Colorimetric and ratiometric fluorescence sensing of fluoride: Tuning selectivity in proton transfer

Article abstract of DOI:10.1021/jo051766q

Phenyl-1H-anthra[1,2-d]imidazole-6,11-dione (1) and its derivatives (2 and 3) have been investigated as new colorimetric and ratiometric fluorescent chemosensors for fluoride. Acute spectral responses of 1 and 3 to fluoride in acetonitrile have been obser

Full text of DOI:10.1021/jo051766q

Colorimetric and Ratiometric Fluorescence Sensing of Fluoride:
Tuning Selectivity in Proton Transfer
Xiaojun Peng,*,† Yunkou Wu,† Jiangli Fan,† Maozhong Tian,† and Keli Han*,‡
State Key Laboratory of Fine Chemicals, Dalian University of Technology, 158 Zhongshan Road, Dalian
116012, P. R. China and Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457
Zhongshan Road, Dalian 116023, P. R. China
pengxj@dlut.edu.cn
Received August 22, 2005
Phenyl-1H-anthra[1,2-d]imidazole-6,11-dione (1) and its derivatives (2 and 3) have been investigated
as new colorimetric and ratiometric fluorescent chemosensors for fluoride. Acute spectral responses
of 1 and 3 to fluoride in acetonitrile have been observed: an approximately 100 nm red shift in
absorption and fluorescence emission and a very large ratiometric fluorescent response (Rmax/Rmin
is 88 for sensor 1 and 548 for sensor 3). From the changes in the absorption, fluorescence, and 1H
NMR titration spectra, proton-transfer mechanisms have been deduced. In ground states, a two-
step process has been observed: first, the formation of the sensor-fluoride hydrogen-bond complex
[LH‚‚‚F]- and then the fluoride-induced deprotonation of the complex to form L- and FHF-. In
excited states, the excited-state intermolecular proton-transfer made a contribution to the
deprotonation. The selectivity for F- can be tuned by electron push-pull properties of the
substituents on the phenyl para position of the sensors. Sensor 1 shows the best selectivity. The
excellent selectivity of 1 for F- is attributed to the fitness in the acidity of its NH-group, which is
tuned to be able to distinguish the subtle difference in the affinity of F-, CH3CO2-, and H2PO4- to
proton.
Introduction
ative atom, fluoride has unique chemical properties and
can form the strongest hydrogen-bond interaction with
hydrogen-bond donors. The major of the reported fluoride
sensors are based on colorimetric changes or fluorescent
quenchings;4 few of them experience fluorescence en-
hancement.5 Up to now, however, there has been a
paucity of reports of fluoride sensors based on the
ratiometric fluorescence,6 the fluorescent emission wave-
length changes upon interaction with fluoride.
Considerable efforts have been made to design chemo-
sensors for anions. The reason for this intensive interest
is the importance of the detection and quantification of
anions in disciplines such as biology and environmental
science.1 Among the interests in biologically functional
anions, fluoride is one of particular importance owing to
its established role in dental care2 and treatment of
osteoporosis.3 As the smallest and the most electroneg-
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† Dalian University of Technology.
‡ Chinese Academy of Sciences.
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R.; Sanceno´n, F. Chem. Rev. 2003, 103, 4419-4476. (d) Suksai, C.;
Tuntulani, T. Chem. Soc. Rev. 2003, 32, 192-202. (c) Sessler, J. L.;
Davis, J. M. Acc. Chem. Res. 2001, 34, 989-997. (e) Schmidtchen, F.
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10.1021/jo051766q CCC: $30.25 © 2005 American Chemical Society
Published on Web 11/05/2005
10524
J. Org. Chem. 2005, 70, 10524-10531

Fluorescence Sensing of Fluoride
Ratiometric fluorescence measurements7 can increase
the selectivity and the sensitivity of the detection,
because the ratio of the fluorescent intensities at two
wavelengths is independent of the concentration of the
sensor, the fluctuation of source-light intensity, and the
sensitivity of instrument. Different kinds of mechanisms
have been used to design the ratiometric fluorescent
sensors for anions, such as intramolecular charge trans-
fer (ICT),8a fluorescence resonance energy transfer
(FRET),8b excimer/exciplex formation,8c luminescent lan-
thanide-anion complexation,8d chemodosimetry,8e and
anion-sensitive dual chromophore recognization.8f
SCHEME 1. Molecular Structures 1, 2, and 3
SCHEME 2. Synthesis of 1, 2, and 3
Proton transfer9 is another mechanism utilized in the
design of the ratiometric fluorescent sensor. Hamilton et
-
al.9a reported a ratiometric fluorescent H2PO4 sensor
based on the macrocyclic amide containing coumarin
fluorophore that involves both the excited-state charge
transfer and proton-transfer dual channels. More re-
cently, Tian et al.6b reported a naphthalimide-containing
fluorescent chemosensor for fluoride based on a proton
transfer signaling mechanism. However, the detailed
mechanisms, in particular, the relation between the
ground-state and excited-state proton transfer process
existing in the anion recognition, have not been disclosed,
and consequently the relationship between the selectivity
and the molecular structure is not clear yet.
Recently, based on imidazole ion, biimidazolate dia-
mides, dipyrrolylquinoxalines, indolocarbazoles, calix[4]-
pyrrole or its derivatives, and urea or thiourea recep-
tors,10 various kinds of anion sensors have been developed.
In the presence of the anions, the NH-anion hydrogen-
bond or anion-induced deprotonation of the NH groups
was observed, which resulted in fluorescence quenching
by photoinduced electron transfer (PET) mechanism or
red shift of the absorption by a charge transfer (CT)
mechanism. To gain an insight into hydrogen-bond
formation and neat proton-transfer existing in the anion
recognition process, Fabbrizzi et al.11 have investigated
various colorimetric anion receptors containing NH bind-
ing sites and concluded that the deprotonation trend is
enhanced by the increase of the acidity of the hydrogen-
bond donors and the basicity of the anions. Because their
receptors have no fluorescence, they can only investigate
the ground-state receptor-anion interactions.
As a fluorophore, phenyl-1H-anthra[1,2-d]imidazole-
6,11-dione (1),12 which possesses the intramolecular
hydrogen bonding between the NH (hydrogen-bond do-
nors) of the imidazole ring with the neighboring quinone
carbonyl group (hydrogen-bond acceptors), is a new
candidate to investigate hydrogen-bond formation and
proton-transfer process for the receptor-anion interac-
tions. The intramolecular hydrogen bonding existing
between the donors and the acceptors could enhance the
acidity of the hydrogen-bond donors.13
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Yoon, J.; Nam, K. C. J. Am. Chem. Soc. 2003, 125, 12376-12377. (b)
Xu. G. X.; Tarr, M. A. Chem. Commun. 2004, 1050-1051. (c) Curiel,
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Biochem. 2004, 327, 82-90. (f) Jayaraman, S.; Biwersi, J.; Verkman,
A. S. Am. J. Physiol. 1999, 276, 747-757.
In the present study, we utilize this intramolecular
hydrogen bond in 1 (Scheme 1) as the fluoride binding
site and reveal first the selectivity-structure relationship
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3912-3915. (b) Tong, H.; Zhou, G.; Wang, L.; Jing, X.; Wang, F.; Zhang,
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L.; Palchetti, A. Chem. Eur. J. 2005, 11, 120-127. (d) Boiocchi, M.;
Del Boca, L.; Go´mez, D. E.; Fabbrizzi, L.; Licchelli, M.; Monzani, E.
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Licchelli, M. J. Org. Chem. 2005, 70 (14), 5717-5720.
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Kim, K. S. J. Org. Chem. 2003, 68, 2467-2470. (c) Chellappan, K.;
Singh, N. J.; Hwang, I. C.; Lee, J. W.; Kim, K. S. Angew. Chem., Int.
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J. Org. Chem, Vol. 70, No. 25, 2005 10525

Peng et al.
FIGURE 1. Change in UV-vis spectra for 1 (1.0 × 10-5 M)
in CH3CN with the addition of [(Bu)4N]F.
by tuning the acidity and the hydrogen-bond donor
property of the NH moiety with p-OCH3 electron-donat-
ing derivative 2 and p-NO2 electron-attracting derivative
1
3. From the absorption titration spectra, H NMR titra-
tion experiments and fluorescence titration spectra, the
detail processes of the ground-state and excited-state
proton-transfer present in the anion recognition have
been disclosed. Also, the sensors show the largest signal/
noise ratio (Rmax/Rmin) in the ratiometric fluorescent
fluoride sensors that have ever reported.
1
FIGURE 2. Partial H NMR (400 MHz) spectra of 1 (1.0 ×
10-2 M) in CD3CN in (a) the absence and the presence of (b)
1.0, (c) 3.0, (d) 5.0, and (e) 10.0 equiv of [(Bu)4N]F.
investigations were carried out on a variety of anions
such as CH3CO2-, H2PO4-, HSO4-, Cl-, and Br-. Only
CH3CO2- and H2PO4- induced some spectral changes, but
the spectral responses were not as sensitive as fluoride
with the increase of anion concentrations. Other anions
such as HSO4-, Cl-, and Br- did not induce any spectra
response.
Results and Discussion
Synthesis. Using the synthesis methods described
previously,12 we could not obtain satisfactory product
yields.
1H NMR Titration and Two-Step Mechanism. H
1
The synthesis of these sensors is improved by following
the methodology shown in Scheme 2. In the first step,
the mixtures of 1,2-diaminoanthraquinone and the cor-
responding benzoyl chloride were refluxed in THF for 10
h to give the R,â-disubstituted acylation intermediates.
Then the acylation products were condensed to form
sensors by refluxing in 95% ethanol in the presence of
sodium hydroxide. The structures of sensors were char-
NMR titration experiments in CD3CN were conducted to
look into the nature of the new peak formed in UV-vis
fluoride titration spectra. For the 1H NMR spectrum, two
effects are responsible for the 1H NMR changes upon NH-
fluoride hydrogen-bond formation:11a (1) through-bond
effects, which increase the electron density of the phenyl
ring and promote an upfield shifts, and (2) through-space
effects, which polarize C-H bond in proximity to hydro-
gen bond, create partial positive charge on the proton,
and cause a downfield shifts. As shown in the partial 1H
NMR fluoride titration spectra of 1 in Figure 2. Upon
addition of 1 molar equiv of fluoride ions, the downfield
shift of protons 3 and 3′ is observed, which is ascribed to
the through-space effects, the polarization C-H bond in
proximity to the hydrogen bond. This indicates the
formation of a hydrogen-bond complex at this stage. With
the addition of a further amount of fluoride ions, the
protons 3 and 3′ almost do not change, while the phenyl
protons adjacent to imidazole ring, especially for proton
1, shift upfield significantly, which indicates the increase
of the electron density on the phenyl ring owing to the
through-bond effects. This indicates the deprotonation of
the NH group of the imidazole ring. The deprotonation
can be directly observed in the NMR titration spectra in
DMSO-d6 (Figure 3), which is a more polar solvent with
a stronger deprotonation ability than CD3CN.11e In Figure
3, the majority of signals on the phenyl rings shift upfield
distinctly after the addition of 1 molar equiv of fluoride
ions owing to the through-bond effects, and the complete
disappearance of the signals for the NH protons (13.2
ppm) was also observed at the same time. Interestingly,
1
acterized on the basis of H and 13C NMR and HRMS.
1
The H NMR spectra (in DMSO-d6) exhibiting a broad
singlet signal at around δH 11-14 ppm support the
formation of intramolecular hydrogen bonding between
the NH of the imidazole ring and the neighboring quinone
carbonyl group.
UV-vis Spectral Responses of 1. The interaction
of sensor 1 with anions was investigated through spec-
trophotometric titrations by adding a standard solution
of the tetrabutylammonium salt of anions to a dry CH3-
CN solution of sensor. Figure 1 shows the UV-vis
spectral changes of 1 during the titration with fluoride
ions. Upon addition of 1 molar equiv of fluoride ions, little
change was observed and care was taken to avoid the
contamination by the water in preparation of the solution
and during titration. However, with the addition of a
ab
max
further amount of fluoride ions, the peak at the λ
of
384 nm, the π-π* transition of the chromophore, disap-
pears gradually, and a new band forms at 479 nm, which
is the charge transfer (CT) band. The yellow color of the
sensor solution turns red at the same time. Though the
isosbestic points are 339 and 427 nm, respectively, the
stoichiometry of the 1-fluoride interaction was confirmed
to be 1:2 from the Job plot (Figure S1). Analogous
10526 J. Org. Chem., Vol. 70, No. 25, 2005

Fluorescence Sensing of Fluoride
Ka
\
LH + X- y
z [LH‚‚‚X]-
(1)
(2)
[LH‚‚‚X]- + X- yKd
\
z L- + [HX2]-
Equation 1 gives the association constant Ka and
stands for a genuine hydrogen-bond formation. Equation
2 gives the dissociation constant Kd and stands for an
anion-induced deprotonation process. In the first step,
sensor-anion hydrogen-bond formation produces minimal
disturbance on the dipole associated with the charge-
transfer transition of sensor 1 and consequently only a
small change was observed in the spectra (Figure 1).
Then the second step produces a deprotonation species.
With the charge redistribution taking place within the
deprotonated species, the UV-vis spectra exhibit a red
shifted CT band. From the results of UV-vis titration
spectra, all anions investigated experience the first step;
only the more basic anion F-, CH3CO2-, and H2PO4- can
undergo the second step.
Because of the small UV-vis spectral changes upon
addition of the 1 molar equiv of fluoride ions, it is
impossible to calculate the log Kaa from UV-vis titration
spectra. However, log Kda (Table 1) can be obtained from
the spectral changes. The log Kda showing the selectivity
of 1 to the anions has the order F- > CH3CO2- > H2PO4
.
-
1
FIGURE 3. Partial H NMR (400 MHz) spectra of 1 (1.0 ×
As the changes in UV-vis spectra associate with the
ground state of the sensors, the log Kd of sensor-anion
interaction compiled in Table 1 are the ground-state
dissociation constants.
10-2 M) in DMSO-d6 in (a) the absence and the presence of (b)
1.0, (c) 3.0, and (d) 5.0 equiv of [(Bu)4N]F.
a
after the addition of 5 molar equiv of fluoride ions, a new
1:2:1 triplet signal at 16.2 ppm appears, which is ascribed
to the FHF- dimer.11a,14 The existence of this new species
indicates the deprotonation of the NH group. The absence
of the NH proton for free 1 and FHF- dimer signal in
the excess of fluoride ions in CD3CN (Figure 2) is ascribed
to the occurrence of a fast proton exchange with water
that is present in solution as impurity. This deprotona-
tion process is also confirmed by the identical UV-vis
spectral changes observed in the titration experiment
with tetrabutylammonium hydroxide as that of with
fluoride ions (Figure S2). With the deprotonation of 1,
charge delocalizes on the entire conjugated system, which
shifts the phenyl rings upfield further. From the result
of 1H NMR titration, it is found that 1 and fluoride form
the hydrogen-bond complex upon addition of 1 molar
equiv of fluoride ions, while the UV-vis spectra have
almost no changes at the same time; with the increase
of the fluoride concentrations, a new deprotonated species
appears, and the CT bond of UV-vis spectra forms
quickly. These results suggest that sensor-fluoride in-
teraction is indeed a two-step process shown in Scheme
3: at low fluoride concentration, sensor-fluoride interac-
tion is the authentic hydrogen binding, and with the
increase of the fluoride ions, excess fluoride interact with
the sensor-fluoride complex and induce the deprotonation
of the sensor.
By combining the eq 1 and eq 2, the overall equilibrium
can be obtained:
LH + 2X- h L- + [HX2]-
(3)
Equation 3 can also be combined with the following
two equilibria:
LH h L- + H+
(4)
(5)
H+ + 2X- h [HX2]-
So the overall constant of eq 3, K3, can be expressed
as follows:
K3 ) K(LH)dissociation × K([HX2]-)association
(6)
Equation 6 suggests two factors make contributions to
the deprotonation process: the acidity of the hydrogen-
bond donors and the thermal stabilization of XHX-
dimer. The high selectivity for fluoride is not only due to
the strong hydrogen-bond ability and the basic nature
of fluoride ions in organic solution but also due to the
particular high stability of the FHF- dimer, for which
the highest hydrogen bond energy in the gas phase has
been calculated.15
Tuning the Acidity of the NH Group. A resonance
structure of the deprotonated form of 1 (Scheme 4) shows
that the electron density of the phenyl para position is
enhanced upon deprotonation. This indicates the acidity
Kd from Absorption Spectra. The two-step process
agrees well with the Fabbrizzi paradigm for anion-
induced urea deprotonation that produced stepwise colo-
rimetric changes.11 So we made use of the equilibrium
they have developed to investigate our system. In par-
ticular, the following two equilibria can express the
processes shown in Scheme 3:
(14) Descalzo, A. B.; Rurack, K.; Weisshoff, H.; Martı´nez-Ma´nˇez, R.;
Marcos, M. D.; Amoro´s, P.; Hoffmann, K.; Soto, J. J. Am. Chem. Soc.
2005, 127, 184-200.
(15) Gronert, S. J. Am. Chem. Soc. 1993, 115, 10258-10266.
J. Org. Chem, Vol. 70, No. 25, 2005 10527

Peng et al.
SCHEME 3. Stepwise Changes for 1 and Fluoride Interaction
TABLE 1. Proton-Dissociation Constants (log Kd) of 1
selectivity. As expected, UV-vis fluoride titration spectra
Interaction with Anionsa
of 2 indeed exhibit stepwise changes (Figure 4). First,
ab
max
a
#
anion
log Kd
log Kd
the λ
at 416 nm of 2 almost do not change until the
F-
3.92 ( 0.07
3.35 ( 0.03
1.48 ( 0.12
4.61 ( 0.08
3.90 ( 0.07
1.96 ( 0.09
addition of a very large amount (up to 233 molar equiv)
of fluoride ions; this step assigns to the 2-fluoride
hydrogen-bond formation. Second, further addition of
fluoride induces the production of the deprotonated
species. CH3CO2- induced similar two-step changes, but
other anions including H2PO4- only experienced the first
step change. The introduction of the electron-donating
group can enhance the electron density of the imidazole
ring and consequently increase the basicity of the hy-
drogen-bind donors, so the deprotonation becomes more
difficult.
-
CH3CO2
-
H2PO4
a From UV-vis titration spectra. # From fluorescence titration
spectra.
SCHEME 4. Resonance Representation of the
Deprotonated Form of 1
As for the -NO2 electron-attracting substituent de-
rivative 3, it also experiences spectral changes (from 380
to 497 nm) upon interaction with fluoride. Compared with
those of 1 and 2, the fluoride titration spectra of 3 take
on the significant CT band upon addition of 1 molar equiv
of fluoride ions (Figure 5a). This result indicates the
strong electron-withdrawing p-NO2 substituent makes
the charge delocalization more easily upon interaction
with fluoride. With the Specfit program,16 best fits of the
of this kind of sensors can be tuned by changing the
electron property of the substituent on the para position.
So 2 (p-OCH3 electron-donating substituent) and 3 (p-
NO2 electron-withdrawing substituent) were synthesized
to investigate the effect of electron properties of p-
substituent on the hydrogen-bond property and fluoride
a
UV-vis titration spectra give the log Ka ) 5.61 ( 0.06
and log Kda ) 4.83 ( 0.06 for the two-step changes. The
corresponding species distribution diagram for this two-
step process is presented in Figure 5b. Upon addition of
the fluoride, the sensor-anion hydrogen-bond complex
LH‚‚‚F- forms first and reaches the maximum concentra-
tion with the added fluoride ions in the range of 1-2
molar equiv, while the deprotonated form L- appears
shortly after the LH‚‚‚F- and increases quickly with the
consumption of the LH and LH‚‚‚F- species. The solution
almost contains only the LH‚‚‚F- and L- after added
fluoride up to 7 molar equiv and the L- increases
gradually with the decrease of the LH‚‚‚F-. For other
anions, CH3CO2- and H2PO4- also induce similar spectral
changes, but HSO4-, Cl-, and Br- did not produce any
spectral responses.
From the trend of the UV-vis titration spectral
changes discussed above, it is found that the electron
properties of substituents on the phenyl para position
correlate well with the spectral stepwise changes. At this
point, it also should be noted that one step of the
Bro¨nsted acid-base reaction can proceed between the
strong acid and strong base. So by increasing the
electron-attracting ability of substituent at the phenyl
para position, sensor-fluoride interactions can experience
from two-step complex-deprotonation to one-step Bro¨n-
sted acid-base reaction transformation. Especially for 3,
FIGURE 4. Change in UV-vis spectra for 2 (1.0 × 10-5 M)
in CH3CN with the addition of [(Bu)4N]F (a) from 0 to 233.3
equiv and (b) from 233.3 to 1500 equiv.
(16) Specfit/32 for Windows: http://www.bio-logic.fr/rapid-kinetics/
specfit/Index.html.
10528 J. Org. Chem., Vol. 70, No. 25, 2005

Fluorescence Sensing of Fluoride
FIGURE 5. (a) Change in UV-vis spectra for 3 (1.0 × 10-5
M) in CH3CN with the addition of [(Bu)4N]F. (b) The corre-
sponding distribution diagram of the species present at the
equilibrium.
FIGURE 6. Change in fluorescent spectra (uncorrected) for
sensors (1.0 × 10-5 M) in CH3CN upon the addition of a
standard solution of [(Bu)4N]F. (a) 1 with the excitation
wavelength of 427 nm (isosbestic wavelength). Insert: the
corresponding ratiometric plot of I600/I520 versus equivalents
of fluoride. (b) 3 with the excitation wavelength of 418 nm
(isosbestic wavelength). Insert: The corresponding ratiometric
plot of I590/I490 versus equivalents of fluoride.
the following acid-base reaction eq 7 maybe also takes
place upon the presence of fluoride besides 3-fluoride
hydrogen-bond complex formation in the ground state.
LH + X- f L- + HX
(7)
TABLE 2. Ratio of the Sensor Quantum Yields (Or) and
the R Values (Rr) of the Solutions Containing Sensors in
the Presence of Excess of Anions to Solutions in the
Absence of Anions
Ratiometric Fluorescence Responses. Spectrofluo-
rimetric titrations were also investigated in CH3CN. The
fluorescence responses of the interaction of 1 with
fluoride ions were recorded with an excitation at the
isosbestic point of 427 nm (Figure 6a). The free 1 exhibits
an emission maximum at 520 nm, while the emission
maximum shifts to 600 nm after the addition of fluoride
ions and a well-defined isoemission point at 568 nm is
observed. The emission intensity ratio, I600/I520, increases
with the increase in the fluoride concentrations, which
allows the detection of fluoride ions ratiometrically.
a
a
b
b
anion
1φr
3φr
1Rr
3Rr
F-
2.7
2.5
2.0
18.0
18.0
16.0
88
32
7
548
548
178
-
CH3CO2
-
H2PO4
a The quantum yield of free 1 is 0.019 and free 3 is 0.006, and
the quinine sulfate with the quantum yields of 0.51 in sulfuric
acid (0.05 M) was used as the standard for quantum yield
measurements. b Rr is the Rmax/Rmin determined at the wave-
lengths shown in Figure 6.
-
Among the anions investigated, only CH3CO2 and
The ratio of the limiting values Rr (Table 2) in the
absence and excess of anions, Rmax/Rmin, reflecting the
limiting dynamic range and resolution for concentration
measurements,17 is a decisive parameter for comparing
the performance of sensors. To our knowledge, Rr values
of 1 (88) and 3 (548) listed in Table 2 are the largest
signal/noise ratio in the ratiometric fluorescent fluoride
sensors that have ever been developed.
From the fluorescent ratiometric responses discussed
above, it is found that the electron property of the
substituent on the phenyl para position can influence the
fluorescence properties of the deprotonated species: the
stronger the electron-attracting ability of the substitu-
ents, the larger the fluorescence enhancement for the
-
H2PO4 induced similar spectral changes, but the ratio-
metric responses were not as sensitive as with F-. The
#
dissociation constants from fluorescence titration, log Kd ,
of 1 with different anions (Table 1) show that the
selectivity of 1 for F- ion is 5-fold larger than that for
CH3CO2 and 440-fold than that for H2PO4-. The excel-
-
lent selectivity of 1 for F- over CH3CO2- is attributed to
the fitness in the acidity of its NH-group.
Different from 1, the fluorescence fluoride titration
spectra of 2 also displays stepwise changes (Figure S3):
the fluorescence increases slightly with the addition of
fluoride, and then a fluorescence-quenched deprotonation
band develops with the excess of fluoride. As for 3, though
its fluoride selectivity is not as good as for 1 (Figure S4),
it exhibits more efficient fluorescence responses during
the interaction with fluoride (Figure 6b).
(17) Henary, M. M.; Wu, Y. G.; Fahrni, C. J. Chem. Eur. J. 2004,
10, 3015-3025.
J. Org. Chem, Vol. 70, No. 25, 2005 10529

Peng et al.
deprotonated sensors but the less fluoride selectivity. By
tuning the acidity of the NH-group with the different
substituents, both the best selectivity and sensitivity
might be obtained.
Excitation:
LH
9
hν8 LH*
(8)
(9)
Excited-State Intermolecular Proton Transfer. It
has been known that excited-state intramolecular proton
transfer (ESIPT) exists in 1,5-dihydroxyanthraquinone
and some 1-(acylamino)anthraquinones,18 which possess
dual fluorescence emissions: short-wavelength emission
(SWE) for the normal structure and long-wavelength
emission (LWE) for the tautomer structure. As 1, 2, and
3 did not exhibit LWE by changing solvent polarity or
donicity, no ESIPT proceeded in this kind of sensor in
the absence of anions. While some NH-containing het-
eroaromatics are more acidic in their lowest excited
singlet states than in their ground states as a result of
the occurrence of the excited-state intermolecular proton
transfer (ESPT) from the proton donors to proton accep-
tors19 and consequently will display larger dissociation
constants of proton in excited states than those in their
ground states after interaction with proton acceptors such
as anions, in fact the existence of the ESPT processes
complicates the determinations of the ground-state dis-
sociation constants with fluorescence measurement be-
cause of the dependence of fluorescence on the acid-base
chemistry of excited-state as well as ground-state.20a
Interferences from the excited-state reaction can be
eliminated if the fluorimetric titration is performed at
the isoemissive point.20b
hν
[LH‚‚‚X]- 98 [LH‚‚‚X]-*
Anion-assisted deprotonation:
kESPT1
[LH‚‚‚X]-*
LH* + X-
8 L-* + HX
(10)
(11)
kESPT2
8 L-* + HX
kESPT3
[LH‚‚‚X]-* + X-
Fluorescence:
8 L-* + XHX-
(12)
kf1
LH*
L-*
98 LH + hvSWE
(13)
(14)
kf2
9
8 L- + hvLWE
First, free sensor LH or sensor-anion complex [LH‚‚‚X]-
is excited to its excited states LH* (eq 8) or [LH‚‚‚X]-*
(eq 9). Then ESPT takes place in the case of [LH‚‚‚X]-*
and produces the excited deprotonation species L-* (eq
10), which is presumed to be the fastest process. Another
pathway involves the diffusion and encounter of the anion
X- with LH* or [LH‚‚‚X]-*, which then undergoes ESPT
(eq 11 or eq 12), which is generally a diffusion-controlled
process. In the case of 3, the best fits of the fluorescence
titration spectra for 3-fluoride interactions give the log
When the fluorimetric titration is performed with the
excitation wavelength at the isosbestic point, the inflec-
tion point of the titration curve is neither the correct
value of ground-state log Kd nor the value of excited-state
log Kd*, but the coaction result of the log Kd and the log
Kd*.20b We define the coaction dissociation constant as
#
#
Ka ) 6.58 ( 0.10 and log Kd ) 4.86 ( 0.07 with the
#
Specfit program. The log Ka calculated from the fluo-
#
the apparent dissociation constant log Kd , and the value
rescence titration is almost 1 unit larger than that from
absorption titration (log Ka ) 5.61 ( 0.06), which
of log Kd# lies just between the log Kd and the log Kd*. So
by simply comparing the titration results from the
absorption spectra and fluorescence spectra, whether the
sensor-anion excited-state intermolecular proton-transfer
processes take place can be deduced
a
indicates the ESPT process of eq 10 or eq 11 takes action.
The identical value of the log Kd from the two titrations
(log Kda ) 4.83 ( 0.06 and log Kd# ) 4.86 ( 0.07) suggests
the process represented by eq 12 did not occur. At last,
the excited species LH* and L-* can decay by nonradia-
tive processes to produce heat or by fluorescence emission
to generate the SWE and LWE, respectively.
The ESPT in this kind of fluoride chemosensors is also
influenced by the electron properties of p-substituents
on the phenyl ring. The electron-attracting substituents
will increase the excited-state acidity and consequently
the easiness of releasing the HX from the excited
hydrogen-bond complexes (eq 10) or the encounters (eq
11). So the ESPT proceeds more easily in 1 and 3.
Because of the lower acidity of 2, the deprotonation
becomes more difficult not only in the ground state but
also in the excited states.
In the case of 1, however, log Kda of ground state from
absorption titration (such as 3.92 ( 0.07 for F-) are
#
smaller than those of log Kd from the fluorescence
titration (such as 4.61 ( 0.07 for F-) (Table 1). This
implies that the ESPT takes place indeed and makes a
contribution to the deprotonation.
In fact, the photoinduced intermolecular proton trans-
fer can proceed by two different mechanisms:21 via
hydrogen-bonded ground-state complex (binding-excita-
tion-deprotonation, eqs 9 and 10) and with dynamic
reaction involving mutual diffusion of the donors and
acceptors (excitation-collision-deprotonation: eq 8, eq 11
or 12). The entire processes are shown:
When the imidazole moieties are deprotonated, charge
redistribution takes place within the molecules. The
deprotonated push-pull chromophores are responsible
for a shift in both absorption (color changing from yellow
to red) and fluorescence (fluorescence changing from
green to red) (Figure 7). With the elimination of the
intramolecular hydrogen bonding that associates with the
rapid internal conversion,18a the quantum yields of the
deprotonated species of 1 and 3 increase 2.7- and 18-fold
(Table 2) as compared with the free sensors 1 and 3,
(18) Flom, S. R.; Barbra, P. F. J. Phys. Chem. 1985, 89, 4489-4494
(b) Smith, T. P.; Zaklika, K, A.; Thakur, K.; Barbra, P. F. J. Am. Chem.
Soc. 1991, 113, 4035-4036.
(19) Schulman, S. G. Acid-Base Chemistry of Excited Singlet
States. In Modern Fluorescence Spectroscopy; Wehry, E. L., Ed.;
Plenum Press: New York, 1976; pp 239-275.
(20) (a) Rosenberg, L. S.; Simons, J.; Schulman, S. G. Talanta 1979,
26, 867-871. (b) Kowalczyk, A.; Boens, N.; Van den Bergh, V.; De
Schryver, F. C. J. Phys. Chem. 1994, 98, 8585-8590.
(21) (a) Tolbert, L. M.; Nesselroth, S. M. J. Phys. Chem. 1991, 95,
10331-10336. (b) Lawrence, M.; Marzzacco, C. J.; Morton, C.; Schwab,
C.; Halpern, A. M. J. Phys. Chem. 1991, 95, 10294-10299.
10530 J. Org. Chem., Vol. 70, No. 25, 2005

Fluorescence Sensing of Fluoride
and NaOH (20 mg, 0.5 mmol) in 95% ethanol (150 mL) was
heated under reflux with stirring for 3 h. After cooling to room
temperature, the reaction mixture was neutralized with aque-
ous HCl, then the solvent was removed by evaporation, and
the residue was diluted with 20 mL of 2 N sodium carbonate
and extracted with dichloromethane. The organic phase was
washed with brine, dried over K2CO3, filtered, and evaporated
to dryness. The crude compound was purified by flash column
chromatography on silica gel (5:1 dichloromethane/EtOAc) to
afford a yellow solid (101 mg, 62%). δH (400 MHz; DMSO-d6;
Me4Si): 7.58-7.60 (m, 3H), 7.94 (t, 2H, J ) 6.0 Hz), 8.09 (d,
1H, J ) 8.0 Hz), 8.14 (d, 1H, J ) 8.0 Hz), 8.21-8.25 (m, 2H),
8.44 (m, 2H), 13.22 (s, 1H). δC (400 MHz; DMSO-d6; Me4Si):
118.0, 122.1, 125.7, 126.5, 127.2, 127.6, 128.6, 129.4, 131.6,
133.1, 133.3, 133.8, 133.9, 134.5, 136.2, 149.4, 156.7, 180.9,
FIGURE 7. Color and fluorescence changes of compound 1
in CH3CN (5.0 × 10-5 M) after addition of 50 equiv of
[(Bu)4N]F. Left to right: 1, 1 + [(Bu)4N]F, 1 (emission), and 1
+ [(Bu)4N]F (emission). Irradiation at 365 nm using UV lamp.
182.6, 185.1. HRMS m/z (TOF MS ES-) calcd for C21H11N2O2
-
([M - H]-), 323.0821, found, 323.0835.
respectively, which result in the large Rr values for 1 (88)
and 3 (548).
Synthesis of 2-(4-Methoxyl-phenyl)-1H-anthra[1,2-d]-
imidazole-6,11-dione (2). Using the method described above,
the R,â-substituted acylation intermediate was condensed to
2 directly without purification, and the crude compound 2 was
purified by flash column chromatography on silica gel (5:1
dichloromethane/EtOAc) to afford a yellow solid (50%). δH (400
MHz; DMSO-d6; Me4Si): 5.32 (s, 3H), 7.05 (d, 2H, J ) 8.8 Hz),
7.78 (m, 2H), 8.04 (d, 1H, J ) 8.4 Hz), 8.07 (d, 2H, J ) 8.8
Hz), 8.24 (m, 2H), 8.31 (m, 2H), 11.13 (s, 1H). δC (400 MHz;
DMSO-d6; Me4Si): 33.6, 53.6, 54.9, 114.8, 117.8, 121.1, 122.1,
125.3, 126.6, 127.7, 128.3, 128.9, 133.3, 133.8, 134.1, 134.5,
149.7, 156.8, 162.4, 182.7, 185.3. HRMS m/z (TOF MS ES-)
calcd for C22H13N2O3- ([M - H]-), 353.0927, found, 353.0931.
Conclusions
In conclusion, we have presented a new kind of
colorimetric and ratiometric fluorescent chemosensors for
fluoride. The colorimetric and ratiometric properties of
these sensors are ascribed to the anion-induced proton
transfer. By changing the electron properties of substit-
uents on the phenyl para position, the sensor-fluoride
interaction mechanism, the fluoride selectivity, and the
fluorescence response can be finely tuned. Generally
fluorescent sensors for fluoride ions cannot tell F- from
CH3CO2-. The excellent selectivity of 1 for F- over
Synthesis of 4-Nitro-N-{1-[2-(4-nitro-phenyl)-acetyl-
amino]-9,10-dioxo-9,10-dihydro-anthracen-2-yl}-benzamide
(3a). Using the method described above, the crude compound
was purified by flash column chromatography on silica gel (9:1
dichloromethane/EtOAc) to afford a yellow solid (90%). δH (400
MHz; DMSO-d6; Me4Si): 7.89-7.95 (m, 2H), 8.11-8.15 (m,
3H), 8.19-8.21 (t, 1H, J ) 8.8 Hz), 8.29-8.32 (m, 3H), 8.37
(d, 2H, J ) 8.8 Hz), 8.42-8.46 (m, 3H), 10.52 (s, 1H) 10.81 (s,
-
CH3CO2 is attributed to the fitness in the acidity of its
NH-group, which can distinguish the subtle difference
in the affinity of F- and CH3CO2 with proton. The
-
correlation between the electron properties of substituent
and the selectivity and the fluorescence responses will
be a very useful clue to design more selective chemosen-
sors to recognize F- in the presence of CH3CO2- and other
anions.
1H). HRMS m/z (TOF MS ES-) calcd for C28H15N4O8 ([M -
-
H]-), 535.0890, found, 535.0874.
Synthesis of 2-(4-Nitro-phenyl)-1H-anthra[1,2-d]imi-
dazole-6,11-dione (3). Using the method described above, the
crude compound was purified by flash column chromatography
on silica gel (5:1 dichloromethane/EtOAc) to afford a yellow
solid (75%). δH (400 MHz; DMSO-d6; Me4Si): 7.94 (s, 2H), 8.14
(d, 1H, J ) 8.0 Hz), 8.19 (d, 1H, J ) 8.0 Hz), 8.25 (s, 2H), 8.39
(d, 2H, J ) 8.0 Hz), 8.71 (d, 2H, J ) 8.0 Hz), 13.43 (s, 1H). δC
(400 MHz; DMSO-d6; Me4Si): 117.8, 122.4, 123.6, 125.8, 125.2,
126.1, 127.9, 133.2, 133.3, 133.6, 134.5, 143.0, 146.3, 146.7,
155.8, 171.3, 179.7, 183.2, 183.5, 185.8. HRMS m/z (TOF MS
Experimental Section
Synthesis and Characterization of 1 and 2. Synthesis
of N-(1-Phenylamino-9,10-dioxo-9,10-dihydro-anthracen-
2-yl)-benzamide (1a). A solution of benzoyl chloride (560 mg,
4 mmol) in THF (10 mL) was added dropwise to a solution of
1,2-diaminoanthraquinone (238 mg, 1 mmol) and K2CO3 (345
mg, 2.5 mmol) in THF (70 mL) with stirring at reflux. After
being stirred for 12 h, the solvent was removed by evaporation,
and the residue was diluted with 20 mL of 2 N sodium
carbonate and extracted with dichloromethane. The organic
phase was washed with brine, dried over K2CO3, filtered, and
evaporated to dryness. The crude compound was purified by
flash column chromatography on silica gel (10:1 dichlo-
romethane/EtOAc) to afford a yellow solid (347 mg, 78%). δH
(400 MHz; DMSO-d6; Me4Si): 7.3 (t, 2H, J ) 7.2 Hz), 7.59-
7.70 (m, 4H), 7.91-7.93 (m, 4H), 8.12-8.20 (m, 4H), 8.28 (d,
1H, J ) 8.8 Hz), 8.47 (d, 1H, J ) 8.8 Hz), 10.19 (s, 1H), 10.83
(s, 1H). δC (400 MHz; DMSO-d6; Me4Si): 125.2, 126.0, 126.7,
126.8, 127.0, 127.2, 127.5, 128.4, 128.5, 129.4, 129.9, 130.3,
131.9, 132.0, 133.5, 133.7, 133.9, 134.0, 134.2, 139.1, 163.3,
164.9, 166.1, 168.9, 181.2, 183.9. HRMS m/z (TOF MS ES-)
calcd for C28H17N2O4- ([M - H]-), 445.1188, found, 445.1187.
Synthesis of 2-Phenyl-1H-anthra[1,2-d]imidazole-6,11-
dione (1). A mixture of the compound 1a (223 mg, 0.5 mmol)
-
ES-) calcd for C21H10N3O4 ([M - H]-), 368.0671, found,
368.0672.
Acknowledgment. This work was supported by the
Ministry of Education of China and National Natural
Science Foundation of China (Projects 20128005,
20376010, and 20472012).
Supporting Information Available: General notes and
procedures; Job plot for fluoride-1 interaction; UV-vis spectral
changes of 1 and 3 in CH3CN solution with the addition of
tetrabutylammonium hydroxide; fluorescence fluoride titration
spectra of 2 in CH3CN solution; fluoride selectivity of 1 and 3.
This material is available free of charge via the Internet at
http://pubs.acs.org.
JO051766Q
J. Org. Chem, Vol. 70, No. 25, 2005 10531