New diketopyrrolopyrrole (DPP) derivative as fluorescent probe for Zn 2+

Article abstract of DOI:10.1016/j.dyepig.2013.06.027

Abstract New turn-on fluorescent probe DPPL₂, was rationally designed and synthesized based on the skeleton of diketopyrrolopyrrole (DPP), which presented sensitivity, selectivity for Zn²⁺ over other metal ions except some disturbance with Cd²⁺. Particularly, results demonstrated fluorescence enhancement and blue shift of DPPL₂ upon Zn²⁺ binding. This phenomenon was a typical photoinduced electron transfer (PET) and intramolecular charge transfer (ICT) process which was attributed to diminishing the electron of the nitrogen lone pair delocalization on the DPP core upon Zn²⁺ binding. For comparison, DPPL₃ (acylation of nitrogen atom of DPPL₂) was synthesized and no fluorescence enhancement was observed, which further indicated that lone pair electrons of nitrogen atoms attached to DPP core were ascribed to PET process. ¹H NMR titrations and DFT calculations also proved that PET and ICT process of system.

Full text of DOI:10.1016/j.dyepig.2013.06.027

Dyes and Pigments 99 (2013) 779e786
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Dyes and Pigments
journal homepage: www.elsevier.com/locate/dyepig
New diketopyrrolopyrrole (DPP) derivative as fluorescent
probe for Zn2þ
*
Guanjun Zhang, Shiming Bi, Longfeng Song, Feng Wang, Jianjun Yu, Limin Wang
Shanghai Key Laboratory of Functional Materials Chemistry, and Institute of Fine Chemicals, East China University of Science and Technology, Shanghai
200237, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
New turn-on fluorescent probe DPPL2, was rationally designed and synthesized based on the skeleton of
diketopyrrolopyrrole (DPP), which presented sensitivity, selectivity for Zn2þ over other metal ions except
some disturbance with Cd2þ. Particularly, results demonstrated fluorescence enhancement and blue shift
of DPPL2 upon Zn2þ binding. This phenomenon was a typical photoinduced electron transfer (PET) and
intramolecular charge transfer (ICT) process which was attributed to diminishing the electron of the
nitrogen lone pair delocalization on the DPP core upon Zn2þ binding. For comparison, DPPL3 (acylation of
nitrogen atom of DPPL2) was synthesized and no fluorescence enhancement was observed, which further
indicated that lone pair electrons of nitrogen atoms attached to DPP core were ascribed to PET process.
1H NMR titrations and DFT calculations also proved that PET and ICT process of system.
Ó 2013 Elsevier Ltd. All rights reserved.
Received 23 May 2013
Received in revised form
17 June 2013
Accepted 20 June 2013
Available online 29 June 2013
Keywords:
Diketopyrrolopyrrole (DPP)
Turn on
Fluorescent probe
Zn2þ
Photoinduced electron transfer (PET)
Intramolecular charge transfer (ICT)
1. Introduction
emission for Zn2þ ions based both on photo-induced electron-
transfer (PET) and intramolecular charge-transfer (ICT) effects were
Zinc ion (Zn2þ) is the second most abundant heavy metal ion in
human body, which plays a great role in physiological and meta-
bolic processes [1]. It is well known that the lack of zinc ion could
result in an increasing risk of kinds of diseases [2]. Therefore, the
development of new and efficient systems for sensing for Zn2þ is of
great current interest [3]. Among several chemical tools, fluores-
cent probes have been proved to be very useful tool to sense in vitro
and in vivo biologically important species because of the simplicity
and high sensitivity [4]. In this regard, a variety of fluorescent Zn2þ
probes have been discussed based on various fluorophores [5].
Because the PET produced fluorescent enhancement or quench-
ing and the ICT usually give a large shift in absorption and fluores-
cence wavelength, which often were turn-on and wavelength-shift
probes allowing visual detection of Zn2þ. Photo-induced electron-
transfer (PET) and intramolecular charge-transfer (ICT) effects have
been widely used for the design of ratiometric fluorescent sensors.
Apart from this, long wavelength excitability and emission are very
important for reduced scattering and securing low background
emissions. However, the assay systems with long wavelength
rare [15].
1,4-Diketo-3,6-diphenylpyrrolo[3,4-c]pyrrole (DPP) derives from
a class of brilliant red and strongly fluorescent high performance
pigments that have exceptional light, weather, and heat stability.
Because of its advantageous optical properties, such as strong ab-
sorption and emission in the visible region, high photostability, large
stokes’ shift, and significant two-photon cross section [6], recently,
significant progress has been made to use DPP-containing materials
in small molecular and polymer solar cells (PSCs), organic field effect
transistors (OFETs), and organic light-emitting diodes (OLEDs). This
work was well reviewed by H. Tian group [7].
Therefore, DPP derivatives would also be good candidates for
the design of novel chemosensors. However, rare examples of DPP-
based chemosensors have been reported [8]. Herein, we designed
and synthesized a novel fluorescent offeon probes (DPPL2, DPPL3)
for Zn2þ ion based on DPP with symmetric receptors of N,N-Di(-
pyridin-2-ylmethyl)ethane-1,2-diamine (DPEA), because of their
high affinity of Zn2þ and water-compatible and membrane-
permeable characters [9]. In addition, two long ether chains were
incorporated to improve water solubility [10]. Target probe DPPL2
presented high sensitivity and selectivity for Zn2þ except some
disturbance with Cd2þ. To the best of our knowledge, it was the first
DPP-based fluorescent chemosensor to recognize Zn2þ ions based
* Corresponding author. Tel./fax: þ86 21 64253881.
E-mail addresses: wanglimin@ecust.edu.cn, wangliminecust@msn.cn (L. Wang).
0143-7208/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.dyepig.2013.06.027

780
G. Zhang et al. / Dyes and Pigments 99 (2013) 779e786
on both photo-induced electron-transfer (PET) and intramolecular
charge-transfer (ICT) effects.
water (1/2) were added, the mixture was refluxed for 3 h. After
filteration and dry, bluish-red solid was obtained (7.00 g, 65%).
2. Materials and methods
2.2.2. Synthesis of compound 1-(2-(2-(2-methoxyethoxy)ethoxy)
ethylsulfonyl)-4-methylbenzene
2.1. Experimental
p-TsCl (11.46 g, 60 mmol) and CH2Cl2 (20 mL) were stirring in a
three-necked flask under N2. The temperature was maintained at
0e5 ꢀC. While the desired hexaethyleneglycolmonoethylether
(60 mmol) and Et3N (60 mmol) were added slowly. After addition
was completed, the mixture was stirred for 12 h, the mixture was
poured into ice water (50 mL) and washed with 100 mL CH2Cl2. The
organic layer was washed with 6 N HCl (100 mL) and reduced to
minimum volume by evaporation in vacuum. The crude product
was straightforward for next step without purification. 1H NMR
2.1.1. General
Unless otherwise stated, reagents were commercially obtained
and used without further purification. All solvents were freshly
distilled: THF from Na/benzophenone, Anhydrous DMF, CH2Cl2 from
CaH2. Reactions were monitored by TLC. Flash chromatography
separations were carried out using silica gel (200e300 mesh). 1
H
NMR and 13C NMR spectra were collected on a Bruker Avance
DPS-300 spectrometer using CDCl3 or DMSO-d6 as solvent and tet-
ramethylsilane as internal reference, respectively. Mass Spectrom-
etry was performed by Bruker Biflex III MALDI-TOF (both positive
and negative ion reflector mode). Absorption spectra were
measured on Thermo UVeVis spectrophotometer. Fluorescence
spectra were obtained on Thermo Fluorescence spectrophotometer.
Both excitation and emission slit widths were 2.5 nm.
(400 MHz, CDCl3) d: 2.46 (s, 3H), 3.38 (s, 3H), 3.54 (m, 2H), 3.60 (m,
6H), 3.70 (t, J ¼ 4.8 Hz, 2H), 4.18 (t, J ¼ 4.8 Hz, 2H), 7.35 (d, J ¼ 8.0 Hz,
2H), 7.81 (d, J ¼ 8.0 Hz, 2H). 13C NMR (100 MHz, CDCl3)
d: 21.60,
58.98, 68.68, 69.20, 70.54, 70.75, 71.91, 127.96, 129.79, 133.12,
144.75 ppm.
2.2.3. Synthesis of compound 3,6-bis(4-bromophenyl)-2,5-bis(2-(2-
(2-methoxyethoxy)ethoxy)ethyl)pyrrolo[3,4-c]pyrrole-1,4(2H,5H)-
dione (2)
2.1.2. Fluorescence spectral measurements
The fluorescence spectra of DPPL2, DPPL3 (50 mM) were measured
at 25 ꢀC in aqueous solution (CH3CN/HEPES buffer 80:20, pH ¼ 7.4)
upon excitation at lex ¼ 500 nm. The amounts of Zn2þ added were 0,
0.2, 0.4, 0.6, 0.8, 1.0, 1.2, 1.4, 1.6, 1.8, 2.0, 2.2, and 2.4 equiv.
Br-DPP (0.22 g, 0.5 mmol), K2CO3 (0.27 g, 2 mmol) and 50 mL
DMF was added into three-necked flask, heated to 120 ꢀC for
30 min, 2-(2-(2-methoxyethoxy) ethoxy)ethyl 2-chloroacetate
(4.00 g, 10 mmol) was added slowly. The mixture was kept under
120 ꢀC for 6 h. Then 50 mL water was poured to quench the reac-
tion, the mixture was extracted with 100 mL ethyl acetate. Dried
with Na2SO4, the solvent was evaporated in vacuum. The resulting
mixture was purified by column chromatography to give the title
2.1.3. Metal-ion selectivity measurements
The fluorescence selectivity of DPPL2, DPPL3 to various metals
was measured in aqueous solution (CH3CN/HEPES buffer 80:20,
pH ¼ 7.4) at 25 ꢀC (lex ¼ 500 nm). Heavy metal ions (30 mM) were
added as AgNO3, Cd(NO3)2, Hg(NO3)2, Pb(NO3)2, MnSO4, FeSO4,
NiSO4, and Cu(NO3)2. Other cations were added as Zn(NO3)2
(30 mM), NaNO3 (300 mM), KCl (300 mM), Ca(NO3)2 (300 mM), and
MgSO4 (300 mM).
compound. (0.18 g, 50%) 1H NMR (400 MHz, CDCl3)
d: 3.36 (s, 6H),
3.50 (m, 4H), 3.56 (m,12H), 3.74 (t, J ¼ 5.2 Hz, 4H), 3.90 (t, J ¼ 5.2 Hz,
4H), 7.65 (d, J ¼ 8.8 Hz, 4H), 7.92 (d, J ¼ 8.8 Hz, 4H). 13C NMR
(100 MHz, CDCl3) d: 42.34, 59.01, 68.64, 58.82, 69.23, 70.47, 70.55,
70.70, 71.87, 109.65, 125.87, 126.71, 127.96, 129.82, 130.97, 132.09,
148.21, 162.75 ppm; HRMS (TOF-ESIþ): m/z: calcd for
2.1.4. Quantum yield measurements
C
32H38Br2N2O8þ: 736.0995; calcd for C32H39Br2N2Oþ8 : 737.1073
The quantum fluorescence yields were determined by compar-
ison of the integrated area of the corrected emission spectrum with
a reference of rhodamine 6G (FF ¼ 0.89, in CH2Cl2). For the metal-
[M þ Hþ]; found: 737.1068.
2.2.4. Synthesis of compound 2,5-bis(2-(2-(2-methoxyethoxy)
ethoxy)ethyl)-3,6-bis(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-
yl)phenyl)pyrrolo[3,4-c]pyrrole-1,4(2H,5H)-dione (3)
free study, 5 mL of 10 mM DPPL2, DPPL3 in aqueous solution (CH3CN/
HEPES buffer 80:20, pH ¼ 7.4) was prepared. For the metal-bound
studies, Zn(NO3)2 (0e20 L, 10 mM) was added to probe(2 mL,
10
M) in aqueous solution (CH3CN/HEPES buffer 80:20, pH ¼ 7.4).
m
2 (0.73 g, 1 mmol), bis(pinacolato)diboron (0.76 g, 3 mmol),
potassium acetate (0.80 g, 8 mmol), and bis(triphenylphosphine)
palladiumdichloride (0.17 g, 0.25 mmol) were mixed with 25 mL
distilled dioxane, then heated to 85 ꢀC for 2 h. After cooled, 20 mL
water was added and the mixture was extracted with 4 ꢁ 20 mL
CH2Cl2. The organic layer was combined and dried over Na2SO4. The
solvent was removed by rotary evaporation in vacuum, and the
residue was purified by column chromatography (silica gel, CH2Cl2/
CH3OH ¼ 100/1) to give the desired product. (0.50 g, 60%) 1H NMR
m
2.1.5. Computational details
The DFT calculations were carried out by using a Gaussian 09
software package. The ground-state geometries of DPPL2, DPPL2-
Zn2þ and DPPL3 were optimized at the DFT level with the B3LYP
hybrid functional in combination with the 6-31G(d) basis set for C,
H, O, and N atoms.
(400 MHz, CDCl3) d: 1.35 (s, 24H), 3.34 (s, 6H), 3.51 (m, 16H), 3.68 (t,
2.2. Synthesis
J ¼ 5.6 Hz, 4H), 3.93 (t, J ¼ 5.6 Hz, 4H), 7.91 (d, J ¼ 8.4 Hz, 4H), 7.94
(d, J ¼ 8.4 Hz, 4H). 13C NMR (100 MHz, CDCl3)
d: 24.56, 29.69, 59.00,
2.2.1. Synthesis of compound 3,6-bis(4-bromophenyl)pyrrolo[3,4-c]
pyrrole-1,4(2H,5H)-dione (1)
68.81, 70.47, 70.50, 70.54, 71.88, 75.05, 83.51, 84.08, 110.02, 128.27,
130.38, 136.05, 149.08, 162.80 ppm; HRMS (TOF-ESIþ): m/z: calcd
for C44H62B2N2Oþ12: 832.4489; cacld for C44H63B2N2O1þ2: 833.4567
[M þ Hþ]; found: 833.4595 [11a].
Sodium (2.30 g, 100 mmol) was dissolved in 50 mL t-amyl
alcohol at about 90 ꢀC over 1 h with a catalytic amount of FeCl3. The
solution was cooled to 50 ꢀC, then 4-bromobenzonitrile was added,
and the mixture was heated to 90 ꢀC, then diisopropyl succinate
(5.05 g, 25 mmol) in 20 mL t-amyl alcohol was added dropwise over
2 h. Subsequently, the resulting suspension was kept for 3 h at
120 ꢀC, the reaction mixture was then cooled to 50 ꢀC. Glacial acetic
acid was slowly added and refluxed briefly, 100 mL methanol and
2.2.5. Synthesis of compound N1-(4-bromophenyl)ethane-1,2-
diamine (4)
1-bromo-4-iodobenzene (2.81 g, 10 mmol), ethylenediamine
(0.60 g, 10 mmol), CuI (0.10 g), 0.5 mL ethylene glycol and 20 mL
isopropyl alcohol were added into single-necked flask. The mixture

G. Zhang et al. / Dyes and Pigments 99 (2013) 779e786
781
was refluxed for 12 h. 1H NMR (400 MHz, CDCl3)
d: 2.97 (t,
2.2.7. Synthesis of compound N-(4-bromophenyl)-2-
J ¼ 7.2 Hz, 2H), 3.16 (t, J ¼ 7.2 Hz, 2H), 6.53 (d, J ¼ 8.8 Hz, 2H), 7.26 (d,
chloroacetamide (6)
J ¼ 8.8 Hz, 2H).
4-Bromoaniline (5.16 g, 30 mmol), Et3N (5.60 g, 30 mmol) and
100 mL driedCH2Cl2 were added intothree-neckedflask, aftercooled
to 0 ꢀC, chloroacetyl chloride (2.40 g, 32 mmol) in 30 mL CH2Cl2 was
added slowly under N2. Then the mixture was stirred 18 h at room
temperature. H2O (50 mL) was added to quench the reaction,
extracted with CH2Cl2 (50 mL) and washed with brine, dried over
Na2SO4, the solvent was removed under vacuum. Column chroma-
tography (silica, CH2Cl2) gave the product as a yellow powder. (6.30 g,
2.2.6. Synthesis of compound N1-(4-bromophenyl)-N2,N2-
bis(pyridin-2-ylmethyl)ethane-1,2-diamine (5)
4 (2.14 g, 10 mmol), KI (0.10 g) DIPEA (80 mmol) and picolyl
chloride hydrochloride (4.92 g, 30 mmol) were dissolved in redis-
tilled CH3CN (50 mL). The mixture was refluxed for 12 h. After
cooling to room temperature, the solvent was removed by rotary
evaporation. The yellow oil dissolved in CH2Cl2 (100 mL) and
washed twice with brine. The organic layer was separated, and dried
over Na2SO4, then filtered and concentrated under vacuum. Column
chromatography (silica gel, CH2Cl2/CH3OH/NH3$H2O ¼ 100/1/1)
gave product as yellow solid. (2.17 g, 55%) 1H NMR (400 MHz, CDCl3)
85%) 1H NMR (400 MHz, CDCl3)
d: 4.21 (s, 2H), 7.49 (m, 4H).
2.2.8. Synthesis of compound 2-(bis(pyridin-2-ylmethyl)amino)-N-
(4-bromophenyl)acetamide (7)
6 (1.24 g, 5 mmol), di-(2-picolyl)amine (DPA) (1.60 g, 8 mmol), N,
N-diisopropylethylamine (DIPEA) (2.50 g) and KI (0.10 g) in CH3CN
(20 mL) were refluxed for 18 h under N2. After cooled, the solvent
was removed under vacuum to give yellow oil, which dissolved in
CH2Cl2 (100 mL). The organic layer was washed with H2O, dried
over Na2SO4. The solvent was evaporated under reduced pressure,
the crude product was purified by column chromatography (Al2O3,
d
: 2.83 (t, J ¼ 5.6 Hz, 2H), 3.07 (t, J ¼ 5.2 Hz, 2H), 5.00 (s, 1H), 3.85 (s,
4H), 6.43 (d, J ¼ 8.8 Hz, 2H), 7.12 (dd, J ¼ 5.2 Hz, J ¼ 6.4 Hz, 2H), 7.18
(d, J ¼ 8.8 Hz, 2H), 7.37 (d, J ¼ 8.0 Hz, 2H), 7.59 (dt, J ¼ 1.6 Hz,
J ¼ 7.6 Hz, 2H), 8.53 (d, J ¼ 4.0 Hz, 2H). 13C NMR (100 MHz, CDCl3)
d:
41.36, 52.56, 60.29, 108.18, 114.33, 122.17, 123.20, 131.71, 136.49,
147.70, 149.11, 159.05 ppm; HRMS (TOF-ESIþ): m/z: calcd for
C
20H21BrNþ4 : 396.0950; cacld for C20H22BrNþ4 : 397.1028 [M þ Hþ];
CH2Cl2) to give (1.53 g, 75%). 1H NMR (400 MHz, CDCl3)
d: 3.47 (s,
2H), 3.92 (s, 4H), 7.18 (dd, J ¼ 5.2 Hz, J ¼ 7.2 Hz, 2H), 7.25 (d,
found: 397.1028.
I
NH2
ib)
N
HN
ia)
Br
NH
N
Br
N
Br
5
4
O
Cl
N
O
NH2
Br
HN
N
iia)
iib)
N
H
HN
N
N
N
Br
6
Br
7
O
B
Br
O
Br
O
O
O
R1
R1
N
N
iii)
iv)
N
N
NH
HN
R1
R1
O
O
O
O
B
O
Br
Br
3
2
1
v)
5, 7
O
O
R1 =
DPPL2 DPPL3
O
Scheme 1. The synthetic routes of probe DPPL2, DPPL3.

782
G. Zhang et al. / Dyes and Pigments 99 (2013) 779e786
Table 1
3. Results and discussions
Photophysical properties of DPPL2, DPPL2-Zn, DPPL3.a
3.1. Design and synthesis
Compound
Absorption
peak lab [nm]
Emission
peak lem [nm]
Fluorescence
quantum yields FF
b
BuchwaldeHartwig reaction was attempted to incorporate the
receptor unit at both the 3- and 6-positions of the DPP core. This
route failed due to the easy decomposition of the DPP fluorophore
at high temperature with strong base. Finally, we synthesized DPP
bearing two pinacol boronate groups via SuzukieMiyaura reaction
under mild conditions in good yield compared with reference
[11b]. With it in hand, Suzuki coupling reaction was preferred to
gaining target product at 50 ꢀC in 50% yield. By this method,
probes DPPL2 and DPPL3 were synthesized with satisfied yields
(Scheme 1).
DPPL2
498
490
492
575
555
557
0.06
0.87
0.76
DPPL2-Znc
DPPL3
a
All data were obtained in aqueous solution (CH3CN:2-[4-(2-hydroxyethyl)-1-
piperazinyl]ethanesulfonic acid (HEPES) 80:20, pH ¼ 7.4).
b
Fluorescent quantum yields were determined in reference to rhodamine 6G
(
FF ¼ 0.89, in CH2Cl2).
c
The data were measured in the presence of Zn2þ (2.0 equiv. Zn2þ with respect to
DPPL2 and DPPL3).
J ¼ 8.0 Hz, 2H), 7.43 (d, J ¼ 8.8 Hz, 2H), 7.61 (dt, J ¼ 1.6 Hz, J ¼ 7.6 Hz,
2H), 7.70 (d, J ¼ 8.8 Hz, 2H), 8.60 (d, J ¼ 4.8 Hz, 2H). 13C NMR
As illustrated in Scheme 1, the target molecules of DPPL2, DPPL3
were conveniently synthesized through three steps from DPP pig-
ments 1. Firstly, compound 1 was treated with K2CO3 in DMF under
refluxing to give 2 in 60% yield. In the following step, by using
Pd(dppf)2Cl2 as catalyst in dry 1,4-dioxane, the two bromo atoms of
2 were substituted with pinacol boronate groups with yield of 50%.
Finally, the target probes DPPL2 and DPPL3 were obtained via
Suzuki coupling reaction with yield of 50%. All compounds were
fully characterized by 1H and 13C NMR spectroscopy and HRMS as
shown in the experimental section.
(100 MHz, CDCl3) d: 58.78, 60.36, 116.18, 121.24, 122.61, 123.30,
131.75, 136.70, 137.82, 149.40, 157.98, 169.95 ppm; HRMS (TOF-
ESIþ): m/z: calcd for C20H19BrN4Oþ: 410.0742; calcd for
C
20H20BrN4Oþ: 411.0820 [M þ Hþ]; found: 411.0817.
2.2.9. Synthesis of compound 3,6-bis(40-(2-(bis(pyridin-2-ylmethyl)
amino)ethylamino)biphenyl-4-yl)-2,5-bis(2-(2-(2-methoxyethoxy)
ethoxy)ethyl)pyrrolo[3,4-c]pyrrole-1,4(2H,5H)-dione (DPPL2)
3 (0.20 g, 0.25 mmol), 5 (0.35 g, 1 mmol), Pd2(dba)3 (0.05 g,
0.05 mmol), P(t-Bu)3$HBF4 (0.03 g, 0.1 mmol), K3PO4 (0.26 g,
1 mmol), 2 mL degassed H2O and 10 mL degassed THF were added
to single-necked flask. The reaction mixture was heated to 80 ꢀC for
2 h under N2, the solvent was removed under vacuum. The purple
red solid (0.15 g, 50%) was purified by column chromatography
A)
3
(Al2O3, CH2Cl2). 1H NMR (400 MHz, CDCl3)
d
: 2.91 (t, J ¼ 5.6 Hz, 4H),
3.23 (t, J ¼ 5.6 Hz, 4H), 3.32 (s, 6H), 3.69 (m, 16H), 3.80 (t, J ¼ 5.6 Hz,
4H), 3.91 (s, 8H), 4.02 (t, J ¼ 5.6 Hz, 4H), 5.29 (s, 1H, NH), 6.67 (d,
J ¼ 8.4 Hz, 4H), 7.16 (dd, J ¼ 5.2 Hz, J ¼ 6.8 Hz, 4H), 7.43 (d, J ¼ 7.6 Hz,
4H), 7.49 (d, J ¼ 8.8 Hz, 4H), 7.63 (td, J ¼ 7.6 Hz, J ¼ 1.6 Hz, 4H), 7.69
2
1
0
(d, J ¼ 8.8 Hz, 4H), 8.05 (d, J ¼ 8.4 Hz, 4H), 8.58 (d, J ¼ 4.0 Hz, 4H). 13
C
NMR (100 MHz, CDCl3) d: 29.70, 41.24, 52.69, 59.02, 60.26, 68.95,
70.56, 70.59, 70.66, 71.91, 109.40, 113.03, 112.20, 123.22, 125.28,
126.07, 127.93, 128.17, 129.82, 136.53, 144.03, 148.62, 148.78, 149.16,
159.10, 163.20 ppm; HRMS (TOF-ESIþ): m/z: calcd for C72H80N10O8þ:
1212.6161; cacld for C72H80N10O8Naþ: 1235.6058 [M þ Naþ];
found: 1235.6050.
300
400
500
600
2.2.10. Synthesis of compound N,N0-(40,400-(2,5-bis(2-(2-(2-
methoxyethoxy)ethoxy)ethyl)-3,6-dioxo-2,3,5,6-tetrahydropyrrolo
[3,4-c]pyrrole-1,4-diyl)bis(biphenyl-40,4-diyl))bis(2-(bis(pyridin-2-
ylmethyl)amino)acetamide) (DPPL3)
Wavelength(nm)
2400
2200
2000
1800
1600
1400
1200
1000
800
B)
3 (0.2 g, 0.25 mmol), 7 (0.35 g, 1 mmol), Pd2(dba)3 (0.05 g,
0.05 mmol), P(t-Bu)3$HBF4 (0.03 g, 0.1 mmol), K3PO4 (0.26 g,
1 mmol), 2 mL degassed H2O and 10 mL degassed THF were added
to single-necked flask. The reaction mixture was heated to 80 ꢀC
for 2 h under N2, the solvent was removed under vacuum. The
purple red solid was purified by column chromatography (Al2O3,
CH2Cl2). (0.15 g, 50%) 1H NMR (400 MHz, CDCl3)
d: 3.34 (s, 6H), 3.52
(m, 8H), 3.62 (m, 12H), 3.83 (t, J ¼ 5.2 Hz, 4H), 3.98 (s, 8H), 4.04 (t,
J ¼ 5.2 Hz, 4H), 7.23 (dd, J ¼ 5.2 Hz, J ¼ 7.2 Hz, 4H), 7.33 (d,
J ¼ 7.6 Hz, 4H), 7.97 (d, J ¼ 8.0 Hz, 4H), 7.66 (td, J ¼ 1.6 Hz, J ¼ 7.2 Hz,
8H), 7.78 (d, J ¼ 8.4 Hz, 4H), 7.93 (d, J ¼ 8.4 Hz, 4H), 8.13 (d,
600
400
J ¼ 8.4 Hz, 4H), 8.68 (d, J ¼ 4.4 Hz, 4H). 13C NMR (100 MHz, CDCl3)
d:
200
53.46, 58.78, 59.03, 60.47, 68.93, 70.55, 70.58, 70.64, 71.91, 109.06,
119.99, 120.07, 122.66, 123.35, 126.45, 126.99, 127.14, 127.58, 129.92,
135.28, 136.77, 138.78, 143.40, 148.70, 149.47, 158.02, 163.13,
0
550
600
650
700
Wavelength(nm)
169.98 ppm; HRMS (TOF-ESIþ): m/z: calcd for C72H76N10Oþ10
:
1240.5746; cacld for C72H76N10O10Naþ: 1263.5644 [M þ Naþ];
Fig. 1. Changes in (A) absorption and (B) emission spectra of DPPL2 in CH3CN/HEPES
buffer 80:20 solutions under pH ¼ 7.4 upon titration of Zn2þ from 0 to 2.0 equiv.
found: 1263.5648.

G. Zhang et al. / Dyes and Pigments 99 (2013) 779e786
783
3.2. Fluorescence and chemical properties
more changed, the fact supported the hypothesis that DPPL2
formed a 1:2 complex with Zn2þ (Fig. 1B).
We assessed the spectroscopic characteristics of probes under
CH3CN:2-[4-(2-hydroxyethyl)-1-piperazinyl]ethanesulfonic acid
(HEPES) 80:20, pH ¼ 7.4 conditions. Correspond to the electron-
donor capability, DPPL2 and DPPL3 showed different emission
wavelengths, 575, 557 nm, respectively, summaries as shown in
Table 1.
The spectra changes were plotted against proportion of CZn/CDPPL2
(Fig. 2). It was found that both of the fluorescence intensity at 555 nm
and absorption at 345 nm increased linearly with Zn2þ increase,
absorption at 400 and 500 nm decreased linearly with Zn2þ increase.
These results indicated that DPPL2 could be potentially utilized as an
excellent optical sensor for the quantitative analysis of Zn2þ
.
As shown in Fig. 1A, the absorption spectrum of DPPL2, changed
1H NMR titration of DPPL2 with Zn2þ was studied, the chemical
shifts in Zn2þ complex showed downfield shift compared with
those in free probe DPPL2. For DPPL2, Zn2þ coordination triggered
clear downfield shift of H in the pyridine and aromatic moieties, but
no longer change when more than two equivalents of Zn2þ added,
which was indicative of the 1:2 binding ratio (Fig. 3).
upon addition of Zn2þ (0e2 equiv), with isosbestic point at
l
¼ 363 nm, and then remained at a plateau upon further addition
of Zn2þ. When excited at 498 nm, DPPL2 displayed weak red fluo-
rescence in the absence of Zn2þ
lem ¼ 575 nm, FF ¼ 0.06). The
complexation of DPPL2 with Zn2þ triggered yellow fluorescence
lem ¼ 555 nm, FF ¼ 0.87).
Upon adding Zn2þ
the emission intensity of DPPL2 was
(
(
As comparison with DPPL2, compound DPPL3 was synthesized to
prove that acylation of nitrogen atom could decrease electron
density of ligand. The photophysical of DPPL3 were similar with the
complex between DPPL2 and Zn2þ. (Table 1) It further proved that
acylation of N atoms could decrease the electron-donation capa-
bility, which blocked PET process.
,
enhanced largely with blue shift of 20 nm, such a blue shift implied
that the nitrogen atoms attached to the DPP moiety were disturbed
by Zn2þ, thus resulting in decrease in the electron donating ability.
Consequently, the large “offeon” enhancement on emission spectra
and the blue-shift in both absorption and emission band for DPPL2
was suggestive of combination of PET and ICT processes [12]. When
adding more than two equiv. Zn2þ, the maximum of fluorescence
intensity at 555 nm was not changed. After adding more than two
equiv. Zn2þ, both the absorption and fluorescence spectra were no
The effect of adding Naþ, Kþ, Ca2þ, Mg2þ, Ba2þ and various heavy
metal ions (Mn2þ, Fe2þ, Co2þ, Ni2þ, Cu2þ, Cd2þ, Pb2þ, Hg2þ, Agþ) on
the fluorescence emission intensity of DPPL2 and DPPL3 was also
examined. Fluorescence emission enhancementof DPPL2 (2 mM) was
2.0
A)
1.9
1.8
1.7
A500
A)
A400
3500
A345
1.6
1.5
1.4
1.3
1.2
1.1
1.0
0.9
0.8
0.7
0.6
0.5
0.4
0.3
3000
2500
2000
1500
1000
500
0.2
0.4
0.6
0.8
1.0
1.2
1.4
1.6
1.8
2.0
2.2
0
probe Zn Cd Pb Fe Ni Cu Hg Co Ag Mn Ba Mg Na
K
CZn/CDPPL2
2500
B)
B)
Equation
y = a + b
35000
30000
25000
20000
15000
10000
5000
0
Adj. R-Squa 0.99901
Value
Standard Err
15.18024
14.53052
2000
1500
1000
500
0
B
B
Intercept -126.0413
Slope 1131.458
0
1
2
3
probe Zn Cd Hg Ni Fe Pb Co Mn Ag Cu Mg Ba Na
K
CZn/CDPPL2
Fig. 2. The relative fluorescence intensity at pH ¼ 7.4 (CH3CN/HEPES buffer 80:20
solution) of various metal ions: (A): DPPL2 M); (B): DPPL3
lem ¼ 555 nm, 50
lem ¼ 557 nm, 50 M).
(
m
Fig. 3. (A) Absorbance at 345, 400, 500 nm and (B) Fluorescence peak intensity at
(
m
555 nm of DPPL2 with increasing Zn2þ ions.

784
G. Zhang et al. / Dyes and Pigments 99 (2013) 779e786
Fig. 4. Partial 1H NMR spectra (400 MHz, [d6]DMSO) in the absence (a) and in the presence of (b) 2.0 equiv. Zn2þ: DPPL2.
not observed upon addition of 20 mM Naþ, Kþ, Ca2þ or Mg2þ (these
ions existed in high concentrations in biological systems) or 2 mM
various heavy metalions, except for Cd2þ and Pb2þ (Fig. 4a). However,
DPPL3 showed no selectivity for Zn2þ over other cations except
fluorescence decreasement for some heavy metal ions (Fig. 4b).
To further prove PET mechanism, DFTcalculation was carried out
by the Gaussian 09 software package [13]. As shown in Fig. 5, the
ground state structures were optimized, MO calculations for DPPL2
and DPPL3 at the DFT (B3LYP/6-31G) level revealed a number of
frontier orbital (using protonation of the donor nitrogen atoms as
Fig. 5. Frontier orbital energy diagrams. (To find the relative order of orbitals upon Zn2þ binding, protonated form of the DPA at nitrogen atoms was used as a reasonable model.)

G. Zhang et al. / Dyes and Pigments 99 (2013) 779e786
785
Scheme 2. Proposed binding mechanism between probe DPPL2 and Zn2þ
.
[2] Noy D, Solomonov I, Sinkevich O, Arad T, Kjaer K, Sagi I. Zinc-amyloid
b in-
reasonable model for metal ion binding). Results demonstrated that
the highest five occupied orbital in DPPL2 were all dye orbital, and
teractions on millisecond time-scale stabilize non-fibrillar Alzheimer-
a
p
related species. J Am Chem Soc 2008;130:1376e83.
the nitrogen lone pair orbital are outside of the highest 20 occupied
orbitals. Compared with HOMO orbital of protonation, the nitrogen
lone pair partly participated HOMO orbitals of DPPL2. Upon binding
with Zn2þ, the electron transferring from the nitrogen lone pair to
[3] a) Que EL, Domaille DW, Chang CJ. Metals in neurobiology: probing their
chemistry and biology with molecular imaging. Chem Rev 2008;108:1517e49;
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Eur J 2005;11:38e49;
c) Xu ZC, Yoon JY, Spring DR. Fluorescent chemosensors for Zn2þ. Chem Soc Rev
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the
p orbital became much more difficult, and the PET process was
[4] Tsien RY. Czarnik AW, editor. Fluorescent and photochemical probes of dy-
namic biochemical signals inside living cells. Washington, DC: American
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blocked. The results were consistent with reported PET systems [14].
According to the above results, we introduced binding mecha-
nism between probe DPPL2 and Zn2þ. (Scheme 2) The fluorescence
enhancement of DPPL2 during the titration with Zn2þ was typical
PET characteristic with a little ICT process. It blocked PET process
from the lone electron pair of the nitrogen atom attached to the
DPP fluorophore [15].
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4. Conclusion
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sensor for zinc ion. Analyst 2012;137:4415e7;
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assay. Inorg Chem 2012;51:10158e68;
f) Jia J, Xu QC, Li RC, Tang X, He YF, Zhang MY, et al. Tetrahydroindazolone
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ratiometric two-photon fluorescent probes for biological Zn2þ detection.
Chem Commun 2012;48:4196e8;
A new fluorescent probe DPPL2 based on DPP was designed and
synthesized, which showed high sensitivity and selectivity for Zn2þ
.
Particularly, DPPL2 exhibited large “offeon” enhancement on emis-
sion spectra and blue shift in both absorption and emission band
based on photoinduced electron transfer (PET) and intramolecular
charge transfer (ICT) process. Our study will be useful for design of
new colorimetric molecular probes and functional materials.
Acknowledgement
h) Mukherjee T, Pessoa JC, Kumar A, Sarkar AR. Synthesis, spectroscopic
characterization, insulin-enhancement, and competitive DNA binding activity
of a new Zn(II) complex with a vitamin B6 derivativeda new fluorescence
probe for Zn(II). Dalton Trans 2012;41:5260e71;
i) Mashraqui SH, Betkar R, Ghorpade S, Tripathi S, Britto S. A new internal
charge transfer probe for the highly selective detection of Zn(II) by means of
This research was financially supported by the National Nature
Science Foundation of China (21272069, 20672035), the Funda-
mental Research Funds for the Central Universities, Baihehua Group
and Key Laboratory of Organofluorine Chemistry, Shanghai Insti-
tute of Organic Chemistry, Chinese Academy of Sciences.
dual colorimetric and fluorescent turn-on responses. Sens Actuators
2012;174:299e305;
B
j) Mandal G, Darragh M, Wang YA, Heyes CD. Cadmium-free quantum dots as
time-gated bioimaging probes in highly-autofluorescent human breast cancer
cells. Chem Commun 2013;49:624e6.
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