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.