Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

Cobalt-mediated selective C-H bond activation. Direct aromatic hydroxylation in the complexes [Co-III{o-OC6H3(R)N=NC5H4N}(2)]ClO4 center dot H2O (R = H, o-Me/Cl, m-Me/Cl or p-Me/Cl). Synthesis, spectroscopic and redox properties

The reactions of low-spin complexes [(CoL3)-L-II][ClO4](2). H2O 1 [L = 2-(arylazo)pyridine, (R)C6H4N=NC5H4N (R = H, o-Me/Cl, m-Me/Cl or p-Me/Cl] with m-chloroperbenzoic acid (m-ClC6H4CO3H) in acetonitrile solvent at room temperature resulted in low-spin [(CoL)-L-III'(2)]ClO4. H2O 2 [L' = o-OC6H3(R)N=NC5H4N]. In complexes 2 the o-carbon-hydrogen bond of the pendant phenyl ring of both parent ligands L has been selectively and spontaneously hydroxylated. During the transformation of 1 to 2 the metal ion is oxidised from the starting Co-II to Co-III. The meridional configuration (cis-trans-cis with respect to the oxygen, azo and pyridine nitrogens respectively) of complexes 2 has been established by H-1 and C-13 NMR spectroscopy. When one methyl or chloro group was present at the meta position of the pendant phenyl ring of L the reaction resulted in two isomeric complexes due to free rotation of the singly bonded meta-substituted phenyl ring with respect to the azo group. In acetonitrile solvent, complexes 2 systematically display one d-d transition ((1)A(1g) --> T-1(1g) near 850 nm, two metal to ligand charge-transfer transitions in the visible region and intraligand transitions in the UV region. In acetonitrile solution all complexes 2 exhibit irreversible Co-III --> Co-IV oxidation near 2 V and reversible Co-III reversible arrow Co-II reduction near 0.0 V versus Ag-AgCl. The ligand-based expected four azo (N=N) reductions are observed sequentially for all the complexes at the negative side of the reference Ag-AgCl. Complexes 2 can be quantitatively and stereoretentively reduced to the low-spin cobalt(II) congeners, [(CoL)-L-II'(2)] 2(-) electrochemically as well as chemically by using hydrazine hydrate. These complexes display eight-line EPR spectra in acetonitrile solution at 77 K. Complex 2a(-) exhibits a ligand to metal charge-transfer transition at 534 nm and intraligand transition at 345 nm. Two possible d-d transitions, E-2 --> T-2(1) and E-2 --> T-2(2) are observed at 700 and 800 nm respectively