| Autor: |
Lu, Yang, Hou, Zhiying, Li, Mengshan, Wang, Ning, Wang, Jinhui, Ni, Feng, Zhao, Yufen, Zhang, Bin, Xi, Ning |
| Předmět: |
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| Zdroj: |
Dalton Transactions: An International Journal of Inorganic Chemistry; 11/14/2022, Vol. 51 Issue 42, p16224-16235, 12p |
| Abstrakt: |
Ruthenium (Ru)-based chemotherapeutic agents are a choice to replace traditional platinum-containing metallodrugs due to fewer side effects. It has been proved that the mechanism of Ru complex drugs is to highly likely bind with DNA and certain proteins, which also highly depends on the electronic structures of Ru complexes. However, the relationship between electronic properties and chemotherapeutic activities has not yet been completely systemically investigated, which limits the effective drug design strategies. Herein, we propose that increasing the electron densities of Ru would enhance the nucleophilic substitution rate of chlorine atoms (Cl) on Ru, providing better bioactivity against both amino acids and nucleic acids. A series of complexes with various optimized electron-donating groups (EDGs) were synthesized according to DFT calculations. In addition, kinetics substitution with L -histidine, DNA binding experiments, and cell cytotoxicity studies verified our assumptions. Surprisingly, these complexes could also be potential cellular imaging probes via an unprecedented "off–on" light-switching mechanism of living cells, which was caused by the "HOMO–LUMO" distribution changes of Ru complexes after interaction with DNA. Accordingly, the reactivity and selectivity demonstrated by these compounds support the further development of these Ru complexes in cancer treatments and afford strategic perspectives on the development of metal complexes as chemotherapeutic agents and bioimaging probes. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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