Hydrolysis Mechanism of the NAMI-A-type Antitumor Complex (HL)[trans-RuCl4L(dmso-S)] (L=1-methyl-1,2,4-triazole)
Hydrolysis Mechanism of the NAMI-A-type Antitumor Complex (HL)[trans-RuCl4L(dmso-S)] (L=1-methyl-1,2,4-triazole)
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NAMI-A型抗肿瘤复合物(HL)[反式-RuCl4L(dmso-S)](L=1-甲基-1,2,4-三唑)的水解机制
DOI：
10.1088/1674-0068/24/04/383-390
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发表时间：
2011-08-01
影响因子：
1
通讯作者：
Zheng, Kang-cheng
中科院分区：
文献类型：
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作者：
Chen, Lan-mei;Chen, Jin-can;Zheng, Kang-cheng
用密度泛函理论结合类导体极化连续模型方法，研究了与著名抗癌药物(HIM)类似的Ru(III)配合物(HL)[反式RuCl4L(DMSO-S)](L=1-甲基-1，2，4-三氮唑和DMSO-S=S-二甲基亚砜)(1)的水解过程。得到了该络合物的结构特征和水解过程的详细能量分布。在第一步，化合物1的势垒能略高于报道的抗癌药物NaMI-A，这一结果与实验结果一致，表明化合物1的半衰期较大。对于第二步，顺式二水化合物的形成比反式异构体的形成具有热力学上的优势。此外，通过对水解过程中物种的电子特征的分析，揭示并预测了相关生物分子对水解产物的亲核攻击能力的趋势。
The hydrolysis process of Ru(III) complex (HL)[trans-RuCl4L(dmso-S)] (L=1-methyl-1,2,4-triazole and dmso-S=S-dimethyl sulfoxide) (1), a potential antitumor complex similar to the well-known antitumor agent (Him)[trans-RuCl4(dmso-S)(im)] (NAMI-A, im=imidazole), was investigated using density functional theory combined with the conductor-like polarizable continuum model approach. The structural characteristics and the detailed energy profiles for the hydrolysis processes of this complex were obtained. For the first hydrolysis step, complex 1 has slightly higher barrier energies than the reported anticancer drug NAMI-A, and the result is in accordance with the experimental evidence indicating larger half-life for complex 1. For the second hydrolysis step, the formation of cis-diaqua species is thermodynamic preferred to that of trans isomers. In addition, on the basis of the analysis of electronic characteristics of species in the hydrolysis process, the trend in nucleophilic attack abilities of hydrolysis products by pertinent biomolecules is revealed and predicted.