Design of a semirigid molecule as a selective fluorescent chemosensor for recognition of Cd(II)

Article abstract of DOI:10.1021/ol801382f

(Chemical Equation Presented) (Graph Presented) A new 8-hydroxyquinoline- based chemosensor possessing a semirigid structure was designed, and its fluorescent sensing behavior toward metalions was investigated. A prominent fluorescence enhancement only for Cd²⁺ was found in aqueous methanol solution. The results clearly suggest that the specific semirigid structure could selectively accommodate Cd²⁺ according to ionic radius, which would effectively suppress the intramolecular radiationless transitions from the nπ* state to enhance the fluorescence response.

Full text of DOI:10.1021/ol801382f

ORGANIC
LETTERS
2008
Vol. 10, No. 17
3653-3656
Design of a Semirigid Molecule as a
Selective Fluorescent Chemosensor for
Recognition of Cd(II)
Xiao-Liang Tang,† Xiao-Hong Peng,† Wei Dou,† Jie Mao,† Jiang-Rong Zheng,†
Wen-Wu Qin,† Wei-Sheng Liu,*,†,‡ Jin Chang,† and Xiao-Jun Yao†
College of Chemistry and Chemical Engineering and State Key Laboratory of Applied
Organic Chemistry, Lanzhou UniVersity, Lanzhou 730000, China, and State Key
Laboratory of Coordination Chemistry, Nanjing UniVersity, Nanjing 210093, China
liuws@lzu.edu.cn
Received March 23, 2008
ABSTRACT
A new 8-hydroxyquinoline-based chemosensor possessing a semirigid structure was designed, and its fluorescent sensing behavior toward
metalions was investigated. A prominent fluorescence enhancement only for Cd2+ was found in aqueous methanol solution. The results
clearly suggest that the specific semirigid structure could selectively accommodate Cd2+ according to ionic radius, which would effectively
suppress the intramolecular radiationless transitions from the nπ* state to enhance the fluorescence response.
The development of selective chemosensors capable of
effectively detecting the presence of transition-metal ions has
received considerable current attention, mostly because these
ions play important roles in living systems and have an
extremely toxic impact on the environment.1 Such sensors
based on ion-induced changes in fluorescence appear to be
particularly attractive due to their simplicity, high sensitivity,
high selectivity, and instantaneous response.2 Therefore,
numerous excellent studies focus on the design of fluorescent
chemosensors and the analysis of transition- or heavy-metal
(2) For reviews, see: (a) Amendola, V.; Fabbrizzi, L.; Forti, F.; Licchelli,
M.; Mangano, C.; Pallavicini, P.; Poggi, A.; Sacchi, D.; Taglieti, A. Coord.
Chem. ReV. 2006, 250, 273. (b) Rurack, K.; Resch-Genger, U. Chem. Soc.
ReV. 2002, 116. (c) Rurack, K. Spectrochim. Acta 2001, 57A, 2161. (d)
Valeur, B.; Leray, I. Coord. Chem. ReV. 2000, 205, 3.
(3) Formercury chemosensors, see: (a) Yang, H.; Zhou, Z.; Huang, K.;
Yu, M.; Li, F.; Yi, T.; Huang, C. Org. Lett. 2007, 9, 4729. (b) Coskun, A.;
Yilmaz, M. D.; Akkaya, E. U. Org. Lett. 2007, 9, 607. (c) Ko, S.-K.; Yang,
Y.-K.; Tae, J.; Shin, I. J. Am. Chem. Soc. 2006, 128, 14150. (d) Zheng, H.;
Qian, Z.-H.; Xu, L.; Yuan, F.-F.; Lan, L.-D.; Xu, J.-G. Org. Lett. 2006, 8,
859. (e) Matsushita, M.; Meijler, M. M.; Wirsching, P.; Lerner, R. A.; Janda,
K. D. Org. Lett. 2005, 7, 4943. For lead-specified probes, see: (f) He, Q.;
Miller, E. W.; Wong, A. P.; Chang, C. J. J. Am. Chem. Soc. 2006, 128,
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Huang, W. P. J. Am. Chem. Soc. 2002, 124, 6246. For copper-responsive
fluorescent sensors, see: (i) Weng, Y.-Q.; Yue, F.; Zhong, Y.-R.; Ye, B.-
H. Inorg. Chem. 2007, 46, 7749. (j) Zeng, L.; Miller, E. W.; Pralle, A.;
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† Lanzhou University.
‡ Nanjing University.
(1) (a) Schraderr, T.; Hamilton, A. D., Eds. Functional Synthetic
Receptors; Wiley-VCH: Weinheim, Germany, 2005. (b) Desvergne, J. P.;
Czarnik, A. W. Chemosensors of Ion and Molecule Recognition; Kluwer:
Dordrecht, 1997. (c) Fluorescent Chemosensors for Ion and Molecule
Recognition; Czarnik, A. W., Ed.; American Chemical Society: Washington,
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44. (e) Beer, P. D.; Gale, P. A. Angew. Chem., Int. Ed. 2001, 40, 486–516.
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10.1021/ol801382f CCC: $40.75
Published on Web 07/24/2008
2008 American Chemical Society

ions such as Hg2+, Pb2+, and Cu2+.3 However, relatively few
examples of fluorescent sensors for Cd2+ have been reported,4
and though more research has developed rapidly in recent
years.5 It is well-known that cadmium is one of the important
resources and is currently used in many processes such as
electroplating, metallurgy, war industry, agriculture, etc.6
These sources lead to cadmium exposure through various
means, and there is evidence of increasing cadmium ac-
cumulation in food and organisms, which will pose severe
harm for human health.7 On the other hand, Cd2+ and some
metal ions, especially Zn2+, have many similar properties,
thus it is difficult to discriminate between them.4,5,8 There-
fore, there is a great need for the design and synthesis of
such chemosensors, which have high sensitivity and selectiv-
ity for detecting and monitoring Cd2+ by employing a simple
response at physiological pH.
ions.11 To take advantage of the 1,3,4-oxadiazole subunit
containing lone electron pairs on N, the semirigid ligand
could effectively chelate Cd2+ according to the ionic radius
and limit the geometric structure of the complex.
The synthesis of 1 is described in Scheme 1. Compound
2 was first prepared according to the literature.12 Compound
Scheme 1. Synthesis of the Chemosensor 1
Based on our previous research on the recognition and
separation of important metal ions,9 it is necessary to choose
an efficient fluorophore and consider the geometry of
coordination sites for a certain cation. Herein, we describe
a new and simple fluorescent Cd2+ sensor 1 based on the
chelation-enhanced fluorescence (CHEF) mechanism. CHEF
is an attractive design principle for developing luminescent
chemical devices, which combine the ability to recognize
and respond to an external input mostly with mediation of
photoinduced electron transfer (PET).10 An important part
within this application is to obtain a suitable semirigid
structure. Upon complexation with a certain metal ion, a large
CHEF effect is observed because the stable chelation
abrogates the PET process from the electron-donating group
to the fluorophore (“turn-on state”). In sensor 1, we chose
the 8-hydroxyquinoline derivative as the fluorophore due to
its good photostability and strong ability to complex metal
1 was then synthesized as a pale brown solid via a simple
one-step reaction of 2 with 2 equiv of 8-hydroxyquinoline
in good yield using anhydrous potassium carbonate in
refluxing acetone (91%).
Sensor 1 should have weak fluorescence on the basis of
the consideration that the N lone electron pairs in the 1,3,4-
oxadiazole are brought into immediate proximity to the
8-hydroxyquinoline fluorophores, as a result of a radiationless
process via the nπ* state. This interpretation is supported
by the fact that 1 in the aprotic solvent acetonitrile exhibits
weaker fluorescence, with quantum yield (Φ) ca. 0.01 (Table
S1, Supporting Information), which obviously differs from
those highly fluorescent ether derivatives, for example, Φ
) 0.5 for 8-(benzyloxy)quinoline.11 Further, in the protic
solvent MeOH and mixed solvent 5% H2O-MeOH, Φ of 1
are 1.24 times and 3.09 times greater than that in acetonitrile,
respectively, due to the hydrogen bonding of the solvent to
the N lone electron pairs. It weakens the intramolecular
radiationless transitions from the nπ* state and makes the
emission maximum (λem) undergo a gradual red shift with
increasing protonation by the solvent. Therefore, 1 appears
to be a promising candidate for enhancing fluorescence
emission upon binding suitable metal ions if their radiation-
less channel could be well blocked.
Fluorescent sensors based on electron donor/acceptor are
usually disturbed by protons in the detection of metal ions,
so it is necessary to consider excluding the pH effect and
finding optimal sensing conditions. The response of 1 toward
pH was investigated in 5% H2O-MeOH mixed solvent in
search of the “turn-off state” (Figure S1, Supporting Infor-
mation). The emission peak of 1 is observed at ca. 397 nm
at neutral pH, and no dramatic change is expected under
alkaline conditions. However, under acidic conditions,
increasing the acid concentration leads to a gradual decrease
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Kim, J.; Lee, H.; Lee, K.-H.; Park, S.; Yoon, J. Tetrahedron Lett. 2008,
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Lett. 2007, 9, 3829. (d) Peng, X.; Du, J.; Fan, J.; Wang, J.; Wu, Y.; Zhao,
J.; Sun, S.; Xu, T. J. Am. Chem. Soc. 2007, 129, 1500. (e) Lu, C.; Xu, Z.;
Cui, J.; Zhang, R.; Qian, X. J. Org. Chem. 2007, 72, 3554. (f) Aragoni,
M. C.; Arca, M.; Bencini, A.; Blake, A. J.; Caltagirone, C.; Danesi, A.;
Devillanova, F. A.; Garau, A.; Gelbrich, T.; Isaia, F.; Lippolis, V.;
Hursthouse, M. B.; Valtancoli, B.; Wilson, C. Inorg. Chem. 2007, 46, 8088.
(g) Luo, H.-Y.; Jiang, J.-H.; Zhang, X.-B.; Li, C.-Y.; Shen, G.-L.; Yu, R.-
Q. Talanta 2007, 72, 575.
(6) Chaney, R. L.; Ryan, J. A.; Li, Y.-M.; Brown, S. L. In Cadmium in
Soils and Plants; McLaughlin, M. J., Singh, B. R., Eds.; Kluwer: Boston,
1999; pp 219-256.
(7) (a) Dobson, S. Cadmium: Environmental Aspects; World Health
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Cadmium;World Health Organization: Geneva, 1992.
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5th ed.; Wiley: New York, 1988; pp 957-1358. (b) Dakternieks, D. Coord.
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3654
Org. Lett., Vol. 10, No. 17, 2008

in the fluorescence intensity at ca. 397 nm and a gradual
increase at ca. 480 nm. This is a red shift of the emission
maximum of about 83 nm (Figure 1). The large change in
Figure 1. Plot of fluorescence emission at 397 and 480 nm of 1
versus pH in MeOH-H2O (95:5, v/v). λex ) 302 nm, [1] ) 2.5 ×
10-5 M.
fluorescence at acidic pH is due to the protonation of
quinoline, which results in the structure change of 1 and
produces the new emission at ca. 480 nm. For 1, a pKa of
4.10 ( 0.05 was determined from these changes. Therefore,
this experiment enabled us to identify the conditions (near
neutral pH) under which the metal-sensing ability of 1 could
be probed.
Figure 2. (a) Fluorescence enhancement of 1 at 410 nm in the
presence of different metal ions in HEPES-buffered (10 mM, pH
) 7.0) MeOH-H2O (95:5, v/v). λex ) 302 nm, white bars, [1] )
2.5 × 10-5 M, [Mn+] ) 2.5 × 10-3 M; black bars, [1] ) 2.5 ×
10-5 M, [Mn+] ) 2.5 × 10-3 M, [AcO-] ) 5.0 × 10-3 M. (b) The
fluorescence responses of 1 at 410 nm containing Cd2+ to different
metal ions in HEPES-buffered (10 mM, pH ) 7.0) MeOH-H2O
After systematically looking for selective signaling toward
different metal ions for potential applications, the fluores-
cence measurements were carried out in 5% H2O-MeOH
solution at pH 7.0 ([1] ) 2.5 × 10-5 M and [Mn+] ) 2.5 ×
10-3 M in HEPES buffer). As shown in Figure 2a, a clear
fluorescence enhancement (ca. 2.1-fold) is observed with
addition of Cd2+, but no increase of fluorescent emission in
the same conditions is detected with other metal ions Li+,
Na+, K+, Mg2+, Ca2+, Ba2+, Mn2+, Co2+, Ni2+, Zn2+, Cd2+,
(95:5, v/v). λex ) 302 nm, white bars, [1] ) 2.5 × 10-5 M, [Cd2+
]
) 2.5 × 10-3 M, [Mn+] ) 2.5 × 10-3 M; black bars, [1] ) 2.5 ×
10-5 M, [Cd2+] ) 2.5 × 10-3 M, [AcO-] ) 5.0 × 10-3 M, [Mn+
]
) 2.5 × 10-3 M.
HSO3- (Figure S5 and S6, Supporting Information), and ca.
3.5-fold fluorescence enhancement can be observed (Figure
2a and Figure S7, Supporting Information). Moreover, this
sensing for Cd2+ is also hardly interfered with by commonly
coexistent ions (Figure 2b).
To gain more insight into the chemosensing properties and
mechanism of 1 toward Cd2+ ions, a fluorescence titration
(Figure 3) and absorption titration (Figure S8, Supporting
Information) with Cd(ClO4)2 in acetonitrile were carried out.
In the fluorescence emission, free 1 exhibits a maximum at
384 nm. Upon the gradual addition of the Cd(ClO4)2 from 0
to 7 equiv, the λem undergoes a red shift to 410 nm. An
isoemissive point at 375 nm and 2.5-fold fluorescence
enhancement are also observed. The emission intensity at
410 nm (F410, Figure S9, Supporting Information) and the
intensity ratio, R (F410/F360, Figure S11, Supporting Informa-
tion), increase upon the addition of Cd2+, which allows the
detection of Cd2+ by direct fluorescence and the ratiometric
Hg2+, and Pb2+ (as their Cl- or NO3 salts). Moreover, the
-
addition of Cd2+ causes a slight red shift of λem from 397 to
410 nm (Figure S2, Supporting Information). In this system,
the binding constant log ꢀ is 5.2 ( 0.1 (Figure S3, Supporting
Information) and Cd2+ could be detected at least down to
9.0 × 10-6 M by fluorimetric assay. In addition, fluorescence
detection for all metal ions did not exhibit any appreciable
time-dependent effects. 1H NMR spectra of 1 and its complex
system with Cd2+ in CD3OD were measured as shown in
Figure S4 (Supporting Information). Apparently, the signals
for the methylene and heteroaromatic protons in the 1-Cd2+
complex all shift to downfield in certain degrees in com-
parison to the ligand 1. Furthermore, the competition
experiments of Cd2+ mixed with the above-mentioned metal
ions show that no significant variation is observed in
fluorescence intensity and the 1-Cd2+ system is stable
(Figure 2b). To improve the sensitivity and magnify the
selectivity, the anion responses to the detection systems were
further investigated. The result indicates that only AcO- can
efficiently enhance the fluorescence intensity of 1-Cd(ClO4)2
(13) (a) Pan, B.; Gao, F.; He, R.; Cui, D.; Zhang, Y. J. Colloid Interface
Sci. 2006, 297, 151. (b) Baruah, M.; Qin, W.; Valle¨e, R. A. L.; Beljonne,
D.; Rohand, T.; Dehaen, W.; Boens, N. Org. Lett. 2005, 7, 4377. (c) Cielen,
E.; Stobiecka, A.; Tahri, A.; Hoornaert, G. J.; Schryver, F. C. D.; Gallay,
J.; Vincent, M. J. Chem. Soc., Perkin Trans. 2 2002, 1197.
system over other anions such as F-, Cl-, Br-, I-, NO3 , or
-
Org. Lett., Vol. 10, No. 17, 2008
3655

fluorescence method. From these sigmoidal curves, binding
constant log ꢀ (8.9 ( 0.1) and log ꢀ′ (8.7 ( 0.1) are obtained,
respectively.13 In addition, the absorption titration also shows
small change in the spectral traces, indicative of the formation
of a 1-Cd2+ complex. Job’s plots of fluorescence obtained
for 1-Cd2+ system in acetonitrile clearly suggest a formation
of 1:2 stoichiometry (Figure 3, inset), which is also supported
To understand the selectivity and the configuration of
1-Cd2+, we carried out density functional theory (DFT)
calculations with B3LYP exchange functionals using the
Gaussian 98 package. The 6-31G basis sets were used except
for Cd2+, where LANL2DZ effective core potential (ECP)
was employed. The optimized configuration is shown in
Figure 4, which shows that two Cd2+ ions well occupy the
Figure 4. .
Calculated energy-minimized structureof 1 with Cd2+
coordination centers of 1 and the whole molecule forms a
planar structure. The Cd-O bond length is 2.25 Å, and the
Cd-N bond lengths are 2.17 Å (Cd-Nquinoline) and 2.44 Å
(Cd-Noxadiazole), respectively. Based on these data, it is
indicated that the design of semirigid structure can effectively
create suitable space to better match corresponding ions and
influence the emission of fluorophore itself with the help of
protic solvent.
In summary, we have designed and prepared an 8-hy-
droxyquinoline-based chemosensor possessing a semirigid
structure and investigated its chemosensing properties. It was
found that the selectivity experiment of this sensor for Cd2+
ion mostly relies on a specific space of the semirigid ligand,
sensitive fluorophore, and suitable protic solvent. Compound
1, with a specific semirigid framework, exhibits a selective
coordinate with Cd2+ at pH 7.0 in H2O-MeOH solution,
which causes a CHEF effect by suppressing the intramo-
lecular radiationless transitions from the nπ* state. The
strategy will help us in the design of more chemosensors
for some specific ions.
Figure 3. Fluorescence spectra of 1 in acetonitrile in the presence
of increasing concentration of Cd(ClO4)2. λex) 319 nm, [1] ) 1.0
× 10-5 M. Each spectrum was acquired 2 min after Cd2+ addition.
Inset: Job’s plots according to the method for continuous variations,
indicating the 1:2 stoichiometry for 1-Cd2+ (the total concentration
of 1 and Cd2+ is 20 µM).
by fitting a Hill coefficient of 2 (1.9473 in Figure S10 and
2.0519 in Figure S12, Supporting Information).
However, compared with a fluorescence titration with Cd2+,
we also find that the λem of 1 undergoes a similar red shift and
fluorescence enhancement uponaddition of Zn(ClO4)2 in aceto-
nitrile (Figure S13, Supporting Information), which does not
appear in aqueous methanol solution. This result indicates that
the semirigid structure of 1 plays an important role in recogni-
tion of Cd2+. In aprotic solvents, 1 can self-assemble with Cd2+
and Zn2+ to form complexes by modulating the flexible part
despite different ion radii (0.74 Å for Zn2+, 0.97 Å for Cd2+).
However, the complex of Zn2+ without suitable ion radius is
easily disrupted by protic solvent molecules and the fluorescence
of this complex is easily quenched because of solvent’s O-H
high energy oscillation. Accordingly, there is no obvious change
for 1 in the fluorescence intensity upon addition of Zn2+ in protic
solvents.
Acknowledgment. This study was supported by the NSFC
(Grant Nos. 20771048, 20431010, 20621091, J0630962). We
thank Dr. Wen-Hao Chen (Lanzhou University) for NMR
measurements.
Supporting Information Available: Experimental details,
characterization for the compound, and selected fluorescence
data are reported. This material is available free of charge
via the Internet at http://pubs.acs.org.
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