Synthesis and Characterization of Aminochloroquinoline Ruthenium(II) Complexes as Potential Antimalarial Agents

Malaria is a serious infectious disease caused by parasites of the genus Plasmodium. It affects millions of people every year, especially in many countries of Sub-Saharan Africa. For many years, chloroquine has been widely used to treat malaria. However, many Plasmodium strains have developed resistance to this drug, reducing its effectiveness. For this reason, medicinal chemistry research is focused on developing new antimalarial compounds. In this thesis, five new Ru(II) p-cymene half-sandwich complexes with piano-stool geometry were synthesized and characterized as potential antimalarial agents. All complexes contain N,O bidentate ligands (L1–L5) belonging to the Schiff base family. These ligands are built on a 4-chloroquinoline framework structurally related to chloroquine, a drug widely used in antimalarial therapy. Ligands L1–L5 are salicylaldimine derivatives. Starting from ligand L1, containing (E)-2-(((7-chloroquinolin-4-yl)imino)methyl)phenol, the hydrogen atom at position 3 of the aromatic ring was replaced with halogen atoms (F, Cl, Br and I) to obtain the analogues L2–L5. The complexes [Ru(p-cymene)(L1–L5)Cl] (C1–C5) were characterized by ¹H NMR, FT-IR and UV-Vis spectroscopy, confirming the formation of the desired compounds. The ¹H NMR spectra showed that the main products were accompanied by small amounts of side-products, likely isomers due to different ligand orientations around the metal center, or substitution products such as [Ru(p-cymene)(L1–L5)(OH)] or [Ru(p-cymene)(L1–L5)(S)]⁺ (S = solvent). The typical piano-stool geometry was confirmed by single-crystal X-ray diffraction of [Ru(η⁶-cymene)(L3)Cl]. The structure shows the p-cymene ring coordinated to ruthenium in the apical position, while the three lower coordination sites are occupied by the chloride ligand and the two N,O donor atoms of the bidentate ligand.