The reduction of (ImH)[trans-RuIIICl4(dmso)(Im)] under physiological conditions:: preferential reaction of the reduced complex with human serum albumin
The reduction of (ImH)[trans-RuIIICl4(dmso)(Im)] under physiological conditions:: preferential reaction of the reduced complex with human serum albumin
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DOI：
10.1007/s00775-008-0378-3
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发表时间：
2008-08-01
影响因子：
3
通讯作者：
van Eldik, Rudi
中科院分区：
文献类型：
--
作者：
Brindell, Malgorzata;Stawoska, Iwona;van Eldik, Rudi
本文报道了在生理条件下L-抗坏血酸还原（ImH）[trans-RuCl（4）（dmso）（Im）]（NAMI-A; dmso为二甲基亚砜，Im为咪唑）的系统研究。在血浆条件下（pH7.4，0.1-0.15 M NaCl，37 ℃），反式-[Ru（III）Cl（4）（dmso）（Im）]（-）的快速还原导致在数秒内形成反式-[Ru（II）Cl（4）（dmso）（Im）]（2-），随后是氯化物配体的连续解离，而在反应过程中既不释放dmso也不释放咪唑配体.在我们的实验条件下，抗坏血酸二价阴离子的形成是速率决定步骤，一旦形成，它就会迅速与NAMI-A反应。此外，NAMI-A复合物在生理pH（7.4）下非常不稳定;因此，不能排除NAMI-A的水解是竞争反应。在水解过程中，通过氯化物和DMSO配体的逐步解离形成了水合衍生物，并且这些物质中的大多数具有更高的氧化还原电位，并且预计更容易被抗坏血酸还原。因此，NAMI-A的还原形式或其水解衍生物的还原产物很可能与白蛋白反应。还原的NAMI-A与人血清白蛋白的反应导致形成稳定的加合物，其结合效率与母体复合物非常相似，即，3.2分别为每摩尔白蛋白+/-0.3和4.0 +/-0.4摩尔Ru（II）和Ru（III），然而具有显著更高的反应性。
A systematic study of the reduction of (ImH)[trans-RuCl(4)(dmso)(Im)] (NAMI-A; dmso is dimethyl sulfoxide, Im is imidazole), a promising antimetastasing agent, by L-ascorbic acid under physiological conditions is reported. Under blood plasma conditions (pH 7.4, 0.1-0.15 M NaCl , 37 C) the rapid reduction of trans-[Ru(III)Cl(4)(dmso)(Im)](-) results in the formation of trans-[Ru(II)Cl(4)(dmso)(Im)](2-)within seconds, and is followed by successive dissociation of the chloride ligands, whereas neither dmso nor imidazole ligands are released during the reaction. Under our experimental conditions, the formation of the ascorbate dianion is the rate-determining step, and once it has formed it reacts rapidly with NAMI-A. Moreover, the NAMI-A complex is very unstable at physiological pH (7.4); therefore, the hydrolysis of NAMI-A cannot be excluded as a competing reaction. During hydrolysis, aquated derivatives via stepwise dissociation of chloride and dmso ligands are formed, and most of these species have a higher redox potential and are expected to be even more easily reduced by ascorbic acid. Thus, it is very likely that the reduced form of NAMI-A or the reduction products of its hydrolytic derivatives react with albumin. The reaction of reduced NAMI-A with human serum albumin leads to the formation of stable adducts, with a binding efficiency very similar to that of the parent complex, viz., 3.2 +/- 0.3 and 4.0 +/- 0.4 mol of Ru(II) and Ru(III) per mole of albumin, respectively, however with a significantly higher reactivity.