For present purposes, a protein-bound metal site consists of one or more metal ions and all protein side chain and exogenous bridging and terminal ligands that define the first coordination sphere of each metal ion. Such sites can be classified into five basic types with the indicated functions: (1) structural -- configuration (in part) of protein tertiary and/or quaternary structure; (2) storage -- uptake, binding, and release of metals in soluble form: (3) electron transfer -- uptake, release, and storage of electrons; (4) dioxygen binding -- metal-O{sub 2} coordination and decoordination; and (5) catalytic -- substrate binding, activation, and turnover. The authors present here a classification and structure/function analysis of native metal sites based on these functions, where 5 is an extensive class subdivided by the type of reaction catalyzed. Within this purview, coverage of the various site types is extensive, but not exhaustive. The purpose of this exposition is to present examples of all types of sites and to relate, insofar as is currently feasible, the structure and function of selected types. The authors largely confine their considerations to the sites themselves, with due recognition that these site features are coupled to protein structure at all levels. In themore » next section, the coordination chemistry of metalloprotein sites and the unique properties of a protein as a ligand are briefly summarized. Structure/function relationships are systematically explored and tabulations of structurally defined sites presented. Finally, future directions in bioinorganic research in the context of metal site chemistry are considered. 620 refs.« less

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Structural and Functional Aspects of Metal Sites in Biology

Advances in copper complexes as anticancer agents.

Polyoxometalates (POMs) have remarkable properties and a great deal of potential to meet contemporary societal demands regarding health, environment, energy and information technologies. However, implementation of POMs in various functional architectures, devices or materials requires a processing step. Most developments have considered the exchange of POM counterions in an electrostatically driven approach: immobilization of POMs on electrodes and other surfaces including oxides, embedding in polymers, incorporation into Layer-by-Layer assemblies or Langmuir–Blodgett films and hierarchical self-assembly of surfactant-encapsulated POMs have thus been thoroughly investigated. Meanwhile, the field of organic–inorganic POM hybrids has expanded and offers the opportunity to explore the covalent approach for the organization or immobilization of POMs. In this critical review, we focus on the use of POM hybrids in selected fields of applications such as catalysis, energy conversion and molecular nanosciences and we endeavor to discuss the impact of the covalent approach compared to the electrostatic one. The synthesis of organic–inorganic POM hybrids starting from bare POMs, that is the direct functionalization of POMs, is well documented and reliable and efficient synthetic procedures are available. However, as the complexity of the targeted functional system increases a multi-step strategy relying on the post-functionalization of preformed hybrid POM platforms could prove more appealing. In the second part of this review, we thus survey the synthetic methodologies of post-functionalization of POMs and critically discuss the opportunities it offers compared to direct functionalization.

Functionalization and post-functionalization: a step towards polyoxometalate-based materials

Copper is found in all living organisms and is a crucial trace element in redox chemistry, growth and development. It is important for the function of several enzymes and proteins involved in energy metabolism, respiration, and DNA synthesis, notably cytochrome oxidase, superoxide dismutase, ascorbate oxidase, and tyrosinase. The major functions of copper-biological molecules involve oxidation-reduction reactions in which they react directly with molecular oxygen to produce free radicals. Therefore, copper requires tightly regulated homeostatic mechanisms to ensure adequate supplies without any toxic effects. Overload or deficiency of copper is associated, respectively, with Wilson disease (WD) and Menkes disease (MD), which are of genetic origin. Researches on Menkes and Wilson disorders have provided useful insights in the field of copper homeostasis and in particular into the understanding of intracellular trafficking and distribution of copper at molecular levels. Therapies based on metal supplementation with copper histidine or removal of copper excess by means of specific copper chelators are currently effective in treating MD and WD, respectively. Copper chelation therapy is now attracting much attention for the investigation and treatment of various neurodegenerative disorders such as Alzheimer, Parkinson and CreutzfeldtJakob. An excess of copper appears to be an essential co-factor for angiogenesis. Moreover, elevated levels of copper have been found in many types of human cancers, including prostate, breast, colon, lung, and brain. On these basis, the employment of copper chelators has been reported to be of therapeutic value in the treatment of several types of cancers as anti-angiogenic molecules. More recently, mixtures of copper chelators with copper salts have been found to act as efficient proteasome inhibitors and apoptosis inducers, specifically in cancer cells. Moreover, following the worldwide success of platinum(II) compounds in cancer chemotherapy, several families of individual copper complexes have been studied as potential antitumor agents. These investigations, revealing the occurrence of mechanisms of action quite different from platinum drugs, head toward the development of new anticancer metallodrugs with improved specificity and decreased toxic side effects.

Copper in diseases and treatments, and copper-based anticancer strategies.

Transition metal complexes containing organoimido (nr) and related ligands

Improved preparation of tertiary phosphine and related substitution products of group VI metal carbonyls

Dinitrogen complexes of rhenium(I) are prepared by the reaction of benzoylazo-complexes, [Re(NNCOPh)Cl2(PPh3)xLy](L = monodentate ligand or ½ bidentate ligand; x= 0 or 2, x+y= 3), with certain ligands in boiling methanol. The dinitrogen complexes are of the type trans-[ReCl(N2)LxL′y](L = a variety of organophosphines; L′= L or some other organophosphine, CO or PF3; x+y= 4). For L = L′= PMe2Ph the dinitrogen complex has an exceptionally low ν(N2)(1925 cm–1). Despite its low ν(N2), it is not easily reduced and strong Bronsted acids protonate the metal rather than the bound dinitrogen. On oxidation, the dinitrogen complexes form moderately stable paramagnetic cations, e.g., trans-[ReCl(N2)(Ph2PCH2CH2PPh2)2]+.

G.J. Leigh

Papers

Improved preparation of tertiary phosphine and related substitution products of group VI metal carbonyls

Dinitrogen complexes of rhenium(I) and rhenium(II)

Comprehensive coordination chemistry II From Biology to Nanotechnology

New synthetic routes to mono-, di- and tri-carbonyl halido complexes of rhenium(I) and rhenium(III) with tertiary phosphine

Gmelin handbook of inorganic and organometallic chemistry