Cu(II) complex of a flexible tripodal receptor as a highly selective fluorescent probe for iodide

Article abstract of DOI:10.1016/j.tetlet.2008.10.088

A Cu(II) complex of a tripodal receptor bearing an anthracene moiety on one pod as a fluorophore was synthesized. The anion recognition behavior of the Cu(II) complex was evaluated in CH₃CN/H₂O (95:5, v/v), resulting in an extremely

Full text of DOI:10.1016/j.tetlet.2008.10.088

Tetrahedron Letters 50 (2009) 71–74
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Tetrahedron Letters
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Cu(II) complex of a flexible tripodal receptor as
a highly selective fluorescent probe for iodide
*
Narinder Singh, Hee Jung Jung, Doo Ok Jang
Department of Chemistry, Yonsei University, Wonju 220-710, Republic of Korea
a r t i c l e i n f o
a b s t r a c t
Article history:
A Cu(II) complex of a tripodal receptor bearing an anthracene moiety on one pod as a fluorophore was
Received 12 September 2008
Revised 16 October 2008
Accepted 20 October 2008
Available online 1 November 2008
synthesized. The anion recognition behavior of the Cu(II) complex was evaluated in CH3CN/H2O (95:5,
v/v), resulting in an extremely high selectivity for iodide over other anions such as FÀ, ClÀ, BrÀ, NO3
,
À
CH3COOÀ, and H2PO2À. The Cu(II) complex acts as a selective probe for estimating iodide even in the pres-
ence of other anions without any interference.
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords:
Anion recognition
Hydrogen bonding
Cu(II) complex
Fluorescent probe
Iodide
1. Introduction
employs electrostatic interactions from a metal-ion center along
with the hydrogen bonding with the receptor.
Anion recognition by artificial receptors has attracted increas-
ing attention over the past years because anions play important
roles in biological and chemical systems as well as in ecological
systems.1 Anions are recognized mainly through coordination of
metal ions,2 electrostatic interaction of ammonium and guanidi-
nium,3 or hydrogen bonding of amides and ureas.4 Recently, me-
tal-based receptors have received considerable attention in the
area of the anion recognition, since they show a greater enhance-
ment in anion-binding affinity than purely organic receptors.5
The metal centers preorganize the binding sites structurally for
optimal anion-binding and strong affinities through hydrogen
bonding and metal-ion coordination.
Anion recognition through hydrogen bonding is extremely diffi-
cult in aqueous medium.2a Even in the presence of a small amount
of water, the binding affinity of the receptors decreases drastically
owing to the strong hydration of anions and the competition of
water for the hydrogen bonding sites. Therefore, additional bond-
ing interactions are required for recognizing anions in aqueous
organic medium. Metal-based receptors may provide additional
binding sites to the anions resulting in high affinity. These electro-
static interactions are responsible for the anion recognition in
aqueous organic medium. In our continuing research on anion
recognition,6 we herein report on a new metal-based receptor that
The receptor employed mixed nitrogen and sulfur donors. In
nature, the Cu(II) exists in the cavities of various proteins and is
coordinated through four or five sulfur and nitrogen donors.7 These
mixed sulfur and nitrogen donors afford a variety of coordination
geometries in the naturally occurring proteins. Keeping these facts
in mind, we designed a flexible receptor in which possible coordi-
nation modes are much more abundant than in a rigid receptor.
The reasonable flexibility of the receptor will ensure that the
receptor may adopt conformation for encapsulating large size
anions such as iodide.
Iodide is one of the key elements that influence neurological
and thyroid activities.8 The estimation of iodide anions is per-
formed frequently to examine thyroid disorders in clinics. Thus,
there is a great demand for the development of synthetic receptors
capable of selectively recognizing iodide over other anions.
Although iodide is such a biologically important anion, only a
few papers have reported on recognition of iodide.6d,9
2. Results and discussion
Tripodal receptor 2 was synthesized as shown in Scheme 1.
Receptor 2 was prepared in 67% yield by condensing anthracene-
9-carbaldehyde with tripodal amine 1, which was prepared by
the literature method,10 and followed by reduction with NaBH4.
The structure of the product was established by using the spectro-
scopic methods. The 1H NMR spectrum of receptor 2 revealed the
presence of two characteristic N–H resonances at 4.39 and
* Corresponding author. Tel.: +82 337602261; fax: +82 337602182.
E-mail address: dojang@yonsei.ac.kr (D. O. Jang).
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.10.088

72
N. Singh et al. / Tetrahedron Letters 50 (2009) 71–74
O
N
S
S
1) MeOH
2) NaBH4
+
S
H2N
NH2
NH2
1
N
S
S
Cu(NO3)2.2.5H2O
MeOH
S
2.
HN
NH2
Cu(II)
NH2
2
Scheme 1.
6.69 ppm, respectively, which disappeared upon adding D2O, con-
firming the position of –NH2 and –NH proton signals.
The photophysical behaviors of receptor 2 were investigated
using 1.0 lM solutions of receptor 2 in CH3CN/H2O (95:5, v/v).
The emission maxima at an excitation wavelength of 365 nm was
observed at 412 nm, sandwiched by two other low intensity bands
at 395 and 440 nm, which is a characteristic emission spectrum of
anthracene moiety. Receptor 2 was designed in such a way that
only a single pod of the receptor bears the fluorophore. The ratio-
nale behind the design of the receptor is based on the idea that me-
tal binding to the receptor pods (that are devoid of fluorophore)
will not bring changes in the fluorescence intensity of the receptor
although the anion binding between the metal center and the NH
of secondary amine will cause changes in the fluorescence
intensity.
Figure 1. Energy minimized structure of complex 2ÁCu(II) calculated by Macro-
Model (A) and possible binding mode for anion recognition with complex 2ÁCu(II)
(B).
The changes in the fluorescence intensity are shown in Figure 2,
and the fluorescence ratio (I0 À I)/I0 is displayed in Figure 3. The
addition of iodide caused a significant quenching in fluorescence
intensity whereas much smaller quenching was observed upon
addition of anions such as FÀ, ClÀ, BrÀ, NO3À, CH3COOÀ, and
À
H2PO4
.
With these thoughts in mind, we prepared complex 2ÁCu(II) by
reacting receptor 2 with Cu(NO3)2Á2.5H2O in dry MeOH at room
temperature (Scheme 1). FAB mass spectrum supports the forma-
tion of mononuclear complex 2ÁCu(II), showing m/z = 723.1711
which corresponds to complex 2ÁCu(II) (the theoretical calculated
value is m/z = 723.1710). Attempts to grow crystals of complex
2ÁCu(II) suitable for X-ray structure determination were not suc-
cessful. The fluorescence spectrum of complex 2ÁCu(II) is similar
to that of receptor 2, indicating that the pod bearing anthracene
moiety does not participate much in the coordination to Cu(II) me-
tal center. To understand the interactions between receptor 2 and
The preference for iodide suggests that iodide has a comple-
mentary size to the pseudocavity formed by the receptor binding
sites. Thus, it is an example of better encapsulation of iodide
according to its size, not according to its basicity.13 Iodide may also
change the fluorescent intensity of the receptor because of a heavy
atomic effect. However, the changes in the fluorescent intensity of
the complex are not the result of heavy atomic effect of iodide be-
cause the addition of iodide did not alter the fluorescent intensity
of receptor 2. The changes in fluorescent intensity of complex
2ÁCu(II) without spectral shifts indicate that the fluorescent
quenching takes place via a photo-induced electron transfer
(PET) process.1g,6g The fluorescence behavior of complex 2ÁCu(II)
was also investigated in more polar solvent systems such as
*
the Cu(II) metal center, the MacroModel calculations using MM2
force field were performed (Fig. 1, A).11 The MacroModel calcula-
tions showed a binding mode of complex 2ÁCu(II), in which recep-
tor 2 may act as a mixed nitrogen–sulfur donor ligand. In the
system, receptor 2 tends to impose a trigonal bipyramidal struc-
ture. Consequently, the metal presents a vacant axial position,
which is available for the coordination of an anion (Fig. 1, B). The
structure of complex 2ÁCu(II) is similar to the skeleton of the Cu(II)
complex with tris(2-aminoethyl)amine (Tren), which recognizes
anions.12h Many other copper complexes have been reported for
anion recognition studies, where the copper center acts as a gen-
eral binding site for the anion recognition, and the selectivity of
such copper complexes for a particular anion is governed by the
other binding sites.12 Thus, the copper center has no clear cut
inherited binding affinity for any particular anions. The structure
of complex 2ÁCu(II) also provides a hydrogen bonding array con-
sisting of both primary and secondary amines. These structural
characteristics might provide a preorganized binding site for opti-
mal anion recognition.
We evaluated the anion-binding affinity of complex 2ÁCu(II) by
following the changes in the fluorescence intensity of the complex
upon addition of tetrabutylammonium salt of a particular anion.
Figure 2. Changes in fluorescence intensity of complex 2ÁCu(II) (1
addition of 5 M of a particular tetrabutylammonium anion salt in CH3CN/H2O
(95:5, v/v) with excitation at 365 nm.
lM) upon
l

N. Singh et al. / Tetrahedron Letters 50 (2009) 71–74
73
complex 2ÁCu(II). The association constant Ka of complex 2ÁCu(II)
for iodide was calculated on the basis of the literature method,14
and it was found to be 6.12 Â 105 MÀ1. To determine the stoichio-
metric ratio of complex 2ÁCu(II) and iodide, continuous variation
methods were used (Fig. 5).15 The results illustrate that in this case,
the receptor–guest complex concentration approaches a maximum
when the molar fraction of complex 2ÁCu(II) is about 0.5, indicating
the formation of a 1:1 complex between complex 2ÁCu(II) and
iodide.
Nitrate
Dihydrogen
Acetate
Iodide
Figure 2 shows that there were no significant changes in the
fluorescence intensity of complex 2ÁCu(II) upon addition of FÀ,
ClÀ, BrÀ, NO3À, CH3COOÀ, and H2PO4À, showing that complex
2ÁCu(II) is highly selective in its response to iodide as compared
to the other anions. Thus, complex 2ÁCu(II) can be used as a probe
for selective recognition of iodide, and it can detect iodide as low as
Bromide
Chloride
Fluoride
0.2 l
M.16 This detection limit is better than any of the iodide-selec-
tive fluorescent receptor reported in the literatures.6d,9
0
0.5
(Io- I)/Io
1
To evaluate the analytical application of complex 2ÁCu(II) as a
probe for iodide, the estimation of iodide was conducted in the
presence of other anions, which may interfere in the estimation
(Fig. 6). In these typical experiments, the fluorescence intensities
of a series of solutions were measured. These solutions contained
complex 2ÁCu(II), different amounts of iodide, and other anions
having a concentration five times greater than the concentration
of iodide in CH3CN/H2O (95:5, v/v). The fluorescence intensity
was almost identical to that obtained in the absence of anions.
Figure 3. Fluorescence ratio (I0 À I/I0) of complex 2ÁCu(II) (1
l
M) at 412 nm upon
addition of 5
(95:5, v/v).
lM of a particular tetrabutylammonium anion salt in CH3CN/H2O
CH3CN/H2O (90:10, v/v), resulting in inhibition in iodide binding.
This is due to the fact that the an increase in the proportion of
water enhances the competition of water with iodide for the
hydrogen bond donor binding sites. This observation indicates that
hydrogen bonding through the NH bond is responsible for iodide
binding. The hydrogen bonding was further confirmed by the com-
parison of IR spectrum of complex 2ÁCu(II) and complex
2ÁCu(II) + IÀ.
3.5
3
2.5
2
To investigate the properties of complex 2ÁCu(II) as a receptor
for iodide in detail, the fluorescence titration was carried out.
The fluorescence intensity of a 1
decreased as the concentration of tetrabutylammonium iodide salt
increased as shown in Figure 4.
l
M solution of complex 2ÁCu(II)
1.5
1
During the course of titration, the complex exhibited a high sen-
sitivity toward iodide, by quenching the fluorescence intensity of
0.5
0
0
0.2
0.4
0.6
0.8
1
[H]/[H]+[G]
180
Figure 5. Job plot between complex 2ÁCu(II) and iodide. The concentration of [HG]
was calculated by the equation [HG] =
D
I/I0X [H].
Host
0.2
0.4
0.6
0.8
1
0.1
0.3
0.5
0.7
0.9
1.5
2.5
3.5
4.5
160
140
120
100
80
180
160
140
120
100
80
2
3
4
5
60
40
60
0
1
2
3
4
5
6
Equiv of Iodide
20
Iodide only
Iodide + Fluoride
Iodide + Bromide
Iodide + Dihydrogen Phosphate
0
380
Iodide + Chloride
Iodide + Acetate
Iodide + Nitrate
405
430
455
480
Wavelength (nm)
Figure 4. Fluorescence spectra changes of complex 2ÁCu(II) (1
l
M) upon addition of
Figure 6. Estimation of iodide in the presence of other anions in CH3CN/H2O (95:5,
v/v) at 412 nm.
tetrabutylammonium iodide (0–5 M) in CH3CN/H2O (95:5, v/v).
l

74
N. Singh et al. / Tetrahedron Letters 50 (2009) 71–74
3. Conclusions
Supplementary data
We synthesized a flexible tripodal receptor comprising an
anthracene moiety on one pod. The tripodal receptor forms a stable
1:1 complex with Cu(II). The complex provides a preorganized an-
ion-binding site for optimal anion binding, resulting in high bind-
ing affinity and selectivity for iodide over a wide range of anions.
The Cu(II) complex provides a selective probe for estimating iodide
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2008.10.088.
References and notes
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at the lM level in the presence of other anions in aqueous acetoni-
trile without any interference.
4. Experimental
4.1. Synthesis of receptor 2
To a solution of compound 1 (470 mg, 1.0 mmol) in MeOH was
added anthracene-9-carbaldehyde (206 mg, 1.0 mmol) portion-
wise in the presence of a trace of zinc perchlorate. The reaction
was monitored with TLC. Upon completion of the reaction, NaBH4
(190 mg, 5.0 mmol) was added to the reaction mixture portion-
wise. The reaction mixture was allowed to be stirred for 3 h at
room temperature. After evaporation of the solvent, the crude
product was dissolved in CH2Cl2, washed with water, and dried
over anhydrous MgSO4. After evaporation, the residue was purified
by column chromatography on silica gel eluting with hexane/
EtOAc (8:2) to give receptor 2 (445 mg, 67%). IR (CHCl3): 3465,
3355 (N–H) cmÀ1 1H NMR (400 MHz, CDCl3) d 2.32–2.41 (m, 4H,
;
–CH2), 2.64–2.71 (m, 8H, –CH2), 4.39 (s, 4H, NH2), 5.17 (s, 2H,
CH2), 6.59–6.67 (m, 5H, Ar), 6.69 (s, 1H, NH), 7.06–7.11 (m, 4H,
Ar), 7.21 (d, 1H, J = 8.0 Hz, Ar), 7.31(d, 1H, J = 8.0 Hz, Ar), 7.40 (t,
2H, J = 8.0 Hz, Ar), 7.47–7.51 (m, 4H, Ar), 8.04 (t, 2H, J = 8.0 Hz,
Ar), 8.24 (t, 1H, J = 8.0 Hz, Ar), 8.52 (s, 1H, Ar); 13C NMR
(100 MHz, CDCl3) d 45.9 (–CH2), 47.8 (–CH2), 61.1 (–CH2), 65.1
(–CH2), 66.6 (–CH2), 94.8 (Ar), 111.0 (Ar), 120.7 (Ar), 121.2 (Ar),
121.8 (Ar), 125.4 (Ar), 125.9 (Ar), 128.1 (Ar), 129.2 (Ar), 130.0
(Ar), 130.2 (Ar), 133.4 (Ar), 136.5 (Ar), 142.4 (Ar), 147.7 (Ar),
149.3 (Ar), 149.4 (Ar), 156.6 (Ar), 161.9 (Ar); HRMS (FAB) calcd
for C39H41N4S3 [M+H]+: 661.2493, found 661.2493.
10. Singh, N.; Kumar, M.; Hundal, G. Inorg. Chim. Acta 2004, 357, 4286.
11. Mohamedi, F.; Richards, N. G. T.; Liskamp, T.; Still, W. C. J. Comp. Chem. 1990,
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Delgado, R.; Drew, M. G. B.; Félix, V. Dalton Trans. 2007, 2431; (d) Zhang, T.;
Anslyn, E. V. Tetrahedron 2004, 60, 11117; (e) Tobey, S. L.; Anslyn, E. V. J. Am.
Chem. Soc. 2003, 125, 14807; (f) Tobey, S. L.; Jones, B. D.; Anslyn, E. V. J. Am.
Chem. Soc. 2003, 125, 4026; (g) Cabell, L. A.; Best, M. D.; Lavigne, J. J.; Schneider,
S. E.; Perreault, D. M.; Monahan, M.-K.; Anslyn, E. V. J. Chem. Soc., Perkin Trans. 2
2001, 315; (h) Amendola, V.; Fabbrizzi, L.; Mangano, C.; Pallavicini, P.; Poggi,
A.; Taglietti, A. Coord. Chem. Rev. 2001, 219, 821.
13. (a) Kang, J.; Kim, J. Tetrahedron Lett. 2005, 46, 1759; (b) Stastny, V.; Lhotak, P.;
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6233.
4.2. Synthesis of complex 2ÁCu(II)
A solution of receptor 2 (132 mg, 0.2 mmol) and Cu(NO3)2Á
2.5H2O (46 mg, 0.2 mmol) in dry methanol was stirred at room
temperature. The color of the solution changed immediately to
greenish yellow, and after 10 min the solid precipitated. The solid
was filtered and washed with methanol and dried under vacuum
affording complex 2ÁCu(II). (162 mg, 96%). Mp >300 oC (dec.), IR
(CHCl3): 3320 (N–H) cmÀ1; HRMS (FAB) calcd for C39H40CuN4S3:
723.1711, found 723.1710.
Acknowledgment
This work was supported by the Center for Bioactive Molecular
Hybrids.
15. Job, P. Ann. Chim. 1928, 9, 113.
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