Luminescent biological probes derived from ruthenium(II) estradiol polypyridine complexes

Four luminescent ruthenium(II) polypyridine estradiol complexes [Ru(N∧N)₂(bpy-estradiol)](PF₆)₂ (N∧N = 2,2′-bipyridine (bpy), 4,7-diphenyl-1,10-phenanthroline (Ph ₂-phen); bpy-estradiol = 5-(4-(17α-ethynylestradiolyl)phenyl)- 2,2′-bipyridine (bpy-ph-est), 4-(N-(6-(4-(17α-ethynylestradiolyl) benzoylamino)hexyl)aminomethyl)-4′-methyl-2,2′-bipyridine (mbpy-C6-est)) have been designed as new luminescent biological probes. The lipophilicity and photophysical and electrochemical properties of these complexes have been investigated. Upon photoexcitation, all the complexes exhibited intense and long-lived triplet metal-to-ligand charge-transfer ( ³MLCT) (dπ(Ru) → π*(diimine)) emission in fluid solutions at 298 K and in low-temperature glass. The binding of the complexes to estrogen receptor-α (ERα) has been studied by emission titrations. The Ph₂-phen complexes showed emission enhancement and increased lifetimes upon binding to the protein. Additionally, the cytotoxicity of the complexes toward the HeLa cell line has been examined by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide (MTT) assay and the IC₅₀ values ranged from 83.1 to 166.6 μM (cisplatin showed an IC₅₀ value of 34.3 μM under the same experimental conditions). Furthermore, the cellular uptake of the complexes has been investigated by flow cytometry and laser-scanning confocal microscopy. © 2008 American Chemical Society.