivalve Mytilus edulis L.

It has been proposed that emission of anthropogenic carbon dioxide to the atmosphere will lead to increased concentrations of CO(2) in sea water corresponding to a decrease of pH of several tenths of pH units. An experiment was performed to test the effects of increased sea water concentrations of CO(2) on shell growth of the blue mussel Mytilus edulis. The experiment was performed in aquaria continuously flushed with sea water spiked with CO(2) to provide five different levels of pH between 6.7 and control sea water with a pH of 8.1. The shell length of the mussels was measured at the start and end of the 44 days experimental period. No mortality was observed during the first 23 days of the experiment. The growth increment in mm was much larger for small mussels than for large mussels, but relative growth profile as function of pH was more similar in the two size groups; observed differences may be random variation between samples. The experiments showed that CO(2) induced reduction of pH affects the growth of M. edulis negatively. There was a strong and statistically significant decrease in growth at the lowest pH values, with virtually no growth at pH = 6.7 and reduced growth at pH = 7.1. The effect seems to set in between pH 7.4 and 7.1; at mean pH levels 7.4 and 7.6 the growth increments were not significantly different from growth at normal pH 8.1.

Disposition of polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) in two Norwegian epibenthic marine food webs.

Polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs) are a group of halogenated hydrocarbons, comprising 210 different, theoretically possible congeners. They are relatively hydrophobic and persistent to biodegradation, thereby rendering them subject to bioaccumulation. This study was conducted in Frierfjord and Eidangerfjord in the Grenland fjord system, Norway, heavily polluted by PCDD/PCDF discharges from the 16,600,859 magnesium production at Herøya from 1951 to 2001. Pooled samples of surface-sediments and the following organisms were collected for the Frierfjord and Eidangerfjord study areas: common shrimp (Crangon crangon), polychaetes (mainly Nereis diversicolor), shore crab (Carcinus maenas), cod (Gadus morhua), flounder (Platichthys flesus), trout (Salmo trutta), herring (Clupea harengus), benthic amphipods and zooplankton. Concentrations of 2,3,7,8-PCDD/Fs were quantified in pooled samples for all species. The relative abundances of stable isotopes of nitrogen (delta(15)N) were evaluated in the organisms as a measure of chemically-derived trophic level. Contrary to earlier studies on other persistent organochlorines, it was found that the concentrations of PCDD/Fs declined with increasing trophic level. Principal Component Analysis (PCA) also showed differences between species in the pattern of PCDD/Fs. Higher chlorinated congeners constituted lower percentages of the PCDD/F-concentrations higher in the food chain as compared to lower trophic levels. In general, congener patterns did not differ between fjords. Infauna (polychaetes) and zooplankton had congener patterns most similar to the pollution source. The results indicate lower accumulation of higher chlorinated congeners in species at higher trophic levels (fish), presumably due to low membrane permeability (high molecular size) and possibly slow transport through intestinal aqueous phases because of low aqueous solubility.

Room temperature palladium catalysed coupling of acyl chlorides with terminal alkynes.

Conditions are reported for the facile, high-yielding coupling of acyl chlorides with terminal alkynes in a reaction involving palladium and copper iodide; the reaction is tolerant of a wide variety of acyl chlorides and terminal alkynes and provides a convenient one-pot route to acetylenic ketones.

Integrated biomarker assessment of the effects of tailing discharges from an iron ore mine using blue mussels (Mytilus spp.).

The blue mussel (Mytilus spp.) has been used to assess the potential biological effects of the discharge effluent from the Sydvaranger mine, which releases its tailings into Bøk fjord at Kirkenes in the north of Norway. Metal bioaccumulation and a suite of biomarkers were measured in mussels positioned for 6 weeks at varying distances from the discharge outlet. The biomarkers used included: stress on stress (SS); condition index (CI); cellular energy allocation (CEA); micronuclei formation (MN); lysosomal membrane stability (LMS), basophilic cell volume (VvBAS); and neutral lipid (NL) accumulation. The individual biomarkers were integrated using the integrated biological response (IBR/n) index. The accumulation of Fe was significantly higher in mussels located closer to the discharge outlet, indicating that these mussels had been exposed to the suspended mine effluent. The IBR/n results were in good agreement with the location of the mussels in relation to the distance from the discharge outlet and expected exposure to the mine effluent. Several biomarkers showed responses resulting in higher IBR/n values of analysed mussels within a 3 km distance from the tailing discharge.

Nanomolar inhibitors of Staphylococcus aureus methionyl tRNA synthetase with potent antibacterial activity against gram-positive pathogens.

Potent nanomolar inhibitors of Staphylococcus aureus methionyl tRNA synthetase have been derived from a file compound high throughput screening hit. Optimized compounds show excellent antibacterial activity against staphylococcal and enterococcal pathogens, including strains resistant to clinical antibiotics. Compound 11 demonstrated in vivo efficacy in an S. aureus rat abscess infection model.

Effects of CO2 on benthic biota: an in situ benthic chamber experiment in Storfjorden (Norway).

Carbon capture and storage (CCS) methods, either sub-seabed or in ocean depths, introduces risk of CO2 leakage and subsequent interaction with the ecosystem. It is therefore important to obtain information on possible effects of CO2. In situ CO2 exposure experiments were carried out twice for 10 days during 2005 using a Benthic Chamber system at 400 m depth in Storfjorden, Norway. pCO2 in the water above the sediment in the chambers was controlled at approximately 500, 5000 and 20,000 µatm, respectively. This article describes the experiment and the results from measured the biological responses within the chamber sediments. The results show effects of elevated CO2 concentrations on biological processes such as increased nanobenthos density. Methane production and sulphate reduction was enhanced in the approximately 5000 µatm chamber.

Tunable bulk acoustic wave resonators based on Ba0.25Sr0.75TiO3 thin films and a HfO2/SiO2 bragg reflector.

A switchable and tunable bulk acoustic wave resonator based on a paraelectric phase Ba(0.25)Sr(0.75)TiO(3) thin film and an all-dielectric HfO(2)/SiO(2) Bragg reflector is presented. The achieved tuning range (3.8%) and effective electromechanical coupling coefficient (7.1%) are the highest reported for solidly mounted tunable bulk acoustic wave resonators. The non-conductive Bragg reflector stack provides excellent integration possibilities.

Diastereomer-specific bioaccumulation of hexabromocyclododecane (HBCD) in a coastal food web, Western Norway.

The present study reports diastereomer-specific accumulation of HBCD from a point source in five marine species representing a typical food web in a Norwegian coastal area. Samples of mussels, polychaetes, crabs and seabird eggs were analyzed for the diastereomers α-, ß- and γ-HBCD, as well as lipid content and stable isotopes of nitrogen ((15)N/(14)N) to estimate trophic level. Accumulated HBCD did not correlate well with lipid content for most of the species, thus wet-weight based concentrations were included in an assessment of biomagnification. In contrast to ß- and γ-HBCD, the α-diastereomer increased significantly with trophic level, resulting in magnification factors >1 in this coastal marine ecosystem. Data for poikilotherms did not show the same positive correlation between the α-diastereomer and trophic position as homeotherms. The apparent biomagnification of the α-HBCD could be due to bioisomerization or diastereomer-specific elimination that differed between poikilotherms and homeotherms.

Bioavailability of hexabromocyclododecane to the polychaete Hediste diversicolor: exposure through sediment and food from a contaminated fjord.

Knowledge of the bioavailability of brominated flame retardants for sediment-dwelling organisms is limited. The present study investigated bioaccumulation of hexabromocyclododecane (HBCD) in the ragworm Hediste diversicolor exposed to field-contaminated sediments and food. Sediments and blue mussels (Mytilus edulis) were sampled from a fjord on the Norwegian west coast known to be highly contaminated with the brominated flame retardant HBCD. During a four-week experiment, ragworms were either exposed to sediment containing moderate or high concentrations of HBCD, or they were fed contaminated soft tissue from mussel. Although mean sediment concentrations were as high as 40 microg/g dry weight in the contaminated sediments, no HBCD were detected in the exposed ragworms (detection limit up to 2.0 ng/g wet wt). In contrast, the exposure to contaminated food (mussel) resulted in elevated body concentrations of 9.1 ng HBCD/g wet weight. The partitioning of HBCD in the test-sediments appeared to be influenced by the quantity and quality of the sediment organic matter (up to 15% total organic carbon). The presence of small plastic beads (<2 mm), which were shown to contain a mean of 50 microg/g dry weight of HBCD, could explain the low bioavailability of the flame retardant in the sediment. Hexabromocyclododecane in food appeared to be readily assimilated in the ragworm, however, and the diastereomer pattern indicated a relative increase of alpha-HBCD from mussel to ragworm. Hence, in the sampled areas of the fjord, trophic transfer appeared to be a more important mechanism for the entry of HBCD into the local benthic food web than sediment-to-biota accumulation.

Spatial diastereomer patterns of hexabromocyclododecane (HBCD) in a Norwegian fjord.

Hexabromocyclododecane (HBCD) is the third most used brominated flame retardant globally, and has been found widely distributed in the environment. The present study reports concentrations and spatial patterns of alpha, beta and gamma-HBCD in a contaminated Norwegian fjord. Intertidal surface sediment and selected species from the marine food web were sampled at five locations in increasing distance from a known point source of HBCD. All sediment and biota samples were analyzed for the three HBCD diastereomers by liquid chromatography and mass spectrometry (LC/MS). The results demonstrated a HBCD gradient with decreasing concentrations at increasing distance from the point source in sediment and sedentary species, but less so in the species with large feeding ranges. Mean concentrations of Sigma HBCD at the closest/most remote locations relative to the point source were 9000/300 ng g(-1) TOC in sediment and 150/90 ng g(-1) lw in the species with largest feeding range (great black-backed gull). The HBCD diastereomer patterns were similar for each of the matrices (sediment, organisms) independent of distance from the source, indicating no difference in environmental partitioning between the diastereomers. However, the concentration ratio of diastereomers in each matrix ranged from 3:1:10 (alpha:beta:gamma) in the sediments to 55:1 (alpha:gamma) in the highest trophic level species, suggesting diastereomer-specific bioaccumulation in the organisms.

Fluorescence polarization method to characterize macrolide-ribosome interactions.

A fluorescence polarization assay is described that measures the binding of fluorescently labeled erythromycin to 70S ribosomes from Escherichia coli and the displacement of the erythromycin from these ribosomes. The assay has been validated with several macrolide derivatives and other known antibiotics. We demonstrate that this assay is suitable for determining the dissociation constants of novel compounds that have binding sites overlapping those of macrolides. This homogeneous binding assay provides a valuable tool for defining structure-activity relationships among compounds during the discovery and development of new ribosome-targeting drugs.

Organotin compounds in a Norwegian fjord. A comparison of concentration levels in semipermeable membrane devices (SPMDs), blue mussels (Mytilus edulis) and water samples.

Monitoring concentrations of organic pollutants in water is essential to predict effects and to initiate preventive steps. Results from the analysis of water samples provide snapshots of a situation, whereas monitoring using semipermeable membrane devices (SPMDs) provides a time-integrated picture of the concentration of pollutants in water. In this investigation, SPMDs, caged mussels and water samples were used to monitor the levels of organotin compounds in the inner Oslofjord, Norway, over a period of 12 weeks. The work-up procedure for the analysis of organotins was optimised, focusing on the clean-up procedure using gel permeation chromatography (GPC). By using several GPC columns, as much as 1 g of triolein could be employed. This reduces the background emission noise on the baseline, leading to an improvement in the detection limits. The main uptake of tributyltin (TBT) in mussels and SPMDs levelled off after 14 days. A longer uptake period was indicated for SPMDs at stations with a high water concentration of TBT (5-10 ng Sn L(-1)) compared with those with a low water concentration of TBT (approximately 1 ng Sn L(-1)). A concentration gradient was observed for water, SPMDs and mussels from the innermost station close to Oslo harbour to the station further out in the fjord, indicating that the three analysed matrices give approximately the same pollution gradient. The bioconcentration factor (BCF) for TBT in mussels was in the range 12-14 000 (wet weight) and, for SPMDs, 10-12 000 (fat). A good correlation with the TBT water concentrations was achieved within a period of 14-30 days of exposure for mussels and after 2-3 months for SPMDs. A good correlation was also found between the TBT concentration in SPMDs and mussels at the end of the experiment. SPMDs can therefore be used to predict concentrations of TBT in both water and mussels.

Indium mediated allylation of glyoxylate oxime ethers, esters and cyanoformates.

An indium mediated procedure has been developed for the allylation of activated O-functionalised oximes and nitriles as exemplified by a variety of glyoxylate derivatives. This method gives the corresponding free (or protected) amine in a one pot-process. The method is regiospecific and is carried out under remarkably mild conditions so that even oxime esters can be subjected to the typical reaction conditions.

Organotins in marine mammals and seabirds from Norwegian territory.

An increasing number of studies indicate that marine mammals and some seabirds are exposed to organotins. However, results from northern and Arctic areas are few. Here results from analysis of tributyltin (TBT), dibutyltin (DBT), monobutyltin (MBT), triphenyltin (TPhT), diphenyltin (DPhT) and monophenyltin (MPhT) in harbour porpoise (Phocoena phocoena), common seal (Phoca vitulina), ringed seal (Phoca hispida) and glaucous gull (Larus hyperboreus) from Norwegian territory are presented. Relatively high concentrations of DBT, TBT and MBT were observed in muscle, kidney and liver from harbour porpoises caught in northern Norway in 1988, just before restrictions on the use of tributyltin (TBT)(mainly on small boats) were introduced in several European countries. The concentrations in harbour porpoise muscle tissue were reduced significantly 11 years later, possibly as a result of the introduced restrictions. Considerably lower concentrations of butyltins were observed in the seals compared to porpoises. The lowest levels of organotins were found in ringed seals from Spitsbergen, where only traces of dibutyltin (DBT) and monobutyltin (MBT) were observed. Traces of DBT and MBT were also found in some individual glaucous gulls from Bear Island. The sum of the degradation products MBT and DBT in liver samples from all analysed species were generally higher than TBT itself. Triphenyltin (TPhT) was observed in all porpoise samples and in livers of common seals. Also the sum of the degradation products MPhT and DPhT in liver samples from porpoise and common seals were higher than TPhT. No traces of phenyltins were found in ringed seals from Spitsbergen or in glaucous gulls from Bear Island. The limited data available indicate low to moderate exposure to organotins in northern areas (Spitsbergen and Bear Island). Marine mammals are however more exposed further south along the Norwegian Coast.

Conformational restriction of methionyl tRNA synthetase inhibitors leading to analogues with potent inhibition and excellent gram-positive antibacterial activity.

Conformationally restricted analogues of the central linker unit of bacterial methionyl tRNA synthetase (MRS) inhibitors have been prepared. The (1S,2R)-cyclopentylmethyl moiety was identified as the preferred cyclic linker, with significant diastereo- and enantioselectivity of activity. Combination of this linker with an optimal substituted aryl right-hand side has resulted in a compound with exceptionally good antibacterial activity against staphylococci and enterococci, including antibiotic resistant strains.