A highly selective colorimetric and fluorescent probe for Cu2+ and Hg2+ ions based on a distyryl BODIPY with two bis(1,2,3-triazole)amino receptors

Article abstract of DOI:10.1002/asia.201100598

A new distyryl boron dipyrromethene (BODIPY) with two bis(1,2,3-triazole) amino substituents has been prepared by typical Knoevenagel condensation followed by click reaction. The compound selectively binds to Cu²⁺ and Hg²⁺ ions in CH₃CN/H₂O (1:1 v/v) to give remarkably blueshifted electronic absorption and fluorescence bands as a result of inhibition of the intramolecular charge-transfer process upon binding to these metal ions. The color changes can be easily seen by the naked eye. The binding stoichiometry between this probe and Cu²⁺ ions has been determined to be 1:2 by a Job plot of the fluorescence data with a binding constant of ((6.2±0.6)×10⁹) M^-2. The corresponding value for Hg²⁺ ions is about sixfold smaller.

Full text of DOI:10.1002/asia.201100598

FULL PAPERS
DOI: 10.1002/asia.201100598
A Highly Selective Colorimetric and Fluorescent Probe for Cu2+ and Hg2+
Ions Based on a Distyryl BODIPY with Two Bis(1,2,3-triazole)amino
Receptors**
Wen-Jing Shi, Jian-Yong Liu, and Dennis K. P. Ng*[a]
Abstract: A new distyryl boron dipyr-
romethene (BODIPY) with two
and fluorescence bands as a result of
inhibition of the intramolecular charge-
transfer process upon binding to these
metal ions. The color changes can be
easily seen by the naked eye. The bind-
ing stoichiometry between this probe
and Cu2+ ions has been determined to
be 1:2 by a Job plot of the fluorescence
data with a binding constant of ((6.2ꢀ
0.6)ꢀ109)mꢁ2. The corresponding value
for Hg2+ ions is about sixfold smaller.
bis(1,2,3-triazole)amino
substituents
has been prepared by typical Knoeve-
nagel condensation followed by click
reaction. The compound selectively
binds to Cu2+ and Hg2+ ions in
CH3CN/H2O (1:1 v/v) to give remarka-
bly blueshifted electronic absorption
Keywords: boron dipyrromethene ·
copper · fluorescence · sensors ·
mercury
Introduction
classes of biomacromolecules.[5] By linking two of these
units to an aniline, the resulting bis(1,2,3-triazole)amino
moiety may function as a versatile multidentate ligand for
specific metal ions. Complexation is expected to result in in-
hibition of the intramolecular charge-transfer (ICT) process,
thus leading to remarkable spectral and color changes. To
the best of our knowledge, the use of these click-derived tri-
azole moieties in chemosensors has just emerged and re-
mains little studied.[6]
There has been considerable interest in the development of
selective and sensitive probes for metal ions, particularly
those that are of biological interest and environmental rele-
vance.[1] Cu2+ and Hg2+ ions are two common metal pollu-
tants, the harmful effects of which on living systems have
been well documented. The former is also an essential trace
element in biological systems. As a result, a large number of
chemosensors based on different chromophores with differ-
ent receptors have been developed for the selective detec-
tion of these ions.[2,3] This field of research is still under in-
tensive investigation with the goal of further improving the
performance of these ion-selective probes and extending
their scope of application. We report herein a highly selec-
tive colorimetric and fluorescent sensor that can detect both
of these metal ions even with the naked eye. The probe is
based on a distyryl boron dipyrromethene (BODIPY),
which has a number of advantages, including strong absorp-
tion in the near-infrared (NIR) region, high fluorescence
quantum yield, and high solubility and stability in many sol-
vent systems.[4] The receptor part contains two bis(1,2,3-tria-
zole)amino moieties linked directly to the chromophore.
The 1,2,3-triazole ring formed by click chemistry is a very
useful linker for different components, including different
Results and Discussion
The synthetic route used to prepare this probe is shown in
Scheme 1. Knoevenagel condensation of BODIPY 1[7] with
benzaldehyde 2, which was prepared by formylation of N,N-
dipropargyl aniline with phosphorus oxychloride in N,N-di-
methylformamide (DMF), afforded the distyryl BODIPY 3
in 39% yield. This compound then underwent a typical click
reaction with triethylene glycol substituted azide 4[8] to give
the click-derived probe 5, which was purified by column
chromatography followed by size-exclusion chromatography
with Bio-Beads S-X1 beads.
The electronic absorption spectrum of 5 in CH3CN/H2O
(1:1 v/v; Figure S1 in the Supporting Information) showed
three bands at 327, 418, and 686 nm. The Q band at 686 nm
followed Lambert–Beer law, thereby indicating that the
compound was not significantly aggregated in this solvent
system. The absorption was redshifted by about 50 nm com-
pared with those of distyryl BODIPYs without amino sub-
stituents.[4] This observation suggested the presence of
strong ICT in compound 5.
[a] W.-J. Shi, Dr. J.-Y. Liu, Prof. D. K. P. Ng
Department of Chemistry and Center of Novel Functional Molecules
The Chinese University of Hong Kong
Shatin, N.T., Hong Kong (China)
Fax : (+852)2603-5057
E-mail: dkpn@cuhk.edu.hk
[**] BODIPY=boron dipyrromethene.
Figure 1 shows the change in absorption spectrum of 5
upon the addition of different metal salts in CH3CN/H2O
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/asia.201100598.
196
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Chem. Asian J. 2012, 7, 196 – 200

ably from green to grey–blue
(for Hg2+) or deep blue (for
Cu2+) (Figure S2 in the Sup-
porting
Information).
This
change could be seen easily by
the naked eye.
Similar changes were ob-
served in the fluorescence spec-
tra. As shown in Figure 2, the
emission band was blueshifted
(by 40 nm from 726 to 686 nm)
upon the addition of Hg2+ ions.
The effect of Cu2+ ions is even
more substantial, as shown by
the much stronger, blueshifted
band (by 82 nm from 726 to
644 nm). Again, the color
change could be easily seen by
the naked eye (Figure S2 in the
Supporting Information). Simi-
larly, the other metal ions did
not induce significant effects on
the fluorescence
spectrum.
Based on the fact that the spec-
tral properties of 5 changed re-
markably in the presence of
Hg2+ and Cu2+ ions, but not for
the other metal ions, and the
extent of change was also very
different for Hg2+ and Cu2+
Scheme 1. Synthesis of click-derived probe 5.
Figure 2. Change in fluorescence spectrum of 5 (6 mm) in CH3CN/H2O
(1:1 v/v) upon addition of different metal ions (10 equiv) (lex =620 nm).
Figure 1. Change in absorption spectrum of 5 (6 mm) in CH3CN/H2O (1:1
v/v) upon addition of different metal ions (10 equiv).
ꢁ
(1:1 v/v). The ClO4 salt was used for all of the metal ions
ions, it was clear that compound 5 could serve as a highly se-
lective colorimetric and fluorescent probe for Hg2+ and
Cu2+ ions, which was responsive in the NIR region. The
blue spectral shifts could be ascribed to inhibition of ICT
upon binding to these metal ions.[9]
ꢁ
except Ba2+ and Ni2+ (as the Clꢁ salt), Ag+ (as the NO3
2ꢁ
salt), and Mn2+ (as the SO4 salt). While the effects of most
of the metal ions, including Cd2+, Zn2+, Pb2+, Ba2+, Ag+,
Ni2+, Mn2+, Ca2+, Mg2+, K+, and Na+, were negligible, in-
terestingly, the Q band was significantly blueshifted by 36 or
81 nm (from 686 nm) upon addition of Hg2+ or Cu2+ ions,
respectively. The color of the solution also changed remark-
To further study the binding properties of 5 with Cu2+
and Hg2+ ions, spectroscopic titrations were performed.
Figure 3 shows the change in absorption spectrum of 5 in
Chem. Asian J. 2012, 7, 196 – 200
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www.chemasianj.org
197

D. K. P. Ng et al.
FULL PAPERS
Figure 5. Change in fluorescence intensity at 644 nm of a mixture of 5
(6 mm) and Cu2+ ions (10 equiv) in CH3CN/H2O (1:1 v/v) upon addition
of different metal ions (10 equiv) (lex =620 nm).
Figure 3. Change in absorption spectrum of 5 (6 mm) in CH3CN/H2O (1:1
v/v) upon titration with Cu2+ ions (from 0 to 120 mm).
CH3CN/H2O (1:1 v/v) upon gradual addition of up to
20 equivalents of Cu2+ ions. The Q band at 686 nm shifts to
605 nm and the other absorptions at 418 and 327 nm gradu-
ally reduce in intensity. The binding stoichiometry between
5 and Cu2+ was determined to be 1:2 by a Job plot of the
fluorescence data (Figure S3 in the Supporting Information).
It is reasonable to propose that each of the bis(1,2,3-triazo-
le)amino moieties of 5 binds to a Cu2+ ion to form a bimet-
allic complex, as shown in Figure S4 in the Supporting Infor-
mation. Accordingly, by applying the 1:2 binding equation
derived by Liu et al.,[10] the binding constant (K) was deter-
mined to be ((6.2ꢀ0.6)ꢀ109)mꢁ2 by linear least-squares fit-
ting of the change in absorbance at 605 nm (Figure S5 in the
Supporting Information). The large K value suggests a
strong binding between the two components. The corre-
sponding change in the fluorescence spectrum is shown in
Figure 4. Upon addition of Cu2+ ions, the relatively weak
metal ions to a solution of 5 and Cu2+ ions (10 equiv) in
CH3CN/H2O (1:1 v/v; Figure 5). It can be seen that for all
the metal ions studied the change is insignificant, thus show-
ing that these metal ions cannot displace Cu2+ ions from the
complex. The only exception is Hg2+ ions, which significant-
ly reduce the fluorescence intensity, showing that they can
compete with Cu2+ ions for receptor 5.
Figure 6 shows the change in absorption spectrum of 5 in
CH3CN/H2O (1:1 v/v) upon titration with Hg2+ ions. The ab-
Figure 6. Change in absorption spectrum of 5 (6 mm) in CH3CN/H2O (1:1
v/v) upon titration with Hg2+ ions (from 0 to 120 mm).
sorptions at 686 and 418 nm shifted gradually to 650 and
391 nm, respectively, and the band at 327 nm decreased in
intensity. By monitoring the change in absorbance at 360 nm
and by using a 1:2 binding equation,[10] the binding constant
of 5/Hg2+ was determined to be ((1.1ꢀ0.1)ꢀ109)mꢁ2 (Fig-
ure S6 in the Supporting Information), which was about six-
fold smaller than that for 5/Cu2+. The larger binding con-
stant for 5/Cu2+ is in accordance with the larger spectral
changes induced by Cu2+ ions. The corresponding change in
fluorescence spectrum is shown in Figure 7. The emission
band at 726 nm was blueshifted gradually to 686 nm upon
addition of Hg2+ ions.
Figure 4. Change in fluorescence spectrum of 5 (6 mm) in CH3CN/H2O
(1:1 v/v) upon titration with Cu2+ ions (from 0 to 120 mm) (lex =620 nm).
The inset plots the intensity ratio at 644 and 726 nm versus the concen-
tration of Cu2+ ions.
emission band at 726 nm shifted to 644 nm with a much
stronger intensity.
Competition experiments were performed by monitoring
the change in fluorescence intensity at 644 nm (due to the 5/
Cu2+ complex) upon addition of 10 equivalents of different
Similarly, competition experiments were also carried out
by monitoring the change in fluorescence intensity at
198
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Chem. Asian J. 2012, 7, 196 – 200

Colorimetric and Fluorescent Probe for Cu2+ and Hg2+ Ions
Experimental Section
General
All reactions were performed under an atmosphere of nitrogen. DMF,
pyridine, toluene, and dichloromethane were distilled from barium oxide,
potassium hydroxide, sodium, and calcium hydride, respectively. Deion-
ized water without fluorescent impurities was used for the spectroscopic
measurements. Chromatographic purifications were performed on silica-
gel (Macherey–Nagel 230–400 mesh) columns with the indicated eluents.
Size-exclusion chromatography was carried out on Bio-Beads S-X1 beads
(200–400 mesh) with tetrahydrofuran (THF) as the eluent. All other sol-
vents and reagents were of analytical grade and used as received.
BODIPY 1[7] and azide 4[8] were prepared as described.
1H and 13C{1H} NMR spectra were recorded on a Bruker AVANCE III
400 spectrometer (1H, 400; 13C, 100.6 MHz) in CDCl3. Spectra were refer-
enced internally by using the residual solvent (1H: d=7.26 ppm) or sol-
vent (13C: d=77.2 ppm) resonances relative to SiMe4. Electrospray ioni-
zation (ESI) mass spectra were recorded on a Thermo Finnigan MAT 95
XL mass spectrometer. Elemental analyses were performed by the
Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences,
China.
Figure 7. Change in fluorescence spectrum of 5 (6 mm) in CH3CN/H2O
(1:1 v/v) upon titration with Hg2+ ions (from 0 to 120 mm) (lex =664 nm).
The inset plots the intensity ratio at 686 and 726 nm versus the concen-
tration of Hg2+ ions.
Electronic absorption and steady-state fluorescence spectra were record-
ed on a Cary 5G UV/Vis/NIR spectrophotometer and a Hitachi F-4500
spectrofluorometer, respectively. Stock solutions of compound 5 (2 mm)
and the perchlorate salts of Hg2+, Zn2+, Cd2+, Pb2+, Cu2+, Ca2+, Mg2+
,
K+, and Na+ (all in 6 mm) in CH3CN and NiCl2·6H2O (or Ni-
(NO3)2·6H2O), MnSO4·H2O, AgNO3, and BaCl2·2H2O (or Ba(NO3)2) (all
N
ACHTUNGTRENNUNG
in 6 mm) in deionized water were prepared. All measurements were
taken on solutions with 6 mm of compound 5 and various concentrations
of metal salts in CH3CN/H2O (1:1 v/v).
Determination of Binding Constants (K)
The values of K were determined by linear least-squares analysis of the
electronic absorption data by using Equation (1) for 1:2 host–guest com-
plexes:[10]
Figure 8. Change in fluorescence intensity at 686 nm of a mixture of 5
(6 mm) and Hg2+ ions (10 equiv) in CH3CN/H2O (1:1 v/v) upon addition
of different metal ions (10 equiv) (lex =664 nm).
2
½Hꢂ0½Gꢂ0
DA
1
½Gꢂ0ð½Gꢂ0þ4½Hꢂ0Þ
þ
Dea
ð1Þ
¼
DeaK
686 nm (due to the 5/Hg2+ complex) upon addition of
10 equivalents of different metal ions to a solution of 5 and
Hg2+ ions (10 equiv) in CH3CN/H2O (1:1 v/v; Figure 8). It
can be seen that none of the metal ions exert virtually any
effect on the fluorescence intensity. It is worth mentioning
in which [H]0 and [G]0 are the initial concentrations of the host and
guest, respectively, and DA and Dea denote changes in the absorbance
and molar absorption coefficient, respectively, of the host upon complex-
ation with the guest. The binding constant (K) of each complex was de-
2
termined from the linear plot of [H]0[G]0 /DA against [G]0([G]0+4[H]0).
N,N-Dipropargylaniline[11]
that, in this study, the NO3 instead of the Clꢁ salts of Ba2+
ꢁ
A mixture of aniline (1.68 g, 18.0 mmol), propargyl bromide (16.4 g,
138 mmol), and N,N-diisopropylethylamine (8.63 g, 66.8 mmol) in
CH3CN (100 mL) was stirred at 808C for 20 h. After being cooled to
room temperature, the mixture was evaporated to dryness in vacuo. The
residue was dissolved in CH2Cl2 (100 mL) and the solution was washed
with water (100 mL). The aqueous layer was extracted with CH2Cl2
(100 mLꢀ2). The combined organic portions were dried over anhydrous
Na2SO4 and then evaporated in vacuo. The residue was purified by
column chromatography with CH2Cl2/hexane (1:2 v/v) as the eluent to
give a white solid (2.23 g, 73%). 1H NMR: d=7.28–7.32 (m, 2H; ArH),
6.97 (d, J=8.0 Hz, 2H; ArH), 6.89 (t, J=7.6 Hz, 1H; ArH), 4.13 (d, J=
2.4 Hz, 4H; CH2), 2.25 ppm (t, J=2.4 Hz, 2H; CꢃCH).
and Ni2+ were used. The presence of Clꢁ ions significantly
reduced the fluorescence intensity. It is likely that they com-
pete with the bis(1,2,3-triazole)amino ligand of 5 for the
Hg2+ ions, which resumes the ICT process and leads to a de-
crease in emission intensity at 686 nm.
Conclusion
We have reported a highly selective colorimetric and fluo-
rescent probe that can detect both Cu2+ and Hg2+ ions in
CH3CN/H2O (1:1 v/v). The color changes can be easily de-
tected by the naked eye (Figure S7 in the Supporting Infor-
mation). This sensor contains a distyryl BODIPY chromo-
phore and two click-derived bis(1,2,3-triazole)amino sub-
stituents as the receptors, and is responsive in the NIR
region.
4-(N,N-Dipropargylamino)benzaldehyde (2)
POCl3 (20 mL, 0.21 mol) was added dropwise to a solution of N,N-dipro-
pargylaniline (0.83 g, 4.9 mmol) in DMF (25 mL) and pyridine (5 mL)
over 4 h at 08C. The resulting mixture was heated with stirring at 758C
for 1 h and then allowed to cool to room temperature. The mixture was
poured into ice and neutralized with a saturated aqueous solution of
Na2CO3 (ca. 100 mL). The solution was then extracted with CH2Cl2 (3ꢀ
100 mL). The combined organic portions were dried over anhydrous
Na2SO4 and then evaporated in vacuo. The residue was purified by
Chem. Asian J. 2012, 7, 196 – 200
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199

D. K. P. Ng et al.
FULL PAPERS
column chromatography with CH2Cl2 as the eluent to give a light yellow
solid (0.57 g, 59%). 1H NMR: d=9.82 (s, 1H; CHO), 7.81 (d, J=8.8 Hz,
2H; ArH), 6.96 (d, J=8.8 Hz, 2H; ArH), 4.22 (d, J=2.4 Hz, 4H; CH2),
2.30 ppm (t, J=2.4 Hz, 2H; CꢃCH); 13C NMR: d=190.7, 152.0, 132.0,
127.8, 113.5, 78.3, 73.2, 40.3 ppm; MS (ESI): m/z (%): 198 (100) [M+H]+
; HRMS (ESI): m/z calcd for C13H12NO [M+H]+: 198.0913; found:
198.0920; elemental analysis calcd (%) for C13H11NO: C 79.17, H 5.62, N
7.10; found: C 78.54, H 5.58, N 7.08.
70.8, 70.7, 70.6, 69.9, 69.6, 67.6, 59.2, 59.1, 50.4, 46.9, 14.9 ppm (some of
the signals are overlapped); MS (ESI): m/z (%): 1624 (48) [M+Na]+;
HRMS (ESI): m/z calcd for C80H111BF2N16NaO16 [M+Na]+: 1623.8317;
found: 1623.8328.
Acknowledgements
Distyryl BODIPY 3
A mixture of BODIPY 1 (50.3 mg, 0.10 mmol), benzaldehyde 2 (223 mg,
1.1 mmol), piperidine (1.2 mL), acetic acid (1.0 mL), and a small amount
This work was supported by a strategic investments scheme administered
by The Chinese University of Hong Kong.
of MgACHTUNGTRENNUNG(ClO4)2 in toluene (30 mL) was heated at reflux for 12 h. The water
formed during the reaction was removed azeotropically with a Dean–
Stark apparatus. The solvent was removed under reduced pressure then
the residue was dissolved in CH2Cl2 (50 mL). The solution was washed
with water (50 mL) and the aqueous layer was extracted with CH2Cl2 (2ꢀ
50 mL). The combined organic portions were dried over anhydrous
Na2SO4 and then evaporated in vacuo. The residue was purified by
column chromatography using CH2Cl2/ethyl acetate (10:1 v/v) as the
eluent. The crude product was further purified by size-exclusion chroma-
tography using THF as the eluent to give a green solid (33.7 mg, 39%).
1H NMR: d=7.58–7.63 (m, 6H; C=CH and ArH), 7.17–7.21 (m, 4H; C=
CH and ArH), 7.02 (d, J=8.8 Hz, 2H; ArH), 6.96 (d, J=8.8 Hz, 4H;
ArH), 6.60 (s, 2H; pyrrole-H), 4.18 (virtual d, J=2.4 Hz, 10H; NCH2
and OCH2), 3.92 (virtual t, J=4.8 Hz, 2H; OCH2), 3.77–3.80 (m, 2H;
OCH2), 3.71–3.73 (m, 2H; OCH2), 3.67–3.69 (m, 2H; OCH2), 3.56–3.59
(m, 2H; OCH2), 3.40 (s, 3H; OCH3), 2.29 (t, J=2.4 Hz, 4H; CꢃCH),
1.47 ppm (s, 6H; CH3); 13C NMR: d=159.4, 152.7, 148.1, 141.6, 137.6,
135.8, 133.6, 129.9, 129.0, 128.2, 127.8, 117.4, 116.8, 115.1, 79.0, 73.0, 72.1,
71.0, 70.8, 70.7, 69.9, 67.6, 59.2, 40.4, 15.0 ppm; MS (ESI): m/z (%): 867
(100) [M+Na]+; HRMS (ESI): m/z calcd for C52H51BF2N4NaO4
[M+Na]+: 867.3864; found: 867.3861; elemental analysis calcd (%) for
C52H51BF2N4O4: C 73.93, H 6.08, N 6.63; found: C 73.18, H 6.15, N 7.37.
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Distyryl BODIPY 5
A mixture of distyryl BODIPY 3 (25.3 mg, 0.03 mmol), azide 4 (0.45 g,
2.4 mmol), CuSO4·5H2O (28.3 mg, 0.11 mmol), and sodium ascorbate
(56.7 mg, 0.29 mmol) in CH2Cl2/ethanol/H2O (6 mL/0.5 mL/0.5 mL) was
stirred at room temperature for 12 h. It was then mixed with CH2Cl2
(50 mL) and the mixture was washed with water (50 mL). The aqueous
layer was extracted with CH2Cl2 (2ꢀ50 mL). The combined organic por-
tions were dried over anhydrous Na2SO4 and then evaporated in vacuo.
The residue was purified by column chromatography with CH2Cl2/metha-
nol (from 50:1 to 5:1 v/v) as the eluent. The crude product was further
purified by size-exclusion chromatography with THF as the eluent to give
an oily green solid (22.3 mg, 47%). 1H NMR: d=7.60 (s, 4H; triazole-
H), 7.43 (d, J=16.0 Hz, 2H; C=CH), 7.48 (d, J=8.8 Hz, 4H; ArH), 7.19
(d, J=8.8 Hz, 2H; ArH), 7.13 (d, J=16.0 Hz, 2H; C=CH), 7.01 (d, J=
8.8 Hz, 2H; ArH), 6.90 (d, J=8.8 Hz, 4H; ArH), 6.57 (s, 2H; pyrrole-H),
4.76 (s, 8H; NCH2), 4.50 (t, J=4.8 Hz, 8H; OCH2), 4.19 (virtual t, J=
4.8 Hz, 2H; OCH2), 3.91 (virtual t, J=4.8 Hz, 2H; OCH2), 2.83 (t, J=
4.8 Hz, 8H; OCH2), 3.77–3.79 (m, 2H; OCH2), 3.70–3.73 (m, 2H;
OCH2), 3.67–3.69 (m, 2H; OCH2), 3.53–3.58 (m, 26H; OCH2), 3.46–3.48
(m, 8H; OCH2), 3.39 (s, 3H; CH3), 3.32 (s, 12H; CH3), 1.46 ppm (s, 6H;
CH3); 13C NMR: d=159.3, 152.6, 148.5, 144.9, 141.4, 137.0, 135.8, 133.5,
129.9, 129.1, 127.8, 126.4, 123.3, 117.2, 115.7, 115.1, 113.4, 72.0, 71.9, 71.0,
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Received: July 7, 2011
Published online: October 26, 2011
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