Synthesis, Cellular Uptake and Biological Activity Against Pathogenic Microorganisms and Cancer Cells of Rhodium and Iridium N‐Heterocyclic Carbene Complexes Bearing Charged Substituents
Synthesis, Cellular Uptake and Biological Activity Against Pathogenic Microorganisms and Cancer Cells of Rhodium and Iridium N‐Heterocyclic Carbene Complexes Bearing Charged Substituents
复制标题
DOI：
10.1002/ejic.201300820
复制
发表时间：
2013-11
影响因子：
2.3
通讯作者：
P. Simpson;C. Schmidt;I. Ott;H. Bruhn;U. Schatzschneider
中科院分区：
文献类型：
--
作者：
P. Simpson;C. Schmidt;I. Ott;H. Bruhn;U. Schatzschneider
合成并表征了四种新的N-杂环卡宾（NHC）铑、铱配合物，并对其进行了阴离子或阳离子侧基修饰，以提高其水溶性和生物活性。测定络合物的亲脂性，并且含有阳离子鳞基团的络合物可以被认为是离域亲脂性阳离子（DLC）。所有的配合物进行了测试，其抗菌，抗寄生虫和抗癌活性，只有膦官能化的配合物显示出中度至高度的活性，而金属从铑到铱的交换具有可忽略不计的影响。最有希望的是对布氏锥虫的活性，IC 50值在150-400 nM范围内，选择性指数（SI）高达50。然而，对哺乳动物细胞系的一般毒性是一个普遍问题，需要在今后的工作中加以缓解。细胞摄取研究清楚地证实，阳离子鳞基团促进摄取，这与更高的生物活性有关。
Four new N-heterocyclic carbene (NHC) rhodium and iridium complexes decorated with anionic or cationic pendant groups to increase their water solubility and biological activity have been synthesised and characterised. The lipophilicity of the complexes was determined and the complexes that contained cationic phosphonium groups can be considered delocalised lipophilic cations (DLCs). All complexes were tested for their antibacterial, antiparasitic and anticancer activity, with only the phosphonium-functionalised complexes showing moderate to high activity, whereas the exchange of metal from rhodium to iridium had a negligible effect. Most promising was the activity on Trypanosoma brucei, with IC50 values in the range of 150–400 nM and a selectivity index (SI) of up to 50. General toxicity on mammalian cell lines was a general problem, though, and needs to be mitigated in future work. Cellular uptake studies clearly confirmed that the cationic phosphonium groups facilitated uptake, which was linked with higher biological activity.