摘要
采用高效液相色谱研究了新型铂类抗癌药草酸铂与Cl-的取代反应动力学,并讨论了酸性条件下H+对取代反应的影响。结果表明,Cl-大量存在时,体系中草酸铂与Cl-的取代反应为优势反应,反应对草酸铂和Cl-均为一级。根据动力学数据提出了可能的反应机理,并由此推导出反应速率r=(KClk5'+K1'k3)犤L-OHP犦犤Cl-犦,与实验结果相吻合;当H+也大量存在时,取代反应被加速,此时表观速率常数kobs与犤H+犦、犤Cl-犦之间呈非线性递增,但反应对草酸铂仍为一级。在生理盐水中,反应的准一级速率常数kobs=3.6×10-4min-1,1%～2%的草酸铂发生反应所需时间不足1h,因此临床使用草酸铂时要避免与Cl-配伍。
The substitution reactions of oxaliplatin with Cl^- have been studied by high performance liquid chromatograph in neutral and acid aqueous solution.The experimental results show that under the condition ofCl - 0L-OHP 0 the reactions of oxaliplatin with Cl - are first order in both oxaliplatin a nd Cl - ,which have advantage over other reactions.In this paper,the p ossible mechanism has been proposed.From it,the rate law r=(K Cl k 5 ' +K 1 ' k 3 )Cl - L-OHPis deduced,which is in perfect agreement with the experiment results.Wh en excess acid is added to the systems,the reactions o f oxaliplatin with Cl - are accelerated by H + and the observed rate constants k obs are nonlinearly increased with the i mprovement ofH +orCl -.However,the rates of the reactions still follow to the first order dependence on L-OHP.In 0.9%NaCl solution,the pseu do-first-order rate constant k obs is3.6×10 -4 min -1 ,which determines that it takes less one hour for 1%～2%of oxaliplatin reacting with Cl - .As a result,the physiological saline so lution should not be used to dissolve or dilute the complex in clinical.
出处
《无机化学学报》
SCIE
CAS
CSCD
北大核心
2002年第7期679-682,共4页
Chinese Journal of Inorganic Chemistry
