Slobodan V. Jovanovic

Antioxidants in Nutrition

Abstract: The harmful effects of oxidative processes in living organisms, in addition to chemical and biochemical media, can be reduced by antioxidants. The efficacy of an antioxidant depends on its reduction potential and kinetics of elimination of diverse free radicals. Redox potentials and reaction rate constants of selected gallocatechins and flavonoids were measured by pulse radiolysis and laser photolysis. The reduction potentials of the flavonoids studied were in the range of 0.33 V (quercetin) and 0.75 V (kaempferol). The rate constants of the superoxide radical with 15 flavonoids ranged from 105‐107 M−1 s−1. Singlet oxygen quenching by flavonoids was also very rapid (from 105 to 108 M−1 s−1). These studies may be crucial in optimizing health and increasing longevity by reducing oxidative stress and biological damage.

Reduction potentials of flavonoid and model phenoxyl radicals. Which ring in flavonoids is responsible for antioxidant activity

Model phenoxyl and more complex flavonoid radicals were generated by azide radical induced one-electron oxidation in aqueous solutions. Spectral, acid–base and redox properties of the radicals were investigated by the pulse radiolysis technique. The physicochemical characteristics of the flavonoid radicals closely match those of the ring with the lower reduction potential. In flavonoids which have a 3,5-dihydroxyanisole (catechins), or a 2,4-dihydroxyacetophenone (hesperidin, rutin, quercetin)-like A ring and a catechol- or 2-methoxyphenol-like B ring, the antioxidant active moiety is clearly the B ring [reduction potential difference between the model phenoxyls is ΔE(A–B ring models) > 0.1 V]. In galangin, where the B ring is unsubstituted phenyl, the antioxidant active moiety is the A ring. Even though the A ring is not a good electron donor, E7 > 0.8/NHE V, it can still scavenge alkyl peroxyl radicals, E7= 1.06 V, and the superoxide radical, E7 > 1.06 V. Quercetin is the best electron donor of all investigated flavonoids (measured E10.8= 0.09 V, and calculated E7= 0.33 V). The favourable electron-donating properties originate from the electron donating 0-3 hydroxy group in the C ring, which is conjugated to the catechol (B ring) radical through the 2,3-double bond. The conjugation of the A and B rings is apparently minimal, amounting to less than 2.5% of the substituent effect in either direction. Thus, neglecting the acid–base equilibria of the A ring, and using those of the B ring and the measured values of the reduction potentials at pH 3, 7 and 13.5, the pH dependence of the reduction potentials of the flavonoid radicals can be calculated. In neutral and slightly alkaline media (pH 7–9), all investigated flavonoids are inferior electron donors to ascorbate. Quercetin, E7= 0.33 V, and gallocatechins, E7= 0.43 V, can reduce vitamin E radicals (assuming the same reduction potential as Trolox C radicals, E7= 0.48 V). Since all investigated flavonoid radicals have reduction potentials lower than E, =1.06 V of alkyl peroxyl radicals, the parent flavonoids qualify as chain-breaking antioxidants in any oxidation process mediated by these radicals.

Heterocyclic thiols as antioxidants: why ovothiol C is a better antioxidant than ergothioneine.

Spectral, acid-base, and redox properties of 4-mercaptoimidazoles were investigated by pulse radiolysis in aqueous solutions. Thiyl radicals of 1-methyl-5-ethyl-4-mercaptoimidazole (MEMI) have weak absorption band at 330 nm, epsilon = 300 +/- 60 M-1 cm-1. Because the ionic strength variation from 0.01 to 0.1 M in the pH range from 3 to 14 does not influence the rate constant of the radical decay, it is concluded that the MEMI thiyl radical is neutral. At pH 7, the reduction potential of the MEMI radical, E7 = 0.45 V, is lower than E7 = 0.48 V of the Trolox C radical, which means that MEMI may restitute vitamin E under physiological conditions (assuming similar reduction potentials of Trolox C and vitamin E radicals). Because pKa = 10.3 of the SH group in MEMI is lower than pKa = 11.9 of the OH group of Trolox C, the redox equilibrium with Trolox C is reversed at pH 13, and E13(MEMI-radical) = 0.29 +/- 0.04 V is determined against E13(Trolox C--radical) = 0.19 V. In contrast to extraordinary electron donating properties, MEMI is only a moderately good H-atom donor. k(.CH3 + MEMI) = (1.5 +/- 0.3) x 10(5) M-1 s-1 in neutral media is considerably lower than k(.CH3 + GSH) = 5 x 10(7) M-1 s-1, which is explained by the zwitterionic structure of MEMI. The ability of MEMI to act as antioxidant in biological systems is further demonstrated by its ability to efficiently scavenge superoxide and linoleate peroxyl radicals.(ABSTRACT TRUNCATED AT 250 WORDS)

Free Radical Mechanisms of DNA Base Damage

In many respects, DNA is a simple system where the reactions of free radicals are concerned. The reactive components in DNA are the four bases (thymine, T; cytosine, C; adenine, A; and guanine, G) and the sugar moiety (deoxyribose, dR). The sixth component — phosphate — is relatively unreactive towards free radicals.

Redox Properties of Oxy and Antioxidant Radicals

Defense mechanisms against damaging effects of oxy radicals are elaborate and numerous,1-3 which suggests that these mechanisms may have evolved over a long period of time with the development of biological and environmental oxidations which are inadvertently associated with generation of oxy radicals. What are the criteria that determined the choice of defense mechanisms? On the molecular level the efficiency of a particular defense mechanism depends on the reactivities of its subcomponents with oxy radicals, and its ability to reverse or prevent the damaging consequences of oxy radical reactions. Antioxidants are an important part of the defense system. Mechanistic aspects of some well-known and some potential physiological antioxidants are discussed.

Mechanisms of Inactivation of Oxygen Radicals by Dietary Antioxidants and Their Models

Numerous anticarcinogens (38) and antimutagens (15,39) have antioxidant properties, i.e., the ability to inhibit propagation of peroxidation processes by peroxy radicals (31), ROO·. Peroxy products (H2O2, ROOH) and various oxygen radicals (·OH, ·02, ROO·, RO·, ArO·) (35), which are sometimes called active oxygen species, appear to play an important role in carcinogenesis in general and promotion in particular (7). Consequently, the suggestion that dietary antioxidants (2) are critical in cancer prevention is gaining recognition and interest (8,10,21,27).

Electron vs. H-Atom Transfer in Chemical Repair

Free radicals are generated by ionizing radiations (e.g., X rays, γ rays, electrons, neutrons, and Rn α-particles),1 and the biological effects they cause are in some ways a consequence of their reactions.2 Free radicals may also be generated by other processes and agents and numerous chemicals generate them under physiological conditions. Cancer promoters3 and antineoplastic drugs4 cause DNA strand breaks via free radical reactions. Metabolic processes are also perceived as possible sources of free radicals.5–7 The repair of free radicals and the elimination (or reduction) of their biological effects by radioprotectors (mainly sulfhydryls) is a well-established defense mechanism in biological systems8. Although the interaction of anticarcinogens (primarily antioxidants) with free radicals is feasible, this is a poorly understood process.8,9

Free Radical Chemistry of Ergothioneine, A Potential Radioprotector and Antimutagen

Aliphatic thiols, RSH, have been shown to possess radioprotective and antimutagenic properties.1–3 The proposed mechanisms of these protective effects are based on the ability of thiols to donate H atom to various free radicals, whereby these radicals are repaired and inactivated.4