Quinoline-triazole half-sandwich iridium(iii) complexes : Synthesis, antiplasmodial activity and preliminary transfer hydrogenation studies

Summary, in English

Iridium(iii) half-sandwich complexes containing 7-chloroquinoline-1,2,3-triazole hybrid ligands were synthesised and their inhibitory activities evaluated against the Plasmodium falciparum malaria parasite. Supporting computational analysis revealed that metal coordination to the quinoline nitrogen occurs first, forming a kinetic product that, upon heating over time, forms a more stable cyclometallated thermodynamic product. Single crystal X-ray diffraction confirmed the proposed molecular structures of both isolated kinetic and thermodynamic products. Complexation with iridium significantly enhances the in vitro activity of selected ligands against the chloroquine-sensitive (NF54) Plasmodium falciparum strain, with selected complexes being over one hundred times more active than their respective ligands. No cross-resistance was observed in the chloroquine-resistant (K1) strain. No cytotoxicity was observed for selected complexes tested against the mammalian Chinese Hamster Ovarian (CHO) cell line. In addition, speed-of-action assays and β-haematin inhibition studies were performed. Through preliminary qualitative and quantitative cell-free experiments, it was found that the two most active neutral, cyclometallated complexes can act as transfer hydrogenation catalysts, by reducing β-nicotinamide adenine dinucleotide (NAD+) to NADH in the presence of a hydrogen source, sodium formate.

• Author: Diana R. Melis; Christopher B. Barnett; Lubbe Wiesner; Ebbe Nordlander; Gregory S. Smith
• Department/s: Chemical Physics
• Publishing year: 2020
• Language: English
• Pages: 11543-11555
• Publication/Series: Dalton Transactions
• Volume: 49
• Issue: 33
• Links: http://dx.doi.org/10.1039/d0dt01935f
• Document type: Journal article
• Publisher: Royal Society of Chemistry
• Topic: Chemical Sciences
• Status: Published
• ISBN/ISSN/Other: ISSN: 1477-9226