Kinetics of redox interaction between substituted quinones and ascorbate under aerobic conditions

Abstract

One-electron reduction of quinones (Q) by ascorbate (AscH −); (1) AscH −+Q→Q − +Asc − +H +, followed by the oxidation of semiquinone (Q − ) by molecular oxygen; (2) Q − +O 2→Q+O 2 − , results in the catalytic oxidation of ascorbate (with Q as a catalyst) and formation of active forms of oxygen. Along with enzymatic redox cycling of Q, this process may be related to Q cytotoxicity and underlie an antitumor activity of some Qs. In this work, the kinetics of oxygen consumption accompanied the interaction of ascorbate with 55 Qs including substituted 1,4- and 1,2-benzoquinones, naphthoquinones and other quinoid compounds were studied in 50 mM sodium phosphate buffer, pH 7.40, at 37°C by using the Clark electrode technique. The capability of Q to catalyze ascorbate oxidation was characterized by the effective value of k EFF calculated from the initial rate of oxygen consumption ( R OX) by the equation R OX= k EFF[Q][AscH −] as well as by a temporary change in R OX. The correlation of k EFF with one-electron reduction potential, E(Q/Q − ), showed a sigma-like plot, the same for different kinds of Qs. Only the Qs which reduction potential E(Q/Q − ) ranged from nearly −250 to +50 mV displayed a pronounced catalytic activity, k EFF increased with shifting E(Q/Q − ) to positive values. The following linear correlation between k EFF (in M −1 s −1) and E(Q/Q − ) (in mV) might be suggested for these Qs: lg( k EFF)=3.91+0.0143 E(Q/Q − ). In contrast, Qs with E(Q/Q − )<−250 mV and E(Q/Q − )>+50 mV showed no measurable catalytic activity. The Qs studied displayed a wide variety in the kinetic regularities of oxygen consumption. When E(Q/Q − ) was more negative than −100 mV, Q displayed a simple (‘standard’) kinetic behavior— R OX was proportional to [AscH −][Q] independently of concentration of individual reagents, [AscH −] and [Q]; R OX did not decrease with time if [AscH −] was held constant; Q recycling was almost reversible. Meanwhile, Qs with E(Q/Q − )>−100 mV demonstrated a dramatic deviation from the ‘standard’ behavior that was manifested by the fast decrease in R OX with time and non-linear dependence of even starting values of R OX on [Q] and [AscH −]. These deviations were caused basically by the participation of Q − in side reactions different from (2). The above findings were confirmed by kinetic computer simulations. Some biological implications of Q–AscH − interaction were discussed.