SIOC English
化学学报
高级检索

化学学报 >

2012 , Vol. 70 >Issue 07: 864 - 872

DOI: https://doi.org/10.6023/A1109051

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 ,
  • 刘彦忠 ,
  • 毕葳 ,
  • 梁国刚
展开
  • 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

  网络出版日期: 2011-12-23

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.

收起

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

  • Liang Yaohua ,
  • Liu Yanzhong ,
  • Bi Wei ,
  • Liang Guogang
Expand
  • 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 date: 2011-09-05

  Revised date: 2011-12-02

  Online 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).

Fold

摘要

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

本文引用格式

梁曜华 , 刘彦忠 , 毕葳 , 梁国刚 . 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[J]. 化学学报, 2012 , 70(07) : 864 -872 . DOI: 10.6023/A1109051

Abstract

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

参考文献

1 Chen, Y.; Du, K.-J.; Chao, H.; Ji, L.-N. Prog. Chem. 2009,21, 836 (in Chinese). (陈禹, 杜可杰, 巢晖, 计亮年, 化学进展, 2009, 21, 836.)

2 Alessio, E.; Mestroni, G.; Bergamo, A.; Sava, G. Curr. Top. Med. Chem. 2004, 4, 1525.  

3 Bergamo, A.; Messori, L.; Piccioli, F.; Cocchietto, M.; Sava, G. Invest. New Drugs 2003, 21, 401.  

4 Pluim, D.; van Waardenburg, R. C.; Beijnen, J. H.; Schellens, J. H. Cancer Chemother. Pharmacol. 2004, 54, 71.  

5 Sava, G.; Pacor, S.; Bergamo, A.; Cocchietto, M.; Mestroni, G.; Alessio, E. Chem. Biol. Interact. 1995, 95, 109.  

6 Sava, G.; Capozzi, I.; Bergamo, A.; Gagliardi, R.; Cocchietto, M.; Masiero, L.; Onisto, M.; Alessio, E.; Mestroni, G.; Garbisa, S. Int. J. Cancer 1996, 68, 60.

7 Liu, J.; Ji, L.-N. Prog. Chem. 2004, 16, 969 (in Chinese). (刘杰, 计亮年, 化学进展, 2004, 16, 969.)

8 Alessio, E.; Mestroni, G.; Pocar, S.; Sava, G.; Spinelli, S. US5409893, 1995 [Chem. Abstr. 1991, 115, 125668y].

9 Heffeter, P.; Bock, K.; Atil, B.; Reza Hoda, M. A.; Korner, W.; Bartel, C.; Jungwirth, U.; Keppler, B. K.; Micksche, M.; Berger, W.; Koellensperger, G. J. Biol. Inorg. Chem.2010, 15, 737.  

10 Messori, L.; Orioli, P.; Vullo, D.; Alessio, E.; Iengo, E. Eur. J. Biochem. 2000, 267, 1206.

11 Chen, J.; Chen, L.; Liao, S.; Zheng, K.; Ji, L. J. Phys. Chem. B 2007, 111, 7862.  

12 Bacac, M.; Hotze, A. C.; van der Schilden, K.; Haasnoot, J. G.; Pacor, S.; Alessio, E.; Sava, G.; Reedijk, J. J. Inorg. Biochem. 2004, 98, 402.  

13 Frausin, F.; Scarcia, V.; Cocchietto, M.; Furlani, A.; Serli, B.; Alessio, E.; Sava, G. J. Pharmacol. Exp. Ther. 2005,313, 227.

14 Bouma, M.; Nuijen, B.; Jansen, M. T.; Sava, G.; Flaibani, A.; Bult, A.; Beijnen, J. H. Int. J. Pharm. 2002, 248, 239.

15 Bouma, M.; Nuijen, B.; Sava, G.; Perbellini, A.; Flaibani, A.; van Steenbergen, M. J.; Talsma, H.; Kettenes-van den Bosch, J. J.; Bult, A.; Beijnen, J. H. Int. J. Pharm. 2002,248, 247.

16 Vargiu, A. V.; Robertazzi, A.; Magistrato, A.; Ruggerone, P.; Carloni, P. J. Phys. Chem. B 2008, 112, 4401.  

17 Besker, N.; Coletti, C.; Marrone, A.; Re, N. J. Phys. Chem. B 2008, 112, 3871.  

18 Liang, Y.-H.; Bi, W.; Yang, B.; Zhao, L.; Liang, G.-G. Chem. J. Chin. Univ. 2011, 32, 210 (in Chinese). (梁曜华, 毕葳, 杨滨, 赵良, 梁国刚, 高等学校化学学 报, 2011, 32, 210.)

19 Liang, Y.-H.; Liang, G.-G. Chinese J. Inorg. Chem. 2008,24, 1983 (in Chinese). (梁曜华, 梁国刚, 无机化学学报, 2008, 24, 1983.)

20 Liang, Y.-H.; Liang, G.-G. J. Macau Univ. Sci. Technol.2008, 2, 36 (in Chinese). (梁曜华, 梁国刚, 澳门科技大学学报, 2008, 2, 36.)

21 Ravera, M.; Baracco, S.; Cassino, C.; Zanello, P.; Osella, D. Dalton Trans. 2004, 15, 2347.

22 Liang, Y.-H.; Bi, W.; Liang, G.-G. Chinese J. Inorg. Chem.2011, 27, 595 (in Chinese). (梁曜华, 毕葳, 梁国刚, 无机化学学报, 2011, 27, 595.)

23 Mestroni, G.; Alessio, E.; Sava, G.; Pacor, S.; Coluccia, M.; Boccarelli, A. Met.-Based Drugs 1994, 1, 41.  

Options
文章导航

/

〈 〉