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

doi:10.6023/A1109051

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

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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

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 Yaohua^a,b,c, Liu Yanzhong^c, Bi Wei^c, Liang Guogang^a,b,c

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 k_obs and t_1/2 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

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Liang Yaohua, Liu Yanzhong, Bi Wei, Liang Guogang. Influence of Ligand Structure on the Hydrolysis and Stability of NAMI Derivatives Containing 2-Methyl imidazole and N-Ethyl imidazole[J]. Acta Chimica Sinica, 2012, 70(07): 864-872 .

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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

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

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