An unprecedented rhodamine-based fluorescent and colorimetric chemosensor for Fe3+ in aqueous media

Article abstract of DOI:10.1007/s00706-010-0311-7

A novel rhodamine-based chemosensor has been designed and synthesized. The chemosensor, a colorless and nonfluorescent compound, exhibited remarkable fluorescent and colorimetric response toward Fe³⁺ in aqueous media with high selectivity and sensitivity, and no significant response toward other metal ions such as Hg²⁺, Ag⁺, Pb²⁺, Sr ²⁺, Ba²⁺, Cd²⁺, Ni²⁺, Co ²⁺, Fe²⁺, Mn²⁺, Cu²⁺, Zn ²⁺, Ce³⁺, Mg²⁺, K⁺, and Na ⁺. Springer-Verlag 2010.

Full text of DOI:10.1007/s00706-010-0311-7

Monatsh Chem (2010) 141:615–620
DOI 10.1007/s00706-010-0311-7
ORIGINAL PAPER
An unprecedented rhodamine-based fluorescent and colorimetric
chemosensor for Fe in aqueous media
3
+
Lijun Tang
Jianhua Qian
•
Ye Li
•
Raju Nandhakumar
•
Received: 30 July 2009 / Accepted: 18 March 2010 / Published online: 16 April 2010
Ó Springer-Verlag 2010
Abstract A novel rhodamine-based chemosensor has
been designed and synthesized. The chemosensor, a col-
orless and nonfluorescent compound, exhibited remarkable
heme and acts as a cofactor in many enzymatic reactions
involved in the mitochondrial respiratory chain.
3
?
It is well known that Fe
acts as a fluorescence
3
?
fluorescent and colorimetric response toward Fe
in
quencher due to its paramagnetic nature, and in general the
fluorescence turn-off response leads to less sensitivity than
the turn-on response because of the low signal-to-noise
ratio. Interestingly, relatively few examples of fluorescent
chemosensors that selectively identify iron cations with
amplified fluorescence have been documented [10–14].
Thus, there is an urgent need to develop selective fluo-
aqueous media with high selectivity and sensitivity, and no
2
?
significant response toward other metal ions such as Hg
,
,
?
2?
2?
2?
2?
2?
2?
2?
Ag , Pb , Sr , Ba , Cd , Ni , Co , Fe , Mn
2?
2
Cu , Zn , Ce , Mg , K , and Na .
?
2?
3?
2?
?
?
Keywords Fluorescence ꢀ Colorimetric ꢀ Chemosensor ꢀ
3
?
Rhodamine B spirolactam
rescence turn-on chemosensors for Fe .
Rhodamines are an important class of fluorogenic and
chromogenic probes and are ideal platforms for develop-
ment of fluorescent chemosensors for specific HTM
cations, due to their unique properties such as long-wave-
length emission, high fluorescence quantum yield, and
large molar extinction coefficient. They are generally
nonfluorescent and colorless, whereas metal-induced ring-
opening of the corresponding spirolactam gives rise to
strong fluorescence emission and pink color [15–20].
Herein, we report the synthesis and the sensing prop-
erties of a new derivative of rhodamine-based fluorescent
and colorimetric chemosensor 1, which exhibited high
Introduction
In recent years, considerable efforts have been devoted to
development of artificial fluorescent receptors for detection
of biologically and environmentally important ionic spe-
cies, especially heavy transition-metal (HTM) cations
3
?
[
1–6]. Among them, the Fe ion plays vital roles in many
biological processes, and deficiencies or excesses of this
ion are toxic or can lead to a variety of diseases [7–9]. For
3
instance, Fe provides the oxygen-carrying capacity of
?
3
?
selectivity and sensitivity toward Fe in aqueous media
Scheme 1).
(
L. Tang (&) ꢀ Y. Li ꢀ J. Qian
College of Chemistry and Chemical Engineering,
Liaoning Key Laboratory for the Synthesis and Application
of Functional Compounds, Bohai University,
Jinzhou 121013, China
Results and discussion
Recently, Kim and coworkers [21] reported a new rhoda-
mine 6G derivative 2, as a fluorescent and colorimetric
chemodosimeter in aqueous solution with broad pH span
e-mail: lijuntang@tom.com
R. Nandhakumar
2?
and high selectivity towards Hg through a guanylation
Division of Nano Sciences, Ewha Womans University,
Seoul 120-750, South Korea
e-mail: rajunandhakumar@yahoo.com
reaction. Based on this irreversible desulfurization reac-
tion, we envisioned that the introduction of an additional
123

6
16
L. Tang et al.
Scheme 1
O
HN
S
O
H
N
HN
S
H
N
O
N
N
N
O
N
N
H
O
N
H
1
2
Scheme 2
O
O
O
NH2
N
HN
O
S
N
H
N
C NCS
N
N
O
N
O
N
3
1
carbonyl group in 2 could have an activating effect on the
guanylation reaction [22–25]. Therefore, compound 1
2000
1500
1000
500
0
2?
bearing a benzoyl group was designed to detect Hg in
aqueous media in order to obtain pronounced fluorescent
emission and high selectivity compared with other HTMs.
Contrary to our expectation, 1 showed almost no detectable
2
?
binding affinity toward Hg , instead behaving as a turn-on
3
chemosensor for Fe with high selectivity and sensitivity.
?
Synthesis of chemosensor 1
Chemosensor 1 was readily prepared from rhodamine B
through a two-step protocol. According to Scheme 2,
reaction of rhodamine B and ethylenediamine (EDA) in
ethanol gave 3 [26], which on treatment with benzoyl
isothiocyanate in acetone under reflux afforded 1 in 51%
yield. Compound 1 was confirmed by spectroscopic and
analytical data, which are in good agreement with the
presented structure.
0
20
40
60
Time/min
3?
Fig. 1 Time course of response of 1 to Fe (10 lM 1 and 0.2 mM
3
?
Fe ) in methanol–water (9:1, v/v). Excitation wavelength was
30 nm
5
investigated, and the results are shown in Fig. 2a.
Chemosensor 1, without any metal ion, is colorless and has
a weak fluorescent emission at 567 nm when excited at
Spectral studies
3
?
Time evolution of the response of 1 (10 lM) in the pres-
ence of 20 equivalents of Fe in methanol–water (9:1,
v/v) was first studied. As shown in Fig. 1, the recognition
530 nm. Upon addition of 20 equivalents Fe to a solution
of 1, a red-shift and strong fluorescence peak at 580 nm
with 92-fold fluorescence enhancement were observed. At
the same time, under identical conditions, none of the other
tested metal ions led to considerable fluorescence increase.
Hence, in order to verify the high selectivity of 1 toward
3
?
3
?
interaction was completed at 40 min after addition of Fe
.
Thus, further optical spectral data in this work were
recorded at 40 min after addition of ionic species.
The fluorescence response of 1 (10 lM) toward various
3
?
Fe , competition experiments in the presence of poten-
tially competitive metal ions were also conducted.
3?
2
?
?
2?
2?
2?
2?
2?
metal ions (Hg , Ag , Pb , Sr , Ba , Cd , Ni
,
2
?
2?
3?
2?
2?
2?
3?
2?
?
Co , Fe , Fe , Mn , Cu , Zn , Ce , Mg , K ,
Figure 2b shows that, except for Fe , other metal ions
?
and Na ) in methanol–water (9/1, v/v) was then
(100 equiv to 1) did not produce any noticeable increase in
1
23

An unprecedented rhodamine-based fluorescent and colorimetric chemosensor
617
3
?
a
fluorescence intensity. Nevertheless, upon addition of Fe
20 equiv to 1) to the solution containing 1 and competitive
cations, a significant increase in fluorescence intensity was
(
observed. These results indicate that the recognition of
3
?
Fe by 1 is not significantly influenced by other coexisting
cations and therefore that 1 exhibits very high selectivity
3
toward Fe . Furthermore, the behavior of chemosensor
?
3
?
-
-
–Fe in the presence of various anions such as Cl , Br ,
1
NO , CO3 , HCO , CH COO , H PO , ClO , and
-
2-
-
-
-
-
4
3
3
3
2
4
2
4
-
SO in methanol–water (9/1, v/v) was investigated. As
shown in Fig. 2c, no significant variation in fluorescence
2
-
intensity was found, except for 47% quenching by CO
3
-
-
and 26% quenching by HCO and CH COO . Due to their
3
competitive affinity with Fe , the spirocyclic form of 1 is
3
3
?
2
1
1
000
500
000
b
2-
3
-
3
reproduced in the mixture, thus CO , HCO , and
-
CH COO can cause some interferences for chemosensor
3
3
1–Fe in the proposed method.
?
Figure 3 shows the fluorescence titration of 1 (10 lM)
3
?
with Fe under excitation at kex = 530 nm in methanol–
water (9:1, v/v). Incremental addition of Fe resulted in
3?
gradual increase of the fluorescence intensity with emission
peak at 580 nm, reaching saturation at addition of 150
equivalents. Nonlinear least-squares fitting of the titration
profiles based on the 1:1 binding model strongly support the
5
00
0
3
?
1:1stoichiometryof1andFe , andthebindingconstant was
5
calculated to be 4.27 9 10 [27]. The equation used was:
1
2
3
4
5
6
7
8
9
10 11 12 13 14 15 16 17 18
Metals
ꢀ
Ylim ꢁ Y0
CM
1
Y ¼ Y0 þ
1 þ CL
þ
c
2
K C
s
L
2
1
1
000
500
000
9
=
"
#
1
ꢁ
ꢂ
2
2
CM
1
CM
ꢁ
1 þ CL
þ
ꢁ4CL
;
KsCL
;
where Y is the recorded fluorescent intensity, Y is the start
0
3?
value without addition of Fe , Ylim is the limiting value,
5
4
3
2
1
000
000
000
000
000
0
5
00
5000
4
3
2
1
000
000
000
000
0
3+
Fe
0
1
2
3
4
5
6
7
8
9
10
Fe3++anions
0
.0000
0.0005
0.0010
0.0015
0.0020
0.0025
Fig. 2 a Fluorescent emission changes of 1 (10 lM) upon addition of
various metal ions (20 equiv) in methanol–water (9:1, v/v). Excitation
wavelength was 530 nm. b Fluorescence responses of 1 (10 lM) to
various metal ions in methanol–water (9:1, v/v) at 580 nm. Black bars
represent the addition of an excess of the appropriate metal ion (1.0 mM
cFe3+/M
3?
for all other cations and 0.2 mM for Fe ) to a 10 lM solution of 1.
White bars represent the addition of Fe (0.2 mM) to the solutions
3?
2
?
5
50
600
650
700
containing 1 and 100 equiv. of the cations studied. 1 none; 2 Hg ; 3
?
2?
2?
?
2?
2?
2?
2?
Ag ; 4 Pb ; 5 Sr ; 6 K ; 7 Ba ; 8 Cd ; 9 Ni ; 10 Co ; 11 Fe
2?
;
3?
2 Mn ; 13 Cu ; 14 Zn ; 15 Ce ; 16 Mg ; 17. Na ; 18 Fe .
Wavelength/nm
2?
2?
2?
3?
2?
?
1
3?
c Fluorescence responses of 1 (10 lM) containing 0.2 mM Fe to the
selected anions (0.2 mM) in methanol–water (9:1, v/v) at 580 nm.
Fig. 3 Fluorescence titration spectra of 1 (10 lM) in methanol–water
3?
(9:1, v/v) upon gradual addition of Fe
changes in fluorescence intensity at 580 nm against concentration of
3?
Fe . Excitation wavelength was 530 nm (excitation slit 2.5 nm;
emission slit 5.0 nm)
(kex = 530 nm). Inset:
-
; 3 Br ; 4 NO
-
3
2-
3
-
3
-
COO ;
1
8
5
none; 2 FeCl
-
3
; 5 CO
(excitation slit 2.5 nm; emission slit
; 6 HCO
; 7 CH
3
- 2-
; 10 SO
4
H
2
PO
.0 nm)
4
; 9 ClO
4
123

6
18
L. Tang et al.
3
?
CM is the Fe
concentration.
concentration, and CL is the sensor
0.3
L
Furthermore, upon addition of an increasing amount of
L+50eqFe(III)
3
Fe ions to 1, as shown in Fig. 4, a new absorption band
?
0
.2
.1
centered at 557 nm appeared with increasing absorbance,
which corresponds to the ring-opening process of the spi-
rolactam moiety in 1. The binding stoichiometry of 1 and
0
3
?
Fe was further proved by a Job plot according to the
continuous variations with a total concentration of
3
?
[
Fe ] ? [1] of 200 lM (Fig. 5). The absorbance approa-
ched a maximum when the molar ratio of Fe was 0.5,
3
?
0.0
3
?
indicating a 1:1 stoichiometry for the 1–Fe complex.
We also investigated the reversibility of the 1–Fe
binding by a simple titration methodology with EDA.
2
4
6
8
10
12
14
3
?
pH
Fig. 6 Effect of pH on the absorbance of 1 (10 lM) in methanol–
water (9:1, v/v) in absence and presence of Fe at 557 nm
3
?
Accordingly, titration of 1–Fe with EDA led to signifi-
cant decrease of absorbance and fluorescence intensity. At
the end point, the solution returned to its original colorless
3?
3
?
state, which reveals that the response of 1 to Fe
is
reversible rather than a cation-catalyzed reaction. This
colorless solution was further confirmed as compound 1 by
thin-layer chromatography (TLC) and mass spectrometry
(MS) analysis. For practical applicability, the effect of pH
on the absorbance of 1 in both the presence and absence of
3
Fe in methanol–water (9:1, v/v) was evaluated. Figure 6
?
clearly indicates that the chemosensor 1, which has weak
3
?
absorbance, can detect Fe ions in the pH range between 4
and 7 because of its remarkable increase of absorbance on
3?
addition of Fe ions.
Binding mechanism
3
?
The possible binding mechanism of 1 with Fe that led to
the absorbance and fluorescence changes is shown in
Scheme 3. According to the proposed mechanism of some
rhodamine-based chemosensors reported so far, it may be
Fig. 4 UV–Vis titration spectra of 1 (10 lM) in methanol–water
3
?
3?
that Fe coordinates with the corresponding atom of 1 and
induces ring-opening of the spirolactam. However, in
recently reported rhodamine-based chemodosimeters with
(
9:1, v/v) upon gradual addition of Fe
2
?
high selectivity and sensitivity toward Hg [16, 18–26],
the desulfurization guanylation mechanism is usually
considered to be main reason for the recognition event.
Nevertheless, during the spirolactam ring-opening and
guanylation processes, the metal-induced spirolactam ring-
opening is the first and critical step, which leads to sig-
nificant absorbance and fluorescence enhancement, as they
are the most important signals for the recognition event.
Although chemosensor 1 has the potential model structure
0
0
0
0
0
0
.25
.20
.15
.10
.05
.00
2
?
for the Hg -promoted guanylation reaction, it exhibits
3?
higher binding affinity toward Fe than other metal ions
0
.2
0.4
0.6
0.8
1.0
xFe3+
and leads to the easily detectable ring-opening process.
This result may be attributed to the addition of a more
electron-withdrawing carbonyl group to the thiourea moi-
ety of 1. The electron density on the sulfur atom of the
Fig. 5 Job plot according to the method of continuous variations,
indicating the 1:1 stoichiometry of 1 and Fe . The total concentra-
3
3?
?
tion of ([Fe ] ? [1]) was 200 lM
1
23

An unprecedented rhodamine-based fluorescent and colorimetric chemosensor
619
Scheme 3
Fe3+
O
O
N
O
HN
S
NH
H
N
NH
O
Fe3+
N
S
+
N
O
N
N
O
N
OFF
ON
1
thiourea group may decrease and lower the mercury
M.p.: 199–201 °C; H NMR (300 MHz, CDCl
(s, 1H), 7.51 (m, 9H), 6.27 (m, 2H), 6.19 (m, 6H), 3.51 (t,
3
): d = 8.84
3
?
affinity, and thus the relatively harder Fe can easily bind
with 1 according to the proposed mechanism depicted in
Scheme 3.
1
3
2H), 3.33 (dd, 8H), 1.26 (t, 1H), 1.16 (t, 12H) ppm;
NMR (75 MHz, CDCl ): d = 167.83, 153.97, 153.30,
52.97, 152.56, 152.24, 152.09, 151.85, 149.41, 148.88,
C
3
1
1
1
1
46.15, 145.59, 136.78, 136.23, 135.97, 134.93, 134.52,
33.24, 132.53, 128.96, 128.62, 128.02, 127.48, 123.82,
23.03, 108.34, 97.94, 44.73, 44.36, 38.52, 12.61 ppm;
Conclusions
HRMS (ESI) calcd. for C H N O S 647.8286, found
38 41 5 3
We report herein a new simple rhodamine-based turn-on
3
647.8288.
?
chemosensor 1 which displays high selectivity toward Fe
3
with no significant response to other metal ions. The Fe
?
-
Acknowledgments We are grateful to the Foundation of the
Educational Department of Liaoning Province for financial support
induced ring-opening of the rhodamine spirolactam
(
no. 2008T002).
moiety of 1 leads to dramatic absorption and fluorescent
3
?
enhancement. The binding of 1 and Fe is reversible with
:1 binding stoichiometry.
1
References
1
2
. Prodi L, Bolletta F, Montalti M, Zaccheroni N (2000) Coord
Chem Rev 205:59
. Amendola V, Fabbrizzi L, Foti F, Licchelli M, Mangano C,
Pallavicini P, Poggi A, Sacchi D, Taglietti A (2006) Coord Chem
Rev 250:273
Experimental
Compound 3 was prepared according to a literature pro-
˚
cedure [26]. Acetone was dried over 4-A molecular sieves
3. Rurack K, Resch-Genger U (2002) Chem Soc Rev 31:116
4
5
6
. Mart ´ı nez-M a´ n˜ ez R, Sancen o´ n F (2003) Chem Rev 103:4419
. Sessler JL, Davis JM (2001) Acc Chem Res 34:989
. Yang Y-K, Yook K-J, Tae J (2005) J Am Chem Soc 127:16760
prior to use. All other chemicals were purchased directly
from commercial suppliers. Column chromatography was
performed on silica gel (100–200 mesh). Nuclear magnetic
resonance (NMR) spectra were recorded on a Bruker
7. Aisen P, Wessling-Resnick M, Leibold EA (1999) Curr Opin
Chem Biol 3:2000
8
. Weizman H, Ardon O, Mester B, Libman J, Dwir O, Hadar Y,
Chen Y, Shanzer A (1996) J Am Chem Soc 118:12386
. Touati D (2000) Arch Biochem Biophys 373:1
3
00 MHz NMR spectrometer with tetramethylsilane
(
TMS) as internal standard. High-resolution mass spec-
9
trometry (HRMS) was carried out on a UPLC/Q Tof mass
spectrometer. Ultraviolet (UV) spectra were measured on a
SP-1900 spectrophotometer. Fluorescence spectra were
obtained with a Hitachi F-4500 FL spectrophotometer at
room temperature for aerated solutions.
10. Zhang M, Gao Y-H, Li M-Y, Yu M-X, Li F-Y, Li L, Zhu M-W,
Zhang J-P, Yi T, Huang C-H (2007) Tetrahedron Lett 48:3709
1
1
1. Xiang Y, Tong A-J (2006) Org Lett 8:1549
2. Bricks JL, Kovalchuk A, Trieflinger C, Nofz M, B u¨ schel M,
Tolmachev AI, Daub J, Rurack K (2005) J Am Chem Soc
127:13522
1
3. Mao J, Wang L-N, Dou W, Tang X-L, Yan Y, Liu W-S (2007)
Org Lett 9:4567
14. Fan L-J, Jones WE Jr (2006) J Am Chem Soc 128:6784
5. Kim H-N, Lee M-H, Kim H-J, Kim J-S, Yoon J (2008) Chem Soc
Rev 37:1465
6. Huang J-H, Xu Y-F, Qian X-H (2009) J Org Chem 74:2167
0
0
N-[[[2-[3 ,6 -Bis(diethylamino)-3-oxospiro[1H-isoindole-
0
1 , 9 -[9H]xanthen]-2(3H)-yl]ethyl]amino]thioxomethyl]-
benzamide (1, C H N O S)
1
3
8 41 5 3
Compound 3 (0.6 g, 1.24 mmol) and 0.202 g benzoyl
3
isothiocyanate (1.24 mmol) were dissolved in 30 cm
1
17. Wu H-M, Zhou P, Wang J, Zhao L, Duan C-Y (2009) New J
Chem 33:653
1
acetone and refluxed for 2 h. The solvent was evaporated
under reduced pressure, and the crude solid was purified by
silica-gel column chromatography with dichloromethane
and ethylacetate (10:1) as eluents to give 0.43 g (51%) 1.
8. Lee M-H, Wu J-S, Lee J-W, Jung J-H, Kim J-S (2007) Org Lett
:2501
9
1
9. Wu D-Y, Huang W, Duan C-Y, Lin Z-H, Meng Q-G (2007) Inorg
Chem 46:1538
123

6
2
20
L. Tang et al.
0. Shiraishi Y, Sumiya S, Kohno Y, Hirai T (2008) J Org Chem
7
25. Leng B, Zou L, Jiang J-B, Tian H (2009) Sens Actuators B
140:162
26. Soh JH, Swamy KMK, Kim SK, Kim S, Lee S-H, Yoon J (2007)
Tetrahedron Lett 48:5966
3:8571
1. Wu J-S, Hwang I-C, Kim KS, Kim JS (2007) Org Lett 9:907
2. Cunha S, Costa MB, Napolitano HB, Lariucci C, Vencato I
2
2
(
2001) Tetrahedron 57:1671
27. Connors KA (1987) Binding constants—the measurement of
molecular complex stability. Wiley, New York
2
2
3. Lee M, Cho B-K, Yoon J, Kim JS (2007) Org Lett 9:4515
4. Liu B, Tian H (2005) Chem Commun 3156
1
23