Institute of Drug Discovery Technology (IDDT), Ningbo University, Ningbo 315211, China.
Li Dak Sum Yip Yio Chin Kenneth Li Marine Biopharmaceutical Research Center, Department of Marine Pharmacy, College of Food and Pharmaceutical Sciences, Ningbo University, Ningbo 315800, China.
Molecules. 2023 Jun 27;28(13):5035. doi: 10.3390/molecules28135035.
Ruthenium (Ru)-based organometallic drugs have gained attention as chemotherapeutic and bioimaging agents due to their fewer side effects and excellent physical optical properties. Tuning the electronic structures of Ru complexes has been proven to increase the cytotoxicity of cancer cells and the luminescent efficiency of the analytical probes. However, the relationship between electronic structures and bioactivities is still unclear due to the potential enhancement of both electron donor and acceptor properties. Thus, we investigated the relationship between the electronic structures of Ru(II) complexes and cytotoxicity by optimizing the electron-withdrawing (complex ), electron-neutral (complex ), and electron-donating (complex ) ligands through DFT calculations, bioactivities tests, and docking studies. Our results indicated that it was not sufficient to consider only either the effect of electron-withdrawing or electron-donating effects on biological activities instead of the total electronic effects. Furthermore, these complexes with electron-donating substituents (complex ) featured unique "off-on" luminescent emission phenomena caused by the various "HOMO-LUMO" distributions when they interacted with DNA, while complex with electron-withdrawing substituent showed an "always-on" signature. These findings offer valuable insight into the development of bifunctional chemotherapeutic agents along with bioimaging ability.
钌（Ru）基有机金属药物由于其副作用少和优异的物理光学性质而引起了人们的关注，可作为化疗药物和生物成像剂。事实证明，调节 Ru 配合物的电子结构可以提高癌细胞的细胞毒性和分析探针的发光效率。然而，由于电子给体和受体性质的潜在增强，电子结构和生物活性之间的关系仍不清楚。因此，我们通过 DFT 计算、生物活性测试和对接研究，优化了电子受主（复合物 ）、电子中性（复合物 ）和电子给体（复合物 ）配体，研究了 Ru(II) 配合物的电子结构与细胞毒性之间的关系。结果表明，仅考虑电子受主或供体效应对生物活性的影响，而不考虑总电子效应是不够的。此外，这些具有供电子取代基的配合物（复合物 ）与 DNA 相互作用时，由于不同的“HOMO-LUMO”分布，表现出独特的“关-开”发光发射现象，而具有吸电子取代基的配合物则表现出“常开”特征。这些发现为开发具有双重化疗和生物成像能力的双功能化疗药物提供了有价值的见解。
