BODIPY-based Ru(II) and Ir(III) organometallic complexes of avobenzone, a sunscreen material: Potent anticancer...

The use of organic compounds with known medicinal properties in the synthesis of metal-based complexes is an important alternative to improve the biological activity of metal-based drugs. The reaction of [M(arene)Cl₂]₂ (M = Ru, arene = p-cymene and M = Ir, arene = pentamethylcyclopentadienyl, cp*) with avobenzone (1-(4-tert-butylphenyl)-3-(4-methoxyphenyl)propane-1,3-dione, AVBH) and KOH in methanol leads to the formation of the neutral complexes [Ru(p-cymene)(AVB)Cl] 1 and [Ir(cp*)(AVB)Cl] 2 (cp* = pentamethylcyclopentadienyl). Subsequent reaction of 1 and 2 with pyridyl derivative-BODIPY ligands, BDP and BDPCC (BODIPY = boron dipyrromethene, BDP = 4-dipyridine boron dipyrromethene, BDPCC = 4-ethynylpyridine boron dipyrromethene) in methanol gives a series of four new dicationic supramolecules: [Ru₂(p-cymene)₂(AVB)₂BDP][2CF₃SO₃] 3, [Ir₂(cp*)₂(AVB)₂BDP][2CF₃SO₃] 4, [Ru₂(p-cymene)₂(AVB)₂BDPCC][2CF₃SO₃] 5 and [Ir₂(cp*)₂(AVB)₂BDPCC][2CF₃SO₃] 6. The synthesized complexes are fully characterized using multiple analytical techniques, including elemental analysis, ¹H NMR, ¹³C NMR, ¹⁹F NMR (NMR = Nuclear Magnetic Resonance), Infrared Radiation (IR), Electrospray Ionization-Mass Spectrometry (ESI-MS), Ultraviolet-visible (UV-Vis) and fluorescence spectroscopy. The structures of these complexes are further rationalized using density functional theory (DFT) calculations. The antiproliferative activity of the neutral and dinuclear cationic complexes is evaluated in vitro in different human cancer cell lines. These complexes are found to be active against different cancer cell lines with half maximal inhibitory concentration (IC₅₀) values between 1 and 5 μM. Complexes 5 and 6 displayed the lowest IC₅₀ values in all the cell lines studied. The activity of 5 and 6 is comparable to that of the well-known chemotherapy drug doxorubicin. Detailed biophysical studies indicate that complexes 5 and 6 exhibit very good Deoxyribonucleic acid (DNA) binding properties, causing the unwinding of the double helix, which is a probable reason for their high cytotoxicity.