Hydrogen bond induced fluorescence recovery of coumarin-based sensor system

Article abstract of DOI:10.1016/j.tetlet.2013.05.034

Two coumarin-type fluorescent sensors were synthesized and their fluorescence response to pH value was investigated. The fluorescence intensity of sensor 3 and sensor 4 is obviously enhanced along with the increase of pH from 7 to 12 and the reduction of

Full text of DOI:10.1016/j.tetlet.2013.05.034

Tetrahedron Letters 54 (2013) 3822–3825
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Hydrogen bond induced fluorescence recovery of coumarin-based
sensor system q
Xiaobo Huang a,b, , Yu Dong b, Qianwen Huang a, Yixiang Cheng b,
⇑
⇑
a College of Chemistry and Materials Engineering, Wenzhou University, Wenzhou 325035, PR China
b Key Lab of Mesoscopic Chemistry of MOE, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
Two coumarin-type fluorescent sensors were synthesized and their fluorescence response to pH value
was investigated. The fluorescence intensity of sensor 3 and sensor 4 is obviously enhanced along with
the increase of pH from 7 to 12 and the reduction of pH value from 8 to 1, respectively. Possible mech-
anism for these fluorescence recovery systems is proposed. Intramolecular hydrogen bond could be
formed under different condition, which blocks electron transferring route from nitrogen atom to fluoro-
phore. The blue fluorescence color change of the two sensory systems could be directly detected by naked
eyes under UV-lamp for pH values.
Received 2 February 2013
Revised 22 April 2013
Accepted 10 May 2013
Available online 17 May 2013
Keywords:
Hydrogen bond
Fluorescence chemosensor
Coumarin
Ó 2013 The Authors. Published by Elsevier Ltd. All rights reserved.
pH detection
Hydrogen bond is a kind of nonbonded interaction that widely
exists in natural world. Its significance has been identified by
chemists, biologists, and physical scientists.1 Hydrogen bond par-
ticipates in numbers of functional activities such as spatial struc-
ture of protein and helical conformation of DNA.2 It also shows
its positive help in new drug design, crystal engineering, and func-
tional material synthesis.3 Hydrogen bond is so attractive and
important that IUPAC published an article in which a novel defini-
tion was recommended for this term in 2011.4
Fluorescence technology has been widely used in chemistry and
biology during the last few years. Because of its sensitivity, selec-
tivity, rapid response, and high spatial resolution via microscopic
imaging,5 chemical sensors that can cause fluorescent change re-
sponse are intensively investigated to monitor metal ions and pH
in cell and animal body.6 There are several reports on hydrogen
bond assisted fluorescent sensors in neutral circumstance.7 But
so far there have been very few works on hydrogen bond induced
fluorescence recovery of sensory system.8 In this Letter, a fluores-
cent sensory system was developed via intramolecular hydrogen
bond formation under alkaline condition.
Coumarin is one of the most used fluorophores in the designing
of fluorescent sensors due to its easy accessibility and high quan-
tum yield in aqueous media. Coumarin-based fluorescence sensor
has been developed for detection of Al3+, Mg2+, Hg2+, Cu2+, Zn2+
,
DNA, and saccharides in the past few years.9 Recently, our group
designed and synthesized several coumarin-based sensors that
could exhibit unique fluorescence response features for the detec-
tion of Mg2+ 10
In order to further explore its potentiality in sensor
.
design, herein we synthesized two novel fluorescent pH sensors
based on hydrogen bond induced fluorescence recovery.
Compound 2 was prepared according to reported procedures
(Scheme 1).11 7-Hydroxy-8-((6-methylpyridin-2-ylimino)methyl)
-4-methyl-coumarin could be synthesized via nucleophilic
addition–elimination reaction of compound 2 and 2-amino-6-
methylpyridine in EtOH, which was immediately reduced by
sodium borohydride to afford 7-hydroxy-8-((6-methylpyridin-2-
ylamino)methyl)-4-methylcoumarin (compound 3) in a two-step
yield of 78.5%. Compound 4 was obtained following the similar
procedures of compound 3.
As shown in Figure 1a, the UV–vis spectra of sensor 3 (10 lM,
MeOH/water = 1:1) exhibited a maximal absorption at 319 nm un-
der neutral condition. As the pH value gradually increased from 7
to 12 in the solution, the maximal absorption peak made an obvi-
ous reduction, and a new peak situated at 374 nm arose simulta-
neously. The maximal absorption showed 55 nm red shift when
pH value changed from 7 to 12 with an isosbestic point at
343.5 nm, which could be attributed to the ionization and isomer-
ization of sensor 3. Figure 1b is the UV–vis spectra of sensor 4,
q
This is an open-access article distributed under the terms of the Creative
Commons Attribution-NonCommercial-No Derivative Works License, which per-
mits non-commercial use, distribution, and reproduction in any medium, provided
the original author and source are credited.
⇑
Corresponding authors. Tel./fax: +86 577 88368280 (X.H.); tel.: +86 25
83685199; fax: +86 25 83317761 (Y.C.).
E-mail addresses: xiaobhuang@wzu.edu.cn (X. Huang), yxcheng@nju.edu.cn (Y.
Cheng).
0040-4039/$ - see front matter Ó 2013 The Authors. Published by Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2013.05.034

X. Huang et al. / Tetrahedron Letters 54 (2013) 3822–3825
3823
a
600
500
400
300
200
100
0
N
6
5
4
3
2
1
NH
HO
O
O
pH=12
pH=7
O
H
HO
O
O
i
HO
O
O
3
7
8
9
10 11 12
pH value
NH
1
2
HO
O
O
4
Scheme 1. Synthesis procedures for sensors 3 and 4. Reagents and conditions: (i)
hexamine, HCl, water, 70–80 °C; (ii) 2-amino-6-methylpyridine, EtOH, reflux; (iii)
NaBH4, THF, 0 °C; (iv) aniline, EtOH, reflux; (v) NaBH4, THF, 0 °C.
400
450
500
550
600
Wavelength(nm)
800
600
400
200
0
which exhibits a main maximum absorption peak at 321 nm and
shows no obvious change with decreasing of pH value from 6 to 1.
Quantum yields of sensors 3 and 4 are determined to be 5% and
7% using the quinine sulfate solution in 0.5 mol/LÀ1 H2SO4
b
5
4
3
2
pH=1
pH=8
(Uf = 55%) as a standard, respectively. The low quantum yields of
these two sensors should be attributed to a typical photoinduced
electron transfer (PET) process, herein, the NH group with lone pair
1
1
2
3
4
5
6
7
pH value
319 nm
a
55 nm red shift
374 nm
pH=7
pH=8
0.3
pH=9
pH=10
pH=11
pH=12
350
400
450
500
550
600
0.2
Wavelength(nm)
Figure 2. (a) The fluorescence change with increased pH value of sensor 3 (from pH
7–12; kex = 365 nm, kem = 453 nm), inset: sigmoidal fitting plot of I/I0 versus pH
value. (b) The fluorescence change with decreased pH value of sensor 4 (from pH 8
to 1; kex = 327 nm, kem = 463 nm), inset: sigmoidal fitting plot of I/I0 versus pH
value.
0.1
0.0
of electrons quenches the fluorescence of these systems.12 The
280 300 320 340 360 380 400 420 440
fluorescence response of sensor 3 to pH value was investigated.
As shown in Figure 2a, sensor 3 (10 lM in MeOH/water, 1:1)
Wavelength(nm)
showed a relatively weak peak at pH 7, which was centered at
437 nm. The fluorescence intensity was obviously enhanced as
high as 5.5-fold with the increased pH value from 7 to 12. More-
over, the maximal emission wavelength displayed a red shift from
437 nm to 453 nm in the fluorescence spectra. We also found that a
distinct fluorescent color change of sensor 3 occurred from pale
blue to deep sky blue upon the change of pH value, indicating that
the fluorescence changing could be detected by naked eyes (Fig. 3).
The possible mechanism of this pH responsive sensory system is
shown in Figure 3. Structure 3A is obtained in alkaline solution,
then intramolecular hydrogen bond could be formed with the help
of one water molecule, which confines the electron transfer from N
atom of the N–H group to the fluorophore of the coumarin group;
another reason is that there exists a dynamic resonance balance
between 3A and 3B and the balance makes intramolecular hydro-
gen bond much more stable than its normal style. Figure 2b shows
the fluorescence intensity of sensor 4 is enhanced with the
decreasing of pH value from 8 to 1 and the maximum emission
wavelength shifts from 442 to 463 nm. As shown in Figure 3, under
acidic conditions, the N–H group of sensor 3 is protonated and the
0.6
b
pH=6
pH=5
pH=4
pH=3
pH=2
pH=1
0.5
0.4
0.3
0.2
0.1
0.0
280
300
320
340
360
380
400
Wavelength(nm)
Figure 1. UV–vis spectra of sensor 3 (a, pH 7–12) and sensor 4 (b, from pH 6 to 1)
on H+.

3824
X. Huang et al. / Tetrahedron Letters 54 (2013) 3822–3825
Co2+, Ni2+, Cu2+, Zn2+, Ag2+, Hg2+, Cd2+, and Pb2+) in MeOH/water
N
N
N
H
O
H
O
(1:1) solution, which is shown in Figure 4a and b. Figure 4a shows
that a slight fluorescence quenching is caused by addition of
1.0 equiv of metal ions with exception for Na+ and K+, which
slightly increase the fluorescence of sensor 3. Figure 4b shows all
the metal ions can lead to slight fluorescence quenching for sensor
4. The reason for the fluorescence quenching effect may be attrib-
uted to the formation of hydroxide that disturbs the balance of
intramolecular hydrogen bond forming process.
In summary, two coumarin-based fluorescent pH sensors 3 and
4 were designed and synthesized. These two coumarin-based sen-
sors display completely opposite fluorescence response to pH value
(pH 11 for sensor 3 and pH 2 for sensor 4). We proposed a possible
mechanism for these fluorescence recovery systems that a dy-
namic resonance balance happens under specified condition,
which favors the formation of intramolecular hydrogen bond,
and then the intramolecular hydrogen bond blocks electron trans-
ferring route from nitrogen atom to fluorophore. The fluorescence
color of sensors 3 and 4 could be detected by naked eyes for direct
visual pH discrimination in a lower concentration under a com-
mercially available UV lamp.
+
OH-
H+
+
NH
N
N
H
H
H
O
H
O
HO
O
O
O
O
O
O
3B
3A
3
H+
OH-
+
NH2
O
NH
HO
O
HO
O
O
4A
4
Figure 3. Hydrogen bond forming process with fluorescence enhancement effect;
the photos were taken under UV-lamp with excitation wavelength at 365 nm in
MeOH/H2O (1:1).
lone pair of the nitrogen atom is engaged, electron transfer does
not take place, and an enhancement of the emission intensity is ob-
served.13 Sensors 3 and 4 exhibit ‘‘turn-on’’ fluorescence response
behaviors under different pH ranges, respectively, which should
be attributed to the same effect: the inhibition of PET processes.13
Competition experiment was conducted in the presence of
1.0 equiv of various metal ions (Na+, Mg2+, K+, Ca2+, Cr3+, Fe3+
,
Acknowledgments
This work was supported by the National Natural Science Foun-
dation of China (Nos. 21074054, 51173078, 21204066) and the
Commonweal Project of Science and Technology Department of
Zhejiang Province (No. 2012C23030).
a
600
500
400
300
200
100
0
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.tetlet.2013.
05.034.
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