A New Photoactivatable Ruthenium(II) Complex with an Asymmetric Bis-Thiocarbohydrazone: Chemical and Biological Investigations

Abstract

The synthesis, photoactivation and biological activity of a new piano-stool Ru(II) complex is herein reported. The peculiarity of this complex is that its monodentate ligand which undergoes the photodissociation is an asymmetric bis-thiocarbohydrazone ligand that possesses a pyridine moiety binding to Ru(II) and the other moiety contains a quinoline that endows the ligand with the capacity of chelating other metal ions. In this way, upon dissociation, the ligand can be released in the form of a metal complex. In this article, the double ability of this new Ru(II) complex to photorelease the ligand and to chelate copper and nickel is explored and confirmed. The biological activity of this compound is studied in cell line A549 revealing that, after irradiation, proliferation inhibition is reached at very low half maximal inhibitory concentration (IC50) values. Further, biological assays reveal that the dinuclear complex containing Ni is internalized in cells.

Light Triggers the Antiproliferative Activity of Naphthalimide-Conjugated (η6-arene)ruthenium(II) Complexes

“…Yet, all this notwithstanding, the naphthalimide ligands play a key role in the biological activity of the complexes, first because they act as antennae, and secondly because they may enhance the uptake of the Ru fragment into the cell. The previously synthesized Ru(II) complex [(η 6 - p -cym)Ru(N,N′-bpy)Cl](PF 6 ) (C4) [ 15 ], for example, without naphthalimide ligands, is also completely inactive in cells after 3 h of irradiation ( Table 2 ). C3 is the only complex that exhibits significant photocytotoxicity and the only compound able to absorb in the blue region.…”

“…The two photoproducts are the monodentate NI ligand and the solvated ruthenium complex [(η 6 - p -cym)Ru(N,N′-bpy)(DMSO)] 2+ ( Scheme 2 ; green point). It is also interesting to compare the biological activity of C3 and C5, another Ru(II) complex recently studied in our lab (C5, [(η 6 - p -cym)Ru(N,N′-bpy)L](CF 3 SO 3 ) 2 , L = N -4-formylpyridine-2-quinolinecarboxaldehydethiocarbohydrazone) [ 15 ]. The two IC 50 values are identical after irradiation (10.55 ± 0.30 μM and 10.52 ± 1.95, respectively), and this is probably because the biological activity of the two Ru(II) complexes depends on the formation of the same photoproduct [(η 6 - p -cym)Ru(N,N′-bpy)(DMSO)] 2+ .…”

“…In this paper, pursuing our ongoing interest to explore the photoactivation behavior and the biological activity of piano stool Ru(II) complexes [ 15 ], we have substituted the pyridine moiety with pyridine-functionalized NI ligands, obtaining three piano stool Ru(II) complexes with three different NIs as monodentate ligands ( Figure 1 ); L1 is devoid of functionalization, L2 has a strong electron-withdrawing group in position 3, and L3 has a strong electron donating group in position 4. The choice of the functional groups is important, because the type of substituents and their position with respect to the amide are responsible for the different photophysical properties of the NIs [ 16 ].…”

“…The uniqueness of this class of complexes is their ability to release L when irradiated with UVA light. The release of the ligand L leads to the formation of the aqua complex [(η 6 -arene)Ru(N,N )(OH 2 )] 2+ , a reactive species that is effectively active in cells [14,15].…”