Toxicity studies, transition metal

In 1997, Stohs et al. (27A110) reviewed the potential of metal ions reacting in conjunction with other constituents of tobacco smoke to cause cellular damage by free radical reactions. Various studies had demonstrated the role of reactive oxygen species in the toxicity of transition metals. They conclnded that the presence of several reactive metal ions in tobacco smoke indicates that there may be a role for metal ions in the subsequent toxicity and carcinogenicity of tobacco smoke. They described the metal-catalyzed mechanisms that might be involved. 

Huang, Y.W., Wu, C.H., Aronstam, S.R., 2010. Toxicity of transition metal oxide nanoparticles recent insights from in vitro studies. Materials 3, 4842—4859. 

A review article has appeared (237) which discusses the biological activity of thioethers and their derivatives with particular reference to interactions with transition-metal ions. Accordingly, only some of the more salient points will be discussed here. In any biological studies, the toxicity of Me2SO 482) and of its transition-metal complexes 140) should be borne in mind. 

The transition metal catalysed addition of HCN to alkenes is potentially a very useful reaction in organic synthesis and it certainly would have been more widely applied in the laboratory if its attraction were not largely offset by the toxicity of HCN. Industrially the difficulties can be minimised to an acceptable level and we are not aware of major accidents. DuPont has commercialised the addition of HCN to butadiene for the production of adiponitrile [ADN, NC(CH2)4CN], a precursor to 1,6-hexanediamine, one of the components of 6,6-nylon and polyurethanes (after reaction with diisocyanates). The details of the hydrocyanation process have not been released, but a substantial amount of related basic chemistry has been published. The development of the ligand parameters % and 0 by Tolman formed part of the basic studies carried out in the Du Pont labs related to the ADN process [1],... 

Aluminium is much cheaper than transition metals, and aluminium oxide is non-toxic. Aluminium residues in a polymer would probably not be harmful. Thus, a catalyst based on aluminium could be extremely attractive, even if it were significantly less active than a transition metal catalyst. This has probably contributed to the continued interest in (potential) aluminium polymerization catalysts. However, such studies are difficult, as even traces of transition metal contamination may lead to erroneous conclusions. According to calculations, insertion barriers at aluminium are typically >10 kcal/mol higher than at transition metal catalysts, corresponding to a reactivity difference of 10, so... 

Researchers at Oregon State University are currently studying apphcations of chitosan beads for the removal of toxic metal ions from wastewater. Chitosan has potential applications to waste removal because it selectively adsorbs toxic Group III transition metal ions in preference to less dangerous alkali or alkaline earth metal ions. The technology has been the focus of bench-scale studies and is not commercially available but it is available for licensing. 

There is considerable and widespread interest in the metal complexes of these anions and current research topics comprise for example (i) the spectroscopic study of the binding in these anions (linkage isomerism) and their complexes, (ii) the synthesis of regular polymers of their transition metal complexes and study of the semiconducting properties of these polymers, (iii) the use of the pseudohalides in pharmacological (e.g. low toxicity of —SCN) and biochemical studies (easy complexation of SCN- to metals), and (iv) the use of the activation of these triatomic anions by coordination to metals for their selective conversion in organic synthesis. 

Reactive oxygen species production is largely catalyzed by transition metals (especially copper and iron), and oxidative stress plays a critical role in AD pathogenesis. In one study, the association of metal levels and Ap toxicity was demonstrated by (i) the effect on cell viability by metal alone and in the combination with APP and Ap, (ii) Ap-induced neurotoxicity relevant to oxidative stress indicated by ROS production, and (iii) APPsw cells expressed APP and generated Ap, so that Ap Cu2+ and APP Cu2+ can catalyze more ROS generation than APP cells that only expressed APP. 

The cadmium(II) complex corresponding to 9 (M = Cd n = 2) was the first texaphyrin made [6], This aromatic expanded porphyrin was found to differ substantially from various porphyrin complexes and it was noted that its spectral and photophysical properties were such that it might prove useful as a PDT agent. However, it was also appreciated that the poor aqueous solubility and inherent toxicity of this particular metal complex would likely preclude its use in vivo [29-31], Nonetheless, the coordination chemistry of texaphyrins such as 9 was soon generalized to allow for the coordination of late first row transition metal (Mn(II), Co(II), Ni(II), Zn (II), Fe(III)) and trivalent lanthanide cations [26], This, in turn, opened up several possibilities for rational drag development. For instance, the Mn(II) texaphyrin complex was found to act as a peroxynitrite decomposition catalyst [32] and is being studied currently for possible use in treating amyotrophic lateral sclerosis. This work, which is outside the scope of this review, has recently been summarized by Crow [33],... 

In biological studies, apart from alkali and alkaline earth cations, zinc sensing is very important, especially in neuroscience. Binding of zinc and other (often toxic) transition metal ions requires receptors of different structure and coordination properties. Polypyridines, dendritic pyridines, and thiacrown ethers are the receptors of choice. 

Copper, a redox-active transition metal, is both a blessing and a curse for the living cell. The electronic properties that make it useful as a catalytic cofactor also render it quite toxic. The results of the wide variety of studies... 

Whilst a large number of transition metal complexes have been studied for carbonylation reactions, most transformations can be carried out by selection from a relatively small number of accessible metal complexes (Table 1). Wherever possible, reactions described later in this chapter will avoid the use of volatile and toxic metal carbonyls, particularly [Ni(CO)4], and will concentrate on the use of readily available metal complex catalysts or reagents which can be used in apparatus familiar to the synthetic organic chemist. 

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