化学学报 ›› 2012, Vol. 70 ›› Issue (07): 864-872 .DOI: 10.6023/A1109051 上一篇    下一篇

研究论文

配体结构对含2-甲基咪唑及N-乙基咪唑的NAMI 衍生物水解及溶液稳定性的影响

梁曜华a,b,c, 刘彦忠c, 毕葳c, 梁国刚a,b,c   

  1. a 中药质量研究国家重点实验室 澳门科技大学中医药学院 伟龙马路 氹仔 澳门;
    b 澳门药物及健康应用研究所 澳门科技大学 澳门;
    c 中国中医科学院中药研究所 北京 100700
  • 收稿日期:2011-09-05 修回日期:2011-12-02 出版日期:2012-04-14 发布日期:2011-12-23
  • 通讯作者: 梁国刚
  • 基金资助:

    澳门科技发展基金(No. 012/2009/A1)、中国中医科学院基本科研业务费自主选题(No. ZZ03064)资助项目.

Influence of Ligand Structure on the Hydrolysis and Stability of NAMI Derivatives Containing 2-Methyl imidazole and N-Ethyl imidazole

Liang Yaohuaa,b,c, Liu Yanzhongc, Bi Weic, Liang Guoganga,b,c   

  1. a State Key Laboratory of Quality Research in Chinese Medicine, Faculty of Chinese Medicine, Macau University of Science and Technology, Avenida Wai Long, Taipa, Macau;
    b Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Macau;
    c Institute of Chinese Material Medica, China Academy of Chinese Medical Science, Beijing 100700
  • Received:2011-09-05 Revised:2011-12-02 Online:2012-04-14 Published:2011-12-23
  • Supported by:

    Project supported by the Science and Technology Development Fund in Macau (No. 012/2009/A1), part support from China Academy of Chinese Medical Sciences (No. ZZ03064).

制备并用UV、循环伏安(CV)和NMR 法研究了NAMI(新抗肿瘤转移抑制剂, trans-[RuCl4(DMSO)(imidazole)]Na·2DMSO)衍生物trans-[RuCl4(DMSO)(2-MeIm)]Na·2DMSO (2-MeIm=2-甲基咪唑, 化合物1)和trans-[RuCl4(DMSO)-(N-EtIm)]Na·2DMSO (N-EtIm=N-乙基咪唑, 化合物2)的水解机理-动力学、溶液稳定性和电化学性质. 化合物1 和化合物2 与NAMI 相似, 在pH 7.40 的缓冲溶液中发生两步脱氯水解反应(I 氯水解及II 氯水解) (分步反应); 在酸性溶液(pH 5.00)中脱DMSO 水解. 通过线性拟合得到各水解反应速率常数kobs 及半衰期t1/2. 结果表明化合物在酸性溶液中的稳定性相对较高. 在NAMI 衍生物咪唑环的N 位引入乙基比在2 位引入甲基生成的化合物稳定. 含氮配体相同时,NAMI-A(新抗肿瘤转移抑制剂, A: 该系列中的第一个化合物, trans-[RuCl4(DMSO)(imidazole)][Himidazole])衍生物略比相应的NAMI 衍生物稳定.

关键词: 钌化合物, 2-甲基咪唑, N-乙基咪唑, 抗转移, 水解动力学, 稳定性

Two NAMI (new antitumor metastasis inhibitor; trans-[RuCl4(DMSO)(imidazole)]Na·2DMSO) derivatives, trans-[RuCl4(DMSO)(2-MeIm)Na·2DMSO (2-MeIm=2-methyl imidazole, Compd. 1) and trans-[RuCl4(DMSO)(N-EtIm)]Na·2DMSO (N-EtIm=N-ethyl imidazole, Compd. 2) were prepared. Their hydrolytic mechanism-kinetics in pH 7.40/5.00 buffer solution and stability in physiological condition were investigated by UV, cyclic voltammetry (CV) and NMR. Similar to NAMI, both compounds undergo two well separated steps chloro-hydrolysis in pH 7.40 buffer solution; while dimethyl sulfoxide (DMSO) hydrolyze in pH 5.00 acetic buffer solution. The kobs and t1/2 for each reaction were determined. In conclusion, the stability of the complex in acidic solution is much more stable. The stability of the complex formed by introducing ethyl group at N position of imidazole ring would be much better than that of complex formed by introducing methyl group at 2 position of imidazole. The NAMI-A (new antitumuor metastasis inhibitor, A: this is the first of a series; trans-[RuCl4(DMSO)(imidazole)][Himidazole]) derivatives are somewhat more stable than the relative NAMI derivatives.

Key words: ruthenium complexes, 2-methyl imidazole, N-ethyl imidazole, anti-metastasis, hydrolytic kinetics, stabilities