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The relative reactivities as well as the stoichiometric coefficients for a number of flavonoids, catechols, and--for comparison--standard phenolic antioxidants were determined by analyzing the kinetics of oxygen consumption in organic and micellar systems, with peroxidation initiated by lipid-and water-soluble azo initiators. The results demonstrated that the flavonoids did not behave as classic phenolic antioxidants such as 0t-tocopherol, but showed only moderate chainbreaking activities. The results were in line with other structureactivity relationship studies on the importance of the B-ring catechol structure, the 2,3-double bond, and the 3,5-hydroxy groups. The data are discussed in view of possible explanations of the deviations flavonoids reveal in their behavior compared with regular phenolic antioxidants. JAOCS 73, 777-786 (1996).

Redox cycling is believed to be the most general molecular mechanism of quinone (Q) cytotoxicity. Along with redox cycling induced by a reductase, a similar process is known to occur via electron transfer from ascorbate (AscH-) to Q with formation of a semiquinone radical (Q.-): (1) Q + AscH- (k1)--> Q.- + Asc.- + H+ (2) Q.- + O2 --> Q + O2.-. The net effect of reactions (1) and (2) provides for the catalytic oxidation of AscH-, with Q serving as a catalyst. In this work, the kinetics of oxygen consumption accompanying this process were studied with several substituted 1,4-benzoquinones (BQ) at 37 degrees C in phosphate buffer, pH 7.40, using the Clark electrode technique. The value of k1 determined from the initial rate of oxygen consumption was typically found to increase when the one-electron reduction potential E(Q/Q.-) shifted to more positive values. With Q, for which E(Q/Q.-) is less than -100 mV, the rate of oxygen uptake (R(OX)) was found to be directly correlated with the [Q][AscH-] value independent of the concentration of individual reagents, remaining constant for a long period. With mono- and dialkyl-substituted 1,4-BQs, for which E(Q/Q.-) is higher than -100 mV, significant deviations from the above simple kinetic regularities were observed. In particular, R(OX) decreased dramatically with time and critical phenomena (the existence of certain concentrations of Q and/or AscH- above or below which the catalytic oxidation of AscH- ceased completely after a non-stationary period of short duration) were observed. These abnormalities can be explained on the basis of the kinetic scheme which contains, in addition to reactions (1) and (2), several side reactions including that between Q.- and AscH-. Implications of critical phenomena discovered in this study for the problems of Q toxicity and vitamin C avitaminosis are discussed.

Comparative kinetic studies on the oxidation of catecholamines (CA) (dopamine (DA), epi nephrine (EP). norepinephrine (NEP)) serving as a neurom ediator in the sympathetic nervous system, 3,4-dihydroxyphenylalanine (DOPA) and 6-hydroxydopamine (6-OHDA), a wellknown neurotoxic agent, were perform ed in the presence of ascorbate (A scH -) in 50 mM phos phate buffer, pH 7.40, at 37 °C by using a Clark electrode, EPR and the absorption spectros copy. The oxidation of CA and DOPA alone was found to be a self-accelerating process, with quinone products (Q) acting as autocatalysts. The rate of oxygen consumption (Rox) increased with time and reached a steady-state level. A starting value of Ro x increased in the order: EP < DOPA « NEP « DA « 6-OHDA, whereas a steady-state value of Ro x changed in the or der: DOPA < DA < NEP « EP « 6-OHDA. The changes in R0x with time were found to correlate with the resistance of primary Q to the intramolecular cyclization.The effect of A scH -on CA oxidation depended dramatically on whether A scH -was added to non-oxidized or preoxidized CA. Added to non-oxidized CA and DOPA, A scHinhibited their oxidation (but not that of 6-OHDA). For the case of DA, a pronounced lag period was observed by both a Clark electrode and spectrophotometrically. The addition of A scH -to preoxidized CA. DOPA and 6-OHDA induced an increase in R0 x a°d a steadystate concentration of the ascorbyl radical. The kinetic behaviour of the systems was deter mined by two major factors: 1) A scH -suppressed the formation of Q, a catalyst for CA oxidation, most likely due to the reaction of A scH -with the semiquinone formed from CA; 2) Q derived both from CA and 6-OH D A catalyzed A scH -oxidation. The elevated cytotox icity of 6-OHDA was found to be in part caused by the condition that 6-OHDA oxidation was not inhibited by A scH -and by the high efficiency of 6-OHDA as a redox cycling agent in combination with A scH ". These observations explain the very pronounced and prolonged cytotoxicity of 6-OHDA even at low concentrations that increases at elevated concentrations of A scH -.

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