Highly sensitive determination of enantiomeric composition of chiral acids based on aggregation-induced emission

Article abstract of DOI:10.1039/c2cc30448a

A new chiral tetraphenylethylene derivative with the AIE effect was synthesized and showed not only high enantioselectivity for a wide range of chiral acids but also a high sensitivity of 3.0 × 10^-6 M scale. The enantiomeric purity of chiral acids could be quantitatively determined by this chiral sensor.

Full text of DOI:10.1039/c2cc30448a

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Cite this: Chem. Commun., 2012, 48, 4908–4910
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COMMUNICATION
Highly sensitive determination of enantiomeric composition of chiral
acids based on aggregation-induced emissionw
Ning-Ning Liu, Song Song, Dong-Mi Li and Yan-Song Zheng*
Received 19th January 2012, Accepted 5th March 2012
DOI: 10.1039/c2cc30448a
A new chiral tetraphenylethylene derivative with the AIE effect was
synthesized and showed not only high enantioselectivity for a wide
range of chiral acids but also a high sensitivity of 3.0 ꢀ 10ꢁ6 M scale.
The enantiomeric purity of chiral acids could be quantitatively
determined by this chiral sensor.
Chiral recognition through fluorescence change attracts keen
interest because it can provide time-efficient, accurate, and
sensitive enantiomeric determination of chiral reagents, catalysts,
natural products and drugs.1–3 However, to design and synthesize
Scheme 1 Synthesis of chiral AIE compounds (1S,2R)-2 and
(1R,2S)-2.
excellent fluorescent chiral receptors is still a challenge.1–3
Recently, a new class of organic compounds with an aggregation-
induced emission (AIE) or aggregation-induced emission
enhancement (AIEE) have been developed4 and shown to be
highly selective and stable fluorescence sensors for biological and
chemical analytes, such as for specific detection and quantitative
analysis of carbon dioxide4b and D-glucose.4c Previously, we
have demonstrated that chiral AIE carboxylic acids or amines
can show exceptionally high enantioselectivity for chiral analytes,
but the sensitivity was not high.5 Pu and Hou2a,b also found
enantioselective precipitation and solid-state fluorescence
Fig. 1 Fluorescence spectra of a mixture of (1S,2R)-2 and enantiomers
enhancement in the recognition of a-hydroxycarboxylic acids
of 2,3-di(p-toluoyl)tartaric acid 3 in chloroform. [(1S,2R)-2] = [3] =
5.0 ꢀ 10ꢁ4 M, lex = 323 nm, ex/em slits = 10/10 nm.
by 1,10-bi-2-naphthol-amine receptors, but this chiral recognition
was only obtained at a large concentration of 4.0 ꢀ 10ꢁ3 M.
Recently, Zhu and Cheng et al.2c studied the effect of solvent
(1S,2R)- or (1R,2S)-1,2-diphenyl-2-aminoethanol to give chiral
AIE compounds (1S,2R)-2 and (1R,2S)-2 (Scheme 1). The test
polarity on the sensitivity of chiral recognition of a-hydroxy-
carboxylic acids by salan sensors, and found that a considerable
of mixed solvent confirmed that (1S,2R)-2 and (1R,2S)-2 were
AIE compounds (Fig. S9, ESIw).
enantioselectivity could only be realized at a concentration of
more than 1.0 ꢀ 10ꢁ4 M for the chiral acids in optimized solvents.
Here we report that chiral tetraphenylethylene derivative 2 with
the AIE effect displays not only high enantioselectivity for a wide
range of chiral acids but also very high sensitivity. Even at a low
concentration of 3.0 ꢀ 10ꢁ6 M scale, two enantiomers of a chiral
acid can be efficiently discriminated.
As shown in Fig. 1, Fig. S10–S18 (ESIw) and Table 1, the
chiral recognition ability of (1S,2R)-2 was tested for a large
number of chiral acids. It was noticed that (1S,2R)-2 was
especially suitable for chiral diacids probably due to two amine
groups connected to it. For 2,3-di-p-toluoyltartaric acid 3, the
mixture of (1S,2R)-2 and D-3 produced precipitates but that of
(1S,2R)-2 and L-3 gave a solution in chloroform. The suspended
precipitates strongly fluoresced while the solution did not
(Fig. 1). The fluorescence intensity ratio or enantioselectivity
(I1/I2 in Table 1) resulted from two enantiomers of 3 was 25. For
2,3-dibenzoyltartaric acid 4, malic acid 5, N-Boc-glutamic acid 6
and N-Cbz-aspartic acid 7, (1S,2R)-2 also exhibited a high
enantioselectivity from 20, 14, 20 to 12, respectively (Table 1).
The AIE compound (1S,2R)-2 also exhibited excellent chiral
recognition between two enantiomers of chiral monocarboxylic
acids (Fig. S14–S17, ESIw). The enantioselectivity was 5.0, 13,
Tetraphenylethylene (TPE) and its derivatives are well
known for their excellent AIE effect.4 Therefore, the known
dibromoethoxy TPE 16 was chosen to react with chiral auxiliary
Department of Chemistry, Huazhong University of Science and
Technology, Wuhan 430074, P. R. China.
E-mail: zyansong@hotmail.com; Fax: 0086-27-87543632;
Tel: 0086-27-87543232
w Electronic supplementary information (ESI) available: Experimental
materials and methods, spectra and images. See DOI: 10.1039/c2cc30448a
c
4908 Chem. Commun., 2012, 48, 4908–4910
This journal is The Royal Society of Chemistry 2012

Table 1 The enantioselectivity (I1/I2) of (1S,2R)-2 resulted from two
enantiomers of chiral acids
No.
1
Acids
I1/I2
Statea
25 (D/L)
Pre/Solb
2
3
4
20 (D/L)
14 (D/L)
20 (D/L)
Pre/Solb
Sus/Solc
Sus/Solc
Fig. 2 Change of fluorescence intensity ratio for two enantiomers of 3
with concentration of (1S,2R)-2 in different solvent(s): (A) CHCl3; (B) m
concentration axis n = 5, CHCl3/hexane 1 : 2; K concentration axis n = 6,
CHCl3/hexane 1 : 4 (V/V). [D-3]/[(1S,2R)-2] = [L-3]/[(1S,2R)-2] = 1:1.
5
6
12 (D/L)
5.0 (D/L)
Sus/Solc
Sus/Sold
initially increased from 2.1 to 31 and then decreased from
31 to 1.7 when concentration decreased from 1.0 ꢀ 10ꢁ4 M to
1.0 ꢀ 10ꢁ5 M (Fig. 2B, m). At a concentration of 3.0 ꢀ 10ꢁ5 M,
the mixture of (1S,2R)-2 and L-3 became a solution but that of
(1S,2R)-2 and D-3 remained a suspension. Therefore, the highest
enantioselectivity (31, D/L) was obtained at this concentration. Even
at 2.0 ꢀ 10ꢁ5 M, (1S,2R)-2 also led to a high enantioselectivity of
up to 22. But at 1.0 ꢀ 10ꢁ5 M, it had only 1.7.
7
8
13 (D/L)
Sus/Solc
Sus/Sole
46 (R/S)
When the volume ratio of chloroform and hexane was decreased
to 1 : 4, (1S,2R)-2 could discriminate the two enantiomers even
at a concentration of 10ꢁ6 M scale. As shown in Fig. 2B (K),
the enantioselectivity initially increased from 1 to 16 and then
decreased from 16 to 1.2 when concentration of the mixture of
(1S,2R)-2 and one enantiomer of 3 decreased from 1.0 ꢀ 10ꢁ5 M
to 1.0 ꢀ 10ꢁ6 M. The maximum of enantioselectivity appeared at
5.0 ꢀ 10ꢁ6 M and it was still up to 9.0 even at 3.0 ꢀ 10ꢁ6 M.
Unlike those at high concentration, all mixtures of (1S,2R)-2 and
enantiomers of 3 seemed to be almost a clear solution at a
low concentration of 10ꢁ6 M scale. However, even under a
portable 365 nm UV lamp, the mixture of (1S,2R)-2 and D-3
emitted strong blue light but that of (1S,2R)-2 and L-3 showed
no fluorescence.
9
16 (S/R)
Sus/Solc
Sus/Sold
10
5.6 (D/L)
a
Enantiomer 1/enantiomer 2, Pre = precipitates; Sus = suspension;
Sol = solution. Fluorescence intensity (I) was measured at lmax
.
b
c
d
In CHCl3. In H2O/THF. In CH2Cl2. In CH2Cl2/hexane.
e
46, and 16 for N-Boc-serine 8 and pyroglutamic acid 9 as well as
convenient a-hydroxycarboxylic acids, mandelic acid 10 and
2-chloromandelic acid 11, respectively (Table 1). In addition,
even for a strong acid, camphorsulfonic acid 12, (1S,2R)-2
could also discriminate its two enantiomers with a good
enantioselectivity of 5.6 (Fig. S18 (ESIw) and No. 10 in Table 1).
The enantioselectivity between two enantiomers of chiral
acids could change as concentration and solvent(s) were
changed. In chloroform, all mixtures of (1S,2R)-2 and L-3
from 1.0 ꢀ 10ꢁ4 M to 1.0 ꢀ 10ꢁ3 M were a clear solution, but
those of (1S,2R)-2 and D-3 appeared as a suspension when the
concentration was more than 3.0 ꢀ 10ꢁ4 M. The enantioselectivity
increased from 25, 95 to 160 when concentration increased
from 5.0 ꢀ 10ꢁ4, 8.0 ꢀ 10ꢁ4 to 1.0 ꢀ 10ꢁ3 M. In the range of
concentration less than 3.0 ꢀ 10ꢁ4 M, almost no fluorescence
intensity difference for two enantiomers was observed (Fig. 2A). If
a mixed solvent of chloroform and hexane was used, high enantio
selectivity could be obtained at lower concentration. In chloroform
mixed with hexane (volume ratio 1 : 2), the enantioselectivity
1H NMR titration of (1S,2R)-2 with D-3 or L-3 was carried
in d-chloroform (Fig. S20–S23, ESIw). From the Job plots,
it was found that both D-3 and L-3 formed a 1 : 1 complex
with (1S,2R)-2. The association constants of (1S,2R)-2–D-3
complexes and (1S,2R)-2–L-3 complexes were 6.3 ꢀ 104 Mꢁ1
and 1.3 ꢀ 105
M
ꢁ1, respectively, demonstrating a different
binding force when D-3 and L-3 interacted with (1S,2R)-2
respectively. FE-SEM images disclosed that the suspension
of (1S,2R)-2–D-3 complexes was pod-like nano-rods with
about 80 nm width and 350 nm length, while the solid resulted
from dryness of the solution of (1S,2R)-2–L-3 complexes was
irregular lamella (Fig. S24 and S25, ESIw). Importantly, ESI+
mass spectra of the mixture of 2 and 3 in chloroform not only
showed a strong peak of 2–3 complexes (m/z 1229.5, M + 1)
but also obvious one of 22–32 tetramers (m/z 2459.1, M + 3)
(Fig. S26–S29, ESIw), indicating oligomers composed of 2 and 3
c
This journal is The Royal Society of Chemistry 2012
Chem. Commun., 2012, 48, 4908–4910 4909

fluorescence quench is limited, therefore, it will emit strong
fluorescence. The more it aggregates, the stronger it emits.
The chiral recognition by chiral AIE compound 2 at very
low concentration could be used for quantitative determination
of enantiomeric composition of chiral acids. Due to inherent
chiral recognition, when (1R,2S)-2 was used as chiral amine, the
interaction of chiral acids with (1R,2S)-2 resulted in a contrary
enantioselective aggregation compared with (1S,2R)-2. When
3.3 ꢀ 10ꢁ5 M solutions of 3 with varying enantiomeric ratios
were tested with (1S,2R)-2 at the same concentration (Fig. S34,
ESIw), the fluorescence intensity increased with increasing molar
percentage of D-3 in two enantiomers of 3. The fluorescence
intensity change was sensitive to the variation of enantiomeric
composition, especially at low molar percentage less than 10% of
D-3. Similarly, the fluorescence intensity of the same experiment
with (1R,2S)-2 increased with increasing molar percentage of L-3.
It also had a sharp increase as long as a little amount of L-3 was
added into D-3, demonstrating the high sensitivity of the chiral
sensor. As a result, the enantiomeric purity of chiral acid 3 could
be obtained from any one of two standard curves drawn from the
above two tests with (1S,2R)-2 and (1R,2S)-2, respectively.
The authors thank National Natural Science Foundation of
China (No. 20872040 and 21072067), the Fundamental Research
Funds for the Central Universities (HUST No. 2010ZD007), and
the Analytical and Testing Centre at Huazhong University of
Science and Technology for support.
Fig. 3 The main intermolecular NOEs between 2 and 3 in 2–3
complexes and probable mechanism of aggregates formation.
in a 1 : 1 ratio could be easily produced. Due to acid–base
interaction of carboxylic and amino groups, methine protons
of the acid were close to protons of two alkanoic chains
connected to amino groups and showed intermolecular NOEs
between Ha–Hd, Ha–He, Ha–Hf, and Ha–Hg in 2D NOESY
spectra of 2–3 complexes. Exceptionally, there were obvious
intermolecular NOEs between the toluoyl protons of the acid
and the protons of the substituted phenyl ring of the TPE part
in 2 (between Hb–Hc) (Fig. 3 and Fig. S30–S33 (ESIw)),
indicating that the toluoyl group of the acid was close to the
TPE part of 2. No intermolecular NOEs between methyl
protons of the toluoyl group and phenyl protons of the TPE
part were found. Therefore, the 2–3 complex formed by
approach of the acid 3 to the amine 2 from exterior of two
amino groups of 2, rather than between two amino groups of 2
(Fig. 3). The intermolecular NOEs also excluded the diacid 3
from forming a bridge between two molecules of 2. The 2–3
complex formed by acid–base interaction can be converted
into a tetramer complex A by dipole–dipole attraction of two
acid–base ion pairs and hydrogen bonds (Fig. 3). By further
acid–base interaction at the x direction, tetramer complexes As
form a 1D network B, which can stack side by side at y and z
directions to give a 3D nano-rod. If the acid is monoacid, the
resultant tetramer complex could stack from the z direction by
hydrogen bonds of acid–base ion pairs to give a 1D network,
which could arrange side by side to give aggregates. This
probable self-assembly of acid–base complexes can be found
in recent literature7 and in crystal structure of the complex of
(1S,2R)-2-amino-1,2-diphenylethanol and (1R)-camphor-10-
sulfonic acid we have obtained (unpublished). In case the inter-
action force between the tetramer complexes is not enough, or the
tetramer is easily soluble in solvents, the 1D network cannot form,
which will lead to no aggregates. Due to different binding force
of two enantiomers to (1S,2R)-2, and different solubility of 2–3
complexes or tetramers from two enantiomers, one enantiomer
results in aggregates, another leads to no or less aggregates. In
aggregates, the intramolecular rotation of (1S,2R)-2 leading to
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4910 Chem. Commun., 2012, 48, 4908–4910
This journal is The Royal Society of Chemistry 2012