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

Iridium(iii) half-sandwich complexes containing 7-chloroquinoline-1,2,3-triazole hybrid ligands were synthesised and their inhibitory activities evaluated against thePlasmodium falciparummalaria 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 thein vitroactivity of selected ligands against the chloroquine-sensitive (NF54)Plasmodium falciparumstrain, 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 beta-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 beta-nicotinamide adenine dinucleotide (NAD(+)) to NADH in the presence of a hydrogen source, sodium formate.