In situ generated 1:1 Zn(II)-containing polymer complex sensor for highly enantioselective recognition of N-Boc-protected alanine

Article abstract of DOI:10.1021/ma301553y

A novel chiral (S)-BINAM-based fluorescence polymer sensor was designed and synthesized by the polymerization of 5,5′-((2,5-dioctyloxy-1,4-phenylene) bis(ethyne-2,1-diyl)bis(2-hydroxy-3-(piperidin-1-ylmethyl)benzaldehyde (M-1) with (S)-2,2′-binaphthyldiamine (S-BINAM, M-2) via Schiffs base formation. The resulting chiral polymer sensor shows very weak fluorescence but exhibits the obvious fluorescence enhancement response toward Zn²⁺. The in situ generated 1:1 Zn(II)-containing complex of chiral polymer can serve as a fluorescence sensor for highly enantioselective recognition of N-Boc-protected alanine, and the value of enantiomeric fluorescence difference ratio (ef) can reach as high as 6.90. This is the first report on the in situ generated chiral polymer complex used as a fluorescence sensor for highly enantioselective recognition of N-Boc-protected alanine.

Full text of DOI:10.1021/ma301553y

Article
pubs.acs.org/Macromolecules
In Situ Generated 1:1 Zn(II)-Containing Polymer Complex Sensor for
Highly Enantioselective Recognition of N‑Boc-Protected Alanine
Jiali Hou, Fengyan Song, Lu Wang, Guo Wei, Yixiang Cheng,* and Chengjian Zhu*
Key Lab of Mesoscopic Chemistry of MOE, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093,
China
S
* Supporting Information
ABSTRACT: A novel chiral (S)-BINAM-based fluorescence
polymer sensor was designed and synthesized by the
polymerization of 5,5′-((2,5-dioctyloxy-1,4-phenylene)bis-
(ethyne-2,1-diyl)bis(2-hydroxy-3-(piperidin-1-ylmethyl)-
benzaldehyde (M-1) with (S)-2,2′-binaphthyldiamine (S-
BINAM, M-2) via Schiff’s base formation. The resulting chiral
polymer sensor shows very weak fluorescence but exhibits the
obvious fluorescence enhancement response toward Zn2+. The
in situ generated 1:1 Zn(II)-containing complex of chiral
polymer can serve as a fluorescence sensor for highly
enantioselective recognition of N-Boc-protected alanine, and the value of enantiomeric fluorescence difference ratio (ef) can
reach as high as 6.90. This is the first report on the in situ generated chiral polymer complex used as a fluorescence sensor for
highly enantioselective recognition of N-Boc-protected alanine.
Although there have been some works on enantioselective
recognition based on metal ion containing complexes as chiral
fluorescence sensors, most of them are based on chiral small
molecules, and fluorescence polymer sensors are very few.33−40
The fluorescence polymer sensors incorporating chiral
recognition moieties are that they can make use of the high
sensitivity of the conjugated polymers to external structural
perturbations and to electron density changes within the
conjugated polymer main backbone when they interact with
chiral organic molecules.41−43 Sensitive detection methods for
sensing chiral molecules involve the exquisite design of “turn-
on” fluorescence sensors based on the photoinduced electron
transfer and energy migration mechanism within the con-
jugated polymer main backbone. Moreover, these chiral
fluorescence-based polymers can also be systematically
modified by the introduction of the different functional groups
with steric and electronic properties at the well-defined
molecular level.
The chirality of 2,2′-binaphthyldiamine (BINAM) is derived
from the restricted rotation of the two naphthalene rings. The
rigid structure and C2 symmetry of the chiral binaphthyl
molecules can play an important role in inherently chiral
induction.33,44−52 In our previous work we reported the chiral
fluorescence polymer sensor incorporating (S)-2,2′-binaphthol
(BINOL) and (S)-2,2′-BINAM moieties in the main chain of
the polymer backbone for enantioselective recognition of
phenylalaninol.33 In this paper, we designed a novel
INTRODUCTION
■
Investigations on highly sensitive and selective enantioselective
recognition of chiral organic molecules have received increasing
attention in recent years. In particular, numerous efforts have
been devoted to the design of novel chiral fluorescence sensors
with unique electrical and optical properties that are capable of
detecting chiral molecule enantioselectivity in a both real time
and reversible fashion1−11 due to its importance for under-
standing the interactions of biological molecules, developing
useful separation processes, designing of asymmetric catalysis
systems, and screening high-throughput chiral catalyst.12−20
Moreover, chiral fluorescence sensors can not only greatly
facilitate rapid determination of enantiometric composition of
chiral compounds with high sensitivity and waste reduction but
also easily achieve high-throughput screening (HTS) determi-
nation.19,21−23 In the past 10 years, many works have been
reported on the design and synthesis of the fluorescent sensors
for the amino acids and their derivatives.24−31 But only some
examples were focused on metal-containing complexes as chiral
fluorescence sensors. Pu and co-workers designed a chiral
BINOL−terpyridine−Cu(II) complex as fluorescence sensor
for enantioselective recognition of chiral amino alcohols.32
Feng also developed a chiral N,N′-dioxide−Ni(II) complex-
based fluorescence sensor for enantioselective recognition of α-
hydroxycarboxylic acids, amino alcohols, amino acids, and their
derivatives.27,28 Recently, our group reported the in situ
generated perazamacrocycle−Cu(II) complex as chiral flor-
escence sensor and successfully realized enantioselective
recognition of unmodified α-amino acids in protic solution
via a ligand displacement mechanism.26
Received: July 25, 2012
Revised: September 12, 2012
Published: September 24, 2012
© 2012 American Chemical Society
7835
dx.doi.org/10.1021/ma301553y | Macromolecules 2012, 45, 7835−7842

Macromolecules
Article
mL), and the combined CH2Cl2 solutions were washed with H2O and
dried over MgSO4. The solution was filtered, and the solvent was
removed by rotary evaporation. The crude product was purified by
silica gel column chromatography (ethyl acetate−petroleum ether,
1:30, v/v) to give the compound (2,5-diethynyl-1,4-dioctyloxyben-
zene) as a light yellow crystal after removal of the solvent (2.48 g,
fluorescence polymer sensor incorporating (S)-BINAM-based
Schiff base moieties in the polymer main-chain backbone. The
resulting polymer sensor can form in situ 1:1 Zn(II)-containing
chiral polymer complex which can serve as a fluorescence
sensor for highly enantioselective recognition of N-Boc-
protected alanine. More importantly, the in situ Zn(II)-
containing chiral polymer complex sensor solution can appear
bright blue fluorescence color change upon addition of (L)-N-
Boc-protected alanine under a commercially available UV lamp,
which can be clearly observed by the naked eye.
1
64%). H NMR (300 MHz, CDCl3): δ 5.97 (s, 2H), 3.99 (t, J = 6.8
Hz, 4H), 3.35 (s, 2H), 1.82 (m, 4H), 1.50−1.30 (m, 24H), 0.91 (t, J =
6.6 Hz, 6H). 13C NMR (75 MHz, CDCl3) δ: 153.9, 117.6, 113.1, 82.3,
79.7, 69.5, 31.7, 29.22, 29.15, 29.03, 25.8, 22.6, 14.1. TOF-MS: m/z
382.2. FT-IR (KBr, cm−1): 3285, 2924, 2851, 1501, 1470, 1385, 1218,
1039, 860, 671, 646. Anal. Calcd for C26H38O2: C, 81.62; H, 10.01;
Found: C, 80.32; H, 11.00.
EXPERIMENTAL SECTION
■
Synthesis of 5-Bromo-2-hydroxy-3-(piperidin-1-ylmethyl)-
benzaldehyde (3). Piperidine (2.0 mL, 20 mmol) was added to a
solution of paraformaldehyde (0.6 g, 20 mmol) dissolved in HAc (30
mL) and stirred for 12 h at room temperature. Then 5-bromo-2-
hydroxybenzaldehyde (4.02 g, 20 mmol) was added, and the mixture
was heated at reflux for 24 h. After cooling to room temperature, the
mixture was brought to pH ∼ 8 with saturated Na2CO3, extracted with
CHCl3, dried over anhydrous Na2SO4, and concentrated. The crude
product was purified by silica gel column chromatography (ethyl
acetate−petroleum ether, 2:1, v/v) to yield 4.61 g (77%) of the
Instruments and Materials. All solvents and reagents were
commercially available and analytical reagent grade. THF and Et3N
were purified by distillation from sodium in the presence of
benzophenone. NMR spectra were collected on a Bruker 300
1
spectrometer (300 MHz for H NMR and 75 MHz for 13C NMR)
and reported as parts per million (ppm) from the internal standard
TMS. Electrospray ionization mass spectra (ESI-MS) were measured
on a Thermo Finnigan LCQ Fleet system, and time-of-flight mass
spectra (TOF-MS) were determined on a Micromass GCT. FT-IR
spectra were taken on a Nexus 870 FT-IR spectrometer. Fluorescence
spectra were obtained from an RF-5301PC spectrometer. The circular
dichroism (CD) spectrum was determined with a Jasco J-810
spectropolarimeter. Specific rotation was determined with a Ruololph
Research Analyfical Autopol I. C, H, and N of elemental analyses were
performed on an Elementar Vario MICRO analyzer. Thermogravi-
metric analyses (TGA) were performed on a PerkinElmer Pyris-1
instrument under a N2 atmosphere. Molecular weight was determined
by gel permeation chromatography (GPC) with a Waters 244 HPLC
pump, and THF was used as solvent relative to polystyrene standards.
Synthesis of 2,5-Diiodo-1,4-dioctyloxybenzene (1). A solution of
hydroquinone (10 g, 90 mmol), n-bromooctane (35 g, 181 mmol),
and K2CO3 (33.8 g, 245 mmol) in 250 mL of ethanol was reflexed for
12 h. Then the solvent was removed by a rotary evaporator, and the
result mixture was diluted by water and extracted by CH2Cl2. The
combined organic layer was washed with brine, dried over anhydrous
Na2SO4, and concentrated. The crude product was obtained as an oil
liquid without further purified and directly used for next reaction. A
mixture of 1,4-dioctyloxybenzene (1) (5.0 g, 14.9 mmol), KIO3 (1.3 g,
6.2 mmol), and iodine (3.2 g, 12.5 mmol) in acetic acid (50 mL),
sulfuric acid (1.3 mL), and water (5 mL) was refluxed for 15 h. A
precipitate formed. The suspension was cooled with an ice bath and
filtered. The isolated solid was washed with saturated aqueous Na2SO3
solution and finally with water and dried in vacuo. Recrystallization
from ethanol give 2,5-diiodo-1,4-dioctyloxybenzene (7.6 g, 87%) as a
1
product as a pale yellow solid after removal of the solvent. H NMR
(300 MHz, CDCl3) δ: 10.36 (s, 1H), 7.78 (d, J = 2.1 Hz, 1H), 7.32 (d,
J = 2.1 Hz, 1H), 3.72 (s, 2H), 2.58 (br, 4H), 1.73−1.65 (m, 4H), 1.55
(br, 2H). 13C NMR (75 MHz, CDCl3) δ: 152.6, 138.5, 132.9, 130.4,
129.0, 128.1, 126.6, 125.9, 121.7, 117.5, 95.3, 55.7, 35.9, 33.8, 22.8,
14.3. 13C NMR (75 MHz, CDCl3) δ: 189.2, 161.3, 136.7, 129.7, 125.4,
124.4, 110.7, 60.6, 53.7, 25.5, 23.5. ESI-MS: [M + 1]+ 298.25. FT-IR
(KBr, cm−1): 3417, 2935, 2864, 1674, 1594, 1448, 1385, 1238, 1110,
989. Anal. Calcd for C13H16BrNO2: C, 52.36; H, 5.41; N, 4.70. Found:
C, 52.29; H, 5.41; N, 4.80.
Synthesis of 5,5′-((2,5-Dioctyl-1,4-phenylene)bis(ethyne-2,1-
diyl))bis(2-hydroxy-3-(piperidin-1-ylmethyl)benzaldehyde (M-1).
The mixture of 5-bromo-2-hydroxy-3-(piperidin-1-ylmethyl)-
benzaldehyde (2.52 g, 8.4 mmol), 1,4-dioctyloxy-2,5-diethynylbenzene
(1.61 g, 4.2 mmol), Pd(PPh3)2Cl2 (121.2 mg, 0.17 mmol), and CuI
(33.1 mg, 0.17 mmol) was dissolved in 50 mL of anhydrous Et3N and
was stirred for 24 h at 70 °C under N2. After being cooled to room
temperature, the solvent was removed by a rotary evaporator. The
residue was purified by flash chromatography on silica gel (ethyl
acetate−triethylamine, 5:1, v/v) by using CH2Cl2 as eluent. The
solvent was removed and washed by ethyl acetate to afford 5,5′-((2,5-
dioctyl-1,4-phenylene)bis(ethyne-2,1-diyl))bis(2-hydroxy-3-(piperi-
din-1-ylmethyl)benzaldehyde (M-1) as a yellow powder (930 mg,
27%). 1H NMR (300 M Hz, CDCl3) δ: 10.70 (br, 2H), 10.41 (s, 2H),
7.87 (s, 2H), 7.40 (s, 2H), 6.98 (s, 2H), 4.03 (t, J = 6.6 Hz, 4H), 3.76
(s, 4H), 2.60 (br, 8H), 1.86 (m, 4H), 1.71−1.29 (m, 32H), 1.04 (t, J =
7.5 Hz, 6H). 13C NMR (75 MHz, CDCl3) δ: 189.9, 162.4, 153.4,
137.0, 131.2, 123.3, 123.1, 116.8, 113.73, 113.67, 93.8, 85.0, 69.5, 60.8,
53.7, 31.8, 29.33, 29.28, 29.22, 26.0, 25.5, 23.6, 22.6, 14.1. ESI-MS: [M
+ 1]+ 817.50. FT-IR (KBr, cm−1): 3428, 2932, 2857, 2358, 1671, 1607,
1465, 1388, 1206, 1110. Anal. Calcd for C52H68N2O6: C, 76.44; H,
8.39; N, 3.43. Found: C, 78.69; H, 9.02; N, 3.80.
1
slightly beige crystals. H NMR (300 MHz, CDCl3) δ: 7.19 (s, 2H),
3.94 (t, J = 6.5 Hz, 4H), 1.82 (m, 4H), 1.57−1.31 (m, 24H), 0.91 (t, J
= 6.6 Hz, 6H). 13C NMR (75 MHz, CDCl3) δ: 152.7, 122.7, 86.2,
70.3, 31.7, 29.18, 29.15, 29.07, 26.0, 22.6, 14.1. TOF-MS: m/z 586.0.
FT-IR (KBr, cm−1): 2921, 2850, 1635, 1486, 1459, 1400, 1352, 1214,
1051, 846, 786. Anal. Calcd for C22H36I2O2: C, 45.07; H, 6.19. Found:
C, 46.02; H, 6.38.
Synthesis of 2,5-Diethynyl-1,4-dioctyloxybenzene (2). A mixture
of 2,5-diiodo-1,4-dioctyloxybenzene (5.86 g, 10 mmol), Pd(PPh3)4
(300 mg, 0.25 mmol), CuI (10 mg, 0.05 mmol), and trimethylsily-
lacetylene (2.4 mL, 20 mmol) was dissolved in 30 mL of Et3N. The
reaction mixture was stirred at 40 °C for 24 h under a N2 atmosphere.
After cooling, the resulting ammonium salt was filtered off, and the
residue was purified by chromatography on a short plug of silica gel
with petroleum ether as eluent. Removal of solvent under vacuum
afforded a gray solid, and the obtained crude product was then
dissolved in 10 mL of THF. KOH (1.12 g, 20.0 mmol) was dissolved
in 5 mL of MeOH and added to the THF solution. The reaction
mixture was stirred at room temperature for 4 h, and then the solvent
was concentrated under reduced pressure. To the residue was added a
mixture of H2O (20 mL) and CH2Cl2 (20 mL) to afford a two-phase
solution. The aqueous layer was further extracted with CH2Cl2 (2 × 20
Synthesis of the Chiral Polymer Sensor. A mixture of M-1 (163.4
mg, 0.2 mmol) and (S)-2,2′-binaphthyldiamine (56.8 mg, 0.2 mmol)
was dissolved in toluene (5 mL) and kept refluxing for 72 h. The
solvent was removed under reduced pressure, and the residue was
dissolved in a small quantity of CH2Cl2; 50 mL of methanol was added
to precipitate the polymer. A dark yellow solid was filtered off and
washed with methanol several times. The polymer was dried under
vacuum at room temperature for 24 h. The final yield was 50% (0.105
mg). [α]D25 = +290.9 (c 0.3, THF). Mw = 32 590, Mn = 18 180, PDI =
1
1.79. H NMR (300 M Hz, CDCl3) δ: 8.63 (s, HCN), 8.10−7.96
(m, ArH), 7.61−7.25 (m, ArH), 6.93 (s, ArH), 6.68 (s, ArH), 4.00−
3.91 (m, CH2N), 3.51−3.37 (m, CH2O), 2.38 (br, CH2N), 1.91−1.26
(m), 0.90−0.84 (m, CH3). IR (KBr): 3415, 2956, 2862, 2361, 1615,
1572, 1505, 1442, 1392, 1261, 1105, 1022, 803.
7836
dx.doi.org/10.1021/ma301553y | Macromolecules 2012, 45, 7835−7842

Macromolecules
Article
Scheme 1. Synthesis Procedures of the Chiral Polymer Sensor
Fluorescence Measurements. The concentrations of the stock
solution of metal salts (nitrate) and N-boc-protected amino acids are
1.0 × 10−3 mol/L in H2O and 1.0 × 10−2 mol/L in CH3CN,
respectively. Each experiment was started with a 3.0 mL of polymer in
THF solution with a known concentration (1.0 × 10−5 mol/L). The
adding amount of each experiment example of metal salt and N-boc-
protected amino acids is shown in the figure and the graphical
shows that polymer sensor has high thermal stability without
weight loss before 260 °C and tends to complete decom-
position at 650 °C, indicating that it has a desirable thermal
property for application as a fluorescence sensor (Supporting
Information Figure SI 1).
UV−vis and Fluorescence Behavior of Chiral Polymer
Sensor upon Zn2+. As shown in Figure 1, UV−vis spectra of
interpretation. All the fluorescence measurements were taken at λex
=
362 nm (slit 3/5) except for Boc-L-Phg and Boc-D-Phg. The slit has
been changed to 3/3 because the fluorescence intensity of complex
sensor upon Boc-L-Phg and Boc-D-Phg overran the measuring range of
the RF-5301PC spectrometer at slit 3/5, and all the other
measurements were carried out under the same conditions.
RESULTS AND DISCUSSION
■
Synthesis and Structure of the Chiral Polymer
Fluorescence Sensor. The synthesis procedures of chiral
polymer sensor are outlined in Scheme 1. 1,4-Dioctyloxy-2,5-
diethynylbenzene (2) was synthesized by four-step reaction in
64% yield according to reported literatures.53−55 5-Bromo-2-
hydroxy-3-(piperidin-1-ylmethyl)benzaldehyde (3) could be
obtained by the Mannich reaction from the starting material
5-bromosalicylaldehyde in 77% yield.56 The monomer M-1 was
synthesized by the reaction of 1,4-dioctyloxy-2,5-diethynylben-
zene with 5-bromo-2-hydroxy-3-(piperidin-1-ylmethyl)-
benzaldehyde via Pd-catalyzed Sonogashira coupling reaction.
The chiral BINAM-based polymer could be obtained by Schiff-
base formation via nucleophilic addition−elimination reaction
Figure 1. UV−vis spectra of the chiral polymer (1.0 × 10−5 mol/L) in
THF with increasing amounts of Zn2+ (0−2.4 equiv).
the chiral polymer sensor exhibit a maximal absorption at 243
nm and two broad bands around 328 and 387 nm before
titrations in THF. Upon addition of Zn2+ (0−2.4 equiv), the
absorbance peaks at 243 nm show a little reduction and
hypsochromic shift with increasing amounts of Zn2+. One the
contrary, the strongest broad-band absorption peak at 387 nm
arisen from the conjugated structure exhibits the gradual
enhancement and an obvious hypsochromic shift. Meanwhile, a
new absorption peak at 278 nm can be observed. Moreover,
there are two isosbestic points at 269 and 390 nm, which
indicate the formation of the UV active zinc complex.54,57 It can
be found that UV−vis absorption spectra of the chiral polymer
sensor can reach the saturated situation with a Zn2+
concentration change from 0.2 to 2.0 × 10−5 mol/L, indicating
between M-1 and (S)-2,2′-BINAM (M-2) to afford a yellow
powder in 50% yield.36,47,54 The specific rotation value ([α]D
)
20
of (S)-BINAM-based chiral polymer is +290.9° (c 0.3, THF).
Mw, Mn, and PDI of the chiral polymer were determined by gel
permeation chromatography using polystyrene standards in
THF, and the values of them are 32 590, 18 180, and 1.79,
respectively. The GPC result of the chiral polymer shows the
moderate molecular weight. The chiral polymer sensor is an air-
stable powder and shows high solubility in common organic
solvents, such as THF, toluene, CH2Cl2, CHCl3, and CH3CN,
which can be attributed to the nonplanarity of the twisted
framework and the flexible n-octyl substituents. TGA result
7837
dx.doi.org/10.1021/ma301553y | Macromolecules 2012, 45, 7835−7842

Macromolecules
Article
that the polymer sensor can form a 1:2 (Zn2+)2−sensor
polymer complex .
0.2 to 2.0. The fluorescence curve of the polymer sensor with
Zn2+ reveals that the fluorescent enhancement value (I/I0 − 1)
exhibited a good linear response to a Zn2+ concentration
change from 0.2 to 2.0 × 10−5 mol/L, indicating that the
polymer sensor can form a 1:2 (Zn2+)2−sensor polymer
complex (Figure 2b). The Job plot analysis also confirmed the
binding number of the chiral polymer is 2 for Zn2+ (Figure 2c).
Moreover, the bright blue color of the polymer sensor can be
observed under a commercially available UV lamp (inset,
Figure 2a). The obvious fluorescence enhancement for the
Zn(II)-containing polymer sensor can be regarded as two
reasons. One is suppressed PET (photoinduced electron
transfer) quenching when Zn2+ coordinates with the nitrogen
atoms of the Schiff-base moiety in the chiral polymer main
chain. Upon complexation, the lone pair of electrons on the
nitrogen atom is no longer available for PET, thus leading to an
enhancement of the emission. On the other hand, the
formation of Zn2+-containing polymer complex can break the
intramolecular hydrogen bonding between imine and hydroxyl
of phenol and promote the planarity and rigidity of the
conjugated segment of the chiral polymer, which can reduce the
nonradiative decay of the excited state and lead to the
pronounced fluorescence enhancement.54,58−60
Figure 2a illustrates the fluorescence titration of chiral
polymer (1.0 × 10−5 mol/L corresponding to (S)-binaphthyl
The experiment of the polymer sensor interacted with other
various metal ions (Ba2+, Ca2+, Co3+, Cr3+, Cu2+, Fe3+, Hg2+, K+,
Mg2+, Mn2+, Na+, Ni2+, and Ag+) was also carried out under the
same determination conditions to reveal the selective
fluorescence response behavior. As shown in Figure 3, almost
Figure 3. Selectivity of the polymer sensor (1.0 × 10−5 mol/L in THF,
λex = 362 nm, λem = 414 nm) toward Zn2+ and other metal ions (2.0 ×
10−5 mol/L): relative fluorescence intensity of the chiral polymer
sensor−metal ion complexes.
no fluorescence response can be observed upon the addition of
Ba2+, Hg2+, Mg2+, and Ni2+ at 1:2 molar ratio. But Ca2+, Cu2+,
Co3+, K+, Na+, Ag+, and Mn2+ can cause the limited fluorescent
enhancement change. Meanwhile, the fluorescent peak situated
at 543 nm appears a slight enhancement upon addition of Fe3+
and Cr3+, but no obvious change at 414 nm (Supporting
Information Figure SI 2). It indicates that the resulting chiral
polymer can act as a “turn-on” fluorescence sensor only for
Zn2+.
Figure 2. (a) Fluorescence spectra of polymer sensor with increasing
concentration Zn2+ from 0.0 to 2.4 × 10−5 mol/L (inset: the photo of
the fluorescent color of polymer sensor (1) and 1:2 Zn2+-containing
polymer complex (2)). (b) Profile of the fluorescent enhancement
value (I/I0 − 1) vs the increasing concentration of Zn2+ from 0.0 to 2.4
× 10−5 mol/L. (c) Fluorescence Jobs plot of chiral polymer and Zn2+.
The total concentrations of polymer sensor and Zn2+ are 1.0 μM. The
fluorescence emission spectra were measured at 25 °C and in THF
solution.
CD Spectra of the Chiral Polymer and Zn(II)-
Containing Polymer Complexes. The CD spectra of the
polymer sensor in the absence/presence of Zn2+ have been
measured in THF (Figure 4 and Supporting Information Table
SI 1). Compared with the chiral polymer, the CD spectra of its
corresponding in situ generated 1:1 and 1:2 Zn(II)-containing
polymer complexes show great difference from the reversed
Cotton effects. As is evident from Figure 4, we found that the
moiety in THF) toward Zn2+. The polymer sensor can emit the
weak fluorescence situated at 414 and 543 nm, which can be
attributed to the strong intramolecular hydrogen bond between
imine and hydroxyl of phenol. The fluorescence intensities of
the chiral polymer show gradual enhancement as high as 10.3-
fold upon the concentration molar ratio addition of Zn2+ from
7838
dx.doi.org/10.1021/ma301553y | Macromolecules 2012, 45, 7835−7842

Macromolecules
Article
Scheme 2. Dihedral Angle Changes of Chiral Polymer with
the Increase of Zn2+ Molar Ratios
Figure 4. CD spectra of the polymer sensor and in situ generated 1:1
and 1:2 Zn(II)-containing complexes (1.0 × 10−5 mol/L in THF).
negative Cotton effects of the chiral polymer centered at 250
nm appears the positive Cotton effect upon addition of Zn2+,
and the intensities gradually enhance as the increase of Zn2+
molar ratios from 1:1 to 1:2, but the Cotton effect at 306 nm
shows a larger red-shift to 326 nm. Moreover, the positive
Cotton effect of the long wavelength at 384 nm gradually turns
the negative Cotton effect with 45 nm blue shift in CD spectra
of the in situ Zn(II)-containing polymer complexes.
The chirality of 1,1′-BINAM is derived from the restricted
rotation of the two naphthalene rings. The rigid structure and
C2 symmetry of the chiral binaphthyl molecules can play an
important role in inherently chiral induction. The dihedral
angle between two naphthalene rings of a binaphthyl molecule
ranges from 60° to 120° which leads to the kinked or twisted
polymer main chain backbone.44,61 According to the Pu Lin and
Mason’s reports, the binaphthyl derivatives have two kind
configurations based on the substituted groups.44,62−64 If the
2,2-substituents of the 1,1-binaphthyl molecules are either small
or capable of intramolecular hydrogen bonding, the compounds
would prefer the cisoid conformation. If the two groups are of
large sizes in binaphthyl molecular, the compounds prefer
transoid conformation in order to reduce the steric interaction.
In this paper the resulting BINAM-based chiral polymer can
adopt a stable ciscoid conformation due to the small groups of
two imine substituents. The reversed Cotton effect can be
attributed to the increase of the dihedral angle between two
naphthalene rings of a binaphthyl molecule from cisoid to
transoid conformation after the formation of the Zn(II)-
containing polymer complexes. As is evident from CD spectra
at long wavelengths, we assumed that the chiral polymer chain
conformation appears reverse change from ciscoid to tanscoid
upon the formation of the Zn(II)-containing complex polymer.
It can be well understood that the whole polymer chain
backbone reverse need very high energy. The coordination
bond between the chelating imine base ligand and Zn2+ is
strong enough to cause the conformation reverse. Moreover, it
can be concluded that the dihedral angle gradually enlarges as
the increase of Zn2+ molar ratios from 1:1 to 1:2 (Scheme 2),
leading to greater Cotton effect change of the 1:2 Zn(II)-
containing polymer complex than the corresponding 1:1
Zn(II)-containing polymer complex.
above, we further investigated the fluorescence response
behaviors of chiral polymer sensor toward Boc-D-Ala and
Boc-L-Ala by using (S)-BINAM-based chiral polymer and in situ
generated 1:2 Zn(II)-containing polymer complex. No obvious
fluorescence response changes and enantioselectivities can be
observed by adding Boc-D-Ala and Boc-L-Ala (Supporting
Information Figure SI 3). But while using in situ generated 1:1
Zn(II)-containing polymer complex as a fluorescence senor, a
remarkable difference in fluorescent enhancement response
behaviors between these two enantiomers could be detected as
demonstrated in Figure 5. Boc-L-ala causes a large increase on
the fluorescent intensity of the polymer complex sensor; on the
contrary, D-isomer only has little influence on the fluorescence
intensity under the same conditions. Interestingly, the chiral
polymer complex sensor solution can appear bright blue
fluorescence color change upon addition of (L)-N-Boc-
protected alanine under a commercially available UV lamp,
which can be clearly observed by the naked eye for directly
visual discrimination in a lower concentration (Figure 5, inset).
It can also be found that the fluorescent emission wavelengths
do not show an obvious difference between guest-free sensor
and guest sensor. The obvious fluorescence enhancement of
chiral polymer complex sensor with N-boc-protected alanine
Enantioselective Recognition of in Situ Generated 1:1
Zn(II)-Containing Chiral Polymer Complex Sensor
toward N-Boc-Protected Amine Acid. Considering the
significant discrepancy of the CD spectra of (S)-BINAM-based
chiral polymer induced by the addition amount of Zn2+ shown
7839
dx.doi.org/10.1021/ma301553y | Macromolecules 2012, 45, 7835−7842

Macromolecules
Article
Figure 5. Fluorescent spectra of in situ 1:1 Zn2+-containing sensor with
Boc-L-ala or Boc-D-ala (inset: the photo of the fluorescence color
changes of complex sensor (1) when it interacted with Boc-D-ala (2)
and Boc-L-ala (3)) (polymer sensor: 1.0 × 10−5 mol/L in THF; Zn2+:
1 × 10−5 mol/L; λex = 362 nm; λem = 414 nm).
can be attributed to the suppressed PET (photoinduced
electron transfer) quenching65−68 when the protons of N-Boc-
protected alanine interact with the nitrogen atoms of imine
moieties of Schiff base in the chiral polymer main chain. On
complexation, the lone pair of electrons on the nitrogen atom is
no longer available for PET, leading to the fluorescence
enhancement.69−74 Herein, we further investigated the
interaction of in situ 1:1 generated Zn(II)-containing chiral
polymer complex sensor with N-boc-protected alanine at a
much broader concentration range. In regard to the
fluorescence signal changes of this chiral polymer complex
sensor on Boc-D-Ala and Boc-L-Ala, the fluorescence intensities
appear gradual enhancement upon addition of Boc-D-Ala and
Boc-L-Ala in the range from 1:5 to 1:100 molar ratios (Figure
6a,b). Meanwhile, it can also be found that the fluorescent
enhancement ratio (I/I0) displays a nearly linear correlation
with concentrations of Boc-L-ala change from 10 to 70 × 10−5
mol/L and Boc-D-ala change from 5 to 100 × 10−5 mol/L,
respectively (Figure 6c). The enantiomeric fluorescence
difference ratio ef (ef = (IL − I0)/(ID − I0) in this case is
6.90 at 1:100 molar ratio, which indicates that this in situ
generated 1:1 Zn(II)-containing chiral polymer complex can
exhibit highly enantioselective response toward Boc-L-ala. The
reason may be attributed to an inherent chiral recognition
based on the steric repulsion of polymer complex precursor for
Boc-L-ala. The building block of 1:1 Zn(II)-containing complex
receptor composed of Schiff base, Zn(II) complex of Schiff
base, and the piperidyl groups, which is also controlled by the
dihedral angle of binaphthyl, can well fit for the formation of a
more stable S-L complex as compared to the S-D diastereomeric
complex. As shown in Scheme 2, we can also draw the
conclusion that either (S)-BINAM-based chiral polymer or in
situ generated 1:2 Zn(II)-containing polymer complex cannot
exhibit fluorescence response and enantioselective recognition
toward Boc-L-Ala or Boc-D-Ala. Therefore, the explanation can
be made as the following reasons: N-Boc-protected alanine
guest molecules cannot enter the small steric space of the
building block in (S)-BINAM-based chiral polymer due to
cisoid configuration. On the other hand, as for in situ generated
1:2 Zn(II)-containing polymer complex, N-boc-protected
alanine guest cannot directly interact with the chiral unit
centers because two (S)-BINAM-based Schiff bases have been
Figure 6. (a) Fluorescent spectra of complex sensor with increasing
concentration Boc-L-ala from 0 to 100 × 10−5 mol/L. (b) Fluorescent
spectra of complex sensor with increasing concentration Boc-D-ala
from 0 to 100 × 10−5 mol/L. (c) Fluorescent enhancement (I/I0) of
complex sensor versus the increasing concentration of Boc-L-ala or
Boc-D-ala (complex sensor: 1.0 × 10−5 mol/L in THF; λex = 362 nm;
λem = 414 nm).
completely occupied by two Zn2+ ions and form 1:2 (Zn2+)2−
Schiff base complex.
In order to ascertain the significance of the presence of Zn2+
for this polymer complex sensor, we further investigated in situ
1:1 other metal ion-containing polymer complexes as
fluorescence sensors for enantioselective recognition toward
Boc-D-Ala and Boc-L-Ala, such as Mg2+, Cu2+, Ni2+, Hg2+, Cr3+,
and Ag+ to replace Zn2+ under the same conditions. As shown
in Supporting Information Figure SI 4, none of these metal-
containing chiral polymer complexes show obvious fluores-
cence response and enantioselectivity toward Boc-D-Ala and
Boc-L-Ala. In a set of comparable experiments, we also studied
the interaction of 1:1 Zn(II)-containing chiral polymer complex
7840
dx.doi.org/10.1021/ma301553y | Macromolecules 2012, 45, 7835−7842

Macromolecules
Article
(4) Li, D. M.; Zheng, Y. S. Chem. Commun. 2011, 47, 10139−10141.
sensor with other N-Boc-protected amino acids including N-
Boc-Phe, N-Boc-Phg, N-Boc-Pro, and N-Boc-Val (Scheme 3);
almost no enantioselective recognition effect could be detected
even the obvious fluorescence enhancement responses can be
observed (Supporting Information Figures SI 5−8).
(5) Nieto, S.; Dragna, J. M.; Anslyn, E. V. Chem.Eur. J. 2010, 16,
227−232.
(6) Zhang, X.; Chi, L.; Ji, S. M.; Wu, Y. B.; Song, P.; Han, K.; Guo, H.
M.; James, T. D.; Zhao, J. Z. J. Am. Chem. Soc. 2009, 131, 17452−
17463.
(7) Nguyen, T. H.; Ansell, R. J. Org. Biomol. Chem. 2009, 7, 1211−
Scheme 3. Guest Molecules Used in the Enantioselective
Recognition with the Complex Sensor
1220.
(8) Wu, Y.; Guo, H.; James, T. D.; Zhao, J. Z. J. Org. Chem. 2011, 76,
5685−5695.
(9) Tu, T.; Fang, W.; Bao, X.; Li, X.; Dotz, K. H. Angew. Chem. 2011,
̈
123, 6731−6735.
(10) Xing, Z.; Wang, H. C.; Cheng, Y. X.; Zhu, C. J.; James, T. D.;
Zhao, J. Z. Eur. J. Org. Chem. 2012, 6, 1223−1229.
(11) Kim, Y. K.; Lee, H. N.; Singh, N. J.; Choi, H. J.; Xue, J. Y.; Kim,
K. S.; Yoon, J.; Hyun, M. H. J. Org. Chem. 2008, 73, 301−304.
(12) Zhang, X. X.; Bradshaw, J. S.; Izatt, R. M. Chem. Rev. 1997, 97,
3313−3361.
(13) Brunel, J. M. Chem. Rev. 2005, 105, 857−898.
(14) Jacques, B.; Chavarot, M.; Rose-Munch, F.; Rose, E. Angew.
Chem., Int. Ed. 2006, 45, 3481−3484.
CONCLUSIONS
■
In summary, we first designed a kind (S)-BINAM-based chiral
polymer which can show the “turn-on” fluorescent sensor only
for Zn2+. The in situ generated 1:1 Zn(II)-containing polymer
complex used as the fluorescence sensor can exhibit the
remarkable fluorescence enhancement response and high
enantioselectivite recognition toward N-Boc-L-protected ala-
nine, which indicates that the building block of Zn(II)-
containing complex receptor containing Schiff base, Zn(II)
complex of Schiff base, and the piperidyl groups, which is also
controlled by the dihedral angle of binaphthyl, can well fit for
the formation of a more stable S-L complex as compared to the
S-D diastereomeric complex. Interestingly, the chiral polymer
complex sensor solution can appear bright blue fluorescence
color change upon addition of (L)-N-Boc-protected alanine
under a commercially available UV lamp, which can be clearly
observed by the naked eye for direct visual discrimination in a
lower concentration. This work can be applied for detection of
chiral enantiomers by a simple, rapid, and sensitive method.
́ ́ ́
(15) Fogassy, E.; Nogradi, M.; Kozma, D.; Egri, G.; Palovics, E.; Kiss,
V. Org. Biomol. Chem. 2006, 4, 3011−3030.
(16) Li, Z. B.; Lin, J.; Qin, Y. C.; Pu, L. Org. Lett. 2005, 7, 3441−
3444.
(17) Tumambac, G. E.; Wolf, C. Org. Lett. 2005, 7, 4045−4048.
(18) Hembury, G. A.; Borovkov, V. V.; Inoue, Y. Chem. Rev. 2008,
108, 1−73.
(19) Korbel, G. A.; Lalic, G.; Shair, M. D. J. Am. Chem. Soc. 2001,
123, 361−362.
(20) Eelkema, R.; Delden, R. A.; Feringa, B. L. Angew. Chem., Int. Ed.
2004, 43, 5013−5016.
(21) Ding, K.; Ishii, A.; Mikami, K. Angew. Chem., Int. Ed. 1999, 38,
497−501.
(22) Matsushita, M.; Yoshida, K.; Yamamoto, N.; Wirsching, P.;
Lerner, R. A.; Janda, K. D. Angew. Chem., Int. Ed. 2003, 42, 5984−
5987.
(23) Gokel, G. W.; Leevy, W. M.; Weber, M. E. Chem. Rev. 2004,
104, 2723−2750.
(24) Ikeda, H.; Li, Q.; Bioorg, A.; Ueno, A. Med. Chem. Lett. 2006,
16, 5420−5423.
ASSOCIATED CONTENT
■
(25) Zhao, J. Z.; Davidson, M. G.; Mahon, M. F.; Kociok-Kohn, G.;
James, T. D. J. Am. Chem. Soc. 2004, 126, 16179−16186.
(26) Yang, X.; Liu, X.; Shen, K.; Zhu, C. J.; Cheng, Y. X. Org. Lett.
2011, 13, 3510−3513.
S
* Supporting Information
Fluorescence and data mentioned in the text; 1H and 13C NMR
spectra of all new compounds as well. This material is available
free of charge via the Internet at http://pubs.acs.org.
(27) He, X.; Zhang, Q.; Liu, X.; Lin, L.; Feng, X. M. Chem. Commun.
2011, 47, 11641−11643.
(28) He, X.; Zhang, Q.; Wang, W.; Lin, L.; Liu, X.; Feng, X. M. Org.
Lett. 2011, 13, 804−807.
AUTHOR INFORMATION
Corresponding Author
*Tel 86-25-83686508; Fax 86-25-83317761; e-mail yxcheng@
nju.edu.cn (Y.-X.C.), cjzhu@nju.edu.cn (C.-J.Z.).
■
(29) Dong, Y.; Mao, X. R.; Jiang, X. X.; Hou, J. L.; Cheng, Y. X.; Zhu,
C. J. Chem. Commun. 2011, 47, 9450−9452.
(30) Zhou, Y.; Yoon, J. Y. Chem. Soc. Rev. 2012, 41, 52−67.
(31) Zhou, Y.; Won, J.; Lee, J. Y.; Yoon, J. Y. Chem. Commun. 2011,
47, 1997−1999.
Notes
The authors declare no competing financial interest.
(32) Chen, X.; Huang, Z.; Chen, S.; Li, K.; Yu, X.; Pu, L. J. Am. Chem.
Soc. 2010, 132, 7297−7299.
ACKNOWLEDGMENTS
■
(33) Meng, J.; Wei, G.; Huang, X. B.; Dong, Y.; Cheng, Y. X.; Zhu, C.
J. Polymer 2011, 52, 363−367.
We gratefully acknowledge the National Natural Science
Foundation of China (No. 21074054, 51173078, and
21172106), National Basic Research Program of China
(2010CB923303), and Zhejiang Provincial Natural Science
Foundation (No. Y4110141) for their financial support.
(34) Bao, Y.; Li, Q.; Liu, B.; Du, F.; Tian, J.; Wang, H.; Wang, Y.; Bai,
R. Chem. Commun. 2012, 48, 118−120.
(35) Zeng, Q.; Zhang, L.; Li, Z.; Qin, J.; Tang, B. Polymer 2009, 50,
434−440.
(36) Xu, Y.; Zheng, L. F.; Huang, X. B.; Cheng, Y. X.; Zhu, C. J.
Polymer 2010, 51, 994−997.
REFERENCES
■
(37) Xi, X. J.; Lou, L. P.; Jiang, L. M.; Sun, W. L.; Shen, Z. Q. Polymer
2008, 49, 2065−2070.
(1) Liu, H. L.; Peng, Q.; Wu, Y. D.; Chen, D.; Hou, X. L.; Sabat, M.;
Pu, L. Angew. Chem., Int. Ed. 2010, 49, 602−606.
(2) Pu, L. Chem. Rev. 2004, 104, 1687−1715.
(3) Zhu, L.; Zhong, Z.; Anslyn, E. V. J. Am. Chem. Soc. 2005, 127,
4260−4269.
(38) Zhang, H. C.; Pu, L. Macromolecules 2004, 37, 2695−2702.
(39) Qing, G. Y.; Sun, T. L.; He, Y. B.; Wang, F.; Chen, Z. H.
Tetrahedron: Asymmetry 2009, 20, 575−583.
7841
dx.doi.org/10.1021/ma301553y | Macromolecules 2012, 45, 7835−7842

Macromolecules
Article
(40) Sakthivel, S.; Punniyamurthy, T. Tetrahedron: Asymmetry 2012,
23, 570−576.
(41) Swager, T. M. Acc. Chem. Res. 1998, 31, 201−207.
(42) McQuade, D. T.; Pullen, A. E.; Swager, T. M. Chem. Rev. 2000,
100, 2537−2574.
(43) Thomas, S. W., III; Joly, G. D.; Swager, T. M. Chem. Rev. 2007,
107, 1339−1386.
(44) Pu, L. Chem. Rev. 1998, 98, 2405−2494.
(45) Huang, X. B.; Xu, Y.; Zheng, L. F.; Meng, J.; Cheng, Y. X.
Polymer 2009, 50, 5996−6000.
(46) Xu, Y. J.; Lin, L. Q.; Kanai, M.; Matsunaga, S.; Shibasaki, M. J.
Am. Chem. Soc. 2011, 133, 5791−5793.
(47) Colombo, F.; Benaglia, M.; Orlandi, S.; Usuelli, F.; Celentano,
G. J. Org. Chem. 2006, 71, 2064−2070.
(48) Wiznycia, A. V.; Desper, J.; Christopher, J. L. Dalton Trans.
2007, 15, 1520−1527.
(49) Wiznycia, A. V.; Desper, J.; Christopher, J. L. Chem. Commun.
2005, 37, 4693−4695.
(50) Chen, Z.; Furutachi, M.; Kato, Y.; Matsunaga, S.; Shibasaki, M.
Angew. Chem., Int. Ed. 2009, 48, 2218−2220.
(51) Chapurina, Y.; Hannedouche, J.; Collin, J.; Guillot, R.; Schulz,
E.; Trifonov, A. Chem. Commun. 2010, 46, 6918−6920.
(52) Che, C. M.; Huang, J. S. Coord. Chem. Rev. 2003, 242, 97−113.
(53) Plater, M. J.; Sinclair, J. P.; Aiken, S.; Gelbrich, T.; Hursthouse,
M. B. Tetrahedron 2004, 60, 6385−6394.
(54) Xu, Y.; Meng, J.; Meng, L. X.; Dong, Y.; Cheng, Y. X.; Zhu, C. J.
Chem.Eur. J. 2010, 16, 12898−12903.
(55) Song, F. Y.; Wei, G.; Wang, Lu.; Jiao, J. M.; Cheng, Y. X.; Zhu,
C. J. J. Org. Chem. 2012, 77, 4759−4764.
(56) DiMauro, E. F.; Kozlowski, M. C. Org. Lett. 2001, 3, 3053−
3056.
(57) Hung, C. H.; Chang, G. F.; Kumar, A.; Lin, G. F.; Luo, L. Y.;
Ching, W. M.; Diauc, E. W. G. Chem. Commun. 2008, 978−980.
(58) Xu, Z. C.; Baek, K. H.; Kim, H. N.; Cui, J. N.; Qian, X. H.;
Spring, D. R.; Shin, I.; Yoon, J. Y. J. Am. Chem. Soc. 2010, 132, 601−
610.
(59) Song, F. Y.; Ma, X.; Hou, J. L.; Huang, X. B.; Cheng, Y. X.; Zhu,
C. J. Polymer 2011, 52, 6029−6036.
(60) Ngwendson, J. N.; Banerjee, A. Tetrahedron Lett. 2007, 48,
7316−7319.
(61) Naciri, J.; Spada, G. P.; Gottarelli, G.; Weiss, R. G. J. Am. Chem.
Soc. 1987, 109, 4352−4357.
(62) Mason, S. F.; Seal, R. H.; Roberts, D. R. Tetrahedron 1974, 30,
1671−1682.
(63) Kuroda, R.; Mason, S. F. Tetrahedron 1981, 37, 1995−1999.
(64) Li, Z. B.; Lin, J.; Sabat, M.; Hyacinth, M.; Pu, L. J. Org. Chem.
2007, 72, 4905−4906.
(65) Bojinov, V. B.; Georgiev, N. I.; Bosch, P. J. Fluoresc. 2009, 19,
127−139.
(66) Bissell, R. A.; de Silva, A. P.; Gunaratne, H. Q. N.; Lynch, P. L.
M.; Maguire, G. E. M.; McCoy, C. P.; Sandanayake, K. R. A. S. Top.
Curr. Chem. 1993, 168, 223−264.
(67) Bissell, R. A.; de Silva, A. P.; Gunaratne, H. Q. N.; Lynch, P. L.
M.; Maguire, G. E. M.; Sandanayake, K. R. A. S. Chem. Soc. Rev. 1992,
21, 187−195.
(68) Czarnik, A. W. Acc. Chem. Res. 1994, 27, 302−308.
(69) Kumar, M.; Badu, J. N.; Bhalla, V.; Kumar, R. Sens. Actuators, B
2010, 144, 183−191.
(70) Luo, H. Y.; Jiang, J. H.; Zhang, X. B.; Li, C. Y.; Shen, G. L.; Yu,
R. Q. Talanta 2007, 72, 575−581.
(71) Yang, Y. Y.; Cheng, T. Y.; Zhu, W. P.; Xu, Y. F.; Qian, X. H. Org.
Lett. 2011, 13, 264−267.
(72) Zhang, Y. M.; Chen, Y. C.; Li, Z. Q.; Li, N.; Liu, Y. Bioorg. Med.
Chem. 2010, 18, 1415−1420.
(73) Cheng, T. Y.; Xu, Y. F.; Zhang, S. Y.; Zhu, W. P.; Qian, X. H.;
Duan, L. P. J. Am. Chem. Soc. 2008, 130, 16160−16161.
(74) Kim, H. N.; Ren, W. X.; Kim, J. S.; Yoon, J. Y. Chem. Soc. Rev.
2012, 41, 3210−3244.
7842
dx.doi.org/10.1021/ma301553y | Macromolecules 2012, 45, 7835−7842