关键词: 抗癌药, 反应机理, 反应动力学, 反应速度常数, 顺铂, 金属硫蛋白

Properties of the reactions of cis-dichlorodiammineplatinum(II) (cis-DDP) and related complexes with rabbit liver zinc- or apothionein have been investigated. Platinumthionein with a same stoichiometry, i.e. Pt7MT, was formed when excess cis-DDP or other Pt(II) complexes reacted with Zn7MT2 at neutral pH. The reactions are characterized by triphasic kinetics as monitored by the formation of Pt-thionein. The pseudo first order rate constants kI, kII and kIII corresponding three rate-limiting steps are determine, resp. The results show that the first rate step is sensitive to the nature of the ligands occupying the other two coordination sites in diammine-Pt(II), whereas kII, and KIII do not change markedly towards different conditions. It has been found for the first time that the rate of the reaction of trans-DDP with MT is about 4 times than that of cis-DDP. The equilibrium is established in 60 and 200 h for trans- and cis-DDP, resp., at pH 7.40 and 37癈. A mechanism for the reactions is proposed in which all of the hydrolysis species of platinum(II) complexes are thought to react directly with metallothionein followed by the loss of ammine ligands as the product formed. On this basis, the role of MT was discussed in relation to the difference of antitumor activity and toxicity of the two isomers of DDP.

Key words: ANTICARCINOGEN, REACTION MECHANISM, REACTION KINETICS, REACTION RATE CONSTANT, CLSPLATINUM, METALLOTHIONEIN