Cyclopalladated complexes containing tridentate thiosemicarbazone ligands of biological significance: Synthesis, structure and antimalarial activity

The C–H activation reaction of two aryl-derived thiosemicarbazones with K2[PdCl4] affords tetranuclear cyclopalladated complexes (3 and 4) where the thiosemicarbazone ligand acts as a tridentate donor [C,N,S] coordinated to palladium via the ortho-carbon of the aryl ring, imine nitrogen and thiolato sulfur. The palladium–sulfur bridging coordination bonds give rise to a Pd4S4 core. These Pd–Sbridging bonds were cleaved with a variety of mono- and bis-phosphines to give a series of mono, di and tetranuclear organopalladium complexes (5–12) where the phosphorus atom coordinates to palladium trans to the imine nitrogen. All of the complexes were fully characterized using various analytical and spectroscopic techniques. These palladium complexes along with their free ligands were evaluated as bioorganometallic antimalarial agents against two Plasmodium falciparum strains, 3D7 (chloroquine sensitive) and K1 (chloroquine and pyrimethamine resistant). Some of the complexes were found to be moderate inhibitors of parasite growth and were more active than the corresponding free ligand.

Graphical abstractSeveral mono, di and tetranuclear cyclopalladated complexes were synthesized through the C–H activation reaction of aryl-derived thiosemicarbazones ligands with K2[PdCl4]. Selected palladium complexes showed moderate antiplasmodial activity, with the biologically active palladium complexes showing greater activity than the corresponding free, uncomplexed ligand.Figure optionsDownload full-size imageDownload as PowerPoint slide