School of Chemistry, National University of Ireland, Galway, Ireland.
J Inorg Biochem. 2010 Apr;104(4):390-6. doi: 10.1016/j.jinorgbio.2009.11.010. Epub 2009 Dec 3.
The interaction of the antitumoural metallocene dihalides, titanocene dichloride (Cp(2)TiCl(2)) and Titanocene Y (bis-[(p-methoxybenzyl)cyclopentadienyl]titanium(IV) chloride), with bis(4-nitrophenyl) phosphate (BNPP), which is a widely used model for the phosphate diester linkages in DNA, has been studied. Cp(2)TiCl(2) has been shown to promote the cleavage of the phosphate diester in weakly acidic solution. At pH 4, 37 degrees C, a 10(6)-fold rate acceleration over the uncatalysed reaction was observed under pseudo-first-order conditions, when freshly prepared solutions of Cp(2)TiCl(2) were applied. The activity of aged solutions dropped significantly due to the formation of insoluble precipitates of hydrolysed Ti species. The precipitates isolated from aged solutions were shown to act as moderately active, heterogeneous catalysts for BNPP cleavage. By contrast, no hydrolysis of the phosphate diester could be observed in the presence of Titanocene Y. Implications for the mode of action of the apoptosis-inducing metallocene dihalides are discussed.
抗癌金属茂二卤化物，二氯二茂钛（Cp(2)TiCl(2)）和钛茂 Y（双-[(对甲氧基苄基)环戊二烯基]钛(IV) 氯化物）与双（4-硝基苯基）膦酸盐（BNPP）的相互作用已被研究。Cp(2)TiCl(2)已被证明可在弱酸性溶液中促进磷酸二酯键的断裂。在 pH 值为 4、37°C 的条件下，在假一级条件下，当应用新鲜制备的 Cp(2)TiCl(2)溶液时，与未催化反应相比，观察到 10(6)倍的速率加速。由于水解 Ti 物种形成不溶性沉淀物，老化溶液的活性显着下降。从老化溶液中分离出的沉淀物被证明是 BNPP 裂解的中等活性、多相催化剂。相比之下，在钛茂 Y 的存在下，不能观察到磷酸二酯的水解。讨论了诱导细胞凋亡的金属茂二卤化物的作用模式。
