Lanthanide Complex-Based Luminescent Probes for Highly Sensitive Time-Gated Luminescence Detection of Hypochlorous Acid

Two novel lanthanide complex-based luminescent probes, ANMTTA-Eu3+ and ANMTTA-Tb3+ {ANMTTA, [4'-(4-amino-3-nitrophenoxy)methylene-2,2':6',2 ''-terpyridine-6,6 ''-diyl] bis(methylenenitrilo) tetrakis(acetic acid)), have been designed and synthesized for the highly sensitive and selective time-gated luminescence detection of hypochlorous acid (HOCl) in aqueous media. The probes are almost nonluminescent due to the photoinduced electron transfer (PET) process from the 4-amino-3-nitrophenyl moiety to the terpyridine-Ln(3+) moiety, which quenches the lanthanide luminescence effectively. Upon reaction with HOCl, the 4-amino-3-nitrophenyl moiety is rapidly cleaved from the probe complexes, which affords strongly luminescent lanthanide complexes HTTA-Eu3+ and HTTA-Tb3+ {HTTA, (4'-hydroxymethyl-2,2':6',2 ''-terpyridine-6,6 '' w-diyl) bis(methylenenitrilo) tetrakis(acetic acid)), accompanied by the remarkable luminescence enhancements. The dose-dependent luminescence enhancements show good linearity with detection limits of 1.3 nM and 0.64 nM for HOCl with ANMTTA-Eu3+ and ANMTTA-Tb3+, respectively. In addition, the luminescence responses of ANMTTA-Eu3+ and ANMTTA-Tb3+ to HOCl are pH-independent with excellent selectivity to distinguish HOCl from other reactive oxygen/nitrogen species (ROS/RNS). The ANMTTA-Ln(3+)-loaded HeLa and RAW 264.7 macrophage cells were prepared, and then the exogenous HOCl in HeLa cells and endogenous HOCl in macrophage cells were successfully imaged with time-gated luminescence mode. The results demonstrated the practical applicability of the probes for the cell imaging application.