Zhao G, Lin H, Zhu S, Sun H, Chen Y
Department of Chemistry, Nankai University, Tianjin, People's Republic of China.
J Inorg Biochem. 1998 Jul;70(3-4):219-26. doi: 10.1016/s0162-0134(98)10019-3.
Two novel dinuclear palladium(II) complexes, ¿[Pd(en)Cl]2(bpse)¿(NO3)2 (1) and ¿[Pd(en)Cl]2 (bpsu)¿(NO3)2 (2), (where en is ethylenediamine; bpse is bis(3-methyl-4-pyridyl) selenide; bpsu is bis(3-methyl-4-pyridyl) sulfide) have been synthesized. The complexes have been characterized by elemental analysis, IR, 1H NMR, and 13C NMR. They have been assayed for antitumor activity in vitro against the mice leukemia L1210 and the human coloadenocarcinoma HCT8 cell lines. The results show that compound 1 has a lower I.D.50 value against the two cancer cell lines as compared to compound 2; the compounds also shows a lower I.D.50 value than cisplatin against the HCT8 cell line, but a higher I.D.50 value than cisplatin against the L1210 cell line. Binding studies indicate that compound 1 possibly interacts with DNA by a nonintercalative mode. Kinetics of binding of the two compounds to DNA are firstly studied using ethidium bromide as a fluorescence probe with stopped-flow spectrophotometer under pseudo-first-order condition. The stronger binding of two steps in the process of the compounds interacting with DNA are observed, and the Kobs and Ea of binding of the two steps (where Kobs is the observed pseudo-first-order rate constant, Ea is the observed energy of activation) are obtained.
合成了两种新型双核钯（II）配合物，即[Pd(en)Cl]2(bpse)(NO3)2（1）和[Pd(en)Cl]2(bpsu)(NO3)2（2）（其中en为乙二胺；bpse为双（3-甲基-4-吡啶基）硒化物；bpsu为双（3-甲基-4-吡啶基）硫化物）。通过元素分析、红外光谱、1H核磁共振和13C核磁共振对配合物进行了表征。对它们进行了体外抗小鼠白血病L1210和人结肠腺癌HCT8细胞系的抗肿瘤活性测定。结果表明，与化合物2相比，化合物1对两种癌细胞系的半数抑制浓度（IC50）值较低；与顺铂相比，这些化合物对HCT8细胞系的IC50值较低，但对L1210细胞系的IC50值高于顺铂。结合研究表明，化合物1可能通过非嵌入模式与DNA相互作用。首次在准一级条件下，使用溴化乙锭作为荧光探针，用停流分光光度计研究了这两种化合物与DNA结合的动力学。观察到化合物与DNA相互作用过程中两步的较强结合，并获得了两步结合的观测伪一级速率常数（Kobs）和观测活化能（Ea）。
