Design of a β-diketonate-Eu3+ complex-based time-gated luminescence probe for visualizing mitochondrial singlet oxygen

Although molecular luminescent probes capable of detecting target analytes in an organelle of interest are especially appreciated, lanthanide complex-based organelle-targetable luminescent probes have rarely been developed. Herein, by using an anthryl-substituted terpyridine derivative, 4'-(9-anthryl)-2,2':6',2 ''-terpyridine (ATPY), as a singlet oxygen (O-1(2))-recognition ligand, and a diphenyl-containing beta-diketone coligand, 6-(1',1 ''-diphenyl-4'-yl)-1,1,1,2,2,3,3-heptafluoro-4,6-hexanedione (DHH), a new beta-diketonate-Eu3+ complex-based luminescent probe, Eu(DHH)(3)(ATPY), has been designed and synthesized for the time-gated luminescence imaging detection of O-1(2) in the mitochondria of living cells. The probe showed only weak luminescence due to the quenching effect of the 9-anthryl group. After the specific reaction of the 9-anthryl group with O-1(2), the corresponding endoperoxide derivative that exhibited great quantum yield (Phi = 53%), Eu(DHH)(3)(EP-ATPY), was formed, accompanied by a remarkable luminescence enhancement. The luminescence response behaviors of Eu(DHH)(3)(ATPY) to O-1(2) were investigated using two different O-1(2) reaction systems in aqueous media. In addition, the time-gated luminescence imaging study has demonstrated the applicability of the probe for monitoring the O-1(2) generation in 5-aminolevulinic acid (a drug for photodynamic therapy) loaded HepG2 cells with high sensitivity and selectivity. Furthermore, by coloading the probe and a mitochondrial indicator, MitoTracker Green, into HepG2 cells, the mitochondria-targetable feature of the probe has also been confirmed by confocal luminescence imaging measurements.