Abstract

Mitochondrial copper is involved in various physiological processes and the dysregulation of mitochondrial copper balance is related to various diseases such as Wilson's disease, Alzheimer's disease and cancer. It is now still a challenge to develop efficient fluorescent sensors for monitoring mitochondrial copper with “turn-on” response due to its inherent paramagnetic quenching effect. In this work, a mitochondria-targeted turn-on fluorescent sensor, CySH, with near-infrared absorption and emission wavelengths, was developed for the selective determination of copper. This probe displays very weak fluorescence at 784 nm due to the photo-induced electron transfer (PET) effect. After the sulfhydryl on the middle position of cyanine is coordinated with copper, the quenching process of PET is inhibited and the fluorescence of probe CySH is turn-on. CySH exhibits high selectivity towards copper and excellent anti-interference ability. Job's plot and high resolution mass spectrometry verified the stoichiometric ratio of 2:1 between CySH and Cu2+. The probe could penetrate the cell membrane well and was utilized to monitor the fluctuation of labile copper in mitochondria. Furthermore, CySH has been successfully used to assess mitochondrial copper variations in copper-overload HepG-2 cells. The proposed feature of the single S-donor might offer a new stratregety for the turn-on fluorescence detection of copper.

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