Metal ions, hydroxyl radical generation

The thermodynamic functions (AH, AS, AG(298 K)) of hydrogen peroxide reactions with transition metal ions in aqueous solutions are presented in Table 10.1. We see that AG(298K) has negative values for reactions of hydroxyl radical generation with Cu1+, Cr2+, and Fe2+ ions and for reactions of hydroperoxyl radical generation with Ce4+, Co3+, and Mn3+. 

Peroxyl radicals with a strong oxidative effect along with ROOH are continuously generated in oxidized organic compounds. They rapidly react with ion-reducing agents such as transition metal cations. Hydroxyl radicals react with transition metal ions in an aqueous solution extremely rapidly. Alkyl radicals are oxidized by transition metal ions in the higher valence state. The rate constants of these reactions are collected in Table 10.5. 

Other phenomena. Prion proteins, the mutated forms of which cause Creutzfeldt-Jacob disease, also appear to interact with metal ions. Spectra of Cu(H) bound to various mutant proteins have indicated anomalous binding behaviour.331 Hydroxyl radical generation during the interaction of mutant forms of a prion protein fragment with Fe(II) has also been reported.332... 

The superoxide oxide radical interacts with nitric oxide to produce peroxynitrite at a rate which three times faster than the rate at which superoxide dismutase utilizes superoxide (Beckman, 1994). Peroxynitrite is capable of diffusing to distant places in neural cells where it induces lipid peroxidation and may be involved in synaptosomal and myelin damage (Van der Veen and Roberts, 1999). After protonation and decomposition, peroxynitrite produces more hydroxyl radicals. This mechanism of hydroxyl radical generation is not dependent on redox active metal ions and may be involved in initiating lipid and protein peroxidation in vivo (Warner et al., 2004). 

Halliwell, B. and Gutteridge, M.C. (1992) Biologically relevant metal ion-dependent hydroxyl radical generation an update. FEBSUtt. 307 108-112. 

Other addic substances, such as ascorbic add, also form metals complexes. Of particular interest is the ternary complex of ascorbic add with oxygen and Fe + or Cu ions, formed during autoxidation of vitamin C (see Section 5.14.6.1.2). Ascorbic add can also reduce metal ions. During the reduction of Fe + ions to Fe + ions, hydroxyl radicals are generated as byproduds (see Section 5.14.6.1.3). In this reaction, ascorbic acid acts as a prooxidant The stability of ferric complexes of aliphatic organic adds decrease in the series citrate sucdnate ascorbate malate > lactate. 

Metal-ion catalysis of hydrogen peroxide decomposition can generate perhydroxyl and hydroxyl free radicals as in Scheme 10.26 [235]. The catalytic effects of Fe2+ and Fe3+ ions are found to be similar [235]. It is not necessary for the active catalyst to be dissolved [237], as rust particles can be a prime cause of local damage. The degradative free-radical reaction competes with the bleaching reaction, as illustrated in Scheme 10.27 [237]. Two adverse consequences arise from the presence of free radicals ... 

Figure 18.16 Hypothetical model for the metallobiology of AP in Alzheimer s disease. (From Bush, 2003. Copyright 2003, with permission from Elsevier.) The proposed sequence of events (1) concentration of iron and copper increase in the cortex with aging. There is an overproduction of APP and AP in an attempt to suppress cellular metal-ion levels. (2) Hyper-metallation of AP occurs which may facilitate H202 production. (3) Hyper-metallated AP reacts with H202 to generate oxidized and cross-linked forms, which are liberated from the membrane. (4) Soluble AP is released from the membrane and is precipitated by zinc which is released from the synaptic vesicles. Oxidized AP is the major component of the plaque deposits. (5) Oxidized AP initiates microglia activation. (6) H202 crosses cellular membranes to react with Cu and Fe, and generate hydroxyl radicals which oxidize a variety of proteins and lipids.

A further use of the system is to mediate the reaction of adamantane with carbon monoxide and oxygen to form 1-adamantanecarboxylic acid . When long-wavelength light (>300 nm) is used, hydroperoxides efficiently generate hydroxyl radicals without the use of metal ions and would be an extremely useful source of hydroxyl radicals, particularly in the design of DNA-cleaving molecules . ... 

The resultant hydroxyl radicals are effective in initiating many chain reactions. The number of metal ions and complexes which are capable of activating hydrogen peroxide in this manner is quite large and is determined in part by the redox potentials of the activator. Related systems in which free radicals are generated by the intervention of suitable metallic catalysts include many in which oxygen is consumed in autoxidations. Cobalt(H) compounds which act as oxygen carriers can often activate radicals in such systems by reactions of the type ... 

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