Electronic structural investigations of ruthenium compounds and anticancer prodrugs
Electronic structural investigations of ruthenium compounds and anticancer prodrugs
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DOI：
10.1007/s00775-009-0501-0
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发表时间：
2009-08-01
影响因子：
3
通讯作者：
Holman, Karen L. McFarlane
中科院分区：
文献类型：
--
作者：
Harris, Travis V.;Szilagyi, Robert K.;Holman, Karen L. McFarlane
一些钌-III化合物是有利的抗癌剂，但确切的作用机制仍然未知。在本文中，我们开始建立一个实验库的X射线吸收光谱（XAS）数据的10钌化合物，其中配体[Cl-，二甲亚砜，咪唑，和吲唑]系统地变化，以提供电子结构信息，为未来使用的相关光谱特征与化学性质。尽管研究的配合物的配位环境有相当大的差异，但使用密度泛函理论计算的光谱特征和电子结构的总体差异出乎意料地小。然而，在XAS数据中观察到的Ru-III前药KP 1019（[IndH][trans-RuCl 4（Ind）（2）]，Ind是吲唑）和ICR（[ImH][trans-RuCl 4（Im）（2）]，Im是咪唑）的电子结构的差异显示了与已知的化学和生物活性的相关性，以及咪唑与吲唑相比的供体能力和络合物的还原电位。这些半定量的结果奠定了基础，为未来的生物化学研究钌基抗癌药物的结构-功能关系。
Several Ru-III compounds are propitious anticancer agents although the precise mechanisms of action remain unknown. With this paper we start to establish an experimental library of X-ray absorption spectroscopy (XAS) data for ten Ru compounds wherein the ligands [Cl-, dimethyl sulfoxide, imidazole, and indazole] were varied systematically to provide electronic structural information for future use in correlating spectroscopic signatures with chemical properties. Despite the considerable difference in the coordination environments of the complexes studied, the overall differences in spectral features and electronic structures calculated using density functional theory are unexpectedly small. However, the differences in the electronic structure of the Ru-III prodrugs KP1019 ([IndH][trans-RuCl4(Ind)(2)], Ind is indazole) and ICR ([ImH][trans-RuCl4(Im)(2)], Im is imidazole) observed in the XAS data show correlation with known chemical and biological activities in addition to the donor abilities of imidazole compared with indazole and reduction potentials of the complexes. These semiquantitative results lay the groundwork for future biochemical studies into the structure-function relationships of Ru-based anticancer drugs.