A new rhodamine-based fluorescent chemosensor for transition metal cations synthesized by one-step facile condensation

Article abstract of DOI:10.1016/j.tetlet.2007.05.171

A new rhodamine-based fluorescent chemosensor (1) for transition metal cations was synthesized by one-step facile condensation of rhodamine B and 2-aminopyridine. Without metal cations, 1 is colorless and nonfluorescent, whereas addition of metal cations (Fe³⁺, Hg²⁺, Pb²⁺, and Fe²⁺) leads to an obvious color change to pink and an appearance of orange fluorescence.

Full text of DOI:10.1016/j.tetlet.2007.05.171

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Tetrahedron Letters 48 (2007) 5455–5459
A new rhodamine-based fluorescent chemosensor for
transition metal cations synthesized by one-step facile condensation
Xuan Zhang, Yasuhiro Shiraishi* and Takayuki Hirai
Research Center for Solar Energy Chemistry, and Division of Chemical Engineering, Graduate School of Engineering Science,
Osaka University, Toyonaka 560-8531, Japan
Received 15 May 2007; accepted 31 May 2007
Available online 5 June 2007
Abstract—A new rhodamine-based fluorescent chemosensor (1) for transition metal cations was synthesized by one-step facile con-
densation of rhodamine B and 2-aminopyridine. Without metal cations, 1 is colorless and nonfluorescent, whereas addition of metal
cations (Fe3+, Hg2+, Pb2+, and Fe2+) leads to an obvious color change to pink and an appearance of orange fluorescence.
Ó 2007 Elsevier Ltd. All rights reserved.
Design of artificial receptors for monitoring biologically
and environmentally important ionic species in solution,
especially heavy and transition metal (HTM) cations, is
currently of great importance.1 Much attention has been
paid to the design of fluorescent chemosensors, because
they allow nondestructive and quick detection of ionic
species by a simple fluorescent enhancement (turn-on)
or quenching (turn-off) response.2 Many HTM cations,
however, usually act as a fluorescent quencher; there-
fore, most of classical and already-reported chemo-
sensors show turn-off response to HTM cations.3 Such
turn-off response is less sensitive than the turn-on
response because of low signal-to-noise ratio.2d The
design of turn-on type fluorescent chemosensors for
HTM cations is, therefore, necessary for practical
applications.4
addition of metal cation allows the spirocycle to be
opened (formation of open-ring form) via coordination
with metal cation.6 This allows appearance of a pink
color and an orange fluorescence (turn-on). On the other
hand, rhodamine-based fluorescent chemodosimeters
have also been studied;7 however, they produce the
open-ring form by a metal-catalyzed irreversible chemi-
cal reaction.7 The design of reusable fluorescent chemo-
sensors is necessary for practical detection of HTM
cations. However, to the best of our knowledge, there
are only five reports of rhodamine-based fluorescent
chemosensor.6 These sensors require two step proce-
dures for synthesis and their overall yields are relatively
low (18–57%). New rhodamine-based fluorescent
chemosensor synthesized with simple one-step proce-
dure is therefore necessary.
Rhodamine is a molecule used extensively as a fluores-
cent labeling reagent and a dye laser source because of
its excellent photophysical properties, such as long
wavelength absorption and emission, high fluorescence
quantum yield, large extinction coefficient, and high sta-
bility against light.5 Recently, rhodamine-based fluores-
cent chemosensors for metal cations have received
increasing interest.6 The on/off fluorescence switching
of these chemosensors is based on structure change of
the rhodamine moiety between spirocyclic and open-
ring forms. The spirocyclic (closed-ring) form is basi-
cally colorless and nonfluorescent (turn-off). In contrast,
Herein, we report a new rhodamine-based fluorescent
chemosensor (1) containing a pyridine moiety, which is
synthesized by one-step facile condensation (Scheme
1). We envisaged that the carbonyl oxygen and the pyr-
idine nitrogen of 1 cooperatively coordinate with metal
O
O
N
X
2-aminopyridine
or aniline
O
POCl3
N
O
N
N
O
N
1 x = N
2 x = CH
*
Corresponding author. Tel.: +81 6 6850 6271; fax: +81 6 6850
6273; e-mail: shiraish@cheng.es.osaka-u.ac.jp
Scheme 1. Synthesis of 1 and control compound 2.
0040-4039/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2007.05.171

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X. Zhang et al. / Tetrahedron Letters 48 (2007) 5455–5459
cations, like N-(2-pyridyl)-acetamide,8 by a six-mem-
bered chelate ring formation, which will result in the spi-
rocycle opening of 1 and, hence, act as a new turn-on
fluorescent sensor. We report here the detailed spiro-
cycle opening mechanism of 1 by a six-membered
chelate ring formation, enabling turn-on detection of
HTM cations. This is the first rhodamine-based fluores-
cent chemosensor forming a six-membered chelate ring,
whereas the early-reported sensors form five- or seven-
membered ring.6
a
1+Fe3+
1
1.2
0.9
0.6
0.3
0.0
b
1.2
0.9
0.6
0.3
0.0
Fe3+
Probe 1 was synthesized by one-step condensation of
rhodamine B and 2-aminopyridine with a catalytic
amount of POCl3 at 70 °C for 30 min (Scheme 1). Wash-
ing the resultant by an aqueous NaOH solution fol-
lowed by recrystallization from acetone gave 1 with
60% yield. Control compound 2 was obtained in a sim-
ilar manner followed by an additional purification by a
silica gel column chromatograph (CHCl3/CH3OH = 30/
0.5eq.
0.0 0.5 1.0 1.5 2.0
[Fe3+] / [1]
0eq.
600
1
400
450
500
550
650
1 v/v) with 20% yield. These were confirmed by H and
13C NMR and FAB-MS.9,10 Absorption and fluores-
cence measurements were performed with respective cat-
Wavelength, nm
ions as perchlorate (Li+, Na+, K+, Fe2+, Cu2+, Zn2+
Cd2+, Hg2+, Pb2+) or nitrate (Fe3+, Ca2+, Mn2+
Co2+, Ni2+, Ag+) salts.
,
,
c
1.2
1.0
0.8
0.6
0.4
0.2
0.0
Figure 1b shows a change in the absorption spectra of 1
(10 lM) dissolved in acetonitrile with an amount of
Fe3+. The free probe 1 scarcely shows absorption at
400–650 nm, indicating that 1 exists as a spirocyclic
form.6,7 This is confirmed by a distinctive spirocycle car-
bon shift at 66.64 ppm in 13C NMR spectrum of 1
(Fig. S2).6 With <0.25 equiv of Fe3+, absorption still
scarcely appears. In contrast, with >0.25 equiv of
Fe3+, a distinctive absorption centered at 558 nm
appears and the absorbance increases drastically, along
with a clear color change from colorless to pink
(Fig. 1a). Absorbance titration shows a typical sigmoi-
dal curve (Fig. 1b, inset); saturation of the absorbance
increase at >0.5 equiv of Fe3+ implies a 1:2 stoichiome-
try for coordination between Fe3+ and 1. This is con-
firmed by the Job’s plot (Fig. 1c). As shown in Figure
2, addition of Hg2+, Pb2+, Fe2+, and Zn2+ cations
(0.5 equiv) shows similar absorption spectra, whose
intensity increase also shows sigmoidal curve (Fig. S7).
In contrast, 10 equiv of others cations (Li+, Na+, K+,
Cu2+, Cd2+, Ca2+, Mn2+, Co2+, Ni2+, Ag+) show
almost no increase in absorbance. These imply that 1
0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0
[Fe3+] / [Fe3+]+[1]
Figure 1. Changes in (a) color and (b) absorption spectra of 1 (10 lM)
upon addition of Fe3+ in acetonitrile (the inset shows the change in
absorbance at 558 nm). (c) Job’s plot of Fe3+ versus
1
([Fe3+] + [1] = 20 lM).
1.2
Fe3+
Hg2+
0.9
Pb2+
0.6
1 only,
Fe2+
Cu2+, Co2+, Ni2+
Mn2+, Ca2+, Ag+,
Li+, Na+, K+
,
allows a naked-eye detection for Fe3+, Hg2+, Pb2+
and Fe2+ cations.
,
0.3
Zn2+
Cd2+
600
0.0
400
450
500
550
650
As shown in Figure 3, 1 dissolved in acetonitrile (1 lM)
is nonfluorescent (kex = 510 nm). Addition of <2.5 equiv
of Fe3+ still does not show fluorescence. However, with
>2.5 equiv of Fe3+, a distinctive emission centered at
580 nm appears and the intensity increases drastically
upon addition of >3 equiv of Fe3+ (Fig. 3b, inset). Sim-
Wavelength, nm
Figure 2. Absorption spectra of 1 (10 lM) obtained with 0.5 equiv of
Fe3+, Hg2+, Pb2+, Fe2+, Zn2+, and 10 equiv of Cd2+, Cu2+, Co2+
Ni2+, Mn2+, Ca2+, Ag+, Li+, Na+, K+.
,
ilar fluorescence enhancement is observed with Hg2+
,
Pb2+, Fe2+, and Zn2+ cations (Figs. 4 and S8): the
respective emission enhancements upon addition of
5 equiv of cations are 627-fold (Fe3+), 602-fold (Hg2+),
547-fold (Pb2+), 438-fold (Fe2+), 134-fold (Zn2+). Probe
1, therefore, acts as a potential turn-on fluorescent
chemosensor for these HTM cations. The fluorescence
quantum yields of 1 with 5 equiv of Fe3+, Hg2+, and
Pb2+ are estimated to be 0.20, 0.20 and 0.19, respec-
tively, using rhodamine B as a standard (U = 0.69).11
In contrast, as shown in Figure 4, almost no emission

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X. Zhang et al. / Tetrahedron Letters 48 (2007) 5455–5459
5457
1+Hg2+
1+Pb2+
1+Fe3+
a
b
1 only
120
100
80
60
40
20
0
120
100
80
1
1+Fe3+
100
80
60
40
20
0
100
80
60
40
20
0
60
160
120
80
40
0
160
120
80
40
0
40
Fe3+
5eq.
20
2000 1800 1600
2000 1800 1600
2000 1800 1600
2000 1800 1600
0
2
4
6
8
10
Wavenumber, cm−1
[Fe3+] / [1]
0eq.
Figure 5. Infrared spectra of 1 (25 mM) measured in acetonitrile with
or without 0.5 equiv of Fe3+, Hg2+, and Pb2+, respectively.
550
600
650
700
Wavelength, nm
cycle opening, resulting in an appearance of visible
absorption and fluorescence.6
Figure 3. Changes in (a) fluorescence color and (b) spectra of 1 (1 lM)
upon addition of Fe3+ in acetonitrile (the inset shows the change in the
fluorescence intensity monitored at 578 nm).
To confirm the binding mechanism, IR spectrum of 1
(25 mM) was measured in acetonitrile (Figs. 5 and S9).
The amide carbonyl absorption of 1 at 1698.98 cmÀ1
drastically shifts to lower frequency upon addition of
0.5 equiv of Fe3+ (1591.47 cmÀ1), Hg2+ (1633.41 cmÀ1),
Pb2+ (1591.47 cmÀ1), Fe2+ (1590.99 cmÀ1), Zn2+
(1590.98 cmÀ1), and Cd2+ (1634.38 cmÀ1). These indi-
cate that the amide carbonyl O of 1 is actually involved
in the coordination with metal cations.6a,8 1H NMR
titration (CD3CN, 303 K) was also performed for further
confirmation. Most of the aromatic protons of 1 (5 mM)
become broader and shift to downfield upon addition of
0.5 equiv of Fe3+, Hg2+, Pb2+, Fe2+, and Zn2+
(Fig. S10). Without metal cations, –CH2CH3 and
–CH2CH3 protons of 1 appear at 1.09 and 3.31 ppm,
respectively. Upon addition of metal cations, new pro-
tons appear at upperfield along with the disappearance
of the original protons (Fig. S11): Fe3+ (1.22 and
3.57 ppm), Hg2+ (1.16 and 3.48 ppm), Pb2+ (1.23 and
3.59 ppm), Fe2+ (1.23 and 3.59 ppm), and Zn2+ (1.21
and 3.54 ppm). This clearly suggests the formation of
open-ring form of 1 via the metal cation coordination.7b
Upon addition of 2 equiv of Cd2+ (Fig. S11), only weak
protons appear at 1.22 and 3.57 ppm. This is indicative
of weak binding of 1 with Cd2+, which is consistent with
weak absorption and fluorescence response to Cd2+
(Figs. 2 and 4).
160
Fe3+ Hg2+
Pb2+
120
Fe2+
80
1 only,
Ca2+, Mn2+, Ni2+
,
Zn2+
Cd2+
40
0
Cu2+, Co2+, Ag+,
Li+, Na+, K+
550
600
650
700
Wavelength, nm
Figure 4. Fluorescence spectra of 1 (1 lM) obtained with 5 equiv of
Fe3+, Hg2+, Pb2+, Fe2+, Zn2+, and 100 equiv of Cd2+, Ca2+, Mn2+
Ni2+, Cu2+, Co2+, Ag+, Li+, Na+, K+.
,
enhancement is observed even upon addition of
100 equiv of other cations, except for Cd2+ (emission
enhancement with 5 and 100 equiv of Cd2+ is 6- and
45-fold, respectively).
Upon addition of ethylenediamine to a solution contain-
ing 1 with Fe3+, Hg2+, Pb2+, Fe2+, or Zn2+, both pink
color and orange fluorescence immediately disappear.
This indicates a reversible coordination of 1 with metal
cations and rules out the occurrence of an irreversible
chemical reaction.7 Considering the behaviors of fluo-
rescence and absorption spectra, the turn-on response
of 1 to HTM cations may be explained by the spirocycle
open–close mechanism, as is also the case for rhoda-
mine-based chemosensors:6 the free probe 1 is the spiro-
cyclic form, which is colorless and nonfluorescent,
whereas the coordination of the amide carbonyl oxygen
and the pyridine nitrogen to cations8 leads to the spiro-
For further clarification of the coordination behavior,
1H NMR titration of 1 was carried out with Cd2+
(Fig. 6).12 Upon Cd2+ addition, aromatic protons (Hb,
Hc, and Hd) on the pyridine moiety of 1 display contin-
uous downfield shift (Dd = 0.14, 0.05, and 0.13 ppm,
with 2 equiv of Cd2+), as is generally observed for coor-
dination of pyridine-based ligands with metal cat-
ions.6a,8,13–16 This is due to the decrease in electron
density of the pyridine moiety upon coordination.8c,16
This indicates that the pyridine N of 1 is involved in
the metal cation coordination. The participation of the
pyridine N to the coordination is confirmed with a

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X. Zhang et al. / Tetrahedron Letters 48 (2007) 5455–5459
a
d
dine ring of 1 shows continuous upperfield shift
(Dd = 0.37 ppm, with 2 equiv of Cd2+), while the other
protons (Hb, Hc, and Hd) show downfield shift. This
means that Ha proton is shielded by metal coordination,
while the others are not.8b,c,15,16 This is due to the aniso-
tropic effect by ring currents from adjacent p electrons
on another 1 moiety (Scheme 2) within the complex.15,16
Such upperfield Ha proton shift (0.11–1.56 ppm) by me-
tal coordination is also observed for several pyridine-
containing ligands forming similar 1:2 complex,16 where
the orientation of the ligands sterically affects each other
by metal coordination. This leads to anisotropic effect
from the other pyridine ligand, resulting in upperfield
proton shift. The upperfield Ha proton shift of 1
(Fig. 6), therefore, supports the formation of 1:2 com-
plex with sterically hindered two 1 ligands (Scheme 2).
O
N
b
c
N
N
O
N
1
Ha
Hd Hc
Hb
(a)
(b)
In conclusion, we have synthesized a new rhodamine-
based fluorescent chemosensor, 1, by one-step condensa-
tion. 1 exhibits a strong fluorescence enhancement upon
addition of Fe3+, Hg2+, Pb2+, and Fe2+ while showing
almost no response to other cations. 1 may therefore
be applicable as a rhodamine-based turn-on type fluo-
rescent chemosensor. The obtained findings also indi-
cate that various rhodamine-based chemosensors for
HTM cations may easily be made by incorporating var-
ious ligand groups. The works are in progress in our
laboratory.
(c)
(d)
8.5
8
7.5
7
6.5
6
δ, ppm
Figure 6. Partial 1H NMR (270 MHz) spectra of 1 (5 mM) measured
in CD3CN (a) without metal cations and with (b) 0.5 equiv, (c)
1.0 equiv, (d) 2.0 equiv of Cd2+
.
Acknowledgments
We are grateful for financial support by Grants-in-Aid
for Scientific Research (No. 19760536) from the Minis-
try of Education, Culture, Sports, Science and Technol-
ogy, Japan (MEXT). We thank Dr. Go Nishimura for
his assistance to IR measurements.
control compound 2, which contains a benzene moiety
in place of pyridine. 2 shows only small changes in
absorption and fluorescence spectra upon Fe3+ addition
(Figs. S12 and S13). This means that, as expected, 2
scarcely produces the open-ring form due to the lack
of the pyridine N binding site. These findings clearly
indicate that the pyridine N of 1 is actually involved in
the cooperative coordination to metal cations.
Supplementary data
1
Considering the Job’s plot result (Fig. 1c) and the above
experimental evidence, coordination of metal cation
with 1 forms a 1:2 complex (Scheme 2), where the two
binding sites (amide carbonyl O and pyridine N) within
each of 1 form a six-membered chelate ring with cation.
Supplementary data (absorption, fluorescence, IR, H
and 13C NMR spectra of 1 and 2 measured with and
without metal cations) associated with this article can
be found, in the online version, at doi:10.1016/j.tetlet.
2007.05.171.
1
The proposed structure is reinforced by H NMR titra-
tion with Cd2+. As shown in Figure 6, Ha on the pyri-
References and notes
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C.; Pallavicini, P.; Parodi, L.; Poggi, A. Coord. Chem. Rev.
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Montalti, M.; Zaccheroni, N. Coord. Chem. Rev. 2000,
205, 59–83; (c) Rurak, K. Spectrochim. Acta A 2001, 57,
2161–2195.
2. (a) Fluorescent Chemosensors for Ion and Molecule Rec-
ognition; Czarnik, A. W., Ed.; American Chemical Society:
Washington DC, 1993; (b) de Silva, A. P.; Gunaratne, H.
Q. N.; Gunnlaugsson, T.; Huxley, A. J. M.; McCoy, C. P.;
Rademacher, J. T.; Rice, T. E. Chem. Rev. 1997, 97, 1515–
1566; (c) Valeur, B.; Leray, I. Coord. Chem. Rev. 2000,
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Rev. 2002, 31, 116–127.
N
O
N
O
N
N
O
N
N
N
Mn+
2
O
N
N
O
N
N
O
N
Scheme 2. Proposed binding structure of 1 to metal cation.