Tetrahedron Letters
1,8-Naphthalimide-based ‘turn-on’ fluorescent sensor for the detection
of zinc ion in aqueous media and its applications for bioimaging
Li Yun Zhao a, Qi Li Mi c,d, Guang Ke Wang a, Jian Hua Chen c, Jun Feng Zhang b, , Qi Hua Zhao a,
,
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Ying Zhou a,
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a Key Laboratory of Medicinal Chemistry for Natural Resource, School of Chemical Science and Technology, Yunnan University, Kunming 650091, PR China
b College of Chemistry and Chemical Engineering, Yunnan Normal University, Kunming 650500, PR China
c Yunnan Academy of Tobacco Science, Kunming 650106, Yunnan Province, PR China
d Yunnan Institute of Microbiology, Yunnan University, Kunming 650091, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 23 January 2013
Revised 7 April 2013
Accepted 15 April 2013
Available online 20 April 2013
A 1,8-naphthalimide derivative (1) was intentionally designed and synthesized as a new turn-on fluores-
cent probe for the detection of zinc ion with high selectivity over other metal ions at pH 7.4 in aqueous
media (CH3CN/HEPES, V/V = 6:4). The reaction mechanism is attributed to the replacement of the protons
of the O–H groups by zinc ion at the binding site and production of fluorescence which is blocked in the
photo-induced electron transfer (PET) process. Remarkable enhancement of up to 13-fold in fluorescence
intensity with a 38 nm red-shift was achieved in the detection of zinc ion. Compound 1 was successfully
applied to the fluorescence imaging of zinc ion, with a fluorescence emission color produced in the cell
nucleus different from that produced in the cytoplasm, in A549, BEAS-2B, CHO, Hela, and HepG2 cells.
Furthermore, cytokinesis-block micronucleus (CBMN) assay was carried out in CHO cells using 1 and zinc
ion as the imaging agents, showing that the 1-Zn2+ agent is a nucleic acid selective stain, which could be
applied in MN assays in different kinds of cell lines.
Keywords:
Fluorescence probe
Zinc ion
1,8-Naphthalimide
Imaging agents
Cytokinesis-block micronucleus
Crown Copyright Ó 2013 Published by Elsevier Ltd. All rights reserved.
1. Introduction
0.3 mM,9 which means that optimized chemical probes are
required to monitor zinc concentration over that broad range.
Because of the high sensitivity, specificity, simplicity of imple-
mentation, and fast response time, fluorescent probes for detecting
metal ions possess innate advantages over other detection meth-
ods developed, such as high performance liquid chromatography1
and capillary electrophoresis.2 Fluorescent probes also offer appli-
cations for both in vitro assays and in vivo imaging studies.3 In par-
ticular, the development of a fluorescent probe for zinc ion in the
presence of a variety of other metal ions has received considerable
attention.4,5 Zn2+ is involved in a variety of physiological and path-
ological processes, such as Alzheimer’s disease, epilepsy, ischemic
stroke, and infantile diarrhea.6 It is also reported that zinc ion is
a potent killer of neurons via oxidative stress.7 A decrease in the
concentration of Zn2+ can cause a reduction in the ability of the
islet cells of the pancreas to produce and secrete insulin.8 Accord-
ingly, development of Zn2+ selective fluorescent sensors and conve-
nient methods to detect intracellular Zn2+ ion are certainly
important issues in recent years. The total concentration of Zn2+
in different cells varies from the nanomolar range up to about
Most of the fluorescence-based probes for Zn2+ suffer from lim-
itations due to tight binding affinity or lack of sufficient selectivity
to detect intrinsic levels of Zn2+ in pancreatic islets. Therefore, it
remains a challenge to develop efficient fluorescent probes with
high sensitivity and selectivity for the detection of metal ions in
biological applications. Recently, a rhodamine-based derivative
bearing a N-butyl-1,8-naphthalimide group was reported in our
work, in which it displayed a selective colorimetric and fluores-
cence change toward Cu2+ based on the rhodamine ring-opening
approach.10 Meanwhile, some simple but efficient fluorescent sen-
sors based on Shift base, which displayed selective optical
responses, were reported.11 In order to further explore the sensing
mechanism of this series of 1,8-naphthalimide-based compounds
and their biological applications, the introduction of new ligands
with different binding points has attracted considerable interest.
Herein, we describe the synthesis and the photophysical prop-
erties of a new 1,8-naphthalimide-based chemosensor 1, which
has been designed for the sensitive and selective ‘turn-on’ fluores-
cence detection of Zn2+ in aqueous solvents (CH3CN/HEPES, V/
V = 6:4, 0.02 M HEPES buffer, pH 7.4) as well as in intracellular
media. As expected, upon addition of 20 equiv of various metal
ions, only Zn2+ leads to a significant enhancement of up to 13-fold
in fluorescence intensity with a 38 nm red-shift, and no obvious
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Corresponding authors.
0040-4039/$ - see front matter Crown Copyright Ó 2013 Published by Elsevier Ltd. All rights reserved.