Abstract
We report the synthesis, characterization, and biological activity of IrI complexes with triazole- (NNHC) and thiazole-based (NSHC) N-heterocyclic carbene ligands. Starting from the dimeric [Ir(COD)Cl]2, we obtained complexes of composition Ir(COD)(NNHC)Cl (4a), Ir(COD)(NNHC)X (4b: X = Cl; 4bBr: X = Br), [Ir(COD)(NNHC)(NHC)]I (5a), [Ir(COD)(NSHC)2]Cl (6a), and [Ir(COD)(NSHC)(NNHC)]Cl (6b) by adaptation of established synthetic methods for metal–NHC complexes. Their interactions with model proteins cytochrome c and lysozyme, as well as with the oligonucleotide hexamer (CG)3 (ODN1), were studied. Although most complexes did not show any strong interactions with these biomolecules, all complexes were active against HT-29 and MCF-7 cancerous cells, with IC50 values ranging between 1 and 60 µm. The most active compounds were the cationic bis(carbene) derivatives 5 and 6. All compounds generated high levels of reactive oxygen species (ROS) after incubation for 48 h in MCF-7 cells, possibly suggesting a redox-mediated mechanism of action. Interestingly, there were distinctive differences in the superoxide/(total ROS) ratios induced by the different groups of compounds.
Original language | English |
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Pages (from-to) | 2461-2470 |
Number of pages | 10 |
Journal | European Journal of Inorganic Chemistry |
Volume | 2018 |
Issue number | 20-21 |
Early online date | 24 May 2018 |
DOIs | |
Publication status | Published - 7 Jun 2018 |
Keywords
- Carbenes
- Iridium
- Medicinal chemistry
- Metal-based drugs
- Protein interactions
ASJC Scopus subject areas
- Inorganic Chemistry