Naphthalimide modified rhodamine derivative: Ratiometric and selective fluorescent Sensor for Cu2+ based on two different approaches

Article abstract of DOI:10.1021/ol101535s

A new rhodamine-based derivative bearing a 1,8-naphthalimide group (1) was synthesized as a dual-mode Cu²⁺-selective sensor via the rhodamine ring-opening approach and ratiometric displacement. A colorimetric and "off-on" signal for Cu²⁺

Full text of DOI:10.1021/ol101535s

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ORGANIC
LETTERS
2010
Vol. 12, No. 17
3852-3855
Naphthalimide Modified Rhodamine
Derivative: Ratiometric and Selective
Fluorescent Sensor for Cu2+ Based on
Two Different Approaches
Jun Feng Zhang,†,§ Ying Zhou,‡ Juyoung Yoon,‡ Youngmee Kim,‡
Sung Jin Kim,‡ and Jong Seung Kim*,†
Department of Chemistry, Korea UniVersity, Seoul 130-701, Korea, Department of
Chemistry and Nano Science, Ewha Womans UniVersity, Seoul 120-750, Korea, and
College of Chemistry and Chemical Engineering, Yunnan Normal UniVersity,
Kunming, 650092, P.R. China
jongskim@korea.ac.kr
Received July 5, 2010
ABSTRACT
A new rhodamine-based derivative bearing a 1,8-naphthalimide group (1) was synthesized as a dual-mode Cu2+-selective sensor via the
rhodamine ring-opening approach and ratiometric displacement. A colorimetric and “off-on” signal for Cu2+ through rhodamine ring opening
in 1 and ratiometric fluorescent signal output when Cu2+ displaces the bound Zn2+ in the 1-Zn2+ complex can be observed.
Fluorescent sensors for the detection and measurement of
transition-metal ions are widely investigated because of their
simplicity and high sensitivity of response.1 In particular, the
development of a fluorescent probe for copper ions in the
presence of a variety of other metal ions has received great
attention. As is well-known, Cu2+ plays an important role in
living systems such as those occurring in the human nervous
system, gene expression, and the functional and structural
enhancement of proteins.2 However, under overloading condi-
tions, copper can be toxic and can cause oxidative stress and
disorders associated with neurodegenerative diseases, including
Menkes and Wilson diseases, familial amyotropic lateral
sclerosis, Alzheimer’s disease, and prion diseases.3
Even though some examples of selective recognition
sensors for Cu2+ have been reported,4 most of these sensors
(2) (a) Tapiero, H.; Townsend, D. M.; Tew, K. D. Biomed. Pharma-
cother. 2003, 57, 386. (b) Linder, M. C.; Hazegh-Azam, M. Am. J. Clin.
Nutr. 1996, 63, 797S. (c) Uauy, R.; Olivares, M.; Gonzalez, M. Am. J.
Clin. Nutr. 1998, 67, 952S.
† Korea University.
§ Yunnan Normal University.
‡ Ewha Womans University.
(3) (a) Muthaup, G.; Schlicksupp, A.; Hess, L.; Beher, D.; Ruppert, T.;
Masters, C. L.; Beyreuther, K. Science 1996, 271, 1406. (b) Løvstad, R. A.
BioMetals 2004, 17, 111.
(1) Lippard, S. J.; Berg, J. M. Principles of Bioinorganic Chemistry;
University Science Books: Mill Valley, CA, 1994.
10.1021/ol101535s  2010 American Chemical Society
Published on Web 08/05/2010

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show “turn-off” manner in emission spectra upon Cu2+
binding due to the fluorescence-quenching nature of para-
magnetic Cu2+.5 Furthermore, only a few examples can
display “turn-on” or ratiometric fluorescent changes in
emission spectra, which are desirable for analytical purposes
by the enhancement of fluorescence or changes in the ratio
of the intensities of the emission at two wavelengths.6
Recently a rhodamine-based derivative bearing a pyrene
group as a chemosensor for Cu2+ was reported in our work, in
which the rhodamine ring-opening process was introduced to
give a colorimetric change and “turn-on” fluorescence signal
toward Cu2+.7,8 Since the fluorescence of pyrene was
quenched upon addition of Cu2+, the signal is not observed
obviously. Introducing another fluorophore to give a strong
fluorescence first upon binding with some other ions and
show the typical rhodamine fluorescence later by the replace-
ment of Cu2+ could ensure the ratiometric signal output. Therefore,
1,8-naphthalimide, as a typical ICT fluorophore, was introduced
to form the ratiometric displacement system in 1.9
mode Cu2+-selective sensor Via two mechanisms: the rhodamine
ring-opening mechanism and ratiometric displacement from
1-Zn2+ complex. As far as we are aware, 1 is the first
rhodamine-based dual-mode ratiometric sensor for Cu2+ ion
utilizing two different mechanisms.
Scheme 1. Synthesis of Chemosensors 1 and Its Crystal Structure
This paper reports design and synthesis of a new rhodamine-
based derivative bearing a N-butyl-1,8-naphthalimide group (1),
which displays a selective colorimetric change and fluorescence
“turn-on” changes at 550 nm Via rhodamine ring-opening
approach toward Cu2+ among the other examined metal ions.
Compound 1 also showed a remarkable ratiometric fluorescence
enhancement toward Zn2+ with 100 nm red-shift by a typical
ICT response. As expected, the naphthalimide moiety served
successfully as a source of these ratiometric changes. Moreover,
another ratiometric fluorescent signal output for Cu2+ can be
observed when Zn2+ in the 1-Zn2+ complex was displaced with
Cu2+. These results demonstrated that 1 could act as a dual-
(4) (a) de Silva, A. P.; Gunaratne, H. Q. N.; Gunnlaugsson, T. A.;
Huxley, T. M.; McCoy, C. P.; Rademacher, J. T.; Rice, T. E. Chem. ReV.
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(d) Liu, B.; Tian, H. Chem. Commun. 2005, 3156. (e) Qi, X.; Jun, E. J.;
Xu, L.; Kim, S.-J.; Hong, J. S. J.; Yoon, Y. J.; Yoon, J. J. Org. Chem.
2006, 71, 2881. (f) Kim, S. H.; Kim, J. S.; Park, S. M.; Chang, S.-K. Org.
Lett. 2006, 8, 371. (g) Jung, H. S.; Kwon, P. S.; Lee, J. W.; Kim, J. I.;
Hong, C. S.; Kim, J. W.; Yan, S.; Lee, J. Y.; Lee, J. H.; Joo, T.; Kim, J. S.
J. Am. Chem. Soc. 2009, 131, 2008. (h) Huang, X.; Guo, Z.; Zhu, W.; Xie,
Y.; Tian, H. Chem. Commun. 2008, 5143.
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119, 7386. (b) Liu, J.; Lu, Y. J. Am. Chem. Soc. 2007, 129, 9838. (c) Xiang,
Y.; Tong, A.; Jin, P.; Ju, Y. Org. Lett. 2006, 8, 2863. (d) Swamy, K. W. K.;
Ko, S.-K.; Kwon, S.; Lee, H.; Mao, C.; Kim, J.-M.; Lee, K.-H.; Kim, J.;
Shin, I.; Yoon, J. Chem. Commun. 2008, 5915. (e) Chen, X.; Jou, M.; Lee,
H.; Kou, S.; Lim, J.; Nam, S.-W.; Park, S.; Kim, K.-M.; Yoon, J. Sens.
Actuat. B 2009, 137, 597. (f) Wen, Z. C.; Yang, R.; He, H.; Jiang, Y. B.
Chem. Commun. 2006, 106. (g) Wu, Q.; Anslyn, E. V. J. Am. Chem. Soc.
2004, 126, 14682. (h) Kim, Y. R.; Kim, H. J.; Kim, J. S.; Kim, H. AdV.
Mater. 2008, 20, 4428. (i) Kim, H. J.; Lee, S. J.; Park, S. Y.; Jung, J. H.;
Kim, J. S. AdV. Mater. 2008, 17, 3229. (j) Jung, H. S.; Park, M.; Han,
D. Y.; Kim, E.; Lee, C.; Ham, S.; Kim, J. S. Org. Lett. 2009, 11, 3378. (k)
Kim, H. J.; Hong, J.; Hong, A.; Ham, S.; Lee, J. H.; Kim, J. S. Org. Lett.
2008, 10, 1963. (l) Li, G. K.; Xu, Z. X.; Chen, C. F.; Huang, Z. T. Chem.
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As shown in Scheme 1, 4-(5′-ethynylsalicylaldehyde)-N-
butyl-1,8-naphthalimides (4) was first synthesized by modi-
fying the reported procedure with an improved yield of
82%.10 Compound 4 was then reacted with rhodamine 6G
hydrazide (5) to give the hydrazone 1 in 56% yield. The
detailed experimental procedures and the characterization of
the new compounds are described in Supporting Information.
Sensor 1 was further confirmed by X-ray analysis (Scheme
1). The single crystal of 1 suitable for X-ray diffraction
studies was grown by the vapor diffusion of diethyl ether
into a CH3CN solution of 1.
To get further insight into the binding of Cu2+ with 1, the
absorption spectra of 1 upon titration with Cu2+ were
recorded (Figure 1). Upon addition of Cu2+, three new
11, 4442
(8) Kim, H. N.; Lee, M. H.; Kim, H. J.; Kim, J. S.; Yoon, J. Chem.
Soc. ReV. 2008, 37, 1465
.
.
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(b) Xu, Z.; Xiao, Y.; Qian, X.; Cui, J.; Cui, D. Org. Lett. 2005, 7, 889. (c)
Xu, Z.; Baek, K.-H.; Kim, H. N.; Cui, J.; Qian, X.; Spring, D. R.; Shin, I.;
Yoon, J. J. Am. Chem. Soc. 2010, 132, 601.
(10) Yang, J. X.; Wang, X. L.; Wang, X. M.; Xu, L. H. Dyes Pigm.
2005, 66, 83.
Org. Lett., Vol. 12, No. 17, 2010
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complex with Cu2+, whose association constant (Ka) was
determined to be about 0.52 × 104 from the titration
experiments. Moreover, the Job’s plot and FAB mass
confirms the 2:2 stoichiometry for the 1-Cu2+ complex,
which also strongly supports the above conclusion (Figures
S6 and S20 in Supporting Information).
To evaluate the selectivity of 1 for Cu2+, absorption and
fluorescence intensity changes upon addition of excess
amount of various metal ions were measured. The unique
absorption change with appearance of the brownish red of 1
was observed only by the addition of Cu2+, which can be
ascribed to the spirolactam bond cleavage of the rhodamine
group. The other metal ions such as Li+, Na+, K+, Rb+, Cs+,
Ag+, Mg2+, Ca2+, Ba2+, Sr2+, Cd2+, Hg2+, Pb2+, Fe2+, Fe3+,
Al3+, In3+, Co2+, and Ni2+ did not cause any significant
changes in the UV spectra as shown in Figure S1 in
Supporting Information. Free 1 showed weak fluorescence
emission around 493 nm upon excitation at 400 nm in buffer
solution because of the efficient PET quenching from amide
of rhodamine 6G to the naphthalic amine fluorophore (Figure
S2 in Supporting Information).
Figure 1. Absorbance spectra of 1 (10 µM) in CH3CN-HEPES
buffer (0.02 M, pH ) 7.4) (5:5, v/v) in the presence of different
amounts of Cu2+. Inset: the ratio of absorbance at 526 nm and
absorbance at 382 nm (black dot line) and the ratio of absorbance
at 437 nm and absorbance at 382 nm (red dot line) as a function of
Cu2+ concentration.
Addition of Li+, Na+, K+, Rb+, Cs+, Ag+, Mg2+, Ca2+,
Ba2+, Sr2+, Cd2+, Hg2+, Pb2+, Fe2+, Fe3+, Al3+, In3+, Co2+,
and Ni2+ exerted little or no effect on the emission of 1,
whereas Cu2+ gave a new weak emission peak centered
at 550 nm (Figure S2 in Supporting Information). The
efficient FRET was not observed since the fluorescent of
absorption band centered at 297, 437, and 526 nm appeared
with increasing intensity, which induced a clear color change
from pale yellow to brownish red. Meanwhile, the absorption
band centered at 382 nm decreased gradually with two
isosbestic points at 359 and 395 nm was observed. A linear
dependence of the ratio of absorbance at 526 nm and
absorbance at 382 nm (black line) and the ratio of absorbance
at 437 nm and absorbance at 382 nm (red line) as a function
of Cu2+ concentration were observed. At the same time, the
fluorescence intensity at 548 nm was obviously enhanced
because of the rhodamine ring-opening process (Figure 2).
The linear dependence of the intensity ratio within the
equivalent range of Cu2+ ion testified that 1 forms a 2:2
naphthalic amine was quenched upon addition of Cu2+
.
Remarkable ratiometric fluorescence enhancements and
red-shift of about 100 nm were detected upon binding
Zn2+, showing a typical response of ICT sensors (Figure
S3 in Supporting Information). The Ka was determined
to be about 0.34 × 103 from the titration experiments.
The ratio of emission intensities (F595 nm/F493 nm) varies
from 0.12 to 3.97 and is saturated up to a molar ratio
(1/Zn2+) of 2:1 (Figure S3 inset in Supporting Informa-
tion). To confirm the stoichiometry between 1 and Zn2+
,
the Job’s plot and FAB mass spectrometry were under-
taken, and the results supported this experimental finding
(Figures S10 and S21 in Supporting Information).
Probe 1 exhibited some difference spectra changes upon
addition of these metal ions in buffer solution by excitation
of the rhodamine fluorophore at 510 nm (Figure 3). Remark-
able fluorescence enhancements were detected upon the
addition of Zn2+ and Cu2+, respectively. Upon binding Zn2+,
1 showed a broad emission band centered at 595 nm, which
is similar as excitation at 400 nm (Figure S3 in Supporting
Information), implicating that a promoted ICT process
occurred. In contrast, upon binding Cu2+, only enhanced
fluorescent intensity at 550 nm were observed, suggesting
that sensor 1 recognizes Cu2+ principally based on the
rhodamine ring-opening mechanism. Furthermore, in the
competition experiment, the absorption and fluorescence
properties of 1 toward other metal ions, including Li+, Na+,
K+, Rb+, Cs+, Ag+, Mg2+, Ca2+, Sr2+, Cd2+, Pb2+, Fe2+,
Cu2+, Zn2+, Co2+, Ni2+, Fe3+, Al3+, and In3+ were also
measured (Figures S4 and S5 in Supporting Information).
The increases of absorbance and fluorescence intensity
Figure 2. Fluorescence spectra of 1 (10 µM) in CH3CN-HEPES
buffer (0.02 M, pH ) 7.4) (5:5, v/v) in the presence of different
amounts of Cu2+. Inset: the fluorescent intensity at 548 nm as a
function of Cu2+ concentration. Excitation wavelength was 510 nm.
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Figure 4.
Fluorescence spectra of 1-Zn2+ (20 µM 1 addition of
Figure 3. Fluorescence spectra of 1 (10 µM) and 1 in the presence
of various metal ions (5 equiv) in CH3CN-HEPES buffer (0.02
M, pH ) 7.4) (5:5, v/v). Excitation wavelength was 510 nm.
100 µM Zn2+) in CH3CN-HEPES buffer (0.02 M, pH ) 7.4) (5:5,
v/v) in the presence of different amounts of Cu2+. Inset: the ratio
of the fluorescent intensity at 550 nm and intensity at 594 nm as a
function of Cu2+ concentration. Excitation wavelength was 510 nm.
resulting from the addition of the Cu2+ ion were not
influenced by the subsequent addition of miscellaneous
cations. All of these indicate that the selectivity of 1 for the
Cu2+ ion over other competitive cations in the water medium
is remarkably high.
In conclusion, we have developed a novel fluorescent
sensor 1, which showed a ratiometric and “off-on” response
to Cu2+ based on rhodamine ring-opening approach. More-
over, the 1-Zn2+ can be displaced by Cu2+, which resulted
in another ratiometric sensing signal output. Thus, 1 can be
a dual mode Cu2+-selective sensor Via the rhodamine ring-
opening mechanism and ratiometric displacement mecha-
nism.
On the basis of the competition experiments, we realized
that 1 had higher binding affinity for Cu2+ than for Zn2+.
As expected, the addition of Cu2+ into a solution of 1-Zn2+
resulted in immediate absorption (Figure S7 in Supporting
Information) and fluorescence (Figure 4) changes. The
emission maximum of 1-Zn2+ underwent a gradual blue-shift
from 594 to 550 nm, implying that Cu2+ can displace Zn2+
to form the 1-Cu2+ complex. The ratio of 1-Cu2+to 1-Zn2+
emission intensities (F550 nm/F594 nm) varied from 0.5 to 4.6.
Further more, in the competition experiment, only Cu2+ ion
exhibited obvious influence of the absorbance and fluores-
cence of 1-Zn2+ complex (Figures S8 and S9 in Supporting
Information). These data indicate that 1-Zn2+ could be used
for sensing Cu2+ in micromolar range. Thus, 1 could be a
dual-mode Cu2+-selective sensor Via the rhodamine ring-
opening mechanism and ratiometric displacement in addition
to ring-opening approach.
Acknowledgment. This work was supported by the CRI
project (2010-0000728) (JSKim). J.F.Z. acknowledges the
“ChunHui Project” Foundation of Ministry of Education of
China, the foundation of Department of Education (08Y0137),
and the Department of Science and Technology (2008CD104)
of Yunnan Province of China.
Supporting Information Available: Experimental pro-
cedures, characterization data of compounds, and additional
spectroscopic data. This material is available free of charge
via the Internet at http://pubs.acs.org.
OL101535S
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