Kinetics And Mechanism Of The Oxidation Of L-cysteine, Glutathione And Ascorbic Acid By Pt(Ⅳ) Complex

In recent years, We found that of Pt （IV） complexes also have anticancer activity in thescreening process on a large number of platinum drugs. Pt（IV） complexes have broadanticancer spectrum, which is similar to Pt（II） complexes. However, the accumulation andtoxicity are lower than those of Pt（II） complexes in body. Some Pt（IV） complexes are oraladministration such as JM216, oxoplatin et al. JM216have been applied to clinical trial.Kinetics and mechanism for the reaction K₂PtBr₆with L-cysteine, glutathione, ascorbicacid at25℃in ionic strength1.00M solution were studied using UV-vis spectrometer andstopped flow spectrometer. The pH ranges for oxidation L-cysteine, glutathione, ascorbic acidwere3.22-4.48,3.22-5.08,3.76-7.01, respectively. The reaction system was tracked at310nm,and the observed rate constants, kobs,were obtained. Plots passing through the origin for kobsasa function of [Reductant] are linear. It is shown that the reaction was first order with respectto each reductant. The reaction rate increased with the increase of pH value. We derived thetransition states and mechanism from the experimental phenomenon and data. The total ratelaw were derived from the reaction mechanism, and the rate-constants for rate-controlled stepwere obtained.Second-order rate constants for reduction of K₂PtBr₆by L-cysteine: k₁=4.79M^-1s^-1、k2=1.50×102M^-1s^-1、k3=1.84×108M^-1s^-1。Second-order rate constants for reduction of K₂PtBr₆by glutathione:k1=0.94M^-1s^-1、k2KA+k2,KB=0.28M^-1s^-1、k3=1.06×103M^-1s^-1、k4=1.86×108M^-1s^-1Second-order rate constants for reduction of K₂PtBr₆by ascorbic acid:k1=2.83M^1-s^-1、k₁=2.83M^-1s^-1,k₂=9.08M^-1s^-1.