Synthesis and Evaluation of a Carbosilane Congener of Ferroquine and Its Corresponding Half-Sandwich Ruthenium and Rhodium Complexes for Antiplasmodial and β-Hematin Inhibition Activity

Abstract

A silicon-containing congener of ferroquine (1) was synthesized by incorporating an organosilicon motif in the lateral side chain of ferroquine. Compound 1 was then further reacted with dinuclear half-sandwich transition-metal precursors [Ru(Ar)(μ-Cl)Cl]2 (Ar = η6-p-iPrC6H4Me, η6-C6H6, η6-C6H5OCH2CH2OH), [Rh(COD)(μ-Cl)]2, and [RhCp*(μ-Cl)Cl]2, to yield a series of heterometallic organometallic complexes (2–6). Compound 1 coordinates selectively in a monodentate manner to the transition metals via the quinoline nitrogen of the aminoquinoline scaffold. All of the compounds were characterized using various analytical and spectroscopic techniques, and the molecular structure of compound 1 was elucidated by single-crystal X-ray diffraction analysis. Furthermore, the in vitro antiplasmodial activity of compounds 1–6 was established against the chloroquine-sensitive (NF54) and chloroquine-resistant (Dd2) strains of the malaria parasite Plasmodium falciparum.