Strained, Photoejecting Ru(II) Complexes that are Cytotoxic Under Hypoxic Conditions
Strained, Photoejecting Ru(II) Complexes that are Cytotoxic Under Hypoxic Conditions
复制标题
DOI：
10.1111/php.13174
复制
发表时间：
2019-12-06
影响因子：
3.3
通讯作者：
McFarland, Sherri A.
中科院分区：
文献类型：
--
作者：
Roque, John, III;Havrylyuk, Dmytro;McFarland, Sherri A.
研究了一系列应变Ru(II)配合物在低氧组织中的潜在抗癌活性。这些配合物的甲基化配体是光敏性的，而亚胺并[4，5-f][1，10]邻菲咯啉配体含有一个附加的芳基，从而潜在地允许以配体为中心的激发态的贡献。利用含有1-4个稠环的体系系统地改变了芳香族基团的大小和能量，并对所有配合物的光化学和光生物行为进行了评估。芳香族基团的结构和性质对光化学有微妙的影响，改变了环境敏感性，并对细胞毒性和光生物学有重大影响。在没有光激活的情况下，观察到的细胞毒性差异高达5倍；当暴露在453 nm的光下时，这一差异上升到50倍。最重要的是，一个复合体在含1%O-2的条件下保持了活性，用于诱导低氧变化。该体系的光细胞毒性指数(PI)为15，与大多数其他Ru(II)络合物形成鲜明对比，包括那些为氧-2非依赖性作用机制设计的络合物。
A series of strained Ru(II) complexes were studied for potential anticancer activity in hypoxic tissues. The complexes were constructed with methylated ligands that were photolabile and an imidizo[4,5-f][1,10]phenanthroline ligand that contained an appended aromatic group to potentially allow for contributions of ligand-centered excited states. A systematic variation of the size and energy of the aromatic group was performed using systems containing 1-4 fused rings, and the photochemical and photobiological behaviors of all complexes were assessed. The structure and nature of the aromatic group had a subtle impact on photochemistry, altering environmental sensitivity, and had a significant impact on cellular cytotoxicity and photobiology. Up to 5-fold differences in cytotoxicity were observed in the absence of light activation; this rose to 50-fold differences upon exposure to 453 nm light. Most significantly, one complex retained activity under conditions with 1% O-2, which is used to induce hypoxic changes. This system exhibited a photocytotoxicity index (PI) of 15, which is in marked contrast to most other Ru(II) complexes, including those designed for O-2-independent mechanisms of action.