Ruthenium pincer complexes for light activated toxicity: Lipophilic groups enhance toxicity
Ruthenium pincer complexes for light activated toxicity: Lipophilic groups enhance toxicity
复制标题
用于光激活毒性的钌钳形配合物：亲脂基团增强毒性
DOI：
10.1016/j.jinorgbio.2022.112110
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发表时间：
2023
影响因子：
3.9
通讯作者：
Papish, Elizabeth T.
中科院分区：
文献类型：
--
作者：
Sun, Yifei;Das, Sanjit;Brown, Spenser R.;Blevins, Emily R.;Qu, Fengrui;Ward, Nicholas A.;Gregory, Shawn Aiden;Boudreaux, Chance M.;Kim, Yonghyun;Papish, Elizabeth T.
在黑暗和光照条件下，对9个Ru-Cnc钳形化合物(1-9)在细胞培养中的抗癌活性进行了测试。这些配合物包括不同的Cnc钳形配体，包括吡啶环上的OH、OMe或Me取代基，以及翼尖N-杂环卡宾(NHC)基团，这些基团包括甲基(Me)、苯基(Ph)、均三甲基(Mes)和2，6-二异丙基苯基(Dipp)。支持配体包括乙腈、氯和2，2‘-联吡啶(BPY)供体。本文介绍了配合物8和9的合成方法，并用波谱(1HNMR，IR，UV-Vis，MS)和分析技术进行了充分的表征。本文报告了8号和9号单晶的X射线衍射结果。其他络合物(1-7)在别处有报道。四种亲脂性最强的Ru络合物(6、7、8和9)对MCF7癌细胞的活性最好，其中6和9表现出细胞毒性，而7和8表现出光激活的光细胞毒性。这些化合物在辛醇和水之间的分布被报告为对数(DO/w)值，并且对数(DO/w)值的增加与对癌细胞活性的改善大致相关。总体而言，NHC环上的亲脂性翼尖基团(例如Ph、Mes、Dipp)和较低的阳离子电荷(1+对2+)似乎有利于提高抗癌活性。
Nine ruthenium CNC pincer complexes (1–9) were tested for anticancer activity in cell culture under both dark and light conditions. These complexes included varied CNC pincer ligands including OH, OMe, or Me substituents on the pyridyl ring and wingtip N-heterocyclic carbene (NHC) groups which varied as methyl (Me), phenyl (Ph), mesityl (Mes), and 2,6-diisopropylphenyl (Dipp). The supporting ligands included acetonitrile, Cl, and 2,2′-bipyridine (bpy) donors. The synthesis of complexes8and9is described herein and are fully characterized by spectroscopic (1H NMR, IR, UV–Vis, MS) and analytical techniques. Single crystal X-ray diffraction results are reported herein for8and9. The other complexes (1–7) are reported elsewhere. The four most lipophilic ruthenium complexes (6,7,8, and9) showed the best activity vs. MCF7 cancer cells with complexes6and9showing cytotoxicity and complex7and8showing light activated photocytotoxicity. The distribution of these compounds between octanol and water is reported as log(Do/w) values, and increasing log(Do/w) values correlate roughly with improved activity vs. cancer cells. Overall, lipophilic wingtip groups (e.g. Ph, Mes, Dipp) on the NHC ring and a lower cationic charge (1+ vs. 2+) appears to be beneficial for improved anticancer activity.