Luminescent Biological Probes Derived from Ruthenium(II) Estradiol Polypyridine Complexes

Abstract

Four luminescent ruthenium(II) polypyridine estradiol complexes [Ru(N boolean AND N)(2)(bpy-estradiol)](PF6)(2) (N boolean AND N = 2,2'-bipyridine (bpy), 4,7-diphenyl-1,10-phenanthroline (Ph-2-phen); bpy-estradiol = 5-(4-(17 alpha-ethynylestradiolyl)phenyl)-2,2'-bipyridine (bpy-ph-est), 4-(N-(6-(4-(17 alpha-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 ((MLCT)-M-3) (d pi(Ru)-->pi*(diimine)) emission in fluid solutions at 298 K and in low-temperature glass. The binding of the complexes to estrogen receptor-alpha (ER(alpha) has been studied by emission titrations. The Ph-2-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 mu M (cisplatin showed an IC50 value of 34.3 mu M under the same experimental conditions). Furthermore, the cellular uptake of the complexes has been investigated by flow cytometry and laser-scanning confocal microscopy.