Redox-active transition metals

Very recently evidence was provided that Hmd contains a low-molecular-mass, thermolabile cofactor that is tightly bound to the enzyme but could be released upon enzyme denaturation in urea or guanidinium chloride (Buurman et al. 2000). No indications were found that the cofactor contains a redox-active transition metal. Further studies are needed to determine the structure of the cofactor and its putative role in the catalytic mechanism. 

Our aim has been the construction of dendrimers that incorporate in their building blocks specific pieces of information such as the capability to absorb and emit visible light and to reversibly exchange electrons.To pursue this aim, we have designed a synthetic strategy to build up dendrimers based on luminescent and redox-active transition metal complexes. Species containing 4, 6, iP 10,2W7 28 gjjj 222930 metal-based units have already been obtained. We will see... 

In the development of effective catalytic oxidation systems, there is a qualitative correlation between the desirability of the net or terminal oxidant, (OX in equation 1 and DO in equation 2) and the complexity of its chemistry and the difficulty of its use. The desirability of an oxidant is inversely proportional to its cost and directly proportional to the selectivity, rate, and stability of the associated oxidation reaction. The weight % of active oxygen, ease of deployment, and environmental friendliness of the oxidant are also key issues. Pertinent data for representative oxidants are summarized in Table I (4). The most desirable oxidant, in principle, but the one with the most complex chemistry, is O2. The radical chain or autoxidation chemistry inherent in 02-based organic oxidations, whether it is mediated by redox active transition metal ions, nonmetal species, metal oxide surfaces, or other species, is fascinatingly complex and represents nearly a field unto itself (7,75). Although initiation, termination, hydroperoxide breakdown, concentration dependent inhibition... 

Cytochrome c has 4 methionine residues, two of which are covalently linked to the haem moiety One of the other two methionine residues is coordinated to the iron in the axial position The major S 2 p band of the crystalline compound appears at 162.6 eV attributable to the methionine residues. Prolongued irradiation causes an increase of the RSOJ or the sulphate band from 28% to 40% (Table 2). When aqueous cytochrome c is recorded, the amount of oxidised sulphur rises to 63% of the methionine sulphur band. The possible extraneously bound redox active transition metals, probably, have created a metal driven Haber Weiss reaction which led to the marked amount of oxidised sulphur observed. Splitting of the iron-sulphur bonding by cyanide results in dramatic increase of the 167.7 band and the additional appearance of a S 2p signal at 164.3, probably due to RS=0 species. This oxidation is believed to be catalyzed by the haem iron. Hydrogen peroxide alone converts the methionine sulphur completly to sulphonic acid. 

Moreover, zinc is also known for its antioxidant properties. These appear to be independent of zinc metalloenzyme activity, but are based on protecting sulfhydryl groups or antagonizing redox-active transition metals that cause the site-specific formation of free radicals . 

Mammalian cytochrome oxidase has attracted particular attention. It contains four redox-active transition metal centres, two type a cytochromes (a and a3) and two copper ions. Other oxidases... 

Figure 3.53 A CO substrate is sandwiched between a redox-active transition metal and a Lewis acidic alkali metal cation by a cryptand with both hard and soft donor sites.

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... 

Only one copper ion has been found in the preparations of both F8a and F5a. It was identified as a type 2 copper (Bihoreau et al., 1994 Mann et al., 1984 Tagliavacca et al., 1997). It is beheved that the single copper ion is not involved in any redox reaction and instead it plays a structural role by stabilizing the association of domain Al with domain A3 in the active trimeric complex. This is a very unusual role for a d redox-active transition metal in biology. Mutant F8 in which the type 2 copper ligand His-195 7 was replaced with Ala displayed secretion, active complex assembly, and activity similar to that of wild-type protein, while a mutant in which the second ligand for the type 2 copper, His-99, was replaced with Ala was partially defective for secretion and had low levels of active complex formation and activity (Tagliavacca et al., 1997). 

Thus, re-examination of metal-chelating agents, classical indirect antioxidants, is warranted. NFT and senile plaques have been shown to contain redox-active transition metals (Smith et al., 1997a Sayre et al., 2000) and may exert pro-oxidant... 

Chevion. M. A site-specific mechanism for free radical induced biological damage the essential role of redox-active transition metals. Free Radic. Biol Med 5 2" -37 1988. 

Metalloporphyrins, characterized by a redox-active transitional metal coordinated to a cyclic porphyrin core ligand, mitigate oxidative/nitrosative stress in biological systems. Side-chain substitutions tune redox properties of metalloporphyrins to act as potent superoxide dismutase mimetics, peroxynitrite decomposition catalysts, and redox regulators of transcription factor function. Metalloporphyrins are efficacious in AD models [538],... 

The many methods to initiate lipid peroxidation in vitro, such as azo initiators, metal ions, pulse radiolysis, photoinitiation (Type I), enzymes (oxidases), to mention a few, have been reviewed . However, as Bucala emphasized in a review ", oxidation initiation is a pivotal first step and there is little understanding of how initiation proceeds in vivo. Transition metal ions, iron or copper, are frequently used to initiate lipid oxidation, but free (unchelated) redox-active transition metals are virtually absent from biological systems" and appear to have little bearing on known pathological processes ". 

The vast majority of C-H animation protocols utilize redox active transition metals as catalysts. Recent discoveries have highlighted, however, the performance of redox inactive metal complexes and metal free conditions for effecting C-H to C-N bond conversion. 

Aminyl and amidyl radicals are conveniently generated from the homolytic or reductive cleavage of chloramines and chloramides [32-39]. The latter form under inflammatory conditions when amino acids and/or peptides are exposed, for example, to hypochlorous acid (HOCl). In vivo, the reduction of chloramines and chloramides may proceed through the action of superoxide, eventually catalyzed by redox-active transition metals, M"+, where M may be Fe and/or Cu (Reactions... 

The incorporation a redox-active transition metal head group into a self-assembling molecule provides a ready means for the immobilization of transition-metal complexes onto an electrode surface [13,24]. Unlike other approaches to immobilization which generally yield rough, unordered arrays of molecules, self-assembly techniques can produce well-ordered, atomically smooth molecular arrays. 

Zinc as trace element is as important as iron, but the biochemical function of zinc is opposite to that of iron while iron is the most important redox-active transition metal, zinc is the most important redox-inactive one. Zn(II) is used as Lewis acid and to tether domains of macromolecules into a distinct and concise structure. This ability of zinc results from the completely filled 3d-orbitals of the zinc atoms. 

Catalysis by metal-organic solids may also be applied to redox reactions. An especially intriguing target would be manipulation of hydrocarbon transformations. Many metal-organic networks so far reported in fact contain redox-active transition metals (Cu , Pd", Co" and so on). Metalloporphyrins are potential... 

Redox-Active Transition Metal-Based Receptors... 

When a redox-active transition metal is used as the signalling imit of a receptor, anion binding is coupled to electron transfer, i.e. anion binding changes the redox potential (couple) of the transition metal. This electrochemical shift can be represented as A, the difference in redox potentials between the receptor anion complex and the receptor alone. Concomitantly, electron transfer at the redox centre also changes the affinity of the receptor for the guest species. These coupled processes are linked thermodynamically by Eq. 1, where Kred and Kox are the stability constants of the reduced and oxidised forms of the receptor anion complex respectively [7]. 

The preceding sections have dealt with polymerization by either insertion or GTP mechanisms. Of course, vinyl monomers are also polymerizable by radical, anionic, or cationic mechanisms. In this short section, we summarize the processes which are reasonably well understood from a mechanistic viewpoint, and which involve the intervention of transition metal alkyls (or hydrides), either during initiation, propagation, or chain transfer/termination. A much larger class of polymerization reactions where redox-active transition metal complexes are used to mediate radical polymerizations by reversible atom transfer (ATRP) or other means has been extensively and recently reviewed from a mechanistic perspective and will only be briefly mentioned here. 

Redox-active polymers are conducting polymers containing specific electrostatically isolated but electrochemically active sites which can be oxidized or reduced [99]. Redox centers are either organic molecules or redox-active transition metals covalently bound to polymer backbone. 

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