Simple naphthalimide-based fluorescent sensor for highly sensitive and selective detection of Cd2+ and Cu2+ in aqueous solution and living cells

Article abstract of DOI:10.1039/c2dt32279j

A novel naphthalimide-based fluorescent sensor bearing the N,N′-bis(salicylidene)diethylenetriamine receptor was developed, which exhibited dual signaling behaviors for Cd²⁺ and Cu²⁺, and was applicable to the environmental and biolo

Full text of DOI:10.1039/c2dt32279j

Dalton
Transactions
View Article Online
View Journal | View Issue
PAPER
Simple naphthalimide-based fluorescent sensor for
highly sensitive and selective detection of Cd2+ and
Cu2+ in aqueous solution and living cells
Cite this: Dalton Trans., 2013, 42, 1827
Wei Wang,a Qian Wen,a Yue Zhang,a Xiaoliang Fei,a Yaoxian Li,a Qingbiao Yang*a
and Xiaoyi Xu*b
A novel naphthalimide-based fluorescent sensor bearing the N,N’-bis(salicylidene)diethylenetriamine
receptor was developed, which exhibited dual signaling behaviors for Cd2+ and Cu2+, and was applicable
to the environmental and biological milieus. Upon addition of Cd2+, the fluorescence intensity enhanced
in a linear fashion with the maximum fluorescence intensity increase of about 4-fold. Moreover, with the
sensor 1 and 1–Cd2+ complex, Cu2+ was easily recognized by marked fluorescence quenching. The selec-
tivity and sensitivity of the sensor 1 for Cd2+ were satisfactory and achieving a detection limit at the nano-
molar level. The living cell image experiments demonstrated the value of sensor 1 in fluorescent
visualization of Cd2+ ions in biological systems.
Received 17th May 2012,
Accepted 30th October 2012
DOI: 10.1039/c2dt32279j
www.rsc.org/dalton
seem to be the ideal tool for evaluating and dynamically
mapping the intracellular fluctuations of metal ions by using
1. Introduction
Cd2+ has caused serious harm to the environment and human microscopy techniques to allow real-time local imaging.4–11
health. It can cause serious injury to the human kidney, lung, Up to now, many fluorescent sensors for Cd2+ have been
bone and nerve system, which resulted in renal dysfunction, reported,12,13 but only a few of them are applicable to cellular
calcium metabolism disorders and an increased incidence of imaging,14 their practical application is still restrained due to
certain forms of cancers.1 However, the mechanisms involved their poor water solubility, UV-excitation and pH-dependent
in the Cd2+-uptake and carcinogenesis remain undefined.2 The fluorescence in physiological environments. To date, it is
EPA (United States Environmental Protection Agency) gives an still a tremendous challenge to design Cd2+-selective sensors,
enforceable drinking water standard for Cd of 5 ppb to prevent in particular, fluorescent chemosensors for the accurate
kidney damage and other related diseases, while the WHO detection of Cd2+ in aqueous solutions and biological
(World Health Organization) provides a more strict guideline environments.
value for Cd of 3 ppb for drinking water.3 Therefore, develop-
A practical fluorescent chemosensor must produce a strong
ing reliable methods for Cd2+ trace quantification in environ- fluorescent response upon binding the analyte. 1,8-Naphthal-
mental samples and in living cell/tissue samples is of great imide derivatives are dyes extensively employed in fluorogenic-
significance for clarifying the Cd2+-carcinogenesis and other labeling and fluorescent chemosensors because of their high
biological effects.
absorption coefficient, high fluorescence quantum yield and
In recent years, the development of fluorescent chemosen- high photostability.15 By virtue of these fascinating properties,
sors for sensing and reporting heavy transition-metal ions has the excellent examples of 1,8-naphthalimide-based fluorescent
been receiving considerable attention. Fluorescence tech- chemosensor applications in cell imaging have been
niques have become powerful tools for sensing and imaging reported.16
metal ions in trace amounts because of its simplicity, high
In this paper, we report the synthesis and fluoroionophoric
sensitivity and real-time monitoring with a short response properties of a novel fluorescent sensor aimed at the selective
time. Sensitive and reliable fluorescent molecular sensors recognition of Cd2+ and Cu2+ ions in aqueous solution.
Sensor 1 is composed of an aminonaphthalimide fluorophore
and a receptor of the N,N′-bis(salicylidene)diethylenetriamine
aDepartment of Chemistry, Jilin University, Changchun, 130021, People’s Republic of
attached via a space linker. Sensor 1 exhibits Cd2+-selective
China. E-mail: yangqb@jlu.edu.cn; Fax: +86431 88499576; Tel: +86431 88499576
TURN-ON and Cu2+-selective TURN-OFF type signaling beha-
bCancer Center, The First Hospital, Jilin University, 130021, People’s Republic of
viors that can be used to distinguish Cd2+ and Cu2+ ions. More-
China. E-mail: xiaoyixu06@sohu.com; Fax: +86431 88782046;
over, to the best of our knowledge, this is the first example of a
Tel: +86431 88782046
This journal is © The Royal Society of Chemistry 2013
Dalton Trans., 2013, 42, 1827–1833 | 1827

View Article Online
Paper
Dalton Transactions
cation-induced TURN-ON and TURN-OFF type of fluorescent 4-bromo-1,8-naphthalic anhydride with allyl amine. Sensor 1
signal control behavior with Cd2+ and Cu2+.
was easily synthesized by compounds 2 and 3 in 36.9% yield,
all compounds were characterized by ESI-MS and 1H NMR.
2. Experimental
2.1 Materials
3. Synthesis
Synthesis of intermediate 2
4-Bromo-1,8-naphthalic anhydride (98% purity, Beijing
Hengyue Zongyuan Chemical CO., LTD) was purified by recrys-
tallization from acetic acid. Allyl amine (XinHua Chemical
Reagent Co.) was distilled and then stored at −20 °C prior to
use. N,N-Dimethylformamide (DMF) was distilled and dried by
anhydrous magnesium sulfate. Diethylenetriamine (99%
purity), salicylaldehyde, and all other reagents were purchased
from Sinopharm Chemical Reagent Co., Ltd., and used as
received. The solutions of metal ions were prepared from
NaCl, KCl, CaCl2, MgSO4, FeCl3, Mn(NO3)2·6H2O, CoCl2·6H2O,
To 20 mL anhydrous ethanol containing diethylenetriamine
(1.0 g, 10 mmol), an excess of 2-hydroxy-4-methoxybenzalde-
hyde (2.6 g, 21 mmol) was added and the mixture was stirred
vigorously at room temperature for 24 h. The reaction progress
was monitored by thin-layer chromatography (TLC). After com-
pletion of the reaction, the formed precipitate was filtered,
washed with cold ethanol (3 × 10 mL) and then dried in
vacuum, affording 0.17 g crude product, which was further
purified by silica gel column chromatography using CH2Cl2/
EtOH (20/1, v/v) containing 1% (v/v) triethylamine as eluent.
2.88 g of intermediate 2 as a yellow viscous liquid was
obtained, yield: 92.5%. 1H NMR (CDCl3, 300 MHz) δ 8.34 (s,
2H), 7.30–7.26 (m, 2H), 7.20 (dd, J = 1.5 Hz, 7.8 Hz, 2H), 6.93
(d, J = 8.1 Hz, 2H), 6.87–6.82 (m, 2H), 5.28 (s, 2H), 3.70 (t, J =
5.7 Hz, 4H), 2.98 (t, J = 5.7 Hz, 4H), 1.23 (t, J = 6.9 Hz, 1H).
13C NMR (CDCl3, 300 MHz) d 49.5, 59.26, 116.7, 118.2, 131.0,
118.2, 136.7, 160.9, 165.8. IR (KBr, cm−1): 3427, 2917, 2846,
NiCl2·6H2O,
Zn(NO3)2,
C4H6CdO4·2H2O,
CuCl2·2H2O,
Hg(NO3)2, AgNO3, Pb(NO3)2, respectively, and were dissolved
in deionized water. Aqueous HEPES–NaOH (0.1 mol L−1) solu-
tion was used as a buffer to maintain the pH value (pH =
7.14), and the ionic strength of all solutions used in the
experiments.
2.2 Characterization
1H NMR spectra were measured on a Bruker AV-400 spectro- 2107, 1732, 1633, 1455, 1382, 1280, 1230, 1105, 905, 888, 818,
meter with chemical shifts reported as parts per million (in 753, 699, 665, 620, 569. HRMS calcd for C18H21N3O2. [MH+]:
CDCl3, TMS as internal standard). IR spectra were recorded 311.
on a Bruker Vector-22 spectrometer. The pH values of the test
solutions were measured with a glass electrode connected to a
Mettler-Toledo Instruments DELTA 320 pH meter (Shanghai,
Synthesis of N-allyl-4-bromo-1,8-naphthalimide
(intermediate 3)
China) and adjusted if necessary. Fluorescence spectra were
determined on a Hitachi F-4500. UV-Vis spectra were recorded
on a Hitachi U-3010 UV-Vis spec. All of the measurements
were performed at about 298.0 0.2 K.
The synthesis of sensor 1 is shown in Scheme 1. The inter-
mediate, compound 2, was synthesized from salicylaldehyde
and diethylenetriamine following a literature procedure.17
Compound 3 was prepared in 50.8% yield by coupling
Compound 3 was synthesized from 4-bromo-1,8-naphthali-
mide via
literature procedure.15 Allyl amine (57 mg,
a
1.00 mmol) in ethanol (10 mL) was added dropwise, under
mechanical stirring, to a solution of 4-bromo-1,8-naphthalic
anhydride (270 mg, 0.97 mmol) in ethanol (40 mL). The reac-
tion mixture was refluxed for 1 h and then cooled. After the
removal of the solvent, the crude product was purified by
column chromatography (silica gel, CH2Cl2–EtOH, 20 : 1) to
give compound 2 as a white solid (160 mg, 50.8%). 1H NMR
(CDCl3, 300 MHz) δ 8.66 (dd, J = 0.8 Hz, 7.9 Hz, 1H), 8.58 (dd,
J = 0.8 Hz, 7.9 Hz, 1H), 8.45 (d, J = 7.6 Hz, 1H), 8.05 (d, J =
7.6 Hz, 1H), 7.83–7.88 (m, 1H), 5.93–6.06 (m, 1H), 5.32 (dd, J =
0.7 Hz, 6.2 Hz, 1H), 5.22 (dd, J = 0.8 Hz, 8.2 Hz, 1H), 4.80 (d,
J = 5.6 Hz, 2H). 13C NMR (CDCl3, 300 MHz) d 37.1, 112.6,
122.7, 123.3, 125.8, 125.9, 126.3, 126.6, 126.8, 127.9, 128.0,
128.8, 129.4, 157.9. IR (KBr, cm−1): 3341, 3069, 2021, 1786,
1787, 1735, 1703, 1659, 1592, 1571, 1460, 1426, 1402, 1730,
1345, 1332, 1236, 1222, 1153, 1134, 1019, 950, 932, 849, 777,
746, 718, 568, 556. HRMS calcd for C15H10BrNO2. [MH+]: 316.
Synthesis of sensor 1
Sensor 1 was synthesized as shown in Scheme 1. Intermediate
2 (430 mg, 1.38 mmol) in acetonitrile (10 mL) was added drop-
wise, under mechanical stirring, to a solution of intermediate
3 (300 mg, 0.95 mmol) in acetonitrile (40 mL). The reaction
Scheme 1 Synthesis and structure of 1–3. (a) C2H5OH, room temperature, 3 h,
92.5%; (b) allyl amine, C2H5OH, reflux, 1 h, 50.8%; (c) CH2CN, K2CO3, reflux, 6 h,
36.9%.
1828 | Dalton Trans., 2013, 42, 1827–1833
This journal is © The Royal Society of Chemistry 2013

View Article Online
Dalton Transactions
Paper
mixture was refluxed for 6 h and then cooled. After removal of in aqueous solution in a pH range from 7.0 to 13.5. In con-
the solvent, the crude product was purified by column chrom- sideration of most samples for sensor 1 analysis of Cd2+ ions
atography (silica gel, CH2Cl2–EtOH, 10 : 1) to give compound 1 being neutral, the medium for Cd2+ ions quantification was
as a yellow solid (202 mg, 36.9%). 1H NMR (DMSO-d6, then buffered at pH 7.2.
300 MHz) δ 9.90 (s, 2H), 8.67 (dd, J = 1.2 Hz, 7.3 Hz, 1H), 8.58
(dd, J = 1.1 Hz, 8.5 Hz, 1H), 8.44–8.36 (m, 1H), 8.05 (d, J =
Cd2+-titration and spectral responses
7.9 Hz, 1H), 7.85 (dd, J = 8.5 Hz, 7.3 Hz, 2H), 7.58–7.50 (m, In order to gain an insight into the signaling properties of the
2H), 7.32–7.20 (m, 2H), 7.21 (dd, J = 1.8 Hz, 7.8 Hz, 1H), sensor 1 toward Cd2+, fluorescence titration was conducted.
6.94–6.82 (m, 2H), 6.11–5.93 (m, 1H), 5.30–5.25 (m, 2H), Fluorescence titration of the sensor 1 was investigated in
4.82–4.80 (m, 2H), 3.75–3.71 (m, 2H), 3.32–3.20 (m, 4H), ethanol–water (1 : 10, v/v) solution ([Cd2+] = 0–2.0 × 10−6 mol
3.08–3.02 (m, 4H). 13C NMR (CDCl3, 300 MHz) δ 42.4, 49.5, L−1, 0.1 M HEPES–NaOH buffer at pH = 7.2, λex = 445 nm, λem
59.3, 116.9, 117.5, 117.8, 118.5, 119.7, 122.0, 128.0, 128.5, = 525 nm). Upon addition of Cd2+, about a 4-fold increase in
130.3, 130.6, 130.9, 131.0, 131.2, 131.6, 131.9, 132.0, 132.2, fluorescence intensity was observed (Fig. 2b), but the absor-
133.1, 133.3, 133.6, 134.0, 134.6, 136.9, 161.0, 161.5, 163.2, bance at 445 nm did not change (Fig. 2a). When more than
166.1. IR (KBr, cm−1): 3419, 2923, 2843, 2728, 2023, 1732, 1.0 equiv. Cd2+ was added, the maximum fluorescence inten-
1644, 1458, 1832, 1312, 1233, 1109, 905, 883, 818, 753, 694, sity was retained. The reaction responsible for these changes
671, 615, 505. HRMS calcd for C33H30N4O4. [MH+]: 547.
reached completion well within the time frame (<30 s) of the
measurement. Significantly, the enhancement of fluorescence
intensity of sensor 1 corresponded to the concentration of
Cd2+ in a linear manner (linearly dependent coefficient: R2
=
4. Results and discussion
pH-titration and spectral responses
0.9902) (Fig. 3c), which indicated that sensor 1 had potential
use for the quantitative determination of Cd2+. It should be
noted that this switch on sensing process could be readily
detected not only by fluorescence spectroscopy but also by the
naked eye. As shown in Scheme 2 sensor 1 (5.0 × 10−5 M) alone
exhibited very weak fluorescence, but gave a strong pale green
fluorescence in the presence of Cd2+ (5.0 × 10−5 M). Moreover,
a Job’s plot, which exhibited a maximum at 0.5 mole fraction
of sensor 1, indicated the 1 : 1 stoichiometry between Cd2+ and
sensor 1 (Fig. 3). Therefore, on the basis of 1 : 1 stoichiometry
and fluorescence titration data, the association constant of
Fluorophores are usually disturbed by protons in the detection
of metal ions, so their low sensitivity to the operational pH
value is expected and investigated. Fig. 1 shows the fluore-
scence response of sensor 1 without and with Cd2+ ions as a
function of pH. Experimental results showed that for the Cd2+-
free sensor 1, under acidic conditions (pH < 7.0), an obvious
increase of the emission spectra was observed with the
decrease of pH from 7.0 to 4.5, which was attributed to the
inhibition of the PET (photoinduced electron transfer)
process. In a pH range from 7.0 to 13.5, almost negligible
fluorescence signal (excited at 525 nm) could be observed for
the Cd2+-free sensor 1, suggesting that protonation of 1 takes
place under neutral aqueous media in the ground state. Upon
the addition of Cd2+ ions, there was a remarkable fluorescence
enhancement of sensor 1 at different pH values. And the pH-
control emission measurements revealed that sensor 1 could
respond to Cd2+ ions in a pH range from 7 to 13.5 with little
change of the fluorescent intensity, suggesting that sensor 1
facilitated the quantification of the concentration of Cd2+ ions
sensor 1 with Cd2+ ions was found to be 2.4 × 107
M
−1, the
detection limit was found to be 5.2 × 10−7 mol L−1 (based on
S/N = 3).
The response of sensor 1 to various metal ions
The selectivity is one of the essential requirements for a
chemosensor to signal a specific species in a complex system.
The fluorescence responses of the sensor 1 to various cations
and its selectivity for Cd2+ were illustrated in Fig. 4. The fluor-
oionophoric behavior of sensor 1 was investigated in ethanol–
water (1 : 10, v/v) solution ([sensor 1] = 1 μM, [Mn+] = 1 mM, 0.1
M HEPES–NaOH buffer at pH = 7.14). As expected, sensor 1
showed a weak fluorescence in aqueous solution. Upon
addition of different metal ions, only with Cd2+, did sensor 1
show remarkable fluorescence enhancement (Fig. 4b), the
absorbance at 442 nm did not change (Fig. 4a). Moreover, the
Cu2+ induced a fluorescence decrease effect of sensor 1, and a
slight blue shift in the excitation maximum from 442 to
435 nm was observed. Fig. 5 explained the fluorescent exci-
tation and emission changes of sensor 1 (1 μM) upon the
addition of various concentrations of Cu2+ solutions
(0–2.0 μM). Excitation spectra revealed a feeble blue shift with
the gradual increasing of Cu2+ concentration, also the decrease
of fluorescent emission intensity of sensor 1 corresponded to
the concentration of Cu2+ in a linear manner (linearly
Fig. 1 Fluorescence intensity of sensor 1 in ethanol–water (1 : 10, v/v) with
and without Cd2+ ions measured as a function of pH.
This journal is © The Royal Society of Chemistry 2013
Dalton Trans., 2013, 42, 1827–1833 | 1829

View Article Online
Paper
Dalton Transactions
Fig. 3 Job’s plot for sensor 1 (forms 1 : 1 complexes) in 0.1 M HEPES–NaOH
solution (ethanol–water = 1 : 10, v/v, pH = 7.14). The total concentration of 1
and Cd2+ is 1 μM.
Scheme 2 The proposed binding mode of sensor 1/Cd2+ system and aqueous
solutions of sensor 1 with and without Cd2+ illuminated with a UV lamp at
365 nm ([1] = 1 × 10−6 mol L−1; [Cd] = 1 × 10−6 mol L−1).
were probably due to several combined influences cooperating
to achieve the unique selectivity for Cd2+.
1H NMR spectroscopy of sensor 1, 1–Cd2+, and 1–Cu2+ in
DMSO-d6 was undertaken to determine the complexation
mode of 1 for metal cations, which results in the excimer emis-
sion changes. The spectral differences are depicted in Fig. 6.
Some significant spectral changes are observed in the 1H NMR
spectra on addition of both of the cations. For the aliphatic
region, upon interaction with Cd2+, H1 (Fig. 6) on the receptor
(N,N′-bis(salicylidene)diethylenetriamine) undergoes a down-
field shift by 0.16 ppm to 3.04, the H2 peak is shifted
from 3.38 to 3.42 ppm. Similarly, in the presence of Cu2+, the
H1 peak is downfield shifted by 0.03 ppm and the H2 peak is
downfield shifted by 0.16 ppm. These spectral changes suggest
that both Cd2+ and Cu2+ are bound by the nitrogen atom of the
receptor (N,N′-bis(salicylidene)diethylenetriamine). This puta-
tive binding mode is further elucidated by additional changes
in the spectra which point to the metal being bound by the
under part of the fluorophores with the aid of two phenol
groups. In particular, the phenol-H8 is downfield shifted
by 0.10 and by 0.29 ppm with Cd2+ and Cu2+, respectively,
whereas the Ha peak proximal to the naphthalimides moiety
does not undergo a significant change in the presence of the
metal cations, further corroborating 1 : 1 complex formation
Fig. 2 UV spectra (a) and fluorescence spectra (b) of sensor 1 (1 μM) in the
presence of increasing concentrations of Cd2+ (0–2 equiv.) in HEPES–NaOH
(0.1 M) solution (ethanol–water = 1 : 10, v/v, pH = 7.14). Inset shows fluorescence
intensity as a function of the molar ratio ([Cd2+]/[1]). (c) Curve of fluorescence
intensity at 525 nm of sensor 1 versus increasing concentrations of Cd2+
.
dependent coefficient: R2 = 0.9984) (Fig. 5c). Therefore, on the
basis of fluorescence titration data, the association constant of
sensor 1 with Cu2+ ions was found to be 6.5 × 108 M−1. Other
representative metal ions, such as Na+, K+, Ca2+, Mg2+, Mn2+,
Ni2+, Fe3+, Cd2+, Co2+, Pb2+, Zn2+ ions, particularly some metal
ions like Hg2+ and Pb2+ induced very slight fluorescence
enhancement, whereas Ni2+ and Ca2+ slightly quenched the
fluorescence. However, when the concentrations of Hg2+ and
Pb2+ solutions were lowered to 10−3 mol L−1, these ions did
not induce any obvious interference in fluorescence, which
1830 | Dalton Trans., 2013, 42, 1827–1833
This journal is © The Royal Society of Chemistry 2013

View Article Online
Dalton Transactions
Paper
Fig. 4 (a) The absorption change and (b) the fluorescence intensity change
profile of 1 (1 μM) to different metal ions (1 mM) in 0.1 M HEPES–NaOH solution
(ethanol–water = 1 : 10, v/v, pH 7.14, λex = 445 nm). Inset: corresponding
fluorescent spectra of 1 in the presence of different metal ions.
that we have concluded based on the spectral titration profile.
It is interesting to note that the extent of chemical shift
change is in agreement with the association constants (Cu2+
>
Cd2+) calculated from the fluorescence spectrometry results
suggesting that Cu2+ is likely to interact with the receptor of 1
more strongly than the Cd2+ cation.
The result of metal-ion competition experiments
Fig. 5 UV spectra (a) and fluorescence spectra (b) of sensor 1 (1 μM) in the
presence of increasing concentrations of Cu2+ (0–2 equiv.) in HEPES–NaOH
(0.1 M) solution (ethanol–water = 1 : 10, v/v, pH 7.14). Inset shows fluorescence
intensity as a function of the molar ratio ([Cu2+]/[1]). (c) Curve of fluorescence
In order to further test the interference of other common
cations in the determination of Cd2+, competition experiments
were performed in which the fluorescent sensor was added to
a solution of Cd2+ in the presence of other metal ions (Fig. 7).
Experimental results indicated that these ions showed no
obvious interference in the Cd2+ detection, but the enhanced
fluorescence signal of the 1–Cd2+ complex was obviously
quenched with an increasing amount of Cu2+ (Fig. 7), which
was contributed to a binding competition between Cu2+ and
the 1–Cd2+ complex.18 Thus, the sensor 1 exhibited excellent
selectivity toward Cd2+ and Cu2+, which is its practical
application.
intensity at 525 nm of sensor 1 versus increasing concentrations of Cu2+
.
1 mM solution in DMSO) for 30 min at 37 °C in 5% CO2
atmosphere, then the cells were washed with phosphate
buffered saline (PBS, pH = 7.4) 3 times, which was sufficient
time for the intracellular accumulation of sensor 1 judging
from its weak self-fluorescence inside a living cell (Fig. 8a and
8d). Moreover, no intracellular fluorescence was detected for
cells supplementing cells with 10 μM CdCl2 in the growth
medium for 5 h at 37 °C. However, as shown in Fig. 8b and 8e,
Detection of Cd2+ in living cells
To further explore the potential biological application of this bright intracellular fluorescence was observed for supplement-
sensor, we explored the capability of the sensor 1 to track the ing cells with 10 μM CdCl2 in the growth medium for 5 h at
change in Cd2+ levels in live MCF-7 (human breast cancer 37 °C and then staining with 1 under the same loading con-
cells) and SH-SY-5Y (human neuroblastoma cells) cell lines. ditions. Fig. 8 displayed the fluorescence images for the two
The live cell was first incubated with 5 μM sensor 1 (from kinds of cells stained with the sensor before and after being
This journal is © The Royal Society of Chemistry 2013
Dalton Trans., 2013, 42, 1827–1833 | 1831

View Article Online
Paper
Dalton Transactions
Fig. 8 Fluorescence microscope imaging of MCF-7 and SH-SY-5Y cells stained
with 5 μM of sensor 1 before (a, d) and after (b, e) treating with 10 μM of Cd2+
Bright-field transmission image of MCF-7 and SH-SY-5Y cells incubated with
sensor 1 (1 ppm) are shown in (c, f).
.
Fig. 6 The proposed structure for sensor 1 + metal ions, and 1H NMR spectra
of 1 (5 mM) in DMSO-d6 and in the presence of CdCl2 and CuCl2 in a 1 : 1 ratio.
trace transition metal ions and abundant cellular cations.
Its fluorescence intensity enhanced in a linear fashion with
the concentration of Cd2+ and thus can be used potentially for
quantification of cadmium ions. Furthermore, the 1–Cd2+
complex also behaves as a specific fluorescent sensor for Cu2+.
The selective Cd2+/Cu2+-induced OFF–ON–OFF type fluorescent
signal control behavior described herein could prove useful in
terms of constructing functional molecules switching systems.
Moreover, the cell-permeable experiment showed it can indeed
visualize the changes of intracellular Cd2+ in living cells. It can
thus be predicted that the design strategy of cadmium-induced
inhibition of the resonance process allows one to design new
ratiometric sensors for other metal ions of biological interest.
Fig. 7 The fluorescence intensity of 1 (μM) with 1.5 equiv. of Cd2+, followed by
100 equiv. of Mn+. Conditions: 0.1 M HEPES–NaOH solution (ethanol–water =
1 : 10, v/v, pH = 7.14).
Acknowledgements
treated with Cd2+. These facts implied that sensor 1 was
membrane-permeable and could sense intracellular Cd2+ in
living cells. The living cells image also demonstrated it could
be a useful molecular probe for studying biological processes
involving Cd2+ ions within living cells.
The authors gratefully acknowledge the support of the
National Natural Science Foundation of China (No. 21174052).
Notes and references
1 Cadmium in the Human Environment: Toxicity and Carcino-
genicity, ed. G. F. Nordberg, R. F. M. Herber and L. Alessio,
Oxford University Press, Oxford, UK, 1992.
Conclusions
In conclusion, a simple naphthalimide-based fluorescent
sensor 1 for detection Cd2+ has been developed, which dis-
played very high sensitivity and selectivity for Cd2+ over other
2 (a) M. Waisberg, P. Joseph, B. Hale and D. Beyersmann,
Toxicology, 2003, 192, 95–117; (b) R. K. Zalups and
S. Ahmad, Toxicol. Appl. Pharmacol., 2003, 186, 163–188;
1832 | Dalton Trans., 2013, 42, 1827–1833
This journal is © The Royal Society of Chemistry 2013

View Article Online
Dalton Transactions
Paper
(c) C. C. Bridges and R. K. Zalups, Toxicol. Appl. Pharmacol.,
2005, 204, 274–308.
2011, 657, 98–106; (e) Y. Wanga, X. Hua, L. Wang,
Zh. Shang, J. Chao and W. Jin, Sens. Actuators, B, 2011, 156,
126–131; (f) J. Yin, T. Wu, J. Song, Q. Zhang, S. Liu, R. Xu
and H. Duan, Chem. Mater., 2011, 23, 4756–4764;
(g) N. K. Singhal, B. Ramanujam, V. Mariappanadar and
C. Pulla Rao, Org. Lett., 2006, 8, 3525–3528; (h) N. J. Youn
and S. Chang, Tetrahedron Lett., 2005, 46, 125–129;
(i) H. Chen, Y. Wu, Y. Cheng, H. Yang, F. Li, P. Yang and
C. Huang, Inorg. Chem. Commun., 2007, 10, 1413–1415;
( j) P. Du and S. J. Lippard, Inorg. Chem., 2010, 49, 10753–
10755; (k) Y. Pourghaz, P. Dongare, D. W. Thompson and
Y. Zhao, Chem. Commun., 2011, 47, 11014–11016.
3 (a) United States Environmental Protection Agency, http://
water.epa.gov/drink; (b) World Health Organization, Avenue
Appia 20, 1211 Geneva 27, Switzerland, http://www.who.int/
water_sanitation_health/dwq/chemicals/cadmium/en/
4 L. Zeng, E. W. Miller, A. Pralle, E. Y. Isacoff and
C. J. Chang, J. Am. Chem. Soc., 2006, 128, 10–11.
5 G. Farruggia, S. Iotti, L. Prodi, N. Zaccheroni, M. Montalti,
P. B. Savage, G. Andreani, V. Trapani and F. I. Wolf,
J. Fluoresc., 2008, 19, 11–19.
6 H. Komatsu, T. Miki, D. Citterio, T. Kubota, Y. Schindo,
Y. Kitamura, K. Oka and K. Suzuki, J. Am. Chem. Soc., 2005, 14 (a) L. Xue, G. Li, Q. Liu, H. Wang, C. Liu, X. Ding, S. He
127, 10798–10799.
and H. Jiang, Inorg. Chem., 2011, 50, 3680–3690;
(b) H. S. Jung, P. S. Kwon, J. W. Lee, J. I. Kim, C. S. Hong,
J. W. Kim, S. Yan, J. Y. Lee, J. H. Lee, T. Joo and J. S. Kim,
J. Am. Chem. Soc., 2009, 131, 2008–2012; (c) M. Mameli,
M. C. Aragoni, M. Arca, C. Caltagirone, F. Demartin,
G. Farruggia, G. D. Filippo, F. A. Devillanova, A. Garau,
F. Isaia, V. Lippolis, S. Murgia, L. Prodi, A. Pintus and
N. Zaccheroni, Chem.–Eur. J., 2010, 16, 919–930; (d) Z. Liu,
C. Zhang, W. He, Z. Yang, X. Gaob and Z. Guo, Chem.
Commun., 2010, 46, 6138–6140; (e) T. Cheng, Y. Xu,
S. Zhang, W. Zhu, X. Qian and L. Duan, J. Am. Chem. Soc.,
2008, 130, 16160–16161; (f) X. Peng, J. Du, J. Fan, J. Wang,
Y. Wu, J. Zhao, S. Sun and T. Xu, J. Am. Chem. Soc., 2007,
129, 1500–1501.
7 M. Taki, M. Desaki, A. Ojida, S. Iyoshi, T. Hirayama,
I. Hamachi and Y. Yamamoto, J. Am. Chem. Soc., 2008, 130,
12564–12565.
8 Q. He, E. W. Miller, A. P. Wong and C. J. Chang, J. Am.
Chem. Soc., 2006, 128, 9316–9317.
9 H. Yang, Z. Zho, K. Huang, M. Yu, F. Li, T. Yi and
C. Huang, Org. Lett., 2007, 9, 4729–4732.
10 H. S. Jung, P. S. Kwon, J. W. Lee, J. I. Kim, C. S. Hong,
J. W. Kim, S. Yan, J. Y. Lee, J. H. Lee, T. Joo and J. S. Kim,
J. Am. Chem. Soc., 2009, 131, 2008–2012.
11 E. M. Nolan and S. J. Lippard, Acc. Chem. Res., 2009, 42,
193–203.
12 (a) K. M. K. Swamy, M. J. Kim, H. R. Jeon, J. Y. Jung and
J. Yoon, Bull. Korean Chem. Soc., 2010, 31, 3611–3616; 15 W. Wang, Q. Yang, L. Sun, H. Wang, C. Zhang, X. Fei,
(b) Y. Zhou, Y. Xiao and X. Qian, Tetrahedron Lett., 2008, 49, M. Sun and Y. Li, J. Hazard. Mater., 2011, 194, 185–192.
3380–3384; (c) S. Y. Park, J. H. Yoon, C. S. Hong, R. Souane, 16 (a) Z. Zhou, M. Yu, H. Yang, K. Huang, F. Li, T. Yi and
J. S. Kim, S. E. Matthews and J. Vicens, J. Org. Chem., 2008,
73, 8212–8218; (d) M. Ha-Thi, M. Penhoat, D. Drouin,
M. Blanchard-Desce, V. Michelet and I. Leray, Chem.–Eur.
J., 2008, 14, 5941–5950; (e) L. Xue, Q. Liu and H. Jiang, Org.
Lett., 2009, 11, 3454–3457; (f) H. Li, Y. Yao, C. Han and
J. Zhan, Chem. Commun., 2009, 4812–4814; (g) N. Saleh,
Luminescence, 2009, 24, 30–34.
C. Huang, Chem. Commun., 2008, 3387–3389; (b) B. Zhu,
C. Gao, Y. Zhao, C. Liu, Y. Li, Q. Wei, Z. Ma, B. Du and
X. Zhang, Chem. Commun., 2011, 47, 8656–8658;
(c) J. F. Zhang, S. Kim, J. H. Han, S. J. Lee, T. Pradhan,
Q. Y. Cao, S. J. Lee, C. Kang and J. S. Kim, Org. Lett., 2011,
13, 55264–55297; (d) S. Lee, J. H. Lee, T. Pradhan,
C. S. Lim, B. R. Cho, S. Bhuniya, S. Kim and J. S. Kim, Sens.
Actuators, B, 2011, 160, 1489–1493; (e) Z. Xu, K. H. Baek,
H. N. Kim, J. Cui, X. Qian, D. R. Spring, I. Shin and J. Yoon,
J. Am. Chem. Soc., 2010, 132, 601–610.
13 (a) N. Saleh, Y. A. Al-Soud and W. M. Nauc, Spectrochim.
Acta, Part A, 2008, 71, 818–822; (b) Y. Bao, B. Liu, H. Wang,
F. Du and R. Bai, Anal. Methods, 2011, 3, 1274–1276;
(c) H. N. Lee, H. N. Kim, K. M. K. Swamy, M. S. Park, 17 M. R. Maurya, S. J. Titinchi and S. Chand, J. Mol. Catal.
J. Kim, H. Lee, K. Lee, S. Park and J. Yoon, Tetrahedron A: Chem., 2003, 193, 165–176.
Lett., 2008, 49, 1261–1265; (d) T. Alizadeh, M. R. Ganjali, 18 M. Royzen, Z. Dai and J. W. Canary, J. Am. Chem. Soc., 2005,
P. Nourozi, M. Zare and M. Hoseini, J. Electroanal. Chem.,
127, 1612–1613.
This journal is © The Royal Society of Chemistry 2013
Dalton Trans., 2013, 42, 1827–1833 | 1833