Synthesis, characterization and cytotoxic activity of cationic half-sandwich Ru() complexes stabilized by iminophosphorane N,N,S and N,N,Se tridentate ligands

Five new structurally related half-sandwich cationic Ru( ii ) complexes of general formula [(η 6 - p -cymene)RuL]Cl ( 6 ) and [(η 6 - p -cymene)RuL]PF 6 (L = [2-C 8 H 5 N(Ph 2 P&z.dbd;NC 6 H 4 XR)] − [R = C 6 H 5 , X = S ( 9 ), and Se ( 6 , and 10 ); R = CH 3 , X = S ( 11 ), and Se ( 12 )]) were designed and synthesized in search of new ruthenium anticancer drugs. The complexes were fully characterized by elemental analysis and various spectral methods (multinuclear NMR, and MS). The solid-state molecular structures of complexes 6 , 9 , and 10 were determined by X-ray crystallography and confirm the presence of pseudo-octahedral geometry around ruthenium and the facial tridentate N,N,X coordination of the iminophosphorane ligands. Solubility tests have shown compounds 9-12 to be highly soluble in polar solvents (DMSO, DMF, THF, and CH 2 Cl 2 ), but insoluble in water or mixtures of DMSO/water. Different surfactants have been tested to resolve this issue, and only Tween 80 advantageously prevented precipitation in aqueous medium, and allowed for cytotoxic evaluation of complexes 9-12 using sulforhodamine B (SRB) colorimetric assay against breast carcinoma (MCF-7), prostate carcinoma (PC-3), and cervical carcinoma (SiHa) along with noncancerous HFF cells (human foreskin fibroblasts), using cisplatin as the reference standard drug. All four complexes showed high cytotoxic effects (IC 50 : 0.664-3.496 μg mL −1 |0.717-3.973 μM) against the three cancer cell lines but only complexes 9-11 showed poor cytoxicity in normal fibroblasts (IC 50 : 6.069-7.227 μg mL −1 |6.898-8.214 μM). Complex 10 showed a high selectivity index (SI > 3) for the three cancer types and appeared as a promising cancer therapeutic candidate worthy of further investigation. New Ru( ii ) half-sandwich complexes stabilized by tridentate iminophosphorane N,N,S or N,N,Se ligands show potent cytotoxic activity with high selectivity.