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

作　　者：梁曜华[1,2,3] 刘彦忠[3] 毕葳[3] 梁国刚[1,2,3] 

机构地区：[1]中药质量研究国家重点实验室澳门科技大学中医药学院,中国澳门氹仔伟龙马路 [2]澳门药物及健康应用研究所,澳门科技大学,中国澳门 [3]中国中医科学院中药研究所,北京100700

出　　处：《化学学报》2012年第7期864-872,共9页Acta Chimica Sinica

基　　金：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~~

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.Two NAMI （new antitumor metastasis inhibitor; trans-[RuC14（DMSO）（imidazole）]Nao2DMSO） derivatives, trans-[RuC14（DMSO）（2-MeIm）Na,2DMSO （2-MeIm=2-methyl imidazole, Compd. l） and trans-[RuC14（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 morestable than the relative NAMI derivatives.

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 

分 类 号：TQ460.1[化学工程—制药化工]