Acta Chimica Sinica ›› 2012, Vol. 70 ›› Issue (07): 864-872 .DOI: 10.6023/A1109051 Previous Articles     Next Articles

Full Papers

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
  • 投稿日期:2011-09-05 修回日期:2011-12-02 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 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).

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