Synthesis, Characterization and Anticancer Activity of Porphyrin-Containing Organometallic Cubes

Self-assembly of 5,10,15,20-tetra(4-pyridyl) porphyrin (tpp-H-2) and 5,10,15,20-tetra(4-pyridyl) porphyrin-M(II) (M = Ni (tpp-Ni); Zn(tpp-Zn)) tetradentate panels with the dinuclear p-cymene ruthenium clips [Ru-2(p-cymene)(2)(C2O4)Cl-2] and [Ru-2(p-cymene)(2)(C6H2O4)Cl-2] (C2O4 = oxalato; C6H2O4 = 2,5-dioxydo-1,4-benzoquinonato) affords the cationic organometallic cubes: [Ru-8(p-cymene)(8)(tpp-H-2)(2)(C2O4)(4)](8+) (1); [Ru-8(p-cymene)(8)(tpp-Ni)(2)(C2O4)(4)](8+) (2); [Ru-8(p-cymene)(8)(tpp-Zn)(2)(C2O4)(4)](8+) (3);[Ru-8(p-cymene)(8)(tpp-H-2)(2)(C6H2O4)(4)](8+) (4);[Ru-8(p-cymene)(8)(tpp-Ni)(2)(C6H2O4)(4)](8+) (5); and [Ru-8(p-cymene)(8)(tpp-Zn)(2)(C6H2O4)(4)](8+) (6). In addition, the new dinuclear arene ruthenium 2,5-dioxydo-1,4-benzoquinonato clips [Ru-2(indane)(2)(C6H2O4)Cl-2] (7) and [Ru-2(nonylbenzene)(2)(C6H2O4)Cl-2] (8) react in methanol with tpp-H-2 in the presence of silver triflate to afford the corresponding cationic cubes [Ru-8(indane)(8)(tpp-H-2)(2)(C6H2O4)(4)](8+) (9) and [Ru-8(nonylbenzene)(8)(tpp-H-2)(2)(C6H2O4)(4)](8+) (10) respectively. All cationic metalla-cubes were isolated as triflate salts and characterized by NMR, infrared, electro-spray mass spectrometry and UV-visible spectroscopy. Moreover, the formation of unsymmetrical metalla-cubes built using a mixture of the different porphyrin panels during the self-assembly of the 2,5-dioxydo-1,4-benzoquinonato metalla-cubes, [Ru-8(p-cymene)(8)(tpp-H-2)(tpp-Ni)(C6H2O4)(4)](8+) (11), [Ru-8(p-cymene)(8)(tpp-H-2)(tpp-Zn)(C6H2O4)(4)](8+) (12), and [Ru-8(p-cymene)(8)(tpp-Ni)(tpp-Zn)(C6H2O4)(4)](8+) (13), was studied by electro-spray mass spectrometry. The cytotoxicities of all metalla-cubes as well as the mixtures containing the unsymmetrical metalla-cubes were established on human ovarian A2780 and A2780cisR cancer cell lines. All symmetrical compounds are equally cytotoxic (IC50 = 7-15 mu M) (IC50 being the drug concentration necessary for 50% inhibition of cell viability) against both A2780 and cisplatin-resistant A2780cisR cancer cells, with stronger cytotoxicities (IC50 = 2-5 mu M) observed for the mixtures containing the unsymmetrical 2,5-dioxydo-1,4-benzoquinonato metalla-cubes.