Analytica chimica acta · 2026
Mitochondria-targeted phosphorescent probes for Cu2+/H2S bioimaging and H2S dynamics monitoring in hepatic inflammation.
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Wang Jinbiao, Zhang Xin, Pan Xiaotong, Kuang Chengli, Zhao Shurui, Zhu Yaxuan, Li Minna
Аннотация
BACKGROUND: Cu2+ and H2S participate in vital physiological activities, especially mitochondrial function. Endogenous H2S has served as a critical biomarker of liver injury. Accordingly, detecting Cu2+ and H2S in mitochondria, as well as monitoring H2S fluctuations in living cells and intact organisms (especially in the liver), is of great significance for elucidating their mitochondrial physiological roles and evaluating the progression of liver-related disorders.
RESULTS: Herein, two mitochondria-targeted phosphorescent probes (Ir and its Cu2+ complex Ir-Cu) were rationally designed for mitochondrial and in vivo sensing of Cu2+ and H2S via a metal displacement strategy. Each probe integrates a lipophilic cationic cyclometalated Ir(III) luminophore with mitochondrial targeting capability and a cyclen unit for specific Cu2+ recognition. The system undergoes distinct "on-off" and "off-on" phosphorescence switching at 580 nm and 630 nm upon sequential addition of Cu2+ and H2S. The as-prepared probes possess superior properties including an ultra-large Stokes shift (>200 nm), long lifetime (800 ns), rapid response (Cu2+: 5 min; H2S: 10 s) and high selectivity. They were successfully utilized for imaging Cu2+ and H2S in mitochondria and model organisms such as zebrafish, mice and Arabidopsis thaliana. In particular, Ir-Cu achieved visualization of H2S fluctuations in LPS-induced cells, liver tissues of hepatic inflammatory mice, and serum from normal and diseased mice.
SIGNIFICANCE: The developed mitochondria-targeted phosphorescent probes achieve in vitro and in vivo imaging of Cu2+ and H2S. Distinct from conventional organic fluorophores, these Ir(III) complexes (Ir and Ir-Cu) can effectively eliminate false-positive signals and enhance spatial resolution, exhibiting great promise for studying biological processes and mitochondria-related liver injury.
RESULTS: Herein, two mitochondria-targeted phosphorescent probes (Ir and its Cu2+ complex Ir-Cu) were rationally designed for mitochondrial and in vivo sensing of Cu2+ and H2S via a metal displacement strategy. Each probe integrates a lipophilic cationic cyclometalated Ir(III) luminophore with mitochondrial targeting capability and a cyclen unit for specific Cu2+ recognition. The system undergoes distinct "on-off" and "off-on" phosphorescence switching at 580 nm and 630 nm upon sequential addition of Cu2+ and H2S. The as-prepared probes possess superior properties including an ultra-large Stokes shift (>200 nm), long lifetime (800 ns), rapid response (Cu2+: 5 min; H2S: 10 s) and high selectivity. They were successfully utilized for imaging Cu2+ and H2S in mitochondria and model organisms such as zebrafish, mice and Arabidopsis thaliana. In particular, Ir-Cu achieved visualization of H2S fluctuations in LPS-induced cells, liver tissues of hepatic inflammatory mice, and serum from normal and diseased mice.
SIGNIFICANCE: The developed mitochondria-targeted phosphorescent probes achieve in vitro and in vivo imaging of Cu2+ and H2S. Distinct from conventional organic fluorophores, these Ir(III) complexes (Ir and Ir-Cu) can effectively eliminate false-positive signals and enhance spatial resolution, exhibiting great promise for studying biological processes and mitochondria-related liver injury.