A diaminomaleonitrile-appended BODIPY chemosensor for the selective detection of Cu2+ via oxidative cyclization and imaging in SiHa cells and zebrafish

Xiaochuan Li; Yujie Han; Saisai Sun; Dandan Shan; Xiaoming Ma; Guangjie He; Naveen Mergu; Jong-Su Park; Cheol-Hee Kim; Young-A Son

doi:10.1016/j.saa.2020.118179

A diaminomaleonitrile-appended BODIPY chemosensor for the selective detection of Cu²⁺ via oxidative cyclization and imaging in SiHa cells and zebrafish

Spectrochim Acta A Mol Biomol Spectrosc. 2020 Jun 5:233:118179. doi: 10.1016/j.saa.2020.118179. Epub 2020 Feb 21.

Authors

Xiaochuan Li¹, Yujie Han², Saisai Sun², Dandan Shan², Xiaoming Ma², Guangjie He³, Naveen Mergu⁴, Jong-Su Park⁵, Cheol-Hee Kim⁵, Young-A Son⁶

Affiliations

¹ Henan Key Laboratory of Organic Functional Molecule and Drug Innovation, Collaborative Innovation Center of Henan Province for Green Manufacturing of Fine Chemicals, Key Laboratory of Green Chemical Media and Reactions, Ministry of Education, School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang, Henan 453007, P. R. China. Electronic address: lixiaochuan@henannu.edu.cn.
² Henan Key Laboratory of Organic Functional Molecule and Drug Innovation, Collaborative Innovation Center of Henan Province for Green Manufacturing of Fine Chemicals, Key Laboratory of Green Chemical Media and Reactions, Ministry of Education, School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang, Henan 453007, P. R. China.
³ Department of Forensic Medicine, Xinxiang Medical University, Xinxiang, Henan 453003, P. R. China.
⁴ BK21, Department of Advanced Organic Materials Engineering, Chungnam National University, Daejeon 34134, South Korea.
⁵ Department of Biology, Chungnam National University, Daejeon 34134, South Korea.
⁶ BK21, Department of Advanced Organic Materials Engineering, Chungnam National University, Daejeon 34134, South Korea. Electronic address: yason@cnu.ac.kr.

PMID: 32120291
DOI: 10.1016/j.saa.2020.118179

Abstract

A specific Cu²⁺ sensor, 2-amino-3-(BODIPYmethyleneamino)maleonitrile (BDM), was established by a simple dehydration between BODIPY and diaminomaleonitrile. Cu²⁺ could be recognized by BDM over other competing metal ions in acetonitrile with distinct fluorescence emission signal response. Upon the addition of Cu²⁺ to BDM in acetonitrile, the maximum absorption at approximately 530 nm on the longer wavelength side was quenched, and the emission at 530 nm was ignited simultaneously. The fluorescence intensity enhancement could reach a maximum of 204 times the intensity of the BDM blank solution. The fluorescence "off-on" effect is established according to the Cu²⁺-induced fast intramolecular oxidative cyclization reaction, which could be deduced from the formation of an imidazole ring appended to the cyclization product (2-BODIPY-1H-imidazole-4,5-dicarbonitrile, BMC). Single-crystal structure analysis of the sensor BDM and cyclization product BMC further demonstrated this oxidative cyclization. Finally, the Cu²⁺ recognition property of BDM was validated in SiHa cells and living zebrafish. Additionally, the blood-brain barrier of the zebrafish can be penetrated by the BDM dye and the neuron cells in the brain were stained.

Keywords: BODIPY; Blood-brain barrier; Cu(2+) sensor; Fluorescence; SiHa cells; Zebrafish.

MeSH terms

Animals
Blood-Brain Barrier / metabolism*
Boron Compounds* / chemistry
Boron Compounds* / pharmacokinetics
Boron Compounds* / pharmacology
Cell Line
Copper* / chemistry
Copper* / metabolism
Fluorescent Dyes* / chemistry
Fluorescent Dyes* / pharmacology
Nitriles* / chemistry
Nitriles* / pharmacokinetics
Nitriles* / pharmacology
Optical Imaging*
Spectrometry, Fluorescence
Zebrafish / metabolism*

Substances

4,4-difluoro-4-bora-3a,4a-diaza-s-indacene
Boron Compounds
Fluorescent Dyes
Nitriles
diaminomaleonitrile
Copper