Free radical-induced redox chemistry of Nedaplatin and Satraplatin under physiological conditions.
Temperature-dependent kinetics for the reactions of hydroxyl radicals and hydrated electrons with the anti-cancer drug nedaplatin have been determined using a combination of electron pulse radiolysis and absorption spectroscopy. Under physiological pH and chloride concentrations, the kinetics was well described by the equations [Formula: see text]and [Formula: see text]corresponding to Arrhenius activation energies of 15.88 +/- 1.16 and 14.14 +/- 1.41 kJ mol(-1) for hydroxyl radical oxidation and hydrated electron reduction, respectively. Through a comparison of spectral and kinetic literature it is believed that the oxidation reaction gives predominantly an intermediate Pt(III) species, whereas reduction gives a Pt(I) moiety. Analogous hydrated electron measurements for the Pt(IV) drug satraplatin showed multiple-component decays at higher temperatures (>20 degrees C), indicating that significant thermal degradation of this chemical occurs. From double-exponential curve fitting, the satraplatin reduction kinetics was found to be well described by the equation [Formula: see text]giving an activation energy of 22.78 +/- 1.78 kJ mol(-1) for this reaction. This measured temperature dependence was consistent with several model Pt(IV) compounds also investigated in this study, with all these data suggesting that the metal ion reduction to give Pt(III) was the dominant reaction occurring.
Department of Chemistry and Biochemistry, California State University Long Beach, Long Beach, California 90840, USA.
Katy L
KL
Swancutt
Stephen P
SP
Mezyk
James J
JJ
Kiddle
D000970:Antineoplastic Agents / Q000737:chemistry*; D004583:Electrons; D005609:Free Radicals / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D017665:Hydroxyl Radical / Q000737:chemistry*; D007700:Kinetics; D009944:Organoplatinum Compounds / Q000737:chemistry*; D010084:Oxidation-Reduction; D011675:Pulse Radiolysis; D013057:Spectrum Analysis; D013696:Temperature
D000970:Antineoplastic Agents; D005609:Free Radicals; D009944:Organoplatinum Compounds; D017665:Hydroxyl Radical; C081294:satraplatin; C053989:nedaplatin