Ruthenium Complexes with Hydrophobic Ligands That Are Key Factors for the Optical Imaging of Physiological Hypoxia

Abstract

The phosphorescence emission of ruthenium complexes was applied to the optical imaging of physiological hypoxia. We prepared three complexes with hydrophobic substituents on the phenanthroline ligand and characterized their emission, which was quenched by molecular oxygen. Among the complexes synthesized in this study, a pyrene chromophore-linked ruthenium complex, Ru-Py, exhibited optimal properties for the imaging of hypoxia; the prolonged lifetime of the triplet excited state of the ruthenium chromophore, which was induced by efficient energy distribution and transfer from the pyrene unit, provided the highest sensitivity towards molecular oxygen. The introduction of hydrophobic pyrene increased the lipophilicity of the complex, leading to enhanced cellular uptake. Consequently, the bright phosphorescence of Ru-Py was seen in the cytoplasm of viable hypoxic cells, whereas the signal from aerobic cells was markedly weaker. Thus, we could clearly discriminate between hypoxic and aerobic cells by monitoring the phosphorescence emission. Furthermore, Ru-Py was applied to optical imaging in live mice. An intramuscular injection of Ru-Py successfully visualized ischemia-based hypoxia, which was constructed by leg banding.

A ruthenium(II) complex-based lysosome-targetable multisignal chemosensor for in vivo detection of hypochlorous acid

“…Since the lipophilicity of luminescent chemosensors/probes was reported to be critical to their cellular uptake [16,52], prior to the cellular uptake mechanism investigation, the lipophilicity of ruthenium(II) complexes, Ru-Fc and [Ru(bpy) 2 (COOH-bpy)] 2þ , was examined by determining their partition coefficients (logP o/w , P o/w is the ratio of the ruthenium(II) complex concentrations in 1-octanol and water). The logP o/w values of Ru-Fc and [Ru(bpy) 2 (-COOH-bpy)] 2þ were obtained to be À1.11 and À1.76, respectively, indicating that the presence of Fc moiety in Ru-Fc leads to the increase of the ruthenium(II) complex's lipophilicity, while the presence of carboxyl group in [Ru(bpy) 2 (COOH-bpy)] 2þ results in the increase of water solubility of the ruthenium(II) complex.…”

A highly luminescent and highly oxygen-sensitive Tb(iii) complex with a tris-aryloxide functionalised 1,4,7-triazacyclononane ligand

“…It is noteworthy that the lowest triplet energy of the phenolato moieties ( MeMe ArO À ) in 1 is 26 460 cm À1 , which is estimated (13), O2-Tb1-O4 = 80.90 (14), and O3-Tb1-O4 = 75.87 (13). Inset: the coordination polyhedron of the Tb 3+ ion in 1.…”

A highly selective and sensitive ON–OFF–ON fluorescence chemosensor for cysteine detection in endoplasmic reticulum

“…Given that the log P values of fluorescence chemosensors that are known to have good cellular membrane permeability are within the range of 0-5, we reasoned that CL and CL-Cu 2+ are all able to penetrate the cells through a passive diffusion pathway (Komatsu et al, 2013).…”

“…It is well-known that the lipophilicity of the fluorescence imaging probe is critical for their cellular uptake (Komatsu et al, 2013).…”