A chromone-derived Schiff-base as Al3+“turn-on” fluorescent probe based on photoinduced electron-transfer (PET) and C[dbnd]N isomerization

Article abstract of DOI:10.1016/j.tetlet.2016.09.058

In this study, a novel chromone-derived Schiff-base ligand which was called bis(6-hydroxychromone-3-methylidene)-o-phenylenediimine (1) was designed, synthesized, and evaluated as an Al³⁺“turn on” fluorescent probe. This probe 1 showed good selectivity and high sensitivity towards Al³⁺in the presence of most metal ions, and a remarkable enhancement by about 30.91-fold in fluorescence emission intensity at 459?nm was observed with addition of 1?equiv of Al³⁺, which was attributed to the inhibition of photoinduced electron-transfer (PET) phenomenon and C[dbnd]N isomerization process at the excited state. Moreover, the fluorescence response of 1 to Al³⁺was nearly completed within 10?min. Thus, this probe 1 could be utilized for sensing and monitoring Al³⁺in environmental and biological systems for real-time detection.

Full text of DOI:10.1016/j.tetlet.2016.09.058

Tetrahedron Letters 57 (2016) 4898–4904
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
A chromone-derived Schiff-base as Al3+ ‘‘turn-on” fluorescent probe
based on photoinduced electron-transfer (PET) and C@N
isomerization
Chao-rui Li a, Si-liang Li a,b, Zheng-yin Yang a,
⇑
a College of Chemistry and Chemical Engineering, State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou 730000, PR China
b School of Petrochemical Engineering, Lanzhou University of Technology, Lanzhou 730050, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 13 June 2016
Revised 10 September 2016
Accepted 18 September 2016
Available online 21 September 2016
In this study, a novel chromone-derived Schiff-base ligand which was called bis(6-hydroxychromone-3-
methylidene)-o-phenylenediimine (1) was designed, synthesized, and evaluated as an Al3+ ‘‘turn on” flu-
orescent probe. This probe 1 showed good selectivity and high sensitivity towards Al3+ in the presence of
most metal ions, and a remarkable enhancement by about 30.91-fold in fluorescence emission intensity
at 459 nm was observed with addition of 1 equiv of Al3+, which was attributed to the inhibition of pho-
toinduced electron-transfer (PET) phenomenon and C@N isomerization process at the excited state.
Moreover, the fluorescence response of 1 to Al3+ was nearly completed within 10 min. Thus, this probe
1 could be utilized for sensing and monitoring Al3+ in environmental and biological systems for real-time
detection.
Keywords:
Chromone
Fluorescent probe
Aluminum ion
Selectivity
Ó 2016 Elsevier Ltd. All rights reserved.
Sensitivity
Introduction
Because of its visual simplicity, high sensitivity, inexpensive
apparatus, instantaneous response, real-time detection, and non-
Aluminum, being the third most abundant of all elements and
the most abundant metallic element (approximately 8.3% by
weight) in the earth’s crust,1,2 is the most widely existing metal
in the environment from the origin of acidic rain and human activ-
ities.3,4 It has been extensively utilized in food additives,5 water
purification,6 clinical drugs,7 and packing materials.8 As a non-
essential metal ion for the proper functioning of human body,
the wide distribution of Al3+ in the air, water, and soil makes peo-
ple exposed to it.9 However, when the accumulation of Al3+ reaches
high levels in human body, it can cause damage to kidney, immune
system, and central nervous system,10–12 leading to various dis-
eases like Alzheimer’s disease,13 Parkinson’s disease,14
encephalopathy,15 myopathy,16 osteoporosis,17 and even to the risk
of breast cancer.18 According to the World Health Organization
(WHO) report, the average daily human intake of aluminum is
around 3–10 mg with a weekly tolerable dietary intake at 7 mg/
kg of body weight.19 Additionally, the WHO has limited the con-
centration of Al3+ in drinking water to 7.41 mM.20 Thus, it is highly
desirable and necessary to develop a simple and sensitive method
for detecting and controlling Al3+ concentrations in environmental
systems and biological assays.21
destructive properties compared to traditional analytical methods
for the detection of metal ions, fluorescence detection has been
widely used in enormous fields, such as analytical chemistry,22
environmental biology,23 biochemistry,24 and medical science.25
Nevertheless, owing to the poor coordination ability, strong hydra-
tion ability, and lack of spectroscopic properties of Al3+, it is more
difficult to develop fluorescent probes for sensing Al3+ compared
with recognizing transition metal ions.26–28 As a hard acid, Al3+
prefers to coordinate with hard-base donor sites like N and O
atom.29,30 Moreover, Schiff-bases are well known as hard bases
which can provide nitrogen-oxygen-rich coordination environ-
ments for Al3+ 31,32
Therefore, Schiff-bases can be designed and
.
synthesized as Al3+ fluorescent probes.33–35
Owing to their excellent spectroscopic and pharmacological
properties, chromone-based compounds have been widely applied
in antitumoral agents, cardio cerebrovascular drugs, and fluo-
rophores.36 In recent years, there have been a great many success-
ful fluorescent probes which are developed for sensing various
metal ions based on photoinduced electron-transfer (PET),37
intramolecular charge transfer (ICT),38 fluorescence resonance
energy transfer (FRET),39 excited state intramolecular proton
transfer (ESIPT),40 and excimer mechanism,41 but the ones
based on the mechanism of C@N isomerization are relatively
few.42 Bearing these in mind, we have designed and synthesized
⇑
Corresponding author. Tel.: +86 931 8913515; fax: +86 931 8912582.
E-mail address: yangzy@lzu.edu.cn (Z.-y. Yang).
http://dx.doi.org/10.1016/j.tetlet.2016.09.058
0040-4039/Ó 2016 Elsevier Ltd. All rights reserved.

C.-r. Li et al. / Tetrahedron Letters 57 (2016) 4898–4904
4899
a
chromone-derived Schiff-base ligand called bis(6-hydroxy-
performed using a VarioEL Cube V1.2.1 analyzer. UV–vis absorp-
tion spectra were collected on a Shimadzu UV-240 spectropho-
tometer at 298 K. Fluorescence measurements were performed
on a Hitachi RF-5301 fluorimeter equipped with quartz cuvettes
of 1 cm path length at 298 K. Melting points were determined on
a Beijing XT4-100x microscopic melting point apparatus without
correction.
chromone-3-methylidene)-o-phenylenediimine (1) that was eval-
uated as an Al3+ fluorescent probe based on PET phenomenon
and C@N isomerization mechanism (Scheme 1). On a basis of the
experimental results, it was found that this fluorescent probe 1 dis-
played good selectivity and high sensitivity towards Al3+ over other
common environmentally and biologically important metal ions,
and a significant enhancement in fluorescence emission intensity
at 459 nm with a slight blue-shift was observed in the presence
of Al3+. Hence, this probe 1 could be utilized for detecting and rec-
ognizing Al3+ in the presence of most metal ions in the
environment.
Synthesis
Hydroquinone diacetate (2), acetylquinol (3) and 6-hydroxy-3-
formylchromone (4) were synthesized according to the methods
reported.43 The synthetic route of compound 1 was shown in
Scheme 1.
Experimental
Materials
Synthesis of compound 1 (bis(6-hydroxychromone-3-
methylidene)-o-phenylenediimine)
A solution of o-phenylenediamine (5) (0.108 g, 1 mmol) in abso-
lute ethanol (20 mL) was added dropwise to another solution con-
taining 6-hydroxy-3-formylchromone (4) (0.380 g, 2 mmol) in
absolute ethanol (30 mL) under stirring. The mixture was refluxed
for 24 h under stirring, during which time an orange yellow solid
was separated out from the solution. After the reaction was com-
pleted, the reaction mixture was cooled to room temperature. Then
the solid was filtered under reduced pressure, washing five times
with absolute ethanol (10 mL). The obtained crude product was
recrystallized from absolute ethanol (30 mL) to furnish the desired
product 1 as an orange yellow powder (Scheme 1). Yield: 0.10 g
(22.12%). Mp at least 300 °C, 1H NMR (400 MHz, DMSO-d6)
(Fig. S1): d (ppm): 12.50 (s, 1H, –OH), 10.05 (s, 1H, –OH), 9.28 (s,
1H, H4), 8.41 (s, 1H, H8), 7.70–7.60 (m, 4H, H9,10,11,12), 7.54 (d,
1H, J = 3.2 Hz, H1), 7.41 (d, 1H, J = 8.0 Hz, H3), 7.35–7.15 (m, 5H,
Hydroquinone, acetic anhydride, concentrated sulfuric acid,
aluminum chloride, phosphorus oxychloride, o-phenylenediamine,
absolute ethanol, N,N-dimethyl formamide (DMF), dimethyl sul-
foxide (DMSO), and cationic salts such as Al(NO3)3, Ba(OAc)2, Ca
(NO3)2, Cd(OAc)2, Co(OAc)2, Cr(NO3)3, Cu(NO3)2, Fe(NO3)2, Fe
(NO3)3, K(OAc), Mg(NO3)2, Mn(NO3)2, NaClO4, Ni(NO3)2, Pb(OAc)2,
and Zn(NO3)2 were obtained from commercial suppliers, and used
as received without further purification. Stock solution of com-
pound 1 (10 mM) was prepared in dimethyl sulfoxide (DMSO).
Stock solutions (10 mM) of the salts of Al3+, Ba2+, Ca2+, Cd2+, Co2+
,
Cr3+, Cu2+, Fe2+, Fe3+, K+, Mg2+, Mn2+, Na+, Ni2+, Pb2+, and Zn2+ in
absolute ethanol were also prepared. Distilled water was used
throughout all experiments.
Apparatus
H
2,5,6,7, –CH@N–), 5.19 (s, 1H, –CH@N–). 13C NMR (100 MHz,
1H NMR spectra and 13C NMR spectra were recorded on the
JNM-ECS instruments at 400 MHz and 100 MHz using TMS
(tetramethylsilane) as an internal standard and DMSO-d6 as a sol-
vent. Mass spectra were obtained on high resolution mass spec-
trometer (LTQ-Obitrap-ETD) in ethanol. Elemental analyses were
DMSO-d6) (Fig. S2): d (ppm): 175.99, 175.16, 158.13, 156.10,
155.99, 155.56, 155.48, 149.97, 146.11, 143.37, 135.91, 125.12,
125.06, 124.51, 124.32, 120.56, 120.46, 120.13, 119.80, 118.29,
116.41, 113.87, 111.65, 108.60, 108.49, 108.06. HRMS (ESI)
(Fig. S3): m/z [M+H+]+ calcd 453.4024, found 453.1076; [M+Na+]+
Scheme 1. Synthetic route of compound 1.

4900
C.-r. Li et al. / Tetrahedron Letters 57 (2016) 4898–4904
calcd 475.3842, found 475.0894. Anal. Calcd for C26H16N2O6: C,
69.02; H, 3.56; N, 6.19; O, 21.23. found: C, 68.03; H, 3.48; N,
7.44; O, 21.05.
General information
Test solutions were prepared by placing 10 lL of the probe
stock solution into cuvettes, adding an appropriate aliquot of each
metal ion stock, and diluting the solution to 2 mL with ethanol. The
mixed solution was shaken well and kept for 10 min before the flu-
orescence emission spectra were measured. For all fluorescence
measurements of compound 1, the excitation wavelength was set
at 375 nm, and the emission wavelength was from 380 nm to
650 nm. In the presence of Al3+, two special peaks at 432 nm and
459 nm were observed in the fluorescence emission spectra of 1,
and the fluorescence emission intensity at 459 nm was recorded
in some experiments. Additionally, the excitation and emission slit
widths were 5 nm and 3 nm, respectively.
The binding constant value for complex 1-Al3+ was determined
on the basis of the nonlinear filtting of the fluorescence titration
curve assuming a 1:1 stoichiometry by the Benesi–Hildebrand
method (1):44,45
Figure 1. Change in UV–vis absorption spectra of 1 (100 lM) upon addition of
increasing amounts of Al3+ (0.2, 0.4, 0.6, 0.8, 1.0, 1.2, 1.4, 1.6, 1.8, 2.0, 2.4, 2.8, 3.2,
3.6, 4.0 equiv, respectively) in ethanol.
1
1
1
¼
þ
ð1Þ
could be utilized as an Al3+ fluorescent probe for real-time detec-
tion, the time effect on the fluorescence emission spectra of com-
pound 1 in the presence of 1.0 equiv of Al3+ was explored in
ethanol and the emission intensity at 459 nm was recorded. As
shown in Figure S4, the fluorescence emission intensity at
459 nm enhanced rapidly and stored 83.55% within 5 min. Then
this fluorescence intensity increased much less in the next 5 min,
and 91.71% of fluorescence emission was stored within 10 min.
However, almost no fluorescence change was observed with more
reaction time (Fig. S4), which indicated that the fluorescence
response of our compound 1 to Al3+ was fast so that 1 could be
used as an Al3+ fluorescent probe for real-time detection. As a
result, the fluorescence emission spectra were recorded after
10 min in the following experiments.
KðFmax ꢀ FminÞ½Al3þꢁ
F ꢀ Fmin
Fmax ꢀ Fmin
where Fmin, F, and Fmax are the emission intensities of the
organic moiety considered in the absence of aluminum ion, at an
intermediate aluminum concentration, and at a concentration of
complete interaction, respectively, and where K is the binding con-
stant concentration.
The detection limit was estimated from the fluorescence titra-
tion. The emission intensity of compound 1 without any anion
was measured to determine the S/N ratios46,47, and the standard
deviation of blank measurements was calculated. The detection
limit was calculated based on 3 ꢂ
rblank/k, where rblank is the stan-
dard deviation of the blank solution and k is the slope of the cali-
bration plot.
Selectivity of compound 1 towards Al3+ over other metal ions
Results and discussion
Owing to the poor solubility of compound 1 in pure water, we
carried out the UV–vis absorption spectra and fluorescence emis-
sion spectra of 1 in the absence and presence of metal ions in etha-
nol solution.
Then the fluorescence responses of compound 1 to a variety of
metal ions (Al3+, Ba2+, Ca2+, Cd2+, Co2+, Cr3+, Cu2+, Fe2+, Fe3+, K+,
Mg2+, Mn2+, Na+, Ni2+, Pb2+, Zn2+) were conducted by adding
1 equiv of Al3+ and 5 equiv of other metal ions to the ethanol solu-
tion of 1 respectively. As can be seen from Figure 2, the free 1 dis-
played a relatively weak emission band at 499 nm, and two
intensive peaks centered at 432 nm and 459 nm with a shoulder
at 410 nm were observed and the fluorescence emission intensity
UV–vis titration of compound 1 with increasing concentrations
of Al3+
at 459 nm increased by about 30.91-fold in the presence of Al3+
.
Firstly, UV–vis titration spectra of compound 1 upon addition of
various concentrations of Al3+ were carried out in ethanol. As illus-
trated in Figure 1, the compound 1 in the absence of Al3+ displayed
a weak absorption band centered at 209 nm, which was probably
assignable to chromone moiety. However, the addition of increas-
ing concentrations of Al3+ to the ethanol solution of compound 1
induced gradual enhancement in this band with a slight red-shift
to 212 nm (Fig. 1). These results indicated that the chromone moi-
ety in compound 1 participated in the coordination upon complex-
Nevertheless, other metal ions investigated induced nearly no
changes in the fluorescence emission spectra of compound 1
except for Ba2+ and Zn2+, which also showed negligible effects on
the fluorescence emission of
1 and gave little fluorescence
enhancement (Fig. 2a), but the fluorescence intensity at 459 nm
increased only by 6.49-fold and 5.68-fold, respectively (Fig. 2b).
Therefore, the selectivity of this compound 1 was high for sensing
and recognizing Al3+ over other metal ions.
ation of 1 with Al3+
.
Competition experiments were carried out to further confirm
the selectivity of compound 1 for Al3+ in the presence of other com-
mon coexisting metal ions. For this purpose, fluorescence emission
intensity at 459 nm was recorded by adding 5 equiv of different
Effect of time on the fluorescence response of compound 1 to
Al3+
metal ions (Ba2+, Ca2+, Cd2+, Co2+, Cr3+, Cu2+, Fe2+, Fe3+, K+, Mg2+
,
Mn2+, Na+, Ni2+, Pb2+, Zn2+) to the mixture of 1 and 1 equiv of
Al3+ in ethanol. As depicted in Figure 3, Co2+, Cu2+, Fe2+, Fe3+, and
Ni2+ led to a decrease in fluorescence to a certain degree, which
Fast fluorescence response is an important peculiarity for a flu-
orescent probe to detect metal ions. In order to determine if our
designed compound 1 had fast fluorescence response to Al3+ and

C.-r. Li et al. / Tetrahedron Letters 57 (2016) 4898–4904
4901
Figure 2. (a) Changes in fluorescence emission spectra of 1 (50
(b) The fluorescence intensities at 459 nm of 1 (50
l
M) in ethanol by adding Al3+ (1 equiv) and other respective metal ions (5 equiv) with an excitation at 375 nm.
l
M) in the presence of Al3+ (1 equiv) and other respective metal ions (5 equiv) under the identical conditions in ethanol.
((1) 1; (2) 1 + Al3+; (3) 1 + Ba2+; (4) 1 + Ca2+; (5) 1 + Cd2+; (6) 1 + Co2+; (7) 1 + Cr3+; (8) 1 + Cu2+; (9) 1 + Fe2+; (10) 1 + Fe3+; (11) 1 + K+; (12) 1 + Mg2+; (13) 1 + Mn2+; (14) 1 + Na+;
(15) 1 + Ni2+; (16) 1 + Pb2+; (17) 1 + Zn2+) (kex = 375 nm, slit: 5.0/3.0 nm).
in ethanol and the results were illustrated in Figure 4. Compound
1 in the absence of Al3+ showed a weak emission band at
499 nm, and gradual enhancement in fluorescence emission inten-
sity at 432 nm and 459 nm with a shoulder at 410 nm was
observed with increasing Al3+ equivalences. The emission intensity
at 459 nm was probably assigned to the emission of the chromone
moiety, which confirmed that the chromone moiety in compound
1 took part in the coordination with Al3+. Moreover, when 1.0 equiv
of Al3+ was added to the solution of 1, the fluorescence intensity at
459 nm reached a plateau and hardly changed with further addi-
tion of Al3+ (Fig. 4), which suggested that this compound 1 most
likely formed a stable fluorescent complex with Al3+ and a 1:1
stoichiometry was obtained between them. In addition, a linear
relationship between the fluorescence intensity at 459 nm and
Al3+ concentration was obtained over the range 0–1.0
lM
(R2 = 0.9904), and the fluorescence enhancement could be easily
detected in this concentration range (Fig. 5). On a basis of the
fluorescence titration experiments above, the limit of detection
(LOD) of compound 1 for sensing Al3+ was calculated based on
Figure 3. Characteristic fluorescence responses at 459 nm of 1 (50 l
M) to Al3+
3 ꢂ
r
blank/k and it was found to be 1.05 ꢂ 10ꢀ7 M (Fig. S5), which
(1 equiv) in the presence of other respective metal ions (5 equiv) under the identical
was lower than the tolerable Al3+ concentration in drinking water
(7.41 mM) set by WHO20. From the results above, it was concluded
that compound 1 showed high sensitivity towards Al3+ and could
be utilized for detecting and monitoring Al3+ in environmental
and biological systems.
conditions in ethanol. ((1) Al3+; (2) Al3+ + Ba2+; (3) Al3+ + Ca2+; (4) Al3+ + Cd2+; (5)
Al3+ + Co2+ (6) Al3+ + Cr3+ (7) Al3+ + Cu2+ (8) Al3+ + Fe2+ (9) Al3+ + Fe3+
; ; ; ; ; (10)
Al3+ + K+; (11) Al3+ + Mg2+; (12) Al3+ + Mn2+; (13) Al3+ + Na+; (14) Al3+ + Ni2+; (15)
Al3+ + Pb2+; (16) Al3+ + Zn2+) (kex = 375 nm, slit: 5.0/3.0 nm).
was attributed to the magnetic properties of these five metal ions
that were induced by the electron and energy transfer processes
from ligand to metal ions.48–50 However, no significant changes
in the fluorescence enhancement were observed in the presence
of other metal ions investigated in comparison with that obtained
in the presence of Al3+ alone under identical conditions (Fig. 3),
which demonstrated that most metal ions did not interfere with
Al3+ detection by compound 1, and 1 had good selectivity for Al3+
in the presence of most metal ions.
Binding stoichiometry between compound 1 and Al3+
A Job’s plot was conducted to explore the binding stoichiometry
between compound 1 and Al3+. During this experimental process,
the total concentration of 1 and Al3+ was kept constant at
100 l
M and the molar ratio of Al3+ in complex 1-Al3+ changed from
0.1 to 0.9. As can be seen from Fig. 6, the fluorescence emission
intensity at 459 nm reached maximum at the molar ratio of 0.5,
establishing a 1:1 binding stoichiometry between compound 1
and Al3+. Furthermore, the ESI-MS spectra of 1 and Al3+ in ethanol
Fluorescence titration of compound 1 in the presence of
increasing concentrations of Al3+
showed
a peak at m/z 477.8641 that was assignable to
[1+Al3+ꢀ2H+]+ (calcd m/z 477.3601) (Fig. S6), which further gave
solid evidence for the formation of a 1:1 complex between com-
pound 1 and Al3+. Based on the 1:1 binding stoichiometry which
The change in fluorescence emission spectra of compound 1
upon addition of increasing concentrations of Al3+ was discussed

4902
C.-r. Li et al. / Tetrahedron Letters 57 (2016) 4898–4904
Figure 4. Fluorescence emission spectra of 1 (50
l
M) upon addition of increasing amounts of Al3+ (0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, 1.2, 1.4, 1.6, 1.8, 2.0 equiv,
respectively) in ethanol with an excitation at 375 nm. Insert: A calibration curve of the fluorescence emission intensity at 459 nm versus the equivalence of Al3+ over the
range 0–2.0.
of Al(NO3)3ꢃ9H2O was added to the solution of compound 1, the
proton signal of one hydroxy group was shifted downfield from d
10.052 ppm to d 10.122 ppm and that of another hydroxy group
was shifted upfield from d 12.503 ppm to d 12.270 ppm with a sig-
nificant decrease, respectively, which indicated that one
intramolecular hydrogen bond was formed between these two
hydroxy groups upon complexation of 1 with Al3+. Simultaneously,
the signal of the eighth proton H8 of the chromone moiety (at d
8.407 ppm) and the proton signal of the azomethine group (at d
5.192 ppm) were shifted downfield to
5.207 ppm, respectively. However, nearly no spectral changes were
obtained in other proton signals in the presence of 1.0 equiv of Al3+
d 8.429 ppm and d
,
suggesting that two oxygen atoms of the carbonyl groups from two
Figure 5. Fluorescence emission change of 1 (50 lM) upon addition of various
concentrations of Al3+ (0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1.0
ethanol with an excitation at 375 nm.
lM, respectively) in
was determined by fluorescence titration experiments, Job’s plot
and ESI-MS spectra, the binding constant (K) of compound 1 with
Al3+ was calculated from fluorescence titration spectra using
the Benesi–Hildebrand Eq. (1), and the result was found as
1.13 ꢂ 104 Mꢀ1 (Fig. S7), which was within the range
103–109 Mꢀ1 of those reported Al3+ fluorescent probes.51–53
Binding mode between compound 1 and Al3+
In order to get insight into the binding mode between com-
pound 1 and Al3+ 1H NMR titration experiments were studied in
,
DMSO-d6 and the results are shown in Figure S8. When 1.0 equiv
Figure 6. Job’s plot for determining the stoichiometry between 1 and Al3+ in
ethanol (XAl = [Al3+]/([Al3+] + [1]), the total concentration of 1 and Al3+ was 100
lM).

C.-r. Li et al. / Tetrahedron Letters 57 (2016) 4898–4904
4903
Scheme 2. Proposed binding mechanism for the response of 1 to Al3+
.
chromone moieties and two nitrogen atoms of the azomethine
groups in compound 1 took part in the coordination with Al3+
and formed a 1:1 complex (Scheme 2), which was consistent well
with the UV–vis titration spectra, fluorescence titration spectra,
Job’s plot, and ESI-MS spectra. Moreover, with further addition of
Al(NO3)3ꢃ9H2O to 2.0 equiv, all of the proton signals in compound
1 showed negligible spectra changes (Fig. S8), which proved the
complexation of 1 with Al3+, which was determined by UV–vis
titration spectra, fluorescence titration spectra, Job’s plot, ESI-MS
spectra, and 1H NMR titration experiments. Therefore, this probe
1 could be utilized for detecting and monitoring Al3+ in environ-
mental and biological systems and might accelerate the develop-
ment of other novel chromone-derived fluorescent probes for the
detection of other metal ions.
1:1 binding stoichiometry between compound 1 and Al3+
.
Based on the results above, the proposed binding mechanism
for the fluorescence response of compound 1 to Al3+ was discussed.
As shown in Scheme 2, the fluorescence emission of free 1 was
nearly quenched and it was due to the photoinduced electron-
transfer (PET) phenomenon that was caused by lone pair electron
from Schiff-base nitrogen atom to the chromone moiety and the
C@N isomerization process at the excited state. Nevertheless,
when Al3+ was treated with compound 1, two oxygen atoms of
the carbonyl groups from two chromone moieties and two nitro-
gen atoms of the azomethine groups in 1 participated in the coor-
dination with Al3+ and formed a 1:1 complex. Therefore, the
fluorescence emission was stored by inhibiting the PET phe-
nomenon.54–56 Simultaneously, the process of the C@N isomeriza-
tion at the excited state was restricted upon complexation of 1
with Al3+42,51,57 As a result, the fluorescence emission of compound
1 centered at 459 nm enhanced significantly in the presence of Al3+
(Scheme 2).
Acknowledgments
This work is supported by the National Natural Science Founda-
tion of China (81171337). Gansu NSF (1308RJZA115).
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.tetlet.2016.09.
058.
References and notes
1. Robinson, G. H. Chem. Eng. News 2003, 81, 54.
2. Exley, C. J. Inorg. Biochem. 2005, 99, 1747–1748.
3. Kure, E. H.; Sæbø, M.; Stangeland, A. M.; Hamfjord, J.; Hytterød, S.; Heggenes, J.;
Lydersen, E. Aquat. Toxicol. 2013, 138–139, 98–104.
4. Wang, Z. W.; Ren, J. L.; Zhang, G. L.; Liu, S. M.; Zhang, X. Z.; Liu, Z.; Zhang, J.
Estuar. Coast. Shelf. Sci. 2015, 153, 86–95.
5. Yokel, R. A.; Florence, R. L. Toxicology 2006, 227, 86–93.
6. Wang, W. D.; Li, H.; Ding, Z. Z.; Wang, X. C. J. Environ. Sci.-China 2011, 23, 1079–
1085.
Conclusion
7. Jayme, C. C.; Calori, I. R.; Tedesco, A. C. Spectrochim. Acta, Part A 2016, 153, 178–
183.
In conclusions, we designed and synthesized a chromone-
derived Schiff-base ligand 1 as an Al3+ fluorescent probe. This
probe 1 had good selectivity and high sensitivity for Al3+ in the
presence of most metal ions that they did not interfere with Al3+
detection by 1, for the detection limit of this probe 1 for sensing
Al3+ could reach 1.05 ꢂ 10ꢀ7 M. Furthermore, the fluorescence
emission intensity of 1 at 459 nm increased by about 30.91-fold
in the presence of 1 equiv of Al3+, which was attributed to the inhi-
bition of photoinduced electron-transfer (PET) phenomenon and
C@N isomerization process at the excited state, and the fluores-
cence response of this probe 1 to Al3+ was fast so that 1 could be
used to sense Al3+ for real-time detection. In addition, two oxygen
atoms of the carbonyl groups from two chromone moieties and
two nitrogen atoms of the azomethine groups in probe 1 took part
in the coordination with Al3+ and formed a 1:1 complex upon
8. Nunes, M. A.; Costa, A. S. G.; Barreira, J. C. M.; Vinha, A. F.; Alves, R. C.; Rocha, A.;
Oliveira, M. B. P. P. LWT-Food Sci. Technol. 2016, 65, 70–78.
9. Hagvall, K.; Persson, P.; Karlsson, T. Chem. Geol. 2015, 417, 32–43.
10. Zhang, J. H.; Luo, J. L.; Yu, H. X.; Bai, C. S.; Han, Y. F.; Xia, S. L.; Li, Y. F. J. Northeast
Agric. Univ. 2012, 19, 83–86.
11. Ward, R. J. S.; McCrohan, C. R.; White, K. N. Aquat. Toxicol. 2006, 77, 222–228.
12. Ebina, Y.; Okada, S.; Hamazaki, S.; Midorikawa, O. Toxicol. Appl. Pharm. 1984,
75, 211–218.
13. Bondy, S. C. Neurotoxicology 2016, 52, 222–229.
14. Mendez-Alvarez, E.; Soto-Otero, R.; Hermida-Ameijeiras, A.; Lopez-Real, A. M.;
Labandeira-Garcia, J. L. BBA-Mol. Basis. Dis. 2002, 1586, 155–168.
15. Arieff, A. I. Am. J. Kidney Dis. 1985, 6, 317–321.
16. Ottenheijm, C. A. C.; Hooijman, P.; DeChene, E. T.; Stienen, G. J.; Beggs, A. H.;
Granzier, H. J. Struct. Biol. 2010, 170, 334–343.
17. Sun, X. D.; Cao, Z.; Zhang, Q. Y.; Liu, S. M.; Xu, F. B.; Che, J. F.; Zhu, Y. Z.; Li, Y. F.;
Pan, C. Y.; Liang, W. N. Food Chem. Toxicol. 2015, 86, 154–162.
18. Darbre, P. D.; Mannello, F.; Exley, C. J. Inorg. Biochem. 2013, 128, 257–261.
19. Valeur, B.; Leray, I. Coord. Chem. Rev. 2000, 205, 3–40.

4904
C.-r. Li et al. / Tetrahedron Letters 57 (2016) 4898–4904
20. Krejpcio, Z.; Wojciak, R. W. Pol. J. Environ. Stud. 2002, 11, 251–254.
21. Eleckova, L.; Alexovic, M.; Kuchar, J.; Balogh, I. S.; Andruch, V. Talanta 2015,
133, 27–33.
22. Zhang, Y. H.; Yan, Y. Y.; Chen, S. Y.; Gao, Z. N.; Xu, H. Bioorg. Med. Chem. Lett.
2014, 24, 5373–5376.
39. Zhou, Y.; Chu, K. H.; Zhen, H. F.; Fang, Y.; Yao, C. Spectrochim. Acta, Part A 2013,
106, 197–202.
40. Saluja, P.; Sharma, H.; Kaur, N.; Singh, N.; Jang, D. O. Tetrahedron 2012, 68,
2289–2293.
41. Yang, Y.; Gou, X. J.; Blecha, J.; Cao, H. S. Tetrahedron Lett. 2010, 51, 3422–3425.
42. Liu, Z. D.; Xu, H. J.; Chen, S. S.; Sheng, L. Q.; Zhang, H.; Hao, F. Y.; Su, P. F.; Wang,
W. L. Spectrochim. Acta, Part A 2015, 149, 83–89.
23. Hosseini, M.; Ghafarloo, A.; Ganjali, M. R.; Faridbod, F.; Norouzi, P.; Niasari, M.
S. Sens. Actuators, B 2014, 198, 411–415.
24. Kambam, S.; Wang, B. H.; Wang, F.; Wang, Y.; Chen, H. Y.; Yin, J.; Chen, X. Q.
Sens. Actuators, B 2015, 209, 1005–1010.
43. Wang, B. D.; Yang, Z. Y.; Zhang, D. W.; Wang, Y. Spectrochim. Acta, Part A 2006,
63, 213–219.
25. Wang, H. M.; Mu, L. X.; She, G. W.; Xu, H. T.; Shi, W. S. Sens. Actuators, B 2014,
203, 774–781.
44. Jang, Y. K.; Nam, U. C.; Kwon, H. L.; Hwang, I. H.; Kim, C. Dyes Pigm. 2013, 99, 6–
13.
26. Chemate, S.; Sekar, N. Sens. Actuators, B 2015, 220, 1196–1204.
27. Hu, S. L.; Song, J. J.; Wu, G. Y.; Cheng, C. X.; Gao, Q. Spectrochim. Acta, Part A
2015, 136, 1188–1194.
28. Ye, X. P.; Sun, S. B.; Li, Y. D.; Zhi, L. H.; Wu, W. N.; Wang, Y. J. Lumin. 2014, 155,
180–184.
29. Bandiera, J.; Dufaux, M.; Taarit, Y. B. Appl. Catal., A 1997, 148, 283–300.
30. Park, H. M.; Oh, B. N.; Kim, J. H.; Qiong, W.; Hwang, I. H.; Jung, K. D.; Kim, C.;
Kim, J. Tetrahedron Lett. 2011, 52, 5581–5584.
31. Tiwari, K.; Mishra, M.; Singh, V. P. RSC Adv. 2013, 3, 12124–12132.
32. Guha, S.; Lohar, S.; Sahana, A.; Banerjee, A.; Safin, D. A.; Babashkina, M. G.;
Mitoraj, M. P.; Bolte, M.; Garcia, Y.; Mukhopadhyay, S. K.; Das, D. Dalton Trans.
2013, 42, 10198–10207.
45. Jia, T. J.; Cao, W.; Zheng, X. J.; Jin, L. P. Tetrahedron Lett. 2013, 54, 3471–3474.
46. Long, G. L.; Winefordner, J. D. Anal. Chem. 1983, 55, 712A–724A.
47. Lohani, C. R.; Kim, J. M.; Chung, S. Y.; Yoon, J.; Lee, K. H. Analyst 2010, 135,
2079–2084.
48. Dinca, A. S.; Maxim, C.; Cojocaru, B.; Lloret, F.; Julve, M.; Andruh, M. Inorg. Chim.
Acta 2016, 440, 148–153.
49. Xi, G. X.; Xi, Y. B. Mater. Lett. 2016, 164, 444–448.
50. Uysal, S.; Koc, Z. E. J. Mol. Struct. 2016, 1109, 119–126.
51. Torawane, P.; Tayade, K.; Bothra, S.; Sahoo, S. K.; Singh, N.; Borse, A.; Kuwar, A.
Sens. Actuators, B 2016, 222, 562–566.
52. Yu, F.; Hou, L. J.; Qin, L. Y.; Chao, J. B.; Wang, Y.; Jin, W. J. J. J. Photochem.
Photobiol., A 2016, 315, 8–13.
33. Anand, T.; Sivaraman, G.; Mahesh, A.; Chellappa, D. Anal. Chim. Acta 2015, 853,
596–601.
34. Guo, A. L.; Zhu, R. T.; Ren, Y. H.; Dong, J. L.; Feng, L. H. Spectrochim. Acta, Part A
2016, 153, 530–534.
35. Qin, J. C.; Cheng, X. Y.; Fang, R.; Wang, M. F.; Yang, Z. Y.; Li, T. R.; Li, Y.
Spectrochim. Acta, Part A 2016, 152, 352–357.
36. Cummings, R. T.; Dizio, J. P.; Krafft, G. A. Tetrahedron Lett. 1988, 29, 69–72.
37. Erdemir, S.; Kocyigit, O.; Karakurt, S. Sens. Actuators, B 2015, 220, 381–388.
38. Xu, Z. C.; Xiao, Y.; Qian, X. H.; Cui, J. N.; Cui, D. W. Org. Lett. 2005, 7, 889–892.
53. Mukherjee, S.; Mal, P.; Stoeckli-Evans, H. J. Lumin. 2016, 172, 124–130.
54. Wu, Q. Q.; Fang, A. J.; Li, H. T.; Zhang, Y. Y.; Yao, S. Z. Biosens. Bioelectron. 2016,
77, 957–962.
55. Arrigo, A.; Santoro, A.; Puntoriero, F.; Laine, P. P.; Campagna, S. Coord. Chem.
Rev. 2015, 304–305, 109–116.
56. Yanykin, D. V.; Khorobrykh, A. A.; Mamedov, M. D.; Klimov, V. V. J. J. Photochem.
Photobiol., B 2015, 152, 279–285.
57. Li, L.; Liu, F.; Li, H. W. Spectrochim. Acta, Part A 2011, 79, 1688–1692.