Fridovich identified CuZnSOD in 1969 and manganese superoxide dismutase (MnSOD) in 1973, and proposed ”the Superoxide Theory,” which postulates that superoxide (O2•−) is the origin of most reactive oxygen species (ROS) and that it undergoes a chain reaction in a cell, playing a central role in the ROS producing system. Increased oxidative stress on an organism causes damage to cells, the smallest constituent unit of an organism, which can lead to the onset of a variety of chronic diseases, such as Alzheimer’s, Parkinson’s, amyotrophic lateral sclerosis and other neurological diseases caused by abnormalities in biological defenses or increased intracellular reactive oxygen levels. Oxidative stress also plays a role in aging. Antioxidant systems, including non-enzyme low-molecular-weight antioxidants (such as, vitamins A, C and E, polyphenols, glutathione, and coenzyme Q10) and antioxidant enzymes, fight against oxidants in cells. Superoxide is considered to be a major factor in oxidant toxicity, and mitochondrial MnSOD enzymes constitute an essential defense against superoxide. Mitochondria are the major source of superoxide. The reaction of superoxide generated from mitochondria with nitric oxide is faster than SOD catalyzed reaction, and produces peroxynitrite. Thus, based on research conducted after Fridovich’s seminal studies, we now propose a modified superoxide theory; i.e., superoxide is the origin of reactive oxygen and nitrogen species (RONS) and, as such, causes various redox related diseases and aging.

The scavenging reaction of 2,2-diphenyl-1-picrylhydrazyl radical (DPPH.) or galvinoxyl radical (GO.) by a vitamin E model, 2,2,5,7,8-pentamethylchroman-6-ol (1H), was significantly accelerated by the presence of Mg(ClO4)2 in de-aerated methanol (MeOH). Such an acceleration indicates that the radical-scavenging reaction of 1H in MeOH proceeds via an electron transfer from 1H to the radical, followed by a proton transfer, rather than the one-step hydrogen atom transfer which has been observed in acetonitrile (MeCN). A significant negative shift of the one-electron oxidation potential of 1H in MeOH (0.63 V vs. SCE), due to strong solvation as compared to that in MeCN (0.97 V vs. SCE), may result in change of the radical-scavenging mechanisms between protic and aprotic media.

A catechin analogue in which the geometry was constrained to be planar was synthesized. The planar catechin showed excellent radical-scavenging ability, comparable to that of quercetin, and efficient protection against DNA strand breakage induced by the Fenton reaction.

The rate constants of electron transfer from C60 •- and C60 2- to electron acceptors such as allyl halides and manganese(III) dodecaphenylporphyrin are correlated with those from semiquinone radical anions and their derivatives; linear correlations are obtained between the logarithms of the rate constants and the oxidation potentials of C60 •-, C60 2-, and semiquinone radical anions for different electron acceptors. Such correlations indicate that reorganization energies for the electron-transfer reactions of C60 •- and C60 2- are essentially the same as those of semiquinone radical anions. The self-exchange rate constants between p-benzoquinone and the semiquinone radical anion as well as between tetramethyl-p-benzoquinone and the semiquinone radical anion in benzonitrile are determined at various temperatures by analyzing line width variations of the ESR spectra. The fast-exchange rate constants and small activation enthalpies demonstrate the efficient electron-transfer properties of the p-benzoquinone/semiquinone radical anion, C60/C60 •-, and C60 •-/C60 2- systems. The self-exchange rate constant between t-BuC60 • and t-BuC60 - is also determined by analyzing line width variations of the ESR spectra.

Homogeneous electron-transfer kinetics for the oxidation of seven different iron(III) porphyrins using three different oxidants were examined in deaerated acetonitrile, and the resulting data were evaluated in light of the Marcus theory of electron transfer to determine reorganization energies of the rate-determining oxidation of iron(III) to iron(IV). The investigated compounds are represented as (P)Fe(R), where P = the dianion of 2,3,7,8,12,13,17,18-octaethyl-5,10,15,20-tetraphenylporphyrin (OETPP) and R = C6H5, 3,5-C6F2H3, 2,4,6-C6F3H2, or C6F5 or P = the dianion of 2,3,7,8,12,13,17,18-octaethylporphyrin (OEP) and R = C6H5, 2,4,6-C6F3H2, or 2,3,5,6-C6F4H. The first one-electron transfer from (P)Fe(R) to [Ru(bpy)3]3+ (bpy = 2,2‘-bipyridine) leads to an Fe(IV) σ-bonded complex, [(P)FeIV(R)]+, and occurs at a rate which is much slower than the second one-electron transfer from [(P)FeIV(R)]+ to [Ru(bpy)3]3+ to give [(P)FeIV(R)]•2+. The one- or two-electron oxidation of each (OETPP)Fe(R) or (OEP)Fe(R) derivative was also attained by using [Fe(phen)3]3+ (phen = 1,10-phenanthroline) or [Fe(4,7-Me2phen)3]3+ (Me2phen = 4,7-dimethyl-1,10-phenanthroline) as an electron-transfer oxidant. The reorganization energies (kcal mol-1) for the metal-centered oxidation of (P)FeIII(R) to [(P)FeIV(R)]+ increase in the order (OEP)Fe(R) (83 ± 4) ≪ (OETPP)Fe(C6F5) (99 ± 2) < (OETPP)Fe(2,4,6-C6F3H2) (107 ± 2) < (OETPP)Fe(3,5-C6F2H3) (109 ± 3) < (OETPP)Fe(C6H5) (113 ± 3). Each value is significantly larger than the reorganization energies determined for the porphyrin-centered oxidations involving the same two series of compounds, i.e., the second electron transfer of (P)Fe(R). In each case, the first metal-centered oxidation is the rate-determining step for generation of the iron(IV) porphyrin π radical cation. Coordination of pyridine to (OETPP)Fe(C6F5) as a sixth axial ligand enhances significantly the rate of electron-transfer oxidation.

γ-Cyclodextrin-bicapped C 60 (C 60 /γ-CyD) shows an efficient DNA cleaving-activity in the presence of NADH (β-nicotinamide adenine dinucleotide, reduced form) in an O 2 -saturated aqueous solution under visible-light irradiation. No DNA cleavage has been observed without NADH under experimental conditions that are otherwise the same, although singlet oxygen ( 1 O 2 ) has been detected by the ESR spin-trapping of the C 60 / γ-CyD-O 2 system. This indicates that neither triplet excited state of C 60 /γ-CyD ( 3 C 60 */γ-CyD) nor 1 O 2 produced via an energy transfer from 3 C 60 */γ-CyD to O 2 is an actual reactive species, which is responsible for the DNA damage under the present experimental conditions. In the presence of NADH, photoinduced electron transfer from NADH to 3 C 60 */γ-CyD occurs to yield two equivalents of the radical anion (C 60 •-/γ-CyD), which exhibits its characteristic NIR band at 1080 nm. The dynamics of the photoinduced electron transfer have been examined by monitoring the decay of triplet-triplet absorption band at 740 nm and concomitant rise of the NIR absorption band at 1080 nm due to C 60 •-/γ-CyD with use of the laser flash photolysis for the C 60 /γ-CyD-NADH system. In the presence of O 2 , C 60 •-/γ-CyD disappears via the electron transfer to O 2 and an electron transfer from NADH to 1 O 2 to produced O 2 •-. The formation of O 2 •has been confirmed by the spin trap with DEPMPO (5-diethoxyphosphoryl-5-methyl-1-pyrroline-N-oxide), which is an efficient O 2 •-trapping agent. The reorganization energy for the reduction of O 2 to O 2 •is evaluated as 43.4 kcal mol -1 , which agrees with the literature value determined directly for the self-exchange between 36 O 2 •and 32 O 2 . This indicates that the electron transfer from C 60 •-/γ-CyD to O 2 proceeds via an outer-sphere pathway. The O 2 •thus produced gives H 2 O 2 , ultimately yielding hydroxyl radical, which is shown to be an actual DNAcleaving reagent.

A kinetic study of a hydrogen-transfer reaction from (+)-catechin (1) to galvinoxyl radical (G•) has been performed using UV−vis spectroscopy in the presence of Mg(ClO4)2 in deaerated acetonitrile (MeCN). The rate constants of hydrogen transfer from 1 to G• determined from the decay of the absorbance at 428 nm due to G• increase significantly with an increase in the concentration of Mg2+. The kinetics of hydrogen transfer from 1 to cumylperoxyl radical has also been examined in propionitrile (EtCN) at low temperature with use of ESR. The decay rate of cumylperoxyl radical in the presence of 1 was also accelerated by the presence of scandium triflate [Sc(OTf)3 (OTf = OSO2CF3)]. These results indicate that the hydrogen-transfer reaction of (+)-catechin proceeds via electron transfer from 1 to oxyl radicals followed by proton transfer rather than via a one-step hydrogen atom transfer. The coordination of metal ions to the one-electron reduced anions may stabilize the product, resulting in the acceleration of electron transfer.

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