Potentially toxic metals approaches

Previous syntheses An example of this point can be recognized by examination of one known synthesis of thienobenzazepines (Scheme 6.1). This synthetic route involves a key palladinm-catalyzed cross-conpling of stannyl intermediate 3, prepared by method of Gronowitz et al., with 2-nitrobenzyl bromide. Acetal deprotection and reductive cyclization afforded the desired thienobenzazepine tricycle 4. In support of structure activity relationship studies, this intermediate was conveniently acylated with varions acyl chlorides to yield several biologically active componnds of structure type 5. While this synthetic approach does access intermediate 4 in relatively few synthetic transformations for stractnre activity relationship studies, this route is seemingly nnattractive for preparative scale requiring stoichiometric amounts of potentially toxic metals that are generally difficult to remove and present costly purification problems at the end of the synthesis. 

Metal reclamation of sediments uses many of the same approaches as for soils, except that sediment access is often more difficult. Once removed from the bottom of a lake or river, sediments can be treated and replaced, or landfilled in a hazardous waste containment site. The actual removal of sediments involves dredging. This can pose serious problems since dredging includes the excavation of sediments from benthic anaerobic conditions to more atmospheric oxidizing conditions. This can result in increased solubilization of metals, along with increased bioavailability (see Section 10.3) and potential toxicity, and increased risk of contaminant spreading (Moore, Ficklin Johns, 1988 Jorgensen, 1989 Moore, 1994). There are ongoing discussions as to whether it is more detrimental to remove sediments, whether for treatment or removal, or simply to leave them in place. 

The use of laboratory toxicity tests to monitor industrial effluent discharges has become a common approach to estimating the potential for environmental effects in North America and Europe. Numerous schemes have been developed to characterize and assess potential toxic effects in aquatic receiving environments. The first regulatory application of Environmental Effects Monitoring (EEM) in Canada was within the 1992 Pulp and Paper Liquid Effluent Regulations, promulgated under the Fisheries Act. A second application of EEM in Canada was within the 2002 Metal... 

As shown in the preceding section, toxic metals may be present in a wide variety of physicochemical forms in surface waters, wastewater, landfill leachates, soils, or sediments. Early on, metal speciation in surface waters was determined, using a chemical approach (Giesy et al., 1978). We now know that metal speciation affects their bioavailability and potential toxicity to aquatic organisms (Tessier and Turner,... 

This is a safe, low cost, and more convenient approach as it does not involve special instrumentation, poisonous intermediates, and the growing rate can also be easily controlled. The utility of this process is underlined by the fact that even after continuous exposure to the toxic metal ions, the fungus readily grows and transforms the toxic conditions to nontoxic by reducing Cd to CdS without the use of any external source of sulfur. Another important, potential benefit of the process described is the fact that the semiconductor CdS nanoparticles, which are quite stable in solution, are synthesized extracellularly in large quantities. This is therefore, a very important advantage over other biosynthetic methods where the nanoparticles are entrapped within the cell matrix in limited quantity whereby an additional processing is required to release them from the matrix. 

The association between metal exposure and renal failure can be approached from two points of view. On the one hand environmental/industrial exposure to heavy metals, more particularly, lead, cadmium and mercury and other inorganic substances such as silicon has been linked to a reduced renal function and/or the development of acute or chronic renal failure [1]. This issue has been dealt with in other chapters of this book. On the other hand patients with chronic renal failure, especially those treated by dialysis are at an increased risk for trace element disturbances (Figure 1). Indeed in these subjects the reduced renal function, the presence of proteinuria, metabolic alterations associated with renal insufficiency, the dialysis treatment, medication etc. all may contribute to either accumulation or deficiency of trace metals. With regard to aluminum intensive research on the element s toxic effects has been performed in the past. Recently, new metal-containing medications have been introduced of which the potential toxic effects should be considered and put in a justified context. 

Nevertheless, some issues have to be addressed before this approach can be applied. Firstly, the tyrosinase gene is quite large and would be difficult to add to a delivery vector. Secondly, melanin production may be too low in vivo for effective MR detection of its metal complex [100]. Finally, potentially high toxicity of melanin and its precursors could restrict the applicability of this reporter gene [99]. 

We have addressed the topic of metal bioavailability and metal toxicity in environmental samples. Traditionally, metal availability is investigated using a chemical approach. Afterwards, the concept of Water Effect Ratio (WER) was proposed by the U.S. EPA and employed bioassays (e.g., fish and invertebrate tests) to assess metal bioavailability and toxicity. In the HMBC approach discussed in this review, we have made use of a bacterial assay that is specific for metal toxicity to achieve this goal. This is only a preliminary survey of the potential applications of the HMBC concept. Some preliminary results on the use of MetPLATE for the fractionation of HMBC to obtain information on the factor(s) that control metal bioavailability in environmental samples were also presented. Using MetPLATE eliminates or diminishes the confounding factor represented by the presence of organic toxicants in a given sample. Further work is needed to refine the fractionation scheme. 

---