Subcellular localisation of a quinoline-containing fluorescent cyclometallated Ir(III) complex in Plasmodium falciparum.

Melis, Diana R; Hsiao, Chiao-Yu; Combrinck, Jill M; Wiesner, Lubbe; Smith, Gregory Stuart

A fluorescent analogue of a previously synthesised N,N -chelated Ir(III) complex was prepared by the coordination of the organic ligand to an extrinsic bis(2-phenylpyridine)iridium(III) fluorophore. This cyclometallated Ir(III) complex in itself displays good, micromolar activity against the chloroquine-sensitive NF54 strain of Plasmodium falciparum. Live-cell confocal microscopy found negligible localisation of the fluorescent complex within the digestive vacuole of the parasite, eliminating the haem detoxification pathway as a potential mechanism of action. Similarly, no localisation of the complex within the parasitic nucleus was found, suggesting that this complex likely does not interfere with the DNA replication process. A substantial saturation of fluorescence from the complex was found near phospholipid structures such as the plasma and nuclear membranes but not in neutral lipid bodies. This indicates that an association with these membranes, or organelles such as the endoplasmic reticulum or branched mitochondrion, could be essential to the efficacies of these types of antimalarial compounds.