Ratiometric sensing of fluoride anions based on a BODIPY-coumarin platform

Article abstract of DOI:10.1021/ol202595t

Based on a new coumarin-BODIPY platform, compound 4 was rationally designed and synthesized as a novel ratiometric fluorescent sensor for fluoride anions. The sensor exhibited a large red shift (88 nm) in absorption and a drastic ratiometric fluorescent r

Full text of DOI:10.1021/ol202595t

ORGANIC
LETTERS
2011
Vol. 13, No. 22
6098–6101
Ratiometric Sensing of Fluoride Anions
Based on a BODIPY-Coumarin Platform
Xiaowei Cao, Weiying Lin,* Quanxing Yu, and Jiaoliang Wang
State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry
and Chemical Engineering, Hunan University, Changsha, Hunan 410082, P. R. China
weiyinglin@hnu.edu.cn
Received September 26, 2011
ABSTRACT
Based on a new coumarin-BODIPY platform, compound 4 was rationally designed and synthesized as a novel ratiometric fluorescent sensor for
fluoride anions. The sensor exhibited a large red shift (88 nm) in absorption and a drastic ratiometric fluorescent response (I472/I606 = 17.4) to
fluoride anions. Density function theory and time-dependent density function theory calculations were conducted to rationalize the optical
response of the sensor.
Construction of sensory molecules for recognition and
sensing of anions is a forefront research topic in
chemistry.1 In particular, detection of anions by a fluor-
escent readout has attracted great attention in light of the
advantages of fluorescence sensing including easy opera-
tion and high sensitivity.2 Fluoride, the smallest anion with
a high charge density, is an attractive target for sensor
design due to its roles in dental care and other areas.3
Fluoride is a strong hydrogen bond acceptor and has a
high affinity to silicon and boron. These unique physical
and chemical properties have been widely exploited in the
development of numerous fluorescent sensors for fluoride
anions.4 However, most of them are based on fluorescence
measurement at a single wavelength, which may be influ-
enced by variations in the sample environment. By con-
trast, ratiometric fluorescent sensors allow the
measurement of emission intensities at two wavelengths,
which should provide a built-in correction for environ-
mental effects.5 Thus, it is of interest to develop ratiometric
fluorescent sensors for fluoride anions.
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Difluoroboradiaza-s-indacene dyes (BODIPY) are
highlighted with excellent photophysical and photochemi-
cal properties such as high fluorescence quantum yields,
large extinction coefficients, and good photostability. In
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10.1021/ol202595t
Published on Web 10/27/2011
2011 American Chemical Society

addition, the optical properties of BODIPY are tunable
through chemical modifications on the dye core.6 These favor-
able features render BODIPY as widely used as a fluorophore
core for construction of fluorescent labels,7 sensors,8 light
harvesting systems,9 and photodynamic therapy agents.10
Coumarins are a classic type of pushꢀpull dye, in which
the intramolecular charge transfer (ICT) process from the
electron donor to the acceptor proceeds upon excitation.
Typically, for the efficient ICT, the donor and acceptor are
located in the 7- and 3-position, respectively.11 On the
other hand, it is known that BODIPY dyes undergo an
ICT process with a functional group at the 30-position.12
ICT is an effective signaling mechanism employed in the
design of ratiometric fluorescent sensors.13 Thus, we envi-
sioned that ratiometric fluorescent sensors for fluoride
anions could be constructed by exploiting the ICT proper-
ties of both coumarin and BODIPY dyes. In this work, we
present compound 4 based on a new BODIPY-coumarin
platform as a novel candidate for ratiometric fluorescent
fluoride sensing (Scheme 1). A triisopropylsilyl group was
chosen as the potential reaction site for fluoride anions
owing to the high affinity of fluoride to silicon.14 The
triisopropylsilyl group is judiciously placed in the 7-posi-
tion of the coumarin unit. Upon reaction with fluoride
anions, the triisopropylsilyl group may be unmasked, and
compound 4 could be converted into the deprotected
product (compound 3 in the phenolate form).4iꢀm,15 As
the phenolate group is a much stronger electron donor
than the triisopropylsilyl group, the ICT efficiency should
be markedly modulated upon interactions of compound 4
with fluoride anions. In addition, notably, the BODIPY-
coumarin platform was carefully designed. With the trii-
sopropylsilyl group positioned in the 7-position, the BOD-
IPY wasrationallyplaced inthe 3-positionof the coumarin
unit for effective ICT. Thus, the coumarin unit is located in
the 30-position of the BODIPY dye, consistent with the
typical design of ICT-based BODIPY sensors.12
Scheme 1. Design and Synthesis of Coumarin-BODIPY Con-
jugate 4 As a New Ratiometric Fluorescent Fluoride Sensor
The coumarin-BODIPY-based compound 4 was readily
synthesized in two steps (Scheme 1). The starting materials
BODIPY 1 and coumarin aldehyde 2 were prepared
based on the reported procedures.6b,16 Condensation of
BODIPY 1 with coumarin aldehyde 2 afforded the key
intermediate 3, which was further reacted with chlorotrii-
sopropylsilane to give product 4. All the new compounds
were characterized by 1H NMR, 13C NMR, and HRMS.
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Chem. Commun. 2006, 4398–4400.
Figure 1. Absorption (A) and fluorescence (B) spectra of sensor
4 (3 μM) in DMSO in the presence of Fꢀ anions (0ꢀ300 equiv).
Excitation at 420 nm. The inset shows the fluorescence intensity
ratio (I472 /I606) as a function of equiv of fluoride anions.
ꢂ
(11) (a) Signore, G.; Nifosi, R.; Albertazzi, L.; Storti, B.; Bizzarri, R.
J. Am. Chem. Soc. 2010, 132, 1276–1288. (b) Wang, J.; Qian, X.; Cui, J.
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Wuts, P. G. M., Eds.; Wiley: New York, 1999; pp 113ꢀ148.
With compound 4 in hand, we evaluated its response to
Fꢀ anions by absorption and emission spectroscopy. The
free sensor 4 displayed two major absorption bands at 398
and 592 nm. However, addition of Fꢀ induced a large
red shift in both the absorption peaks (Figure 1A), con-
sistent with the ICT signaling mechanism as designed.
Org. Lett., Vol. 13, No. 22, 2011
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Three well-defined isosbestic points at 420, 510, and 612
nm were observed, indicating the formation of a new
species upon treatment of sensor 4 with Fꢀ. In good
agreement with the findings in absorption, the sensor
exhibited a ratiometric fluorescent response to Fꢀ anions.
Upon excitation at 420 nm, the free sensor displayed an
intense emission band at 606 nm. However, as shown in
Figure 1B, addition of Fꢀ elicited a drastic decrease in the
emission at 606 nm and simultaneous appearance of a new
emission band at 472 nm, attributed to the local emission
(LE). Thus, the sensor provided a significant ratiometric
fluorescent response (I472/I606) to Fꢀ anions (inset in
Figure 1B). However, upon excitation at 612 nm, treat-
ment of the sensor with Fꢀ anions afforded no discernible
emission. This is the typical behavior of BODIPY-based
ICT sensors: the ICT emission band is almost nonfluor-
escent when excited at the ICT absorption band.4j A mass
spectrometry analysis (Figure S1) confirms that the Fꢀ
anion-triggered spectroscopic changes are indeed due to
the removal of the triisopropylsilane and thus the forma-
tion of the deprotected product. The electron donating
ability of the phenolate group is much stronger than that of
the silane group, thereby a large red shift is observed in the
absorption profiles upon treatment of the sensor with Fꢀ
anions. The detection limit (S/N = 3) for sensor 4 was
calculated to be 0.12 μM, and it reacted with fluoride very
rapidly (Figure S2). We also evaluated the effect of water
on the fluorescence response of sensor 4 to fluoride anions.
Whenthe water content increases, the deprotectedreaction
becomes less active due to the strong hydrogen bonding
between water and fluoride (Figure S3).
Figure 3. Fluorescent spectra of sensor 4 (3 μM) to Fꢀ anions
(150 equiv) in the presence of 300 equiv of various relevant
analytes (Clꢀ, Brꢀ, Iꢀ, NO3ꢀ, SO42ꢀ, HCO3ꢀ, PO43ꢀ, CNꢀ, or
SCNꢀ) in DMSO.
displayed a large ratiometric signal (I472/I606 = 17.4) to Fꢀ
anions (Figures 2 and S4). By contrast, other analytes only
induced a minimum ratiometric response with I472/I606 <
0.03. These results indicate that the sensor is highly selec-
tive to Fꢀ over other species tested. To examine whether
sensor 4 could still retain the sensing response to Fꢀ under
the potential competition of relevant analytes, the sensor
(3 μM) was treated with Fꢀ in the presence of Clꢀ, Brꢀ, Iꢀ,
NO3ꢀ, SO42ꢀ, HCO3ꢀ, PO43ꢀ, CNꢀ, or SCNꢀ. As dis-
played in Figures 3 and S5, all the relevant analytes tested
have virtually no influence on the fluorescent detection of
Fꢀ. Thus, sensor 4 seems to be useful for selectively sensing
Fꢀ even with these relevant analytes. Notably, the big red
shift in the absorption and the large ratiometric fluorescent
response render the sensor suitable for detection of Fꢀ
anions by simple visual inspection (Figure 4).
Figure 4. Visible color (A) and visual fluorescence color (B)
changes of sensor 4 (3 μM) with various relevant analytes (150
equiv for Fꢀ, 300 equiv for other anions) in DMSO: (1) Free
sensor 4; (2) sensor 4 þ Clꢀ; (3) sensor 4 þ Brꢀ; (4) sensor 4 þ Iꢀ;
(5) sensor 4 þ SCNꢀ; (6) sensor 4 þ Fꢀ. The visual fluorescence
color was obtained with excitation at 365 nm using a hand-held
UV lamp.
Figure 2. Emission ratios (I472/I606) of sensor 4 (3 μM) in the
presence of various relevant analytes (150 equiv for fluoride
anions, 300 equiv for other anions). Excitation at 420 nm.
Sensor 4 (3 μM) was treated with various anion speciꢀes
represented by Clꢀ, Brꢀ, Iꢀ, NO3ꢀ, SO42ꢀ, HCO3
,
PO43ꢀ, and SCNꢀ to investigate the selectivity. The sensor
To get insight into the optical response of sensor 4 to Fꢀ
anions, the sensor and the corresponding deprotected
product were examined by density function theory
(DFT) and time-dependent density function theory (TD-
DFT) calculations at the B3LYP/6-31G(d) level of the
Guassian 03 program. As shown in Figure 5, for sensor 4,
both the HOMO and LUMO are distributed at the
coumarin-ethenyl bridge-BODIPY scaffold. Thus, the
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Zhang, X. Chem. Commun. 2011, 47, 7098–7100. (b) Ren, J.; Wu, Z.;
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6100
Org. Lett., Vol. 13, No. 22, 2011

ICT character of the sensor is only modest. By sharp
contrast, for the deprotected product, the HOMO is
mainly located between the coumarin moiety and the
ethenyl bridge, and the LUMO is mostly located between
the BODIPY unit and the ethenyl bridge. This indicates
that the deprotected product bears strong ICT character
from the coumarin moiety to the BODIPY unit, consistent
with the design strategy. Furthermore, the energy gap
between the HOMO and LUMO of the deprotected
product is much smaller than that of sensor 4, in good
agreement with the red shift in the absorption observed
upon treatment of sensor 4 with Fꢀ anions.
are located on the coumarin moiety in sensor 4. Thus, the LE
emission from the coumarin moiety is not present in the sensor.
To shed light on the formation of the local emission (LE)
band at 472 nm with excitation at 420 nm upon incubation
of the sensor with Fꢀ anions, sensor 4 and the deprotected
product were optimized by DFT calculations with the
B3LYP exchange functional employing 6-31G(d) basis
sets using a suite of Gaussian 03 programs. As displayed
in Figure S6, the optimized structure of the deprotected
product has a dihedral angle of about ꢀ77.2° between the
coumarin and the BODIPY moieties, whereas the sensor is
essentially planar between the coumarin and the BODIPY
moieties with a dihedral angle of ꢀ5.9°. Thus, the forma-
tion of the LE emission band at 472 nm in the deprotected
product is likely due to the nonplanar and deconjugated
character. In addition, we also performed time-dependent
density function theory (TD-DFT) calculations for both
the deprotected product and the sensor. In the case of the
deprotected product, TD-DFT calculations provide a
calculated absorption band at 414 nm belonging to the
S0 fS11 energy state (Table S1). This is consistent with the
absorbance band at 456 nm obtained experimentally.
The transitions of HOMOꢀ3fLUMO, HOMOꢀ2f
LUMO, HOMOfLUMOþ4, and HOMOfLUMOþ9
contribute 27.4%, 12.0%, 46.4%, and 15.4% of the
S0 fS11 energy state, respectively. The main contribution
transition for the S0 fS11 energy state comes from
HOMOfLUMOþ4. Notably, both the HOMO and
LUMOþ4 orbitals are mainly located at the coumarin
moiety (Figure S7), which translates the LE emission from
the coumarin moiety in the deprotected product. Notably,
the emission profile of the LE band highly resembles
that of the control coumarin 2 (Figure S8), further con-
firming that the LE band originates from the coumarin
moiety in the deprotected product. By contrast, as
shown in Figure S9, no allowed singlet state transitions
Figure 5. HOMOꢀLUMO energy levels and the interfacial plots
of the orbitals for sensor 4 and the deprotected product.
In summary, we have rationally designed and synthe-
sized compound 4 based on the new coumarin-BODIPY
platform as a novel ratiometric fluorescent sensor for
fluoride anions. The sensor exhibited a large red shift
(88 nm) in absorption and a drastic ratiometric fluorescent
response (I472/I606 = 17.4) to fluoride anions. In addition,
the sensor is highly selective for fluoride anions. The large
red shift in the absorption and the ratiometric fluorescent
response render the sensor suitable for detection of Fꢀ
anionsbysimplevisualinspection. Densityfunction theory
and time-dependent density function theory calculations
were conducted to rationalize the optical response of the
sensor. We expect that the unique ICT character of the
coumarin-BODIPY platform will be widely employed to
construct a wide variety of ratiometric fluorescent sensors
based on the ICT signaling mechanism.
Acknowledgment. This work was financially supported
by NSFC (20872032, 20972044, 21172063), NCET (08-
0175), the Doctoral Fund of Chinese Ministry of Educa-
tion (20100161110008), and the Fundamental Research
Funds for the Central Universities, Hunan University.
Supporting Information Available. Experimental pro-
cedures, some spectra of the sensor, and the quantum
calculation data. This material is available free of charge
via the Internet at http://pubs.acs.org.
Org. Lett., Vol. 13, No. 22, 2011
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