Tomonori Konse

Electrocatalytic reduction of oxygen at a pyrolytic graphite electrode modified by adriamycin and its 7-deoxyaglycone

Abstract Anthracycline antibiotics, adriamycin and 7-deoxyadriamycinone, adsorbed on a basal-plane pyrolytic graphite electrode catalyze the reduction of molecular oxygen in pH 7.0 phosphate buffer. Cyclic and rotating-disk voltammetric studies show that the semiquinone radical intermediate is an active species m the catalytic reduction. The theoretical treatment newly developed here gives support to this mechanism. The cyclic and rotating-disk voltammograms are simulated by means of a non-linear least-squares curve-fitting technique. The results are quite good, and the kinetic parameter values thus evaluated by the curve-fitting method and also by the Koutecký-Levich-type equation are discussed.

Electrochemical study of the mechanism and kinetics of reductive glycoside elimination of adriamycin adsorbed on a mercury electrode surface

Abstract The mechanism of the reductive glycoside elimination of adriamycin ( 1 ) adsorbed on a mercury electrode surface has been studied by means of cyclic voltammetry and potential step chronoamperometry in phosphate buffer of pH 7.6. Detailed analyses of the voltammograms and chronoamperometric curves indicate that the quinone part in 1 is reduced to the hydroquinone species ( 3 ) via its semiquinone ( 2 ) and that species 3 eliminates a C 7 -glycoside to form a quinone methide intermediate ( 4 ), which brings about irreversible reactions through two pathways; one goes to the quinone-type species ( 5 ) of 7-deoxyadriamycinone by a protonation-deprotonation process (an apparent intramolecular proton shift), and the other route is a one-electron reduction producing the semiquinone species ( 6 ) of 7-deoxyadriamycinone. Compound 5 is reduced reversibly to the hydroquinone species ( 7 ) of 7-deoxyadriamycinone through 6 . The thermodynamic and kinetic parameters of the electrochemical redox reaction systems of 1 ⇌ 2 ⇌ 3 and 5 ⇌ 6 ⇌ 7 have been determined by analyses of the reversible and quasi-reversible cyclic voltammograms, applying the theory of a two-step one-electron surface-redox reaction. The theoretical equations of the reductive deglycosidation for the chronoamperometry and the cyclic voltammetry have been derived on the grounds of the above reaction mechanism. The apparent rate constants of the glycoside elimination ( 3 to 4 ) and the proton shift ( 4 to 5 ) and the electron-transfer rate constant of the irreversible reduction from 4 to 6 have been estimated by simulation of the chronoamperometric curve and cyclic voltammogram.

Electrochemical Study of the Mechanism and Kinetics of Oxygen Reduction Mediated by Anthracycline Antibiotics Adsorbed on Electrode Surface

It is well known that anthracycline antibiotics having an anthraquinone group in the molecule are an important class of widely used antitumor antibiotics1. Their clinical efficacy is limited by severe doserelated cardiotoxicity1,2. It has been considered that these undesirable side effects as well as the clinical benefits result from their ability to shuttle electrons from NADPH-cytochrome P-450 reductase to molecular oxygen that is, in turn, transformed into activated oxygen species such as superoxide anion radical, hydroxyl radical, and hydrogen peroxide1–3. The activated oxygen species have been proposed to play a fatal role in DNA scission4 and peroxidation of mitochondrial membranes5. However, the detailed mechanism is not yet fully understood.