Targeting the endoplasmic reticulum with a membrane-interactive luminescent ruthenium(ii) polypyridyl complex

Abstract

The characterization and bioactivity of the dinuclear ruthenium(II) complex [(Ru(DIP)₂)₂(tpphz)]⁴⁺ (DIP = 4,7-diphenyl-1,10-phenanthroline and tpphz = tetrapyrido[3,2-a:2′,3′-c:3′′,2′′-h:2′′′,3′′′-j]phenazine) is reported. This new complex is found to be luminescent in acetonitrile, where excitation into MLCT (metal-to-ligand charge-transfer) bands in the visible area of the spectrum (λ_ex = 450 nm, ε = 45 000 M⁻¹ cm⁻¹) result in red emission (λ_em,max = 620 nm, Φ_MLCT = 0.017). Aqueous in vitro binding studies indicate that this complex binds to duplex DNA with an affinity of 1.8 × 10⁶ M⁻¹ through a non-classical groove-binding interaction, however, unlike the parent complex [(Ru(phen)₂)₂(tpphz)]⁴⁺ (phen = 1,10-phenanthroline), it also displays an increase in MLCT luminescence on addition of liposomes. Confocal microscopy and TEM studies show that this lipophilic complex targets the endoplasmic reticulum of eukaryotic cells, where it functions as an imaging agent for this organelle, and cytotoxicity studies in human cancer cell lines indicate a comparable potency to the anti-cancer drug cisplatin.