Lanthanide Complex-Based Probes for Ratiometric Time-Gated Luminescence and <sup>19</sup> F Magnetic Resonance Imaging of Hydrogen Peroxide <i>In Vitro</i> and <i>In Vivo</i>
Xinyue Zhang, Zhixin Tang, Bo Song, Deshu Kong, Jingli Yuan
Abstract
High Resolution Image Download MS PowerPoint Slide Fluorescent bioimaging is a key technique for real-time and in situ visualization of bioactive species in living organisms. However, its utility for in vivo applications is often limited by a low tissue penetration depth. Herein we report novel lanthanide complex-based probes, a ratiometric time-gated luminescence (TGL) probe, Mito-PFTTA-Eu 3+ /Tb 3+, and a 19 F magnetic resonance (MR) probe, Mito-PFTTA-Gd 3+, for the highly sensitive and in situ detection of hydrogen peroxide (H 2 O 2 ) in biological samples. To construct the probe, we first designed and synthesized a multifunctional ligand, (4′-pentafluorobenzenesulfonate-2,2′:6′,2′′-terpyridine-6,6′′-diyl) bis(methylenenitrilo)tetrakis(acetic acid) ( Mito-PFTTA ), by integrating a mitochondria-anchoring motif, triphenylphosphonium cation and a H 2 O 2 -responsive pentafluorobenzenesulfonate (PFBS) moiety into a terpyridine polyacid framework. Then a mixture of its Eu 3+ and Tb 3+ complexes, Mito-PFTTA-Eu 3+ /Tb 3+, were developed as a ratiometric TGL probe for H 2 O 2 detection. In parallel, its Gd 3+ complex, Mito-PFTTA-Gd 3+, was constructed as an 19 F NMR probe for H 2 O 2 sensing. Upon reaction with H 2 O 2, the PFBS group is cleaved from the complex, leading to opposite changes in the emission intensity: an increase in the Tb 3+ emission at 540 nm and a decrease in the Eu 3+ emission at 610 nm. These changes allow Mito-PFTTA-Eu 3+ /Tb 3+ to serve as a ratiometric TGL probe for H 2 O 2 detection using the I 540 / I 610 ratio as a signal output. Thanks to its excellent mitochondrial targeting capability and excellent biocompatibility, Mito-PFTTA-Eu 3+ /Tb 3+ enabled the ratiometric TGL imaging of mitochondrial H 2 O 2 in living cells and in the livers of mice with drug-induced liver injury. Additionally, the 19 F NMR signal of Mito-PFTTA was effectively quenched upon complexation with Gd 3+ ions, but was restored upon H 2 O 2 -triggered PFBS cleavage. This behavior allowed Mito-PFTTA-Gd 3+ to function as a 19 F MRI probe for detection of H 2 O 2 in vitro and in vivo .