铂配合物cis-[Pt(NH_3)_2(4-mepy)Cl]NO_3与甲基-谷胱甘肽作用的NMR研究

使用质子核磁共振方法测定了新的抗癌活性配合物cis－[Pt（NH3）2（4－mepy）Cl]＋与甲基-谷胱甘肽（GS－Me）的反应及其动力学．结果表明Pt与GS－Me间形成1：1加合物．为了解结合部位，对Pt－GS－Me配合物进行pH滴定，由GS－Me的质子核磁共振谱对pH的依赖关系判断Gs－Me只通过S原子与Pt配位，而氨基和羧基不参与配位反应．由配体吡啶环质子核磁共振随时间的变化，提出了两步反应机制：首先GS－Me通过S原子与Pt配位，然后由于S配位的高度反位效应使反应的NH3活动化．通过1HNMR方法测定了第一步反应的速率常数k＝0．017L·mol－1·s－1（pH3．1）和k＝0．013L·mol－1·s－1（pH7．2）．

1~H NMR Study of Interaction of cis-[Pt (NH_3)_2 (4-methylpyridine) Cl]NO_3 with S-methylglutathione

The interaction of antitumor activity complex, cis-[Pt (NH,3)2, (4-methylpyridine )Cl]No3 with S-methylglutathione (GS-Me) was determined using the method of proton NMR. The proton resonances of Pt complex and GS-Me were used as an indication of whether the reaction was completed or not. The results indicate that a Pt- to GS-Me ratio of 1:1 is required to bind all available GS-Me- The complex of Pt with GS-Me were titrated over pH range 1-12. The pH dependence of chemical shifts of g1, g3, g4 and g5 is depicted.It is concluded that GS-Me bind to Pt via S atom and no amino and carboxyl groups coordi-nate to Pt. The reaction mechanism was discussed and the time course of reaction was recorded. The reaction of Pt with GS-Me suggests a process in two steps: the first step in-volves the formation of Pt-GS-Me adduct via S atom, then ammonia coordinated trans to S will be lbaialized due to the high trans effect of S. The rate constant of reaction between Pt complex and GS-Me was determined by proton NMR, k=0.017 L. mol-1. s-1 (pH 3- 1)and 0.013 L. mol-1. s-1(pH 7. 2).