含吡啶的抗肿瘤转移NAMI-A衍生物的制备和水解机理动力学  

Preparation and Mechanism-Kinetics of Antimetastasis of NAMI-A Derivatives Containing Pyridine

作　　者：梁曜华[1,2] 毕葳[2] 梁国刚[1,2] 

机构地区：[1]澳门药物及健康应用研究所,澳门科技大学,中国澳门 [2]中国中医科学院中药研究所,北京100700

出　　处：《无机化学学报》2011年第4期595-603,共9页Chinese Journal of Inorganic Chemistry

基　　金：澳门科技发展基金(No.012/2009/A1);国家科技部国际合作基金(No.2005DFA30990);中国中医科学院基本科研业务费自主选题项目(No.ZZ2006120,Z02089)资助

摘　　要：目的研究配体结构对NAMI-A衍生物水解机理、电化学性质的影响。方法制备了trans-[RuCl4(DMSO)(3-MePy)][(3-MePy)H](3-MePy=3-甲基吡啶,化合物1)和trans-[RuCl4(DMSO)(4-MePy)][(4-MePy)H](4-MePy=4-甲基吡啶,化合物2)。用UV、NMR、CV法研究化合物1、化合物2的水解机理-动力学、溶液稳定性及电化学性质。结果化合物1和化合物2与NAMI-A相似,在pH7.40的缓冲液中发生脱氯水解反应(Ⅰ氯水解及Ⅱ氯水解)(分步反应);在pH 5.00缓冲液中DMSO(二甲亚砜)及少量吡啶水解。测定各水解反应表观速率常数及半衰期、溶液稳定性及氧化还原电位。结论化合物1、化合物2的Ⅰ氯、Ⅱ氯及DMSO水解反应机理与NAMI-A相似,而且各水解速率与NAMI-A相差不大,即用甲基吡啶取代咪唑环,对NAMI-A衍生物的Ⅰ氯、Ⅱ氯及DMSO水解反应速率影响较小。化合物在酸性溶液中的稳定性明显高于中性溶液。Objective To study the influence of ligand structure on the hydrolysis rate of anti-metastasis NAMI-A derivatives trans-[RuCl4（DMSO）（3-MePy）][（3-MePy）H]（3-MePy=3-methypyridine,Compd.1） and trans-[RuCl4（DMSO）（4-MePy）][（4-MePy）H]（4-MePy=4-methypyridine,Compd.2）.Method Hydrolytic mechanism,kinetics,stability and electrochemistry of Compd.1 and Compd.2 were studied by UV-Vis,NMR and CV.Result The complexes undergo two well-separated steps of chloride hydrolysis at pH 7.40;while dimethyl sulfoxide（DMSO） hydrolyzed in pH 5.00 buffer solution.The Kobs and t1/2 for each reaction were determined.Conclusion Very similar to NAMI-A,the compounds loses 1st and 2nd chloride in two separated steps at pH 7.40;and loses DMSO in pH 5.00 buffer solution.The hydrolytic rate of the compounds including two chlorides and DMSO hydrolysis were similar to that of NAMI-A,which demonstrated that the influence of replacing imidazole by methyl pyridine on the hydrolysis rate of NAMI-A derivatives is not remarkable.The stability of the compounds in acidic solution is much more stable than that of in neutral solution.

关 键 词：钌配合物 抗肿瘤转移 水解动力学 稳定性 

分 类 号：O614.821[理学—无机化学]