A selective, sensitive, colorimetric, and fluorescence probe for relay recognition of fluoride and Cu(II) ions with off-On-Off switching in ethanol-water solution

Article abstract of DOI:10.1021/jo301548v

Anion to cation relay recognition was designed and realized for the first time with sequence specificity (F^-→Cu²⁺) via a fluorescence off-on-off mechanism. Probe 1 was a highly selective, sensitive, and turn-on chemodosimeter for F^- through a specific cyclization reaction triggered by the strong affinity of fluoride toward silicon with a significant change of fluorescence color in both ethanol and ethanol-water (1:1, v/v) solution. Fluorescence enhancement factors were dramatic: 833-fold in ethanol and 164-fold in ethanol-water (1:1, v/v) solution, respectively. The in situ system generated from the sensing of F^- showed good relay recognition ability for Cu²⁺ via fast fluorescence quenching by the formation of a 1:1 complex in ethanol-water (1:1, v/v) solution. The isolated pure compound 2 also exhibited high selectivity toward Cu²⁺ in PBS buffer (pH = 7.0) solution. The origin of this sequence specificity of fluorescence recognition was disclosed through the crystal or optimized structures and DFT calculations of corresponding compounds.

Full text of DOI:10.1021/jo301548v

Article
pubs.acs.org/joc
A Selective, Sensitive, Colorimetric, and Fluorescence Probe for Relay
Recognition of Fluoride and Cu(II) Ions with “Off−On−Off” Switching
in Ethanol−Water Solution
Yu Peng,* Yu-Man Dong, Ming Dong, and Ya-Wen Wang*
State Key Laboratory of Applied Organic Chemistry, Key Laboratory of Nonferrous Metals Chemistry and Resources Utilization of
Gansu Province and College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou 730000, People’s Republic of
China
S
* Supporting Information
ABSTRACT: Anion to cation relay recognition was designed
and realized for the first time with sequence specificity (F−→
Cu2+) via a fluorescence “off−on−off” mechanism. Probe 1
was a highly selective, sensitive, and turn-on chemodosimeter
for F− through a specific cyclization reaction triggered by the
strong affinity of fluoride toward silicon with a significant
change of fluorescence color in both ethanol and ethanol−
water (1:1, v/v) solution. Fluorescence enhancement factors were dramatic: 833-fold in ethanol and 164-fold in ethanol−water
(1:1, v/v) solution, respectively. The in situ system generated from the sensing of F− showed good relay recognition ability for
Cu2+ via fast fluorescence quenching by the formation of a 1:1 complex in ethanol−water (1:1, v/v) solution. The isolated pure
compound 2 also exhibited high selectivity toward Cu2+ in PBS buffer (pH = 7.0) solution. The origin of this sequence specificity
of fluorescence recognition was disclosed through the crystal or optimized structures and DFT calculations of corresponding
compounds.
INTRODUCTION
RESULTS AND DISCUSSION
■
■
Design and Synthesis of Probe 1. Excessive ingestion of
Bifunctional probes, which refer to those based on a single host
that can independently recognize two guest species with
distinct spectra responses by the same or different channels,
have already emerged and have gradually become a new
research focus in the field of fluorescence sensors.1 Recently, we
have also reported two bifunctional probes that include
combinations of Hg2+/Au3+ and Al3+/H+.2 Alternatively, we
proposed a relay recognition strategy as a new pathway to dual-
analyte fluorescent probes, which has been preliminarily
demonstrated in the anion relay recognition (ARR) from F−
to CN− based on the chemodosimeter approach associated
with 1,1′-binaphthyl fluorophores (Scheme 1, top).3 However,
this relay probe has some significant drawbacks such as the
extent of fluorescence enhancement, organic solvent media, UV
light excitation, low sensitivity, etc. Herein, we disclose anion to
cation relay recognition (ACRR) of F− and Cu2+ based on the
sequential chemodosimeter and chemosensor approaches
(Scheme 1, bottom), which demonstrates significant improve-
ment of fluorescence performance due to the formation of
iminocoumarin−benzothiazole. Notably, the present fluores-
cence off-on-off switching is also quite different from our
previous on-off-on switching in the CN− to Au3+ relay probe4
that involved a reversible process instead of the forward process
used here.
fluoride can result in fluorosis,5 urolithiasis, or even cancer.
Thus, recognition and sensing of F− has received considerable
attention recently.6 Compared to the traditional chemosensor,
the alternative chemodosimeter approach based on an
irreversible specific chemical reaction has emerged as an active
research area with significant importance recently.7 Some
recent chemodosimeters, utilizing desilylation reaction based
on high affinity between silicon and fluoride ions,8 have been
developed successfully. However, most of these examples can
only be operated in organic solvents9 and are largely limited in
practical application. To this end, design of new F− probes with
good performance in aqueous solution10 by means of the
desilylation reaction is still high desirable for potential
biological applications.
We designed a colorimetric and turn-on chemodosimeter (1)
for the rapid and highly selective detection of F− with
significant improvements to our latest, relatively inferior
fluoride probe.3 As shown in Scheme 2, fluoride triggers Si−
O bond cleavage of probe 1, and subsequent intramolecular
nucleophilic attack of the generated phenolate on the α,β-
unsaturated nitrile moiety by 1,2-addition and in 6-exo-dig
fashion produces imine anion intermediate. This transient
species quickly abstracts a proton from the solvent and
Received: July 26, 2012
Published: September 24, 2012
© 2012 American Chemical Society
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Scheme 1. Relay Recognition Strategy
Scheme 2. Mechanism of Sensing Fluoride
Figure 1. (a) Fluorescence responses of 1 (25.0 μM) with various anions (125.0 μM) in ethanol−water (v/v = 1:1) solution (λex = 460 nm). (b)
Fluorescence spectral changes of 1 + TBAF (25.0 μM + 125.0 μM) with various metal ions (125.0 μM) in ethanol−water (v/v = 1:1) solution (λex
=
460 nm). (c) Fluorescence change (top) and color change (bottom) of 1 (25.0 μM). From left to right: 1 only, F− (1.0 equiv), F− (1.0 equiv) + Cu2+
(1.0 equiv). All the images were obtained after 3 min upon the addition of ions.
eventually leads to the cyclization product iminocoumarin−
benzothiazole 2, which is responsible for the dramatic
fluorescence enhancement. Notably, this cascade11 to 2 is
distinctively different from previous simple deprotection of O-
silyl ethers9b−g,10b−f or desilylation followed by fragmentatio-
n.10a,g The designed chemodosimeter 1 was easily prepared by
silylation of the free phenol hydroxyl group of 4-
(diethylamino)salicylaldehyde with tert-butyldimethylsilyl
chloride (TBSCl) and subsequent Knoevenagel condensation12
with 2-benzothiazoleacetonitrile (see Scheme 3 in Experimental
Section for details). The structure of 1 was identified by 1H and
13C NMR, IR, ESI-MS, HRMS (Figures S4−S8, Supporting
Information), and X-ray crystal structure analysis (Figures 7
and S39, Supporting Information).
Fluorescence Responses of 1 with Relay Recognition
of F− and Cu2+. Next, the fluorescence properties of 1 were
studied. To date, most of the current fluorescence chemo-
dosimeters that respond to F− utilizing the desilylation reaction
need to be excited by UV light,9a−c,f,g,10d−g which would inflict
damage upon intracellular processes. As shown in Figure 1a, 1
exhibits a weak emission band at about 523 nm when excited at
460 nm, which is in the range of visible light and is relatively
rare in aqueous solution.10a,c Subsequently, F−, Cl−, Br−, I−,
AcO−, ClO4 , CF3SO3 , NO3 , HSO4 , H2PO4 , BF4 , N3 ,
CN−, SCN−, and OH− (as the corresponding tetrabutylammo-
nium salt, respectively) were used to measure the selectivity of
probe 1 (25.0 μM) in ethanol−water (1:1, v/v), and
fluorescence spectra were recorded after 3 min upon addition
of 5.0 equiv of each of these anions. Compared to other anions
examined, only F− generated a remarkable fluorescence increase
at 523 nm.
−
−
−
−
−
−
−
Copper is the third most abundant essential trace element in
the human body, plays a critical role in many cellular processes,
and is also required by the human nervous system.13 However,
high levels of copper ions may also lead to neurodegenerative
diseases such as Alzheimer’s and Wilson’s diseases,14 which
probably result from the production of reactive oxygen species
(ROS). Thus, the sensing and recognition of copper ions has
attracted considerable attention in recent years and resulted in
fruitful work.15 Since the pioneering work of Czarnik and co-
workers in the development of a chemodosimeter for Cu2+ that
utilizes rhodamine-B hydrazide,16a related fluorescent probes
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Figure 2. (a) Fluorescence spectra of 1 (25.0 μM) upon the addition of F− in ethanol−water (v/v = 1:1) solution (λex = 460 nm). [F−] = 0, 2.5, 5.0,
7.5, 10.0, 12.5, 15.0, 17.5, 20.0, 22.5, 25.0, 50.0, 75.0, 100.0, 125.0 μM. Inset: Fluorescence intensity at 523 nm as a function of F− concentration. (b)
The selectivity of 1 (25.0 μM). The red bars represent the emission intensity of 1 in the presence of other anions (125.0 μM). The gray bars
represent the emission intensity that occurs upon the subsequent addition of 25.0 μM F− to the above solution. From 1 to 15: none, Cl−, Br−, I−,
−
−
−
−
−
−
−
AcO−, ClO4 , CF3SO3 , NO3 , HSO4 , H2PO4 , BF4 , N3 , CN−, SCN−, and OH− (λem = 523 nm).
Figure 3. (a) Fluorescence spectra of 1 + TBAF (25.0 μM + 25.0 μM) upon the addition of Cu2+ in ethanol−water (v/v = 1:1) solution (λex = 460
nm). [Cu2+] = 0, 2.5, 5.0, 7.5, 10.0, 12.5, 15.0, 17.5, 20.0, 22.5, 25.0, 50.0, 125.0 μM. Inset: Fluorescence intensity as a function of F− concentration.
(b) The selectivity of 1 + TBAF (25.0 μM + 25.0 μM). The red bars represent the emission intensity of 1 + TBAF in the presence of other metal
ions (125.0 μM) (λem = 523 nm). The gray bars represent the emission intensity that occurs upon the subsequent addition of 25.0 μM of Cu2+ to the
above solution (λem = 544 nm). From 1 to 18: none, Na+, Ca2+, Mg2+, Al3+, Ba2+, Zn2+, Cd2+, Co2+, Hg2+, Mn2+, Ag+, Fe2+, Fe3+, Pb2+, Li+, K+, Ni2+.
based on the spiro ring-opening of xanthene derivatives have
been reported,16b−f including our recent contribution.16e
Development of other effective Cu2+ fluorescent probes based
on the chemosensor approach is still in high demand.
chemosensor approach that is very rare. In contrast, conven-
tional demetalation (displacement) of the preassembled
complex (“metal ion→anion recognition sequence”)17 gen-
erally features “on-off-on” switching based on chemosensor
approach.
In the present work, iminocoumarin 2 generated in situ after
recognition of F− would be expected to serve as a relay probe
for the sensing of some metal ions because several binding sites
exist for coordination. Upon the addition of Cu2+ to the 1 + F−
system (2), fluorescence quench was indeed generated (Figure
1b). In contrast, no significant fluorescence changes were
observed when other metal ions (including Na+, Ca2+, Mg2+,
Al3+, Ba2+, Zn2+, Cd2+, Co2+, Hg2+, Mn2+, Ag+, Fe2+, Fe3+, Pb2+,
Relay Fluorescence Titrations with F− and Cu2+. The
pH dependence of the fluorescence intensity change of 1 and
the 1 + F− system in the ethanol−water solution is shown in
Figure S14 (Supporting Information). With the increase of the
pH from 5.5 to 11.5, the fluorescence intensity of the 1 + F−
system increased significantly compared to the fluorescence
intensity of 1. Under extremely acidic or basic conditions, 1
cannot be used for the detection of F−. Eventually ethanol−
water (1:1, v/v, pH = 7.4) solution was used as an ideal media.
The fluorescence titrations of F− were also conducted using a
25.0 μM solution of 1 in ethanol−water (1:1, v/v) solution.
Upon the addition of F− to the solution, a significant increase
(164-fold) in the fluorescence intensity at 523 nm was observed
(Figure 2a) when excited at 460 nm. Further increase in the
concentration of F− (>25.0 μM) led to no further fluorescence
increase (Figure 2a, inset), which clearly demonstrated a
chemodosimeteric fluorescence change between F− and probe
1. The fluorescent quantum yield (Φ) of 1 also increased from
0.08% to 7.09% in the presence of F− (1.0 equiv). The
corresponding detection limit18 was calculated to be 117.7 nM
(2.24 ppb) (Figure S15, Supporting Information), which is
much lower than the concentration allowed in drinking water
−
Li+, K+, and Ni2+) or anions (including Br−, AcO−, ClO4 ,
−
−
−
−
−
−
CF3SO3 , NO3 , HSO4 , H2PO4 , BF4 , N3 , CN−, SCN−, and
OH−) were added (Figures 1b and S13, Supporting
Information). These results suggested that probe 1 displayed
an excellent selectivity toward F− in ethanol−water (1:1, v/v),
and the resulting 1 + F− system showed high selectivity for
Cu2+ in the same media as well. To this end, the designed relay
recognition of these two ions has been achieved with sequence
specificity (F−→Cu2+) via a fluorescence “off−on−off” switch-
ing mechanism and provided a complementary sensing
approach to previous bifunctional probes for F− and Cu2+
ions.1e,f
It is noteworthy that the above relay recognition of two
species (F−→Cu2+) can be defined as “anion→metal ion
sequence” with a combination of the chemodosimeter and
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Figure 4. (a) Fluorescence responses of 1 (25.0 μM) with various anions (100.0 μM) in ethanol (λex = 460 nm). (b) The selectivity of 1 (25.0 μM).
The red bars represent the emission intensity of 1 in the presence of other anions (100.0 μM). The gray bars represent the emission intensity that
−
−
−
occurs upon the subsequent addition of 25.0 μM of F− to the above solution. From 1 to 15: none, Cl−, Br−, I−, AcO−, ClO4 , CF3SO3 , NO3 ,
−
−
−
−
HSO4 , H2PO4 , BF4 , N3 , CN−, SCN−, and OH− (λem = 510 nm). (c) Fluorescence spectra of 1 (25.0 μM) upon the addition of F− in ethanol.
[F−] = 0, 2.5, 5.0, 7.5, 10.0, 12.5, 15.0, 17.5, 20.0, 22.5, 25.0, 50.0, 75.0 μM. Inset: Fluorescence intensity at 510 nm as a function of F− concentration.
(d) Color change (top) and fluorescence change (bottom) of 1 ([1] = 25.0 μM, [F−] = 50.0 μM, [other anions] = 100.0 μM). Left to right: 1 only,
−
−
−
Cl−, AcO−, CF3SO3 , NO3 , BF4 , CN−, F−.
according to the US EPA (1−4 ppm).19 The kinetic behavior of
F− (250.0 μM) to probe 1 (25.0 μM) in ethanol−water (1:1, v/
v) solution at 25 °C was measured (Figure S16, Supporting
Information), and the observed rate constant was estimated to
be kobs = 5.84 × 10−3 s−1 by fitting the initial fluorescent
intensity changes according to a pseudo-first-order kinetics
equation. As shown in Figure 2b, all competitive anions caused
no obvious changes, even at the higher concentration (125.0
μM); therefore, the 1 + F− system was hardly affected by these
coexistent ions. In addition, the fluorescence color changed
from almost nonfluorescent to bright jade green with the
addition of F− (Figure 1c, top). The above results mean that 1
can function as a colorimetric and fluorescent probe for F− via a
fluorescence “turn-on” mechanism.
is observed.20 Based upon a 1:1 stoichiometry, the association
constant K of the complex was then calculated to be 7.93 × 105
M−1 (Figure S19, Supporting Information).21 The correspond-
ing detection limit was calculated to be 1.79 μM (113.7 ppb)
(Figure S20, Supporting Information). The fluorescent
quantum yield (Φ) decreased from 7.09% to 0.24% in the
presence of Cu2+ (1.0 equiv). As shown in Figure 3b, all
competitive metal ions had no obvious interference with the
detection of Cu2+ ion. The 1 + F− system displayed high
sensitivity for Cu2+ owing to the short response time (Figure
S21, Supporting Information). These results clearly indicated
that the 1 + F− system (2) is useful for selectively sensing Cu2+
even under competition from other related metal ions, which
would achieve the purpose of real-time monitoring. The
fluorescence color changed from jade green to almost
nonfluorescent (Figure 1c, top). All of these results suggested
that relay 2 can also function as a fluorescent probe for Cu2+.
Absorption Responses of 1 with Relay Recognition of
F− and Cu2+. In the profile of UV−vis spectra of the probe 1 in
ethanol−water (1:1, v/v) solution, an absorption peak emerged
at about 460 nm, and its intensity slightly increased upon the
addition of F− (Figure S22, Supporting Information). However,
only with the addition of Cu2+ to the 1 + F− system was a new
absorption peak observed, at about 503 nm, and its intensity
gradually increased upon the addition of Cu2+ (Figures S22,
S23, and S24, Supporting Information). Moreover, changes in
the solution color from yellow to yellowish green and then to
brownish yellow were observed by the naked eye upon the
sequential addition of F− and Cu2+ ions to probe 1 (Figure 1c,
bottom). The absorption changes at 460 and 503 nm are in
good agreement with these color changes. These results
Then the generated 1 + F− system was directly used to titrate
Cu2+ without separation and purification. Upon the addition of
Cu2+, a significant decrease in the fluorescence intensity at 523
nm with a bathochromic shift to 544 nm was observed (Figure
3a). The total fluorescence intensity of the 1 + F− system
decreased to 1.9% when 1.0 equiv of Cu2+ was present. The
fluorescence quench is due to LMCT between the 1 + F−
system (2) and Cu2+ by coordination, and this behavior has
been further revealed by DFT calculations (vide infra, see also
Figures 8, S42, S43, and S44, Supporting Information). Increase
in the concentration of Cu2+ led to no further fluorescence
quench (Figure 3a, inset), which demonstrated a 1:1
stoichiometry between the 1 + F− system and Cu2+. This
ratio was also obtained by using Job’s plot (Figures S17,
Supporting Information). Moreover, the positive-ion ESI mass
spectrum provides additional evidence for the formation of a
1:1 complex between the 1 + F− system (2) and Cu2+ (Figure
S18): a peak at m/z 511.0033 assigned to [2 + Cu(II) + ClO4]+
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Figure 5. (a) Fluorescence spectra of 2 (25.0 μM) upon the addition of Cu2+ in PBS buffer (pH = 7.0) solution (λex = 460 nm). [Cu2+] = 0, 2.5, 5.0,
7.5, 10.0, 12.5, 15.0, 17.5, 20.0, 22.5, 25.0, 50.0, 75.0, 100.0, 125.0 μM. Inset: Fluorescence intensity at 533 nm as a function of F− concentration. (b)
The selectivity of 2 (25.0 μM). The red bars represent the emission intensity of 2 in the presence of other metal ions (125.0 μM). The gray bars
represent the emission intensity that occurs upon the subsequent addition of 25.0 μM of Cu2+ to the above solution. From 1 to 18: none, Na+, Ca2+,
Mg2+, Al3+, Ba2+, Zn2+, Cd2+, Co2+, Hg2+, Mn2+, Ag+, Fe2+, Fe3+, Pb2+, Li+, K+, Ni2+ (λem = 533 nm).
indicated that relay recognition of these two ions was realized
through UV−vis spectroscopy as well.
mixture of ethanol and water were further examined (Figure
S29, Supporting Information). Upon the addition of 1.0 equiv
of Cu2+, the total fluorescence intensity of 2 decreased to 1.9%,
2.2%, 3.2%, 4.5%, 8.3%, and 12.4% in ethanol with different
proportions of water (50%, 60%, 70%, 80%, 90%, and 100%),
respectively. Considering practical application, pure water
solution was selected to study the fluorescence response of 2
with Cu2+ in detail. The pH effect on the fluorescence intensity
is shown in Figure S30 (Supporting Information). The
fluorescence intensity of 2 increased gradually in the pH
range from 4.0 to 8.0, which may result from deprotonation of
the protonated form (Et2NH+) of the diethylamino substituent.
Upon the addition of Cu2+ to the solution of 2, the fluorescence
intensity quench may be due to the effective coordination
between 2 and Cu2+. Compared to the fluorescence intensity of
2, the 2 + Cu2+ system quenched the fluorescence intensity
severely between pH 7.0 and 8.0. In subsequent experiments, a
pH 7.0 solution was used as an ideal media. Upon the addition
of Cu2+ to the PBS buffer (pH = 7.0) solution, a decrease in the
fluorescence intensity at 533 nm was observed when excited at
460 nm (Figure 5a). Minimum fluorescence intensity was
shown when 1.0 equiv of Cu2+ was present, and the total
fluorescence intensity of 2 decreased to 12.4%. A further
increase in the concentration of Cu2+ led to no further
fluorescence quench (Figure 5a, inset), which demonstrated a
1:1 stoichiometry between 2 and Cu2+. The corresponding
detection limit was calculated to be 1.15 μM (73.0 ppb) (Figure
S31, Supporting Information), which is much lower than the
concentration allowed in drinking water according to the US
EPA (1.3 ppm). The fluorescent quantum yield (Φ) decreased
from 1.77% to 0.20% in the presence of Cu2+ (1.0 equiv) in
PBS buffer solution. Both Job’s plot and Benesi−Hildbrand plot
experiments also gave rise to the result indicating a 1:1 binding
model between 2 and Cu2+ (Figures S32 and S33, Supporting
Information). The association constant K of the complex was
then calculated to be 4.01 × 106 M−1 by using the emission
changes at 533 nm (Figure S33, Supporting Information). In
contrast, no significant fluorescence changes were observed
when other ions were added (Figures S34 and S35, Supporting
Information). As shown in Figure 4b, all competitive metal ions
had no obvious interference with the detection of Cu2+ ion. A
short response time was observed in the 2 + Cu2+ system
(Figure S36, Supporting Information). These results clearly
indicated that 2 can serve as a relay probe to detect Cu2+ ion in
aqueous solution even in pure water.
Further Spectroscopic Investigation of 1 with F− in
Ethanol. Fluorescence properties of 1 and 1 + TBAF in a
mixture of ethanol and water were further examined (Figure
S25, Supporting Information). Compared to that in pure
ethanol solution, the fluorescence of 1 + F− exhibited a slight
bathochromic shift, and its intensity was quenched to some
extent in ethanol solution with different proportions of H2O.
The total fluorescence intensity of 1 increased to 584-, 459-,
223-, 212-, and 164-fold in ethanol with different proportions of
water (10%, 20%, 30%, 40%, and 50%), respectively. Notablely,
in pure ethanol solution the fluorescence enhancement factor at
510 nm was determined as a dramatic 833-fold, which is the
highest value ever observed.22 Eventually, the system of pure
ethanol solution was selected to study the fluorescence
response of 1 with F− in detail. As shown in Figure 4a,
compared to other anions examined, only F− caused a
remarkable fluorescence increase at 510 nm, and a similar
result was observed by addition of a NaF23 solution. All
competitive anions had no obvious interference with the
detection of F− (Figure 4b). The fluorescence titration
experiment shows that the addition of F− to the solution
resulted in a 833-fold fluorescence enhancement at 510 nm
when excited at 460 nm, and further increase in the
concentration of F− (>25.0 μM) led to no further fluorescence
increase (Figure 4c). The fluorescent quantum yield (Φ) of 1
increased significantly from 0.10% to 31.0% in the presence of
F− (1.0 equiv). The corresponding detection limit was
calculated to be 19.6 nM (0.37 ppb) (Figure S26, Supporting
Information). The observed rate constant at 25 °C was
analogously estimated to be kobs = 7.09 × 10−3 s−1 (Figure S27,
Supporting Information). In addition, only the solution
containing F− showed the change in solution color from
yellow to yellowish green, which was observed by the naked eye
(Figure 4d, top). The significant change in fluorescence color
from almost nonfluorescent to bright jade green was also
demonstrated (Figure 4d, bottom).
There were no changes in the UV−vis spectra of probe 1
after addition of various anions in pure ethanol solution (Figure
S28, Supporting Information). Upon the addition of F−, the
absorbance intensity at about 460 nm was slightly increased.
Further Spectroscopic Investigation of 2 with Cu2+ in
PBS Buffer Solution. Finally, the fluorescence properties of
the isolated pure compound 2 and 2 + Cu2+ were studied in
detail. The fluorescence properties of 2 and 2 + Cu2+ in a
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In the UV−vis spectra of 2 in PBS buffer solution, the
absorbance at about 430 nm decreased with the enhancement
of a new absorbance at about 485 nm only in the case of Cu2+
over other metal ions upon the addition of various metal ions
(Figures S37 and S38, Supporting Information). Moreover,
there was a good linearity between the ratios of the absorbances
that the benzene ring and benzothiazole ring are not planar and
their dihedral angle is about 11.8°. To further understand the
relationship between the structural changes of 1 and 2 and the
respective optical response to F− and Cu2+, we carried out
density function theory (DFT) calculations with the B3LYP/6-
31 G(d) basis set using the Gaussian 03 program. As displayed
in Figures S40 and S41 (Supporting Information), the
optimized structure of probe 1 has a dihedral angle of about
10.3° between the benzene ring and benzothiazole moiety,
which is in good agreement with the corresponding crystallo-
graphic data of 1, whereas the iminocoumarin and benzothia-
zole moieties of cyclization product 2 are essentially planar,
with a dihedral angle of 0.8°, eventually resulting in the
formation of delocalized π bonds. For probe 1, both the
HOMO and LUMO are mainly distributed at the benzene ring
and benzothiazole moieties (Figure 8). By contrast, for the
A
430/A485 and the concentration of Cu2+ in the range of 2.5 to
25.0 μM (Figure S38, inset, Supporting Information) and
therefore allows quantitative detection of Cu2+ by absorption
ratiometry. These results indicated that recognition of Cu2+
ions could be also well realized through UV−vis spectroscopy.
Rationalization of Relay Recognition of F− and Cu2+.
To understand the proposed mechanism (Scheme 1 (bottom)
1
and 2) further, H/13C NMR, IR, and ESI mass spectroscopy
analysis experiments were subsequently carried out (Figures
1
S9−S12, Supporting Information). H NMR spectral analysis
showed that the signal of the double bond proton Ha at around
8.48 ppm of 1 shifted downfield (8.92 ppm) after the addition
of F− and the signals of He,h, Hf, Hg, Hc, and Hd also shifted
downfield to a different extent, while the signal of Hb shifted
upfield, which suggested the formation of cyclization product 2
(Figures 6 and S9, Supporting Information). The broad band
Figure 8. HOMO−LUMO energy levels and the molecular orbital
plots of 1, 2, and 2·Cu2+.
cyclization product 2, the HOMO and the LUMO are located
over the whole molecule. These results indicate that 2 bears
strong fluorescence character, which is the origin of the “turn-
on” fluorescence response of 1 to F− anions. Furthermore, the
energy gap value between the HOMO and LUMO of 2 is
similar to that of 1, in good agreement with no obvious changes
in the absorption spectra observed upon treatment of 1 with F−
anions. The optimized structure of 2·Cu2+ complex shows that
the Cu2+ ion binds to 2 at nitrogen atoms of the imino and
benzothiazole groups, with Cu−N bond lengths 1.943 Å and
1.967 Å, respectively (Figure S42, Supporting Information).
The Cu2+ ion may be chelated by the counteranion or solvent
to satisfy the need for saturated coordination, and the
iminocoumarin, benzothiazole, and Cu2+ ion are almost
planar.24 Considering the “soft” nature of the Cu2+ ion and
the free rotation of the C−C single bond, the S center could
also be involved in the complex, and the optimized structure of
[2·Cu2+]′ complex was obtained accordingly (Figure S43,
Supporting Information). In the 2·Cu2+ complex, the electron
density of HOMO−2 is mainly localized on the iminocoumarin
and benzothiazole moieties while the electron density of
LUMO is localized on the Cu2+ ion, which indicated a strong
ligand-to-metal charge transfer (LMCT) process (Figure 8). A
similar result was also observed in the [2·Cu2+]′ complex
(Figure S44, Supporting Information), and the electron density
change between HOMO−1 and LUMO was not sufficient to
explain the LMCT process compared to that of the 2·Cu2+
complex. Thus, 2 acts as a quenching fluorescent probe toward
Cu2+ ion. The origin of the bathochromic shift in the
1
Figure 6. Partial H NMR spectra (400 MHz) of 1 (bottom) and 2
(top) in CDCl3.
around 3416 cm−1 in the IR spectrum corresponds to the N−H
stretching frequency of 2 (Figure S11, Supporting Informa-
tion). A major peak at m/z 350.3, corresponding to [2 + H]+, is
observed in the ESI mass spectrum (Figure S12, Supporting
Information).
A single crystal of probe 1 was obtained from ethanol, and its
structure (Figures 7 and S39, Supporting Information) shows
Figure 7. X-ray structure of 1.
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Article
absorption spectra of the 2·Cu2+ complex compared with that
for 2 is attributed to LMCT between the 2 and Cu2+ by
effective coordination.
The solvent was removed under reduced pressure, and the residue was
purified by column chromatography (petroleum ether/EtOAc = 50: 1)
to give 39a as a white solid (1.35 g, 44%). H NMR (CDCl3, 400
1
MHz): δ 10.14 (s, 1H), 7.70 (d, J = 9.2 Hz, 1H), 6.33 (dd, J = 9.2, 2.0
Hz, 1H), 5.97 (d, J = 2.4 Hz, 1H), 3.39 (q, J = 7.2 Hz, 4H), 1.21 (t, J =
7.2 Hz, 6H), 1.03 (s, 9H), 0.28 (s, 6H) ppm; 13C NMR (CDCl3, 100
MHz): δ 187.4, 161.0, 153.5, 129.9, 116.4, 105.5, 100.5, 44.7 (2C),
25.7 (3C), 18.3, 12.5 (2C), −4.3 (2C) ppm; ESI−MS: m/z = 308.4
[M + H]+. To a stirred solution of 3 (307 mg, 1 mmol) and 2-
benzothiazoleacetonitrile (174 mg, 1 mmol) in ethanol (10 mL) at
room temperature under argon was added one drop of piperidine. The
reaction mixture was stirred at room temperature for 20 min. The
solvent was evaporated under reduced pressure. The crude product
was purified by column chromatography (petroleum ether/EtOAc =
30:1 → 10:1) on silica gel to afford compound 1 as a yellow solid (232
mg, 50%). Pure 1 was dissolved in EtOH, and single crystals were
obtained by slow evaporation of solvent at room temperature after a
few days. 1H NMR (CDCl3, 400 MHz): δ 8.48 (s, 1H), 8.45 (d, J = 9.2
Hz 1H), 8.00 (d, J = 8.4 Hz, 1H), 7.84 (d, J = 8.0 Hz, 1H), 7.45 (t, J =
8.0 Hz, 1H), 7.33 (t, J = 8.0 Hz, 1H), 6.42 (dd, J = 9.2, 2.4 Hz, 1H),
6.07 (d, J = 2.4 Hz, 1H), 3.41 (q, J = 7.2 Hz, 4H), 1.23 (t, J = 7.2 Hz,
6H), 1.11 (s, 9H), 0.30 (s, 6H); 13C NMR (CDCl3, 100 MHz): δ
165.7, 158.4, 153.9, 152.3, 141.8, 134.3, 130.2, 126.2, 124.8, 122.9,
121.2, 118.3, 112.1, 106.3, 100.8, 96.3, 44.8 (2C), 30.9, 25.8 (2C),
18.3, 12.6 (2C), −4.2 (2C) ppm; IR (film): νmax = 3064, 2959, 2929,
2857, 2206 (−CN), 1608, 1561, 1511, 1404, 1352, 1281, 1246,
1114, 1076, 978, 891, 830, 783, 758 cm−1; ESI−MS: m/z = 464.4 [M
+ H]+; HRMS (ESI): calcd for C26H34N3OSSi+ [M + H]+ 464.2186,
found 464.2188.
CONCLUSION
■
We proposed a novel relay recognition concept from anion to
cation and have realized unprecedented sensing of fluoride and
copper(II) ions with sequence specificity via a fluorescence
“off−on−off” mechanism. The fluorescence “turn-on”7c chemo-
dosimeter 1 for F− based on a specific cyclization reaction
triggered by the strong affinity of fluoride toward silicon
exhibits remarkable fluorescence enhancement, significant
fluorescent quantum yield changes, high selectivity, and a
very low detection limit, both in ethanol and its aqueous
solution. The in situ prepared 1 + F− system or pure 2 shows
superior recognition ability for Cu2+ via fast fluorescence
quenching by the formation of a 1:1 complex in ethanol−water
(1:1, v/v) solution or PBS buffer (pH = 7.0) solution.
Especially, iminocoumarin 2 is also potentially useful for
quantitative determination of Cu2+ by absorption ratiometry in
PBS buffer solution. Moreover, 1 and 2 can be excited by visible
light and may be useful in potential biological applications.
More applications of this efficient strategy might be found in
extended occasions of this concept, such as with combinations
of metal−metal ions and anion−neutral molecules.
Synthesis and Characterization of 2.26 To a stirred solution of
silyl ether 1 (50 mg, 0.108 mmol) in THF (10 mL) was added
tetrabutylammonium fluoride in THF (1.0 M, 0.5 mL) at room
temperature. The mixture was stirred for 3 h, and the solvent was
evaporated under reduced pressure. The resulting crude residue was
purified by flash column chromatography (10:1 → 1:1) on silica gel to
EXPERIMENTAL SECTION
■
General Methods. Unless otherwise noted, materials were
obtained from commercial suppliers and were used without further
purification. Stock solutions (10 mM) of the tetrabutylammonium
−
−
−
−
salts of F−, Cl−, Br−, I−, CN−, AcO−, ClO4 , CF3SO3 , NO3 , HSO4 ,
−
−
−
−
H2PO4 , BF4 , N3 , CN−, and SCN3 in ethanol or deionized water,
and NaF in deionized water, were prepared. Stock solutions (5 mM)
of the perchlorate salts of Na+, K+, Li+, Mg2+, Ca2+, Ba2+, Al3+, Mn2+,
Co2+, Zn2+, Cd2+, Pb2+, Fe2+, Fe3+, Cu2+, Ag+, and Hg2+ were prepared
in deionized water. Stock solution of 1 (5 mM) or 2 (5 mM) was also
prepared in ethanol. Test solutions were prepared by placing 10 μL of
the probe stock solution into a test tube, diluting the solution to 2 mL
with ethanol or ethanol−water (v/v = 1:1) or deionized water, and
adding an appropriate aliquot of each anion stock. For all
measurements, the fluorescence spectra were obtained by excitation
at 460 nm. Both the excitation and emission slit widths were 2.5 nm.
Fluorescence spectra were measured after 3 min upon the addition of
anions. Fluorescent quantum yields were determined by standard
methods, using fluorescein (Φ = 0.85 in 0.1 N NaOH) as a standard.25
1
afford compound 2 as a red solid (30 mg, 80%). H NMR (CDCl3,
400 MHz): δ (there is no signal of NH) 8.92 (s, 1H), 8.03 (d, J =
8.4 Hz, 1H), 7.95 (d, J = 7.6 Hz, 1H), 7.50 (t, J = 8.0 Hz, 1H), 7.49 (d,
J = 9.2 Hz, 1H), 7.37 (t, J = 8.0 Hz, 1H), 6.68 (dd, J = 9.2, 2.4 Hz,
1H), 6.57 (d, J = 2.4 Hz, 1H), 3.48 (q, J = 7.2 Hz, 4H), 1.26 (t, J = 7.2
Hz, 6H); 13C NMR (CDCl3, 100 MHz): δ 161.8, 161.0, 157.0, 152.6,
152.1, 142.0, 136.3, 130.7, 126.0, 124.4, 122.1, 121.5, 112.4, 109.9,
108.6, 96.9, 45.1 (2C), 12.5 (2C); IR (film): νmax = 3416 (NH),
3055, 2967, 2922, 1711, 1616, 1587, 1510, 1412, 1346, 1259, 1189,
1129, 1073, 1010, 936, 818, 756, 725, 674 cm−1; ESI−MS: m/z =
350.3 [M + H]+.
ASSOCIATED CONTENT
■
S
* Supporting Information
Scheme 3. Synthesis of Probes 1 and 2
Spectra data, cif file of the probe 1, copies of 1H/13C NMR and
ESI−MS. This material is available free of charge via the
Internet at http://pubs.acs.org.
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: pengyu@lzu.edu.cn; ywwang@lzu.edu.cn.
Notes
The authors declare no competing financial interest.
Synthesis and Characterization of Probe 1. To a solution of 4-
(diethylamino)salicyaldehyde (1.93 g, 10 mmol) in dry DMF (50 mL)
were added tert-butyldimethylsilyl chloride (TBSCl) (1.81 g, 12
mmol) and then imidazole (816 mg, 12 mmol) and DMAP (61 mg,
0.5 mmol). The mixture was stirred at room temperature for 15 h,
quenched with water (30 mL), and extracted with ether (3 × 50 mL).
The combined organic layers were washed with saturated NH4Cl (50
mL), water (50 mL), and brine (50 mL) and then dried over MgSO4.
ACKNOWLEDGMENTS
■
This work was financially supported by the NSFC (nos.
21001058 and 21172096), the Scientific Research Foundation
for the Returned Overseas Chinese Scholars, the Fundamental
Research Funds for the Central Universities (lzujbky-2012-57),
and the “111” Project of MoE.
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(12) Kurti, L.; Czako,
in Organic Synthesis: Background and Detailed Mechanisms; Elsevier:
Amsterdam, 2005; pp 242−243.
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B. In Strategic Applications of Named Reactions
̈
DEDICATION
■
Dedicated to Professor A. P. de Silva (Queen’s University,
Northern Ireland) on the occasion of his 60th birthday.
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NOTE ADDED AFTER ASAP PUBLICATION
■
Since this published on October 2, 2012, the description of
fluorescence switching in the Introduction and Results and
Discussion has been corrected; it reposted on October 3, 2012.
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