Syntheses, structures, and anticancer activity of novel organometallic ruthenium-maltol complexes

Organometallic ruthenium complexes containing two dehydrogenated maltol ligands Ru ₃(CO) ₈(2L-2H) 1, Ru ₃(CO) ₇PPh ₃(2L-2H) 2, [Ru ₃(CO) ₇ (2L-2H)] ₂(dppm or dppe) 3,4 (L = Maltol) have been synthesized and characterized. The in vitro anticancer activity of compounds 1-4 against seven types of human cancer cell lines was assessed and compared to clinically used drug cisplatin. The anticancer activity of compound 1 (Fig. 3) is many times more potent than cisplatin against seven types of human cancer cell lines. There is a correlation between substituting a CO ligand in 1 with different phosphines decreases the activity following the order 1 > 2 > 3 > 4. The X-ray crystal structures of complexes 1 and 2 are reported. The single crystal X-ray diffraction structure of 1 consists of a triangular ruthenium metal framework in which a Ru-Ru bond is bridged by two maltolate ligands with their two oxygen atoms in a μ-η ²-bonding mode. The dihedral angle between Ru ₃ and maltol planes is 40.2°. The two ruthenium atoms bridged by maltol ligands each have two carbonyl ligands and the third ruthenium atom is bonded to four carbonyl ligands. The greatest structural difference between 1 and 2 is the angle between the best planes of the two coordinated C ₆H ₅O ₃ ^-1 ligands; in 1 it is 27.1° while in 2 it is 42.8°. It is interesting to note that the phosphine substitution occurs at the ruthenium atom not bound by maltol ligands.