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

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k_obs 及半衰期t_1/2. 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.

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

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) hydro-lyze 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 in-troducing 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.