A ratiometric fluorescent chemodosimeter with selective recognition for sulfite in aqueous solution

Article abstract of DOI:10.1021/jo9014744

(Chemical Equation Presented) A fluorescent chemodosimeter containing a guanidiniocarbonylpyrrole and a 9-(aminomethyl)anthracene moiety has been synthesized. The sensor exhibits ratiometric fluorescence changes for SO ₃^2- over other anions in 90% water/DMSO. The interesting ratiometric fluorescent changes for SO₃^2- are attributed to the fluorescence resonance energy transfer (FRET) and the SO₃ ^2- complex induced photochemical reaction. 2009 American Chemical Society.

Full text of DOI:10.1021/jo9014744

pubs.acs.org/joc
wavelengths, allowing precise and quantitative analysis and
3
imaging even in complicated systems. A variety of signaling
A Ratiometric Fluorescent Chemodosimeter with
Selective Recognition for Sulfite in Aqueous Solution
4
mechanisms such as intramolecular charge transfer (ICT),
5
metal-ligand charge transfer (MLCT), excimer/exciplex
formation, and fluorescence resonance energy transfer
Yimin Sun, Cheng Zhong, Rui Gong, Honglei Mu, and
Enqin Fu*
6
7
FRET) can be employed for the design of ratiometric
(
Department of Chemistry, Hubei Key Laboratory on Organic
and Polymeric Optoelectronic Materials, Wuhan University,
Wuhan 430072, P. R. China
measurement. Among them, FRET is a mechanism that is
commonly used for ratiometric signaling for analytes due to
its potential practical benefits in cell physiology, optical
therapy, as well as selective and sensitive sensing toward
8
fueq@whu.edu.cn
target molecular or ionic species. Many efforts have been
made to design FRET-based ratiometric fluorescence for
Received July 9, 2009
9
cations in recent years, but the ratiometric fluorescent
1
0
chemosensor for anion is still rare, especially for those
11
anions with deleterious effects on the environment in
aqueous solution.
Among the various anionic analytes, sulfite is of consider-
able interest due to the significant amount of sulfur dioxide
released in industrial process and its deleterious effects on the
1
2
environment. The traditional method of sulfite sensing is
1
3
ion-selective electrodes. In the past, some guanidinium-
based ion-selective electrodes for sulfite have been re-
1
4
ported, and the response behavior indicates the existence
of a selective interaction between the guanidinium moiety
1
5
and the sulfite anion.
In this paper, we present a new FRET-based ratiometric
fluorescent chemodosimeter 1 for sulfite, in which guanidi-
1
niocarbonyl pyrrole moiety is covalently attached to
6
A fluorescent chemodosimeter containing a guanidinio-
carbonylpyrrole and a 9-(aminomethyl)anthracene moi-
ety has been synthesized. The sensor exhibits ratiometric
(
5) (a) Peng, X.; Xu, Y.; Sun, S.; Wu, Y.; Fan, J. Org. Biomol. Chem. 2007,
, 226. (b) Jang, Y. J.; Jun, E. J.; Lee, Y. J.; Kim, Y. S.; Kim, J. S.; Yoon, J. J.
Org. Chem. 2005, 70, 9603.
6) (a) Yang, R.-H.; Chan, W.-H.; Lee, A. W. M.; Xia, P.-F.; Zhang, H.-
5
2
-
fluorescence changes for SO3 over other anions in 90%
water/DMSO. The interesting ratiometric fluorescent
(
K.; Li, K. J. Am. Chem. Soc. 2003, 125, 2884. (b) Wegner, S. V.; Okesli, A.;
Chen, P.; He, C. J. Am. Chem. Soc. 2007, 129, 3474. (c) Bencini, A.; Bianchi,
A.; Lodeiro, C.; Masotti, A.; Parola, A. J.; Pina, F.; de Melo, J. S.; Valtancoli,
B. Chem. Commun. 2000, 1639.
2
-
changes for SO3
are attributed to the fluorescence
-
2
resonance energy transfer (FRET) and the SO3 com-
plex induced photochemical reaction.
(
7) (a) Albers, A. E.; Okreglak, V. S.; Chang, C. J. J. Am. Chem. Soc.
006, 128, 9640. (b) Li, Y.; Zheng, H.; Li, Y.; Wang, S.; Wu, Z.; Liu, P.; Gao,
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n, R. M.; Cuttle, M.; Mittoo, S.; Bradley, M.
2
(
The development of fluorescent chemosensors for anions
has received considerable attention due to the simplicity and
´
Angew. Chem., Int. Ed. 2006, 45, 5472. (b) Yuan, M.; Li, Y.; Li, J.; Li, C.;
Liu, X.; Lv, J.; Xu, J.; Liu, H.; Wang, S.; Zhu, D. Org. Lett. 2007, 9, 2313. (c)
Lu, C.; Xu, Z.; Cui, J.; Zhang, R.; Qian, X. J. Org. Chem. 2007, 72, 3554.
(10) (a) Schazmann, B.; Alhashimy, N.; Diamond, D. J. Am. Chem. Soc.
1
sensitivity of fluorescence. However, the conventional
fluorescence methodology, which monitors the fluorescence
intensity at a single wavelength, is easily interfered by sensor
concentration, photobleaching, optical path length, and
2
006, 128, 8607. (b) Peng, X.; Wu, Y.; Fan, J.; Tian, M.; Han, K. J. Org.
Chem. 2005, 70, 10524. (c) Joo, T. Y.; Singh, N.; Lee, G. W.; Jang, D. O.
Tetrahedron. Lett. 2007, 48, 8846. (d) Wen, Z.-C.; Jiang, Y.-B. Tetrahedron
2004, 60, 11109.
2
illumination intensity. To eliminate those effects, a ratio-
metric fluorescent measurement is desirable. This technique
uses the ratio of the fluorescent intensities at two different
(
11) Chen, C.-L.; Chen, Y.-H.; Chen, C.-Y.; Sun, S.-S. Org. Lett. 2006, 8,
053.
(12) (a) Mohr, G. J. Chem. Commun. 2002, 2646. (b) Mana, H.; Spohn, U.
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Anal. Chem. 2001, 73, 3187. (c) Zhao, M.; Hibbert, D. B.; Gooding, J. J. Anal.
Chim. Acta 2006, 556, 195. (d) Cassella, I. G.; Marchese, R. Anal. Chim. Acta
1995, 311, 199.
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2007, 2, 257. (b) Ordeig, O.; Banks, C. E.; del Campo, F. J.; Xavier Mu nꢁ oz,
F.; Davis, J.; Compton, R. G. Electroanalysis 2006, 18, 247.
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1) (a) Gunnlaugsson, T.; Lee, T. C.; Parkesh, R. Org. Lett. 2003, 5, 4065.
b) Kwon, J. Y.; Singh, N. J.; Kim, H. N.; Kim, S. K.; Kim, K. S.; Yoon, J. J.
Am. Chem. Soc. 2004, 126, 8892.
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´
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(
´
(
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DOI: 10.1021/jo9014744
r 2009 American Chemical Society
Published on Web 09/22/2009
J. Org. Chem. 2009, 74, 7943–7946 7943

Sun et al.
JOCNote
FIGURE 2. (a) Fluorescence emission changes of 1 (picrate salt,
-
5
2
9
.0 ꢀ 10 M) upon addition of sodium sulfite (0-1500 equiv) in
0% water/DMSO solution (pH 7.2, 10 mM Tris-HCl buffer).
b) Ratiometric calibration curve of I417/I353 as a function of sulfite
(
concentration.
FIGURE 1. Spectral overlap of the guanidiniocarbonyl pyrrole
emission with the anthracene absorption.
further purification, the crude acyl chloride then reacted with
9
-(aminomethyl)anthracene 3 to give 6 in 70% yield. The
SCHEME 1. Synthesis of Compound1 and Reference Material 7
guanidinylation of ester 6 was achieved by refluxing the ester
and an excess of guanidine in dry DMF under nitrogen.
Upon acidification with hydrochloric acid, the hydrochloric
salt of receptor 1 precipitated in 40% yield. After reaction
with picric acid, the picrate salt of receptor 1 was obtained as
yellow powder.
The photophysical properties of receptor 1 were first
studied in 90% water/DMSO solution (10 mM Tris-HCl
buffer, pH = 7.2). The absorption spectra of 1 displayed
three characteristic bands of anthracene appearing at 348,
3
66, and 386 nm, and extinction coefficients were deter-
-
1
-1
mined to be 5250, 7650, and 6900 M cm , respectively.
When excited at 290 nm (the excitation wavelength for
guanidiniocarbonyl pyrrole), receptor 1 would emit fluores-
cence derived from anthracene at 417 nm, which suggested
that intramolecular FRET occur effectively between the
two adjacent fluorophores. Using anthracene as reference
(Φ = 0.27 in EtOH, λ = 365 nm), the quantum yield of
F ex
receptor 1 was determined as 0.16.
The recognition properties of 1 were studied in 90% water/
DMSO (10 mM Tris-HCl buffer, pH = 7.2) with various
anions as substrates by fluorescence spectroscopy. After the
addition of sodium sulfite (0-29 mM) to receptor 1 (picrate
9
-(aminomethyl)anthracene. The spectral overlap between
guanidiniocarbonyl pyrrole emission and anthracene ab-
sorption makes FRET possible (Figure 1). In the presence
of sulfite, receptor 1 interacts with sulfite through a combi-
nation of ion pairing and multiple hydrogen bonds, and then
upon irradiation, the anthracene moiety undergoes an inter-
molecular [4π þ 4π] photodimerization. This minimizes the
spectral overlap between the donor emission and the accep-
tor absorption bands, resulting in the cancellation of the
FRET effect between the two fluorophores. The combined
interaction makes 1 show a ratiometric fluorescence change
-5
salt, 2.0 ꢀ 10 M), the fluorescence intensity derived from
anthracene greatly decreased (Φ = 0.012), while the fluor-
F
escence intensity at 353 nm derived from guanidiniocarbo-
nylpyrrole increased with an isoemissive point at 382 nm,
which made receptor 1 serve as a ratiometric fluorescent
2-
chemodosimeter for SO3 (Figure 2). The complex forma-
tion constant K for the 1-sulfite complex was calculated to
a
-1
be 104 M , and the job analysis indicated that receptor 1
formed a 1:1 complex with sulfite (Supporting Information,
Figures S1 and S2). Addition of nitrite, nitrate, iodide, and
bromide also caused fluorescence decrease of the anthracene
moiety, but no fluorescence enhancement at 353 nm was
observed (Supporting Information, Figures S3 and S4). In
the presence of nitrite (160 mM) and nitrate (330 mM), the
2
3
-
-
-
-
-
for SO
-
over other anions including F , Cl , Br , I ,
-
2-
-
2-
4-
-
AcO , SO , HCO3 , HPO4 , P O , NO3 , and NO2
4
.
2
7
Under the conditions of fluorescent titration, the special
spectroscopic properties are shown to be related to sulfite
concentration, so receptor 1 could be used for the quantita-
tive analysis of sulfite. To the best of our knowledge, receptor
1
is the first ratiometric fluorescence chemodosimeter in-
quantum yields of receptor 1 came to be 0.0036 and 0.017
-
duced by photochemical reaction. Meanwhile, it should be
noted that sulfite-induced anthracene photodimerization has
not been reported so far.
Receptor 1 was synthesized according to Scheme 1. Pyr-
roledicarboxylic acid monomethyl ester 4 was converted into
the acyl chloride 5 by reaction with oxalyl chloride in CH Cl
respectively. The binding constants of receptor 1 to NO
-
2
-1
and NO3 were determined to be 35 and 7 M .Other anions
-
-
-
-
2-
2-
such as F , Cl , AcO , SO , HCO3 , HPO4 , and
4
4
-
P2O7 did not affect emission intensity significantly.
To get a further insight of the ratiometric fluorescent
changes of 1, UV-vis titration was performed under the
same conditions as the fluorescence titrations (Figure 3). The
2
2
in the presence of a catalytic amount of DMF. Without
7
944 J. Org. Chem. Vol. 74, No. 20, 2009

Sun et al.
JOCNote
SCHEME 2. Proposed Photochemical Reaction Mechanism of
2-
Receptor 1 with SO
3
FIGURE 3. Absorption spectrum of receptor 1 (hydrochloride salt,
-
5
2-
2
.0 ꢀ 10 M) upon the addition of SO
3
in 90% water/DMSO
solution (pH 7.2, 10 mM Tris-HCl buffer).
hydrochloride salt of 1 was employed to eliminate the
absorption overlap of picrate and anthracene. We found
that the decrease of anthracene’s absorption spectra
(350-420 nm) was accompanied by that of the fluorescence
spectrum, while other anions did not affect the absorption
spectrum of receptor 1 (Supporting Information, Figure S5).
Subunit 3 showed a typical PET behavior upon sulfite
recognition, and the emission and absorption spectra of
subunit 7 did not change upon the addition of sulfite. Thus,
we propose that the absorption and fluorescence change of
anthracene in receptor 1 is ascribed to its structure change
upon irradiation. Gunnlaugsson and Ito have described
that the symmetric and unsymmetric [4π þ 4π] photocy-
cloaddition dimerization reactions are carried out between
two anthracene derivative molecules upon irradiation. On
the basis of the above facts, a possible explanation for the
ratiometric fluorescence changes is that the binding of sulfite
enhances the rate of the photodimerization reaction of
receptor 1. When the sulfite is added, receptor 1 forms a
performed with a high-pressure mercury lamp (150 W) for 10 h
1
in D O/DMSO-d (4:6, v/v). H NMR, mass spectrometry,
and liquid chromatography experiments had been carried
2
6
1
out for the detection of the photoproducts. From the H
NMR spectrum we found that the anthracene proton signals
[
1
7
18
δ 8.54 (s, 1H, An-H ), δ 8.32 (d, 2H, An-H , H ), δ 8.08
10 4 5
(d, 2H, An-H , H )] disappeared gradually, while new peaks
1 8
appeared at δ 8.01, 7.60-7.70, and 7.21-7.40 (Figure 4). The
new multiple peaks at a range of δ 7.21-7.40 were assigned
1
9
to the protons of the o-xylene system, and the new peaks
at δ 8.01 and 7.60-7.70 were possibly assigned to the proton
of naphthalene (H , H , H ) obtained in the unsymmetric
4
5
8
1
photoreaction. The change of the H NMR spectrum was
consistent with the appearance of the two photoproducts, the
reaction mixture formation of ht and usy-ht anthracene
photodimers. The mixture was analyzed by LC using a C18
reversed-phase column, and the chromatogram exhibited
two main product peaks at the longer retention time, which
were assigned to ht and usy-ht anthracene photodimers,
respectively (Supporting Information, Figure S6). We then
1
:1 complex with sulfite. The binding of sulfite reduces
mobility of receptor 1, and the π-π interaction between
the anthracene moieties makes this 1:1 complex become 2:2
complex. Upon irradiation, the 2:2 complex undergoes a
well-established [4π þ 4π] cycloaddition reaction of anthra-
cene (Scheme 2).
The origin of the fluorescence quenching by nitrite ions is
possibly ascribed to the reasons below. The absorption band
of nitrite coincides with the emission band of guanidiniocar-
bonyl pyrrole, and this makes the FRET between guanidi-
niocarbonylpyrrole and anthracene less effective; as a result,
the fluorescence intensity of anthracene decreased. In this
case, the ground state of anthracene is not affected and the
emission light of guanidiniocarbonyl pyrrole is absorbed
either by nitrite ion or by anthracene, so the fluorescence
of the guanidiniocarbonyl pyrrole group is not present. The
fluorescence quenching of nitrate ion is almost the same as
that of the nitrite ions. The fluorescence decrease of receptor
-
5
diluted this NMR sample to 2.0 ꢀ 10 M, and the UV-vis
and fluorescence spectrum were performed. The spectrosco-
py changes were the same as those of the UV-vis and
fluorescence spectra during the fluorescence titration
(Supporting Information, Figure S7), so we proposed that
the photoreactions under irradiation with a mercury lamp
and under fluorescence titration underwent the same me-
2-
chanism. The photoproduct-SO3 complexes were also
detected by the ESI-MS spectrum in the negative-ion mode.
2
-
The peaks of m/z at 466 were assigned as [M þ 2SO ]
3
(
Supporting Information, Figure S8). Meanwhile, the 1:1
1
“
upon addition of iodide and bromide are ascribed to the
heavy atom effect”. Compared with iodide, the quenching
extent of bromide is smaller.
complex between sulfite and the chemodosimeter could be
identified by this peak.
The experimental results show that the fluorescence de-
To confirm the photodimerization mechanism pro-
posed above, photoreactions of receptor 1 with sulfite were
2-
crease of anthracene moiety should be ascribed to the SO3
complex induced photodimerization. Upon the addition of
2-
SO3 , the fluorescence of anthracene moiety decreases
(
17) Dos Santos, C. M. G.; Glynn, M.; Mccabe, T.; de Melo, J. S. S.;
Burrows, H. D.; Gunnlaugsson, T. Supramol. Chem. 2008, 20, 407.
18) Horiguchi, M.; Ito, Y. J. Org. Chem. 2006, 71, 3608.
(
(19) Ikegami, M.; Ohshiro, I.; Arai, T. Chem. Commun. 2003, 1566.
J. Org. Chem. Vol. 74, No. 20, 2009 7945

Sun et al.
JOCNote
FIGURE 5. Fluorescence emission changes of receptor 1 (picrate
-
5
-
-
salt, 2.0 ꢀ 10 M) with NO
2 3
, NO (1000 equiv) upon addition of
sulfite in 90% water/DMSO solution (pH 7.2, 10 mM Tris-HCl
buffer).
terms of sulfite. While in the presence of interfereferring ions,
receptor 1 also exhibits good selectivity for sulfite and can be
used for the qualitative analysis of sulfite (Figure 5).
In conclusion, we have synthesized a ratiometric fluores-
cent chemodosimeter for sulfite for the first time. The
receptor exhibits a remarkable selectivity for sulfite in aqu-
eous solution which could be used for the quantitative and
qualitative analysis of sulfite. The FRET combined with the
anion-complex sensitized photodimerization reaction is re-
sponsible for the recognition process.
1
FIGURE 4. H NMR of the photodimerization process of receptor
in the presence of sulfite under a mercury lamp: (a) 0 h; (b) 2 h; (c) 5
h; (d) 10 h.
1
gradually, and the guanidiniocarbonyl pyrrole emission at
3
53 nm will increase concomitantly; this can be referred to
the FRET-off effect induced by the minimized spectral
overlap between the donor emission and the acceptor ab-
sorption band. Hence, the fluorescence decrease resulted
from the [4π þ 4π] photodimerization reaction of anthracene
combined with the fluorescence enhancement of guanidinio-
carbonyl pyrrole make receptor 1 serve as a ratiometric
fluorescent chemodosimeter for sulfite.
Experimental Section
The Synthesis of 1. Ester 6 (358 mg, 1 mmol) and guanidine (5
equiv, prepared from guanidinium hydrochloride with sodium
methoxide) were refluxed in 20 mL of dry DMF for 36 h under
nitrogen. The orange solution was poured into water, and upon
acidification with hydrochloric acid (2 M), the crude product
precipitated. It was filtered off and washed thoroughly with
methanol to provide hydrochloride salt of 1 (170 mg, 40%)
as a brown solid. The picrate salt 1 was obtained by dissolv-
ing the hydrochloride salt in an aqueous picric acid solution
The photochemical reaction is a common phenomenon for
-substituted anthracene derivatives. Receptor 1 was found
9
to be dimerized spontaneously in DMSO under room tem-
perature, but the complete conversion to photodimerized
product needed a time scale of almost half a year (Supporting
Information, Figure S9). During the fluorescence measure-
ment, the fluorescent spectrum of 1 without sulfite was
affected only slightly by irradiation with the excitation light
at 1 min intervals for 1 h (Supporting Information, Figure
S10). In the presence of sulfite, the photocyclization of 1 was
accelerated by sulfite complexation, and the fluorescence
emission was greatly altered. Here we should notice that the
rate of the photochemical reaction depended on two pro-
cesses: the association process and the photodimerization
process (as shown in Scheme 2). The association process
depends on the concentration of sulfite, and the photodimer-
ization of anthracene depends on the time, wavelength, and
intensity of irradiation. During the process of the fluores-
cence titrations, the wavelength and the intensity of the
excitation light are stationary and the titration was finished
in a relatively shorter time (the measurement times are
rigorously controlled within 10 min), so the fluorescence
changes are mainly related to the sulfite concentration.
Under this condition, in the absence of interfering ions
and recrystallized from methanol as a yellow powder: mp
1
1
76-178 °C; H NMR (300 MHz, DMSO-d
6
) δ 12.37 (s, 1H,
pyrrole NH), 10.94 (s, 1H, guanidinium amide NH), 8.78 (s, 1H,
carbamoyl NH), 8.64 (s, 1H, An-H10), 8.56 (s, 2H, picrate), 8.41
(
d, 2H, An-H , H ), 8.13 (d, 6H, An-H , H , guanidinium NH ),
4 5 1 8 2
7
2 3 6 7
.58 (m, 4H, An-H , H , H , H ), 6.99 (s, 1H, pyrrole CH), 6.92
13
(
2
s, 1H, pyrrole CH), 5.48 (d, 2H, -CH NH); C NMR (75
MHz, DMSO-d ) δ 35.9, 114.4, 115.6, 124.9, 125.4, 125.9, 126.0,
6
127.2, 128.3, 129.5, 129.6, 130.7, 131.7, 132.6, 142.2, 155.1,
159.3, 159.9; ESI-MS m/z = 386 (M þ H ). Anal. Calcd for
þ
28 22 8 9
C H N O : C, 54.73; H, 3.61; N, 18.23. Found: C, 54.64; H,
3
.65; N, 18.14.
Acknowledgment. We gratefully acknowledge support
from the Natural Science Foundation of China (No.
20672085).
-
-
-
(NO2 , NO3 , I ), the ratio of pyrrole to anthracene emis-
sion can be used for the quantitative analysis of sulfite, and
Supporting Information Available: Synthesis and character-
ization of 6 and 1, Figures S1-S15. This material is available
free of charge via the Internet at http://pubs.acs.org.
-
4
this chemodosimeter has a detection limit of 7.8 ꢀ 10 M in
7
946 J. Org. Chem. Vol. 74, No. 20, 2009