One-electron reduction of adriamycin and daunomycin: short-term stability of the semiquinones.
Pulse radiolysis studies of the one-electron reduction of adriamycin have now been extended to daunomycin. The daunomycin semiquinone has a pKa for phenolic dissociation of 2.8 +/- 0.1. Measurement of the one-electron reduction potential using several redox references at pH values within the range pH 6 to 12 indicated no significant difference between the semiquinones of adriamycin and those of daunomycin. A value of E1(7) = -341 +/- 15 mV (vs NHE) fitted the complete set of data for both compounds, with a pKa of the NH+3 group of the sugar moiety of 9.2 +/- 0.1. Measurement of equilibria between the semiquinones and the parent quinones and their fully reduced products showed a maximum semiquinone stability around pH 9. At pH 7 the stability constant is 0.04 for both adriamycin and daunomycin. From the equilibrium and E1 data, the second one-electron and the two-electron reduction potentials have been calculated over the pH range 7 to 12. E2(7) is -260 +/- 15 mV and Em7 is -300 +/- 15 mV for both compounds. The pKa values for the reduced anthracyclines have been calculated from the equilibrium data in the approximate pH range 7-12 to be 8.1 +/- 0.1 and 9.0 +/- 0.2 for the first two hydroxy groups and the two possible combinations for the ionization of the sugar NH+3 groups, with the remaining two hydroxy groups ionizing above pH 14.
Mukherjee
T
T
Paterson Institute for Cancer Research, Christie Hospital and Holt Radium Institute, Manchester, England.
Land
E J
EJ
Swallow
A J
AJ
Bruce
J M
JM
D003630:Daunorubicin; D004317:Doxorubicin; D005609:Free Radicals; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D010084:Oxidation-Reduction; D011809:Quinones; D013816:Thermodynamics
D005609:Free Radicals; D011809:Quinones; D004317:Doxorubicin; D003630:Daunorubicin