An emissive dual-sensitized bimetallic Eu2III-bioprobe: design strategy, biological interactions, and nucleolus staining studies

Abstract

A new strongly luminescent homodinuclear Eu₂^III-based bioprobe, [Eu₂(tta)₆(μ-pz(tpy)₂)] (1), was developed, where piperazine-4-methyl-phenyl terpyridine (L) (μ-pz(tpy)₂) acts as a bridging ligand containing piperazine (pz) as a linker between two N₃-donor phenyl-terpyridine ends and thenoyltrifluroacetone (tta) acts as a capping antenna ligand. The Eu₂^III bioprobe 1 was designed to show pH responsiveness via its acid-sensitive β-diketonate (tta) ligand and to be a fluorescent cell imaging agent, utilizing the characteristic dual-antenna-sensitized red luminescence of Eu^III ions via intraconfigurational f → f transitions. The structure of the μ-pz(tpy)₂ ligand utilizes the ideal disposition and potential binding capabilities of the terminal N₃-donor tpy moieties toward Eu^III ions. The dinuclear complex 1 is characterized using ESI-MS, FT-IR, and other spectroscopic methods; therein, each Eu^III atom is coordinated to six oxygen atoms from three anionic tta⁻ ligands and one N₃-donor terminal terpyridine to achieve the proposed nine-coordinated {EuN₃O₆}-geometry. The coordinative saturation, thermodynamic stability, absence of exchangeable labile H₂O molecules (q < 1), and the presence of C–F oscillators in the tta ligands minimize possible emission quenching via non-radiative vibrational energy transfer (VET). These design features of 1 result in bright luminescence, photostability, and a long luminescence lifetime in aqueous media, which are desirable for cellular imaging applications. It shows efficient binding interactions with CT-DNA (K_b: ∼10⁶ M⁻¹) and serum albumin protein (BSA) (K_BSA: ∼10⁶ M⁻¹) under physiological conditions. The subcellular localization of the Eu₂^III bioprobe 1 was evaluated using the MCF-7 and MDA-MB-231 cancer cell lines via confocal laser scanning microscopy (CLSM). It showed significant cellular uptake and preferential nucleolus localization, utilizing intrinsic red emission derived from the f–f transitions of the Eu^III ions of the Eu₂^III bioprobe 1.