Deep-Red-Fluorescent Zinc Probe with a Membrane-Targeting Cholesterol Unit

Jin Ju Kim, Jayeon Hong, Seungyeon Yu, Youngmin You

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


Organelle-targeting fluorescence probes are valuable because they can provide spatiotemporal information about the trafficking of analytes of interest. The spatiotemporal resolution can be improved by using low-energy emission signals because they are barely contaminated by autofluorescence noises. In this study, we designed and synthesized a deep-red-fluorescent zinc probe (JJ) with a membrane-targeting cholesterol unit. This zinc probe consists of a boron-azadipyrromethene (aza-BODIPY) fluorophore and a zinc receptor that is tethered to a tri(ethylene glycol)-cholesterol chain. In aqueous solutions buffered to pH 7.4, JJ exhibits weak fluorescence with a peak wavelength of 663 nm upon excitation at 622 nm. The addition of ZnCl2 elicits an approximately 5-fold enhancement of the fluorescence emission with a fluorescence dynamic range of 141000. Our electrochemical and picosecond transient photoluminescence investigations indicate that the fluorescence turn-on response is due to the zinc-induced abrogation of the formation of a nonemissive intramolecularly charge-separated species, which occurs with a driving force of 0.98 eV. The fluorescence zinc response was found to be fully reversible and to be unaffected by pH changes or the presence of biological metal ions. These properties are due to tight zinc binding with a dissociation constant of 4 pM. JJ was found to be nontoxic to HeLa cells up to submicromolar concentrations, which enables cellular imaging. Colocalization experiments were performed with organelle-specific stains and revealed that JJ is rapidly internalized into intracellular organelles, including lysosomes and endoplasmic reticula. Unexpectedly, probe internalization was found to permeabilize the cell membrane, which facilitates the influx of exogens such as zinc ions. Such permeabilization does not arise for a control probe without the tri(ethylene glycol)-cholesterol chain (JJC). Our results show that the membrane-targeting cholesterol unit can disrupt membrane integrity.

Original languageEnglish
Pages (from-to)11562-11576
Number of pages15
JournalInorganic Chemistry
Issue number16
StatePublished - 17 Aug 2020

Bibliographical note

Funding Information:
This work was supported by the Ministry of Science, Information, and Communication Technology (ICT) and Future Planning (MSIP) of Korea through the GFP grant (CISS-2012M3A6A6054204) and by the Midcareer Research Program (NRF2019R1A2C2003969) through the National Research Foundation grant. The authors thank Dr. Seung-Hae Kwon at the Korea Basic Science Institute for the assistance with the microscopic experiments.

Publisher Copyright:
Copyright © 2020 American Chemical Society.


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