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Dredging generates remobilisation of sediments contaminated by non-degradable compounds such as metals, to which aquatic organisms can be exposed. This study aims at assessing the environmental impact of sediments remobilised in the Rhine River (France) during the dredging of Marckolsheim dam by pumping/dilution in 2013 on metal speciation and organisms' exposure. The monitoring coupling chemical and biological tools was performed 2 years before dredging operation on 2 sampling sites, upstream and downstream from the discharge of pumping/dilution, to acquire data on the natural variability of labile (DGT as passive samplers), dissolved and particulate concentrations of Cd, Co, Cr, Cu, Ni, Mn, Pb and Zn in Rhine during full hydrological cycles. In parallel, size-calibrated zebra mussels were transplanted at both sites to monitor continuously metal bioavailability from particulate and dissolved fractions. This long-term monitoring allowed the establishment of reference baselines of Rhine water and mussels' contamination levels and subsequently, the detection of averred environmental changes due to the dredging. Indeed, Co and Mn accumulations in mussels exposed to the discharge were consistent with increasing labile species in Rhine whereas ones of Cr and Pb were likely due to an enhanced particulate bioavailability. Whatever the exposure route, the mussels recovered their basal metal contents 2 weeks after the end of dredging, suggesting a transient impact of sediment remobilisation on bioaccumulation. This long-term monitoring highlights the interest of coupling chemical and biological time-integrated tools for a better assessment of environmental risks because metallic exchanges between organisms and their media are complex and metal-specific.

The aim of this study was to investigate the repeatability and seasonal variability of the biological response of river biofilms chronically exposed to a multi-metal pressure in an urban contamination gradient. Biofilms were grown on immersed plastic membranes at three sites on the Seine river upstream (site 1) and downstream (sites 2 and 3) from Paris (France). They were collected in four different seasons (autumn, spring, summer and winter). Biofilm tolerance to Cu, Ni, Pb and Zn was measured using a PICT (Pollution-Induced Community Tolerance) approach with a previously developed short-term toxicity test based on β-glucosidase (heterotrophic) activity. Metal concentrations in the river and also in the biofilm samples (total and non-exchangeable bioaccumulated metals) were also monitored. Biofilm-accumulated metal concentrations reflected the increase of the multi-metal exposure along the urban gradient. These concentrations were strongly correlated with dissolved and particulate organic carbon and with the total metal fraction in the river water, which recalls the significant influence of the environmental parameters on metal uptake processes in river biofilms. Overall, natural biofilms allow monitoring water quality by integrating the variations of a diffuse metal contamination overtime. Tolerance levels globally increased from site 1 to site 3 reflecting the metal pollution gradient measured in the river water collected at the three sites. Cu tolerance tended to increase during warm seasons but no clear seasonal tendency could be found for Ni, Pb and Zn. Furthermore, principal component analysis clearly discriminated samples collected upstream (site 1) from samples collected downstream (sites 2 and 3) along the first principal component which was correlated to the metal gradient. Samples collected in winter were also separated from the others along the second principal component correlated to parameters like water temperature and Total Suspended Solids concentration. This study shows that chronic in situ exposure to environmental metal concentrations has a significant impact on natural biofilms. Biofilm tolerance to metals and biofilm metal bioaccumulation both reflect metal exposure levels although they remain low when compared to Environmental Quality Standards from the European Water Framework Directive. Yet temperature appears as an important environmental variable shaping community structure and response to toxic exposure which shows that the sampling date is an important parameter to consider when using natural river biofilms to assess the impacts of urban pressure. [ABSTRACT FROM AUTHOR]

We describe a series of indolequinones as efficient mechanism-based inhibitors of NRH:quinone oxidoreductase 2 (NQO2) for use either in cellular or cell-free systems. Compounds were designed to be reduced in the active site of the enzyme leading to loss of a substituted phenol leaving group and generation of a reactive iminium electrophile. Inhibition of NQO2 activity was assessed in both cell-free systems and the human leukemia K562 cell line. Inhibition of recombinant human NQO2 by the indolequinones was NRH-dependent, with kinetic parameters characteristic of mechanism-based inhibition and partition ratios as low as 2.0. Indolequinones inhibited NQO2 activity in K562 cells at nanomolar concentrations that did not inhibit NQO1 and were nontoxic to cells. Computation-based molecular modeling simulations demonstrated favorable conformations of indolequinones positioned directly above and in parallel with the isoalloxazine ring of FAD, and mass spectrometry extended our previous finding of adduction of the FAD in the active site of NQO2 by an indolequinone-derived iminium electrophile to the wider series of indolequinone inhibitors. Modeling combined with biochemical testing identified key structural parameters for effective inhibition, including a 5-aminoalkylamino side chain. Hydrogen bonding of the terminal amine nitrogen in the aminoalkylamino side chain was found to be critical for the correct orientation of the inhibitors in the active site. These indolequinones were irreversible inhibitors and were found to be at least 1 order of magnitude more potent than any previously documented competitive inhibitors of NQO2 and represent the first mechanism-based inhibitors of NQO2 to be characterized in cellular systems. [ABSTRACT FROM AUTHOR]

Abstract: A regioselective Larock approach to 3-substituted-2-pyridin-2-ylindoles from 2-alkynylpyridines and 2-iodoanilines is described herein. The unexpectedly high regioselectivity can be rationalized by a combination of steric, coordinative and electronic effects. [Copyright &y& Elsevier]

We describe a series of indolequinones as efficient mechanism-based inhibitors of NRH:quinone oxidoreductase 2 (NQO2) for use either in cellular or cell-free systems. Compounds were designed to be reduced in the active site of the enzyme leading to loss of a substituted phenol leaving group and generation of a reactive iminium electrophile. Inhibition of NQO2 activity was assessed in both cell-free systems and the human leukemia K562 cell line. Inhibition of recombinant human NQO2 by the indolequinones was NRH-dependent, with kinetic parameters characteristic of mechanism-based inhibition and partition ratios as low as 2.0. Indolequinones inhibited NQO2 activity in K562 cells at nanomolar concentrations that did not inhibit NQO1 and were nontoxic to cells. Computation-based molecular modeling simulations demonstrated favorable conformations of indolequinones positioned directly above and in parallel with the isoalloxazine ring of FAD, and mass spectrometry extended our previous finding of adduction of the FAD in the active site of NQO2 by an indolequinone-derived iminium electrophile to the wider series of indolequinone inhibitors. Modeling combined with biochemical testing identified key structural parameters for effective inhibition, including a 5-aminoalkylamino side chain. Hydrogen bonding of the terminal amine nitrogen in the aminoalkylamino side chain was found to be critical for the correct orientation of the inhibitors in the active site. These indolequinones were irreversible inhibitors and were found to be at least 1 order of magnitude more potent than any previously documented competitive inhibitors of NQO2 and represent the first mechanism-based inhibitors of NQO2 to be characterized in cellular systems., (© 2011 American Chemical Society)

[Structure: see text] A practical one-pot, regiospecific three-component process for the synthesis of 2,3-disubstituted indoles was developed via consecutive Pd-catalyzed Sonogashira coupling, amidopalladation, and reductive elimination.