Iron-dioxygen complexes

It is important to form a stable 1 1 dioxygen-metal complex, because oxyhemoglobin and oxymyoglobin are 1 1 dioxygen-iron complexes which can reversibly... 

One of the major difficulties encountered in attempts to prepare 1 1 dioxygen-iron complexes which can desorb molecular oxygen, particularly oxygenated complexes of ferroheme, is the strong driving force toward the irreversible formation of the stable p-oxo ferriheme dimer, as represented in Eq. (11). The oxygenated... 

A number of binuclear iron complexes have also been isolated (with a neutral base attached to each metal in an axial position). The iron complexes undergo net two-electron redox reactions with dioxygen to yield products containing two identical low-spin Fe(n) metal sites superoxide or peroxide are simultaneously generated. Remarkably, the reaction can be partially reversed by removal of 02 from the system by, for example, flushing with N2 in a mixed aqueous solvent at 0°C. 

A number of model studies of the second type have also been investigated. In these, the iron complex provides a hydrophobic cavity so positioned that it surrounds the bound 02 molecule. These include the lacunar complexes mentioned in Chapter 3 (Goldsby, Beato Busch, 1986) particular complexes of which are quite efficient reversible carriers. A further (early) example of this type was (312) which encloses the dioxygen in a rudimentary cavity. However, this species only binds dioxygen reversibly at low temperatures (Baldwin Huff, 1973). 

The third group of studies involves attachment of the iron complexes to solid substrates in order to inhibit formation of bridged species. In a very early study, dioxygen was found to bind reversibly to haem diethyl ester embedded in a mixture of polystyrene and l-(2-phenylethyl)imidazole (Wang, 1958). 

Other aspects of solvation have included the use of surfactants (SDS, CTAB, Triton X-100), sometimes in pyridine-containing solution, to solubilize and de-aggregate hemes, i.e., to dissolve them in water (see porphyrin complexes, Section 5.4.3.7.2). An example is provided by the solubilization of an iron-copper diporphyrin to permit a study of its reactions with dioxygen and with carbon monoxide in an aqueous environment. Iron complexes have provided the lipophilic and hydrophilic components in the bifunctional phase transfer catalysts [Fe(diimine)2Cl2]Cl and [EtsBzNJpeCU], respectively. 

Over the past 15 years, we developed three procedures for the iron-mediated carbazole synthesis, which differ in the mode of oxidative cyclization arylamine cyclization, quinone imine cyclization, and oxidative cyclization by air (8,10,557,558). The one-pot transformation of the arylamine-substituted tricarbonyl(ri -cyclohexadiene) iron complexes 571 to the 9H-carbazoles 573 proceeds via a sequence of cyclization, aromatization, and demetalation. This iron-mediated arylamine cyclization has been widely applied to the total synthesis of a broad range of 1-oxygenated, 3-oxygenated, and 3,4-dioxygenated carbazole alkaloids (Scheme 5.24). 

Retrosynthetic analysis of the 2,7-dioxygenated carbazole alkaloids, 7-methoxy-O-methylmukonal (48), clausine H (clauszoline-C) (50), clausine K (clauszoline-J) (51), and clausine O (72), based on an iron-mediated approach, led to 2-methoxy-substituted iron complex salt 665 and 3-methoxy-4-methylaniline (655) as precursors (588) (Scheme 5.53). 

Binding of dioxygen to the water-free iron complex 4a leads to 5a (Fig. 10), which has a septet ground state originating from the triplet dioxygen and the quintet iron complex 4a and which is... 

Fig. 10. Water-free iron complex with dioxygen placed above the cofactor (5a) and the transition state for dioxygen coordination to iron (TS[5a-6a] ). Distances are given in angstroms.

The antitumor antibiotic bleomycin (BLM) is believed to cause cytotoxicity through its ability, in the combined presence of dioxygen and a metal ion cofactor (204), to bind to and degrade DNA (205). Iron complexes of BLM have aroused special attention, as such complexes are the first (vide supra concerning the discussion of hemerythrin and hemocyanin) non-heme-iron complexes with a significant capacity for dioxygen activation (206). 

Increase in the ruthenium concentration increases the stoichiometric factor, n in Eq. (2), from about 6 up to about 20, and in these more concentrated solutions rates of ruthenium(III) reduction are no longer first order in ruthenium(III). Under these conditions reaction products depend on the hydroxide concentration and include hydroxy-aromatic ligands [cf. Eq. (3)], carbonate, and trace amounts of dioxygen. Ruthenium complexes of ligands in which one pyridine ring had been completely oxidized were also characterized (2). This accounts for the carbonate, and the minor dioxygen yields could originate from complexes oxidized to ruthenium(IV) (8). Unlike the iron(III) system, neither free 2,2 -bipyridine nor the N-oxide was detected. 

Fen(OPPh3)4+, Fen(bpy)2+, and Fen(MeCN)4+ in acetonitrile (MeCN) under an argon atmosphere. When dioxygen (02) (1 atm, 8.1 mM Em, —0.87 V vs. SCE in MeCN) is present, these iron complexes each exhibit a new irreversible reduction peak at potentials that are significantly less negative than those for the iron(II/I) couples and the 02/02 couple (Figure 9.8). 

It has been suggested that a (dioxygen)iron(II), or perferryl 1 complex, a likely intermediate in the autoxidation of iron(II), could abstract an allylic hydrogen and initiate lipid peroxidation [48]. Such complexes are weak oxidants at best, as has been shown before [49] and, with the exception of iron(II) edta [50], have not been observed. Constraints on the reduction potential... 

A variation on the (dioxygen)iron(II) complex, an Fe Fe111 intermediate, was proposed by Aust and coworkers as the instigator of oxyradical damage [37,51]. There is no thermodynamic data available that allows one to calculate how oxidising such a complex would be. It is conceivable that an equal mixture of iron(II) and iron(III) compounds imposes a reduction potential on the system that is favourable for catalysis of lipid peroxidation. 

Lippard and co-workers (58, 59) proposed a route (Scheme 4) for the production of 37 from 36 based on the stoichiometry of iron complex to dioxygen. Binding of dioxygen to 36 might yield a reactive superoxo or peroxo adduct that might oxidatively react with solvent, ligand, or adventitious protons to yield 37 directly, using one mole of 02 per mole of 36. 

Many of the structurally characterized -superoxo complexes are cobalt containing, or are iron complexes with sterically hindering porphyrins. Co compounds often react with dioxygen to form mononuclear superoxo complexes. 

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