KINETICS OF REDOX INTERACTION BETWEEN SUBSTITUTED 1,4-BENZOQUINONES AND ASCORBATE UNDER AEROBIC CONDITIONS - CRITICAL PHENOMENA

Redox cycling is believed to be the most general molecular mechanism o f quinone (Q) cytotoxicity. Along with redox cycling induced by a redu ctase, 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(.-) + O-2 --> Q + O-2(.- ) The net effect of reactions (1) and (2) provides for the c atalytic oxidation of AscH(-): with Q serving as a catalyst. In this w ork, the kinetics of oxygen consumption accompanying this process were studied with several substituted I,4-benzoquinones (BQ) at 37 degrees C in phosphate buffer, pH 7.40, using the Clark electrode technique. The value of k(1) determined from the initial rate of oxygen consumpti on was typically found to increase when the one-electron reduction pot ential 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 f ound to be directly correlated with the [QI[AscH-] value independent o f the concentration of individual reagents, remaining constant for a l ong period. With mono- and dialkyl-substituted 1,4-BQs, for which E(Q/ Q(.-)) is higher than -100 mV, significant deviations from the above s imple kinetic regularities were observed. In particular, R-OX decrease d dramatically with time and critical phenomena (the existence of cert ain concentrations of Q and/or AscH(-) above or below which the cataly tic oxidation of AscH(-) ceased completely after a non-stationary peri od of short duration) were observed. These abnormalities can be explai ned 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 thi s study for the problems of Q toxicity and vitamin C avitaminosis are discussed.