Influence of stereoregularity and linkage groups on chiral recognition of poly(phenylacetylene) derivatives bearing L -leucine ethyl ester pendants as chiral stationary phases for HPLC

Article abstract of DOI:10.1002/pola.26611

Stereoregular poly(phenylacetylene) derivatives bearing L-leucine ethyl ester pendants, poly-1 and poly-2a, were, respectively, synthesized by the polymerization of N-(4-ethynylphenylcarbamoyl)-L-leucine ethyl ester (1) and N-(4-ethynylphenyl-carbonyl)-L-leucine ethyl ester (2) using Rh(nbd)BPh ₄ as a catalyst, while stereoirregular poly-2b was synthesized by solid-state thermal polymerization of 2. Their chiral recognition abilities for nine racemates were evaluated as chiral stationary phases (CSPs) for high-performance liquid chromatography (HPLC) after coating them on silica gel. Both poly-1 and poly-2a with a helical conformation showed their characteristic recognition depending on coating solvents and the linkage groups between poly(phenylacetylene) and L-leucine ethyl ester pendants. Poly-2a with a shorter amide linkage showed higher chiral recognition than poly-1 with a longer urea linkage. Coating solvents played an important role in the chiral recognition of both poly-1 and poly-2a due to the different conformation of the polymer main chains induced by the solvents. A few racemates were effectively resolved on the poly-2a coated with a MeOH/CHCl₃ (3/7, v/v) mixture. The separation factors for these racemates were comparable to those obtained on the very popular CSPs derived from polysaccharide phenylcarbamates. Stereoirregular poly-2b exhibited much lower chiral recognition than the corresponding stereoregular, helical poly-2a, suggesting that the regular structure of poly(phenylacetylene) main chains is essential to attain high chiral recognition.

Full text of DOI:10.1002/pola.26611

JOURNAL OF
POLYMER SCIENCE
ARTICLE
WWW.POLYMERCHEMISTRY.ORG
Influence of Stereoregularity and Linkage Groups on Chiral Recognition
of Poly(phenylacetylene) Derivatives Bearing L-Leucine Ethyl Ester
Pendants as Chiral Stationary Phases for HPLC
Chunhong Zhang,1,2 Fangbin Liu,1 Yufa Li,1 Xiande Shen,1 Xiaodong Xu,1 Ryosuke Sakai,3
Toshifumi Satoh,4 Toyoji Kakuchi,4 Yoshio Okamoto1,5
1Polymer Materials Research Center, College of Materials Science and Chemical Engineering, Harbin Engineering University,
Harbin 150001, China
2Key Laboratory of Superlight Materials and Surface Technology, College of Materials Science and Chemical Engineering,
Harbin Engineering University, Ministry of Education, Harbin 150001, China
3Department of Materials Chemistry, Asahikawa National College of Technology, Asahikawa 071-8142, Japan
4Division of Biotechnology and Macromolecular Chemistry, Graduate School of Engineering, Hokkaido University,
Sapporo 060-8628, Japan
5Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8603, Japan
Correspondence to: C. Zhang (E-mail: zhangchunhong97@163.com) or Y. Okamoto (E-mail: okamoto@apchem.nagoya-u.ac.jp)
Received 19 November 2012; accepted 29 January 2013; published online 22 February 2013
DOI: 10.1002/pola.26611
ABSTRACT: Stereoregular
poly(phenylacetylene) derivatives
chiral recognition of both poly-1 and poly-2a due to the differ-
ent conformation of the polymer main chains induced by the
solvents. A few racemates were effectively resolved on the
poly-2a coated with a MeOH/CHCl3 (3/7, v/v) mixture. The sepa-
ration factors for these racemates were comparable to those
obtained on the very popular CSPs derived from polysaccha-
ride phenylcarbamates. Stereoirregular poly-2b exhibited much
lower chiral recognition than the corresponding stereoregular,
helical poly-2a, suggesting that the regular structure of poly-
bearing L-leucine ethyl ester pendants, poly-1 and poly-2a,
were, respectively, synthesized by the polymerization of N-(4-
ethynylphenylcarbamoyl)-L-leucine ethyl ester (1) and N-(4-
ethynylphenyl-carbonyl)-L-leucine ethyl ester (2) using
Rh(nbd)BPh4 as a catalyst, while stereoirregular poly-2b was
synthesized by solid-state thermal polymerization of 2. Their
chiral recognition abilities for nine racemates were evaluated
as chiral stationary phases (CSPs) for high-performance liquid
chromatography (HPLC) after coating them on silica gel. Both
poly-1 and poly-2a with a helical conformation showed their
characteristic recognition depending on coating solvents and
the linkage groups between poly(phenylacetylene) and L-leu-
cine ethyl ester pendants. Poly-2a with a shorter amide linkage
showed higher chiral recognition than poly-1 with a longer
urea linkage. Coating solvents played an important role in the
(phenylacetylene) main chains is essential to attain high chiral
C
V
recognition.
2013 Wiley Periodicals, Inc. J. Polym. Sci., Part
A: Polym. Chem. 2013, 51, 2271–2278
KEYWORDS: chiral stationary phase; helical conformation; high-
performance liquid chromatography (HPLC); L-leucine ethyl
ester; poly(phenylacetylene)
determining ee, but also for obtaining pure enantiomers on
analytical and industrial scales, has been significantly
advanced in recent years.3–6
INTRODUCTION Chirality, in particular, that of chiral drugs
has attracted considerable attention in the recent few deca-
des because of the different pharmacologies of enantiomers.
For example, one enantiomer of a chiral drug exhibits the de-
sirable therapeutic effect, while the other may have no effect,
and even shows a side or toxic effect.1,2 Therefore, it is very
important to develop practical techniques for the preparation
of enantiomers with a high enantiomeric excess (ee), and chi-
ral separation, which can easily provide both enantiomers
with a high ee, has attracted great interest. Especially, chiral
separation by high-performance liquid chromatography
(HPLC), which is recognized as a reliable tool not only for
The key to the chromatographic chiral separation is the de-
velopment of effective chiral stationary phases (CSPs) with
high chiral recognition abilities. CSPs for HPLC can be pre-
pared using both chiral molecules and polymers with chiral
recognition abilities.7,8 A wide range of chiral molecules,
such as amino acids and cyclodextrins, can be used as
molecular-type CSPs, which are usually immobilized on silica
gel or organic polymer gel as achiral supports.9,10 The poly-
mer-type CSPs consist of natural and synthetic chiral
C
V
2013 Wiley Periodicals, Inc.
WWW.MATERIALSVIEWS.COM
JOURNAL OF POLYMER SCIENCE, PART A: POLYMER CHEMISTRY 2013, 51, 2271–2278
2271

JOURNAL OF
POLYMER SCIENCE
ARTICLE
WWW.POLYMERCHEMISTRY.ORG
polymers. Polysaccharide derivatives, especially cellulose and
amylose derivatives, are the most popular natural polymer-
type CSPs, which show unique advantages in chiral recogni-
tion and attain effective chiral separation of many race-
mates.4,8,11–14 Currently, a large number of polysaccharide
derivatives have been developed and commercialized as
CSPs for HPLC. However, research on the synthetic polymer-
based CSPs has been mainly focused on polymethacry-
lates,15–17 poly(meth)acrylamides,18,19 poly(phenyl isocya-
nide)s,20–22 poly(phenylacetylene)s,23–25 and polyamides.26
However, up to now, only a few synthetic polymer-based
CSPs are commercially available.
grade. Hexane and 2-propanol used in chromatographic
experiments were of HPLC grade. The racemates were com-
mercially available or were prepared by the usual methods.
Measurements
The 1H NMR spectra (500 MHz) were recorded using a
Bruker AVANCE III-500 instrument at room temperature. The
circular dichroism (CD) and ultraviolet visible (UV–vis) spec-
tra were measured in a 1-mm path length cell using a JASCO
J-815 spectropolarimeter. Thꢀe gel permeation chromatography
(GPC) was performed at 35 C in tetrahydrofuran (THF) using
a Waters 2659 GPC system equipped with Styragel columns
(HT0.5, HT4, and HT5). The number-average molecular weight
(Mn), weight-average molecular weight (Mw), and polydisper-
sity (Mw/Mn) of the polymers were obtained on the basis of a
polystyrene calibration. All chromatographic experiments
were performed using a JASCO PU-2089 chromatograph
equipped with UV–vis (JASCO-UV-2070) and CD (JASCO-CD-
2095) detectors. A solution of a racemate (3 mg/mL) was
injected into the chromatographic system through an intelli-
gent sampler (JASCO AS-2055). The thermogravimetric analy-
ses (TGA) were performed using a TGA Q 50 (TA) instrument.
To the best of our knowledge, there are a few reports so far
on poly(phenylacetylene) derivatives as CSPs for HPLC. Ster-
eoregular poly(phenylacetylene) having chiral carbamoyl
groups with one-handed helical conformation showed chiral
recognition abilities as CSPs for HPLC and resolved some
€
racemates, such as Troger’s base derivatives, spiropyran deriv-
atives, and alcohols.23,24 Recently, Yashima et al. prepared a
series of helical poly(phenylacetylene)s bearing cinchona alka-
loid pendant groups as CSPs for HPLC, whose chiral recogni-
tion abilities were significantly influenced by the macromolec-
ular helicity induced by the alkaloid pendants.25 However, our
previous work on the well-defined helical poly(phenylacety-
lene)s with chiral side chains revealed that the poly(phenyla-
cetylene)s functioned as powerful anion selectors,27–31 sug-
gesting that the polymers may also be good candidates as the
novel CSPs for HPLC because of their helical structure induced
by chiral pendants. This study is mainly focused on the devel-
opment of effective CSPs based on the poly(phenylacetylene)
derivatives with high chiral recognition ability. Herein, three
polymers (poly-1, poly-2a, and poly-2b) were prepared as
CSPs for HPLC according to the previous method27,28 and
their chiral recognition abilities were evaluated by HPLC.
Poly-1 and poly-2a are stereoregular poly(phenylacetylene)
derivatives bearing an L-leucine ethyl ester via a urea linkage
and an amide linkage, respectively, while poly-2b is a stereo-
irregular poly(phenylacetylene) derivative bearing an L-leucine
ethyl ester via amide linkage. Therefore, in this study, the
influence of the linkage between the poly(phenylacetylene)
and the chiral side group and the stereoregularity of the main
chain on chiral recognition will be mainly discussed.
Synthesis of Helical Poly(phenylacetylene) Derivatives
The polymerization of functionalized phenylacetylene mono-
mers 1 and 2 were carried out using Rh(nbd)BPh4 as a catalyst
in a dry flask under a nitrogen atmosphere to give poly-1 and
poly-2a according to previously reported methods.27,28
Poly-1: Yield, 98.5%, Mn ¼ 6.9 ꢁ 103, Mw/Mn ¼ 4.1; Poly-2a:
Yield, 99.3%, Mn ¼ 6.5 ꢁ 104, Mw/Mn ¼ 6.5.
Synthesis of Nonhelical Poly(phenylacetylene) Derivative
Solid-state thermal polymerization of 2 (300 mg) was carried
ꢀ
out under a nitrogen atmosphere at 140 C for 3 days to give
a dark reddish-colored transparent solid.33 It was dissolved in
chloroform (5 mL) and reprecipitated in hexane (100 mL),
then dried under reduced pressure to give poly-2b as a yel-
lowish powder. Yield, 99.2%, Mn ¼ 2.8 ꢁ 103, Mw/Mn ¼ 1.7.
Preparation of CSPs
The poly(phenylacetylene) derivatives poly-1, poly-2a, and
poly-2b (0.2 g each) dissolved in a coating solvent (5 mL)
were coated on aminopropyl silanized silica gel (0.8 g) accord-
ing to the previous method.34 The coating solvents were THF,
N,N-dimethylformamide
(DMF),
N,N-dimethylacetamide
(DMAc), chloroform (CHCl3), methanol (MeOH), or a mixture
of MeOH and CHCl3. The weight ratio of the derivatives to
silica gel was 1:4. The polymer-coated silica gels were then
packed in a stainless-steel tube (25 ꢁ 0.20 cm2 ID) by a slurry
method. The plate numbers of the packed columns were
1200–4500 for benzene using a hexane/2-propanol (95/5,
v/v) mixture as eluent at the flow rate of 0.1 mL/min at 25
ꢀC. The dead time (t0) of the columns was estimated with
1,3,5-tri-tert-butylbenzene as the nonretained compound.35
EXPERIMENTAL
Materials
N-(4-Ethynylphenylcarbamoyl)-L-leucine ethyl ester (1) and
N-(4-ethynylphenyl-carbonyl)-L-leucine ethyl ester (2) were
synthesized according to our previous studies.27,28
Rhþ(2,5-norbornadiene)[(g6-C6H5)B-(C6H5)3] (Rh(nbd)BPh4)
was prepared in accordance with a previous report.32 All sol-
vents used in the reactions were of analytical grade, carefully
dried and distilled before use. The porous spherical silica gel
with a mean particle size of 7 lm and a mean pore diameter
of 100 nm (Daiso gel SP-1000) was kindly supplied by Daiso
Chemicals (Osaka, Japan) and was silaꢀnized with (3-amino-
propyl)triethoxysilane in toluene at 80 C before use. All sol-
vents used in the preparation of CSPs were of analytical
RESULTS AND DISCUSSION
Synthesis of Poly(phenylacetylene) Derivatives
Bearing L-Leucine Ethyl Ester Pendants
To provide the poly(phenylacetylene) derivatives as the
novel CSPs for HPLC, L-leucine ethyl ester functionalized
2272
JOURNAL OF POLYMER SCIENCE, PART A: POLYMER CHEMISTRY 2013, 51, 2271–2278

JOURNAL OF
POLYMER SCIENCE
ARTICLE
WWW.POLYMERCHEMISTRY.ORG
SCHEME 1 Synthesis of poly(phenylacetylene) derivatives bearing L-leucine ethyl ester pendants.
phenylacetylene monomers 1 and 2 were synthesized and
polymerized using Rh(nbd)BPh4 as a catalyst to obtain heli-
cal polymers poly-1 and poly-2a. As shown in Scheme 1, the
difference between the two monomers is only the linkage
group between the phenylacetylene group and the L-leucine
ethyl ester. The linkage of poly-1 is a urea group, and the
linkage of poly-2a is an amide group. The Mn and polydis-
persity (Mw/Mn) of poly-1 were 6.9 ꢁ 103 and 4.1, respec-
tively, while the Mn and Mw/Mn of poly-2a were 6.5 ꢁ 104
and 6.5, respectively. The 1H NMR spectra of poly-1 and
poly2a showed a peak at 5.88 ppm and 5.98 ppm, respec-
tively (Fig. 1), indicating that both of poly-1 and poly2a are
stereoregular with a cis-configuration.27,28
Mw/Mn of poly-2b were 2.8 ꢁ 103 and 1.7, respectively. The
1H NMR spectrum of poly-2b showed no signal due to
cis-poly(phenylacetylene) or trans-poly(phenylacetylene),
suggesting that poly-2b possesses a different configuration
from that of poly-2a and must be a nonhelical polymer.
Chiral Recognition of Poly-1
The chiral recognition of poly-1 was investigated as a CSP for
HPLC. Because the stereoregular poly-1 was soluble in THF,
DMF, and DMAc, these were selected as the solvents for coat-
ing poly-1 on silica gel, and CSP-poly-1-1, CSP-poly-1-2, and
CSP-poly-1-3 were obtained using these coating solvents,
respectively. The chiral recognition abilities of these CSPs
were evaluated with the nine racemates in Figure 2 by HPLC,
and the results are summarized in Table 1. The three CSPs
showed different chiral recognition abilities with low enantio-
selectivities under the same chromatographic conditions with
In addition, solid-state thermal polymerization of 2 was car-
ried out under a nitrogen atmosphere at 140 ꢀC for 3 days
to obtain a stereoirregular polymer poly-2b. The Mn and
WWW.MATERIALSVIEWS.COM
JOURNAL OF POLYMER SCIENCE, PART A: POLYMER CHEMISTRY 2013, 51, 2271–2278
2273

JOURNAL OF
POLYMER SCIENCE
ARTICLE
WWW.POLYMERCHEMISTRY.ORG
FIGURE 1 1H NMR spectra of poly-1, poly-2a, and poly-2b in
DMF-d7.
FIGURE 2 Structures of racemates 3–11.
the eluent hexane/2-propanol (95/5) mixture. The retention
0
factor k1 [¼(t1 ꢂ t0)/t0], which is the factor indicating the
DMAc were observed in the UV–vis wavelength ranging from
300 to 550 nm, where the p-conjugation of the polymer
backbone typically appears. The distinctive Cotton effects in
the polymer backbone absorption clearly indicate that poly-
1 takes a distinct one-handed helical conformation in DMF
and DMAc. The embedded urea group between the L-leucine
ethyl ester and the polymer backbone must be regularly
arrayed in the helical structure when the polymer was dis-
solved in DMF and DMAc. In clear contrast, poly-1 exhibited
a very weak UV–vis absorption and no Cotton effect in THF
in the range from 300 to 550 nm. The very weak UV–vis
absorption indicates the absence of the regular p-conjugation
on the poly-1 backbone. The polymer must be conformation-
ally irregular and nonhelical in THF. Therefore, Poly-1 is a
dynamic helical polymer, and its helical conformation varies
when it is dissolved in different solvents. Combining the re-
solution results with the analyses of the CD spectra, the
strength of interaction between a CSP and a solute, was also
different depending on the coating solvents of the CSPs.
Separation factor a, which is the factor related to chiral
recognition ability of a CSP, was nearly one, indicating a very
low chiral recognition ability of the CSP-poly-1-1 coated with
THF. However, a clear difference in enantioselectivity was
observed on the three CSPs in the resolution of 11 as shown
in Figure 3, where clear separation was attained on CSP-poly-
1-2 and CSP-poly-1-3. These results suggested that the coat-
ing solvents had an obvious effect on the chiral recognition of
poly-1.
The absorption and chiroptical properties of poly-1 were
investigated to obtain fundamental insight into the helical
fashion in the three coating solvents. Figure 4 shows the
UV–vis and CD spectra of poly-1 in DMF, THF, and DMAc at
room temperature. Distinctive Cotton effects in DMF and
TABLE 1 Resolution of Racemates on CSP-poly-1 Prepared with Various Coating Solventsa
CSP-poly-1-1
THF
CSP-poly-1-2
DMF
CSP-poly-1-3
DMAc
0
0
0
Coating Solvents Racemates
k1
a
k1
a
k1
a
3
0.31(þ)
0.27(ꢂ)
1.55
ꢃ1
ꢃ1
2.60(ꢂ)
0.34
ꢃ1
4.68(ꢂ)
0.36
ꢃ1
4
1.00
1.00
5
1.00
0.99
1.00
1.00
1.00
1.00
1.00
1.00
1.08
1.66
1.00
1.00
1.00
1.00
1.00
1.00
1.05
6
0.50
1.00
1.00
0.70
0.66
7
5.17
2.71
4.58
8
2.17(þ)
0.68
ꢃ1
1.00
ꢃ1
1.00
1.14
1.41
9
0.55
0.86
10
11
a
1.64(þ)
5.29
0.25
1.07
2.32(ꢂ)
5.82(ꢂ)
Column: 25 cm ꢁ 0.20 cm ID. Flow rate: 0.1 mL/min. Eluent: hexane/2-propanol (95/5).The signs in parentheses represent the optical rotation of the
first-eluted enantiomer.
2274
JOURNAL OF POLYMER SCIENCE, PART A: POLYMER CHEMISTRY 2013, 51, 2271–2278

JOURNAL OF
POLYMER SCIENCE
ARTICLE
WWW.POLYMERCHEMISTRY.ORG
FIGURE 3 Chromatograms for the resolution of rac-11 on (a) CSP-poly-1-2 and (b) CSP-poly-1-3 with hexane/2-propanol (95/5) as
eluent.
chiral recognition abilities of CSP-poly-1-1, CSP-poly-1-2,
and CSP-poly-1-3 were varied probably due to the different
conformation of poly-1 on the silica surface induced by
changing the coating solvents. Low chiral recognition of the
poly-1 coated with THF for racemate 11 may be due to this
low helicity.
than that of poly-1, and it is quite soluble in THF, MeOH,
DMF, DMAc, and a MeOH/CHCl3 (3/7, v/v) mixture. There-
fore, THF, DMF, MeOH, and a MeOH/CHCl3 (3/7, v/v) mix-
ture were selected for coating poly-2a on silica gel to obtain
CSP-poly-2a-1, CSP-poly-2a-2, CSP-poly-2a-3, and CSP-poly-
2a-4, respectively. The chiral recognition of these CSPs
coated with different solvents was evaluated with eight race-
mates 3-10 by HPLC, and the resolution results are summar-
ized in Table 2.
Chiral Recognition of Poly-2a
To elucidate the role of linkage groups between polymer
main chains and chiral pendants on chiral recognition of pol-
y(phenylacetylene) derivatives, the polymerization of 2 with
an amide linkage was carried out using Rh(nbd)BPh4 as a
catalyst to give poly-2a. The solubility of poly-2a is better
For most racemates, poly-2a showed higher chiral recogni-
tion compared to poly-1. All the tested racemates except for
racemate 8 were resolved on CSP-poly-2a-4. Moreover, race-
mic trans-stilbene oxide (4) and trans-cyclopropanedicarbox-
ylic acid dianilide (10) were resolved with baseline separa-
tion on CSP-poly-2a-2, CSP-poly-2a-3, and CSP-poly-2a-4.
The structures of poly-1 and poly-2 are different only in the
linkage groups between the poly(phenylacetylene) main
chains and L-leucine ethyl ester. This means that linkage
groups play an important role in the chiral recognition of
poly(phenylacetylene) derivatives. The amide linkage of
poly-2a is shorter than the urea linkage of poly-1. The
shorter amide linkage seems to be better for chiral recogni-
tion of the poly(phenylacetylene) derivatives.
Figure 5 shows the chromatograms for racemates 4 and 10
on CSP-poly-2a-4 coated with a mixture of MeOH/CHCl3 (3/
7, v/v). The enantiomers were completely separated result-
ing in the separation factors of 2.19 for 4 and 1.98 for 10.
These large values are rather similar to those obtained on
the very popular CSPs derived from phenylcarbamate deriva-
tives of cellulose and amylose,4,34,36 suggesting that the heli-
cal poly(phenylacetylene) derivatives with the regular
arrangement of chiral side chains may show a high chiral
recognition for some racemates.23–25 The chiral recognition
ability of CSP-poly-2a-4 was maintained for at least several
months, indicating that the poly-2a is conformationally sta-
ble over this period.
As shown in Table 2, the elution orders of the enantiomers
on the four CSPs of poly-2a were the same, but their chiral
recognition abilities were somewhat different. CSP-poly-2a-1,
FIGURE 4 UV–vis (lower) and CD (upper) spectra of poly-1 in
variable solvents (c ¼1 mg/mL) at 25 ꢀC.
WWW.MATERIALSVIEWS.COM
JOURNAL OF POLYMER SCIENCE, PART A: POLYMER CHEMISTRY 2013, 51, 2271–2278
2275

JOURNAL OF
POLYMER SCIENCE
ARTICLE
WWW.POLYMERCHEMISTRY.ORG
TABLE 2 Resolution of Racemates on CSP-poly-2a Prepared with Various Coating Solventsa
CSP-poly-2a-1
CSP-poly-2a-2
CSP-poly-2a-3
CSP-poly-2a-4
MeOH/CHCl3
(3/7, v/v)
THF
DMF
MeOH
Coating Solvents
Racemates
0
0
0
0
k1
a
k1
a
k1
a
k1
a
3
4
5
6
7
8
9
10
a
0.16(þ)
0.22(þ)
1.55
ꢃ1
1.24
1.00
ꢃ1
1.00
ꢃ1
0.44(þ)
0.63(þ)
2.27(þ)
0.90(ꢂ)
5.95
ꢃ1
1.39
1.15
ꢃ1
1.00
1.00
1.00
1.55
0.33(þ)
0.35(þ)
1.66(þ)
0.70(ꢂ)
4.34(ꢂ)
0.29(þ)
0.74(ꢂ)
1.61(þ)
1.21
1.85
1.12
1.11
0.33(þ)
0.31(þ)
0.70(þ)
0.78(ꢂ)
5.55(ꢂ)
0.38
1.26
2.19
1.25
1.13
1.15
1.00
1.12
1.98
0.29(ꢂ)
3.84
ꢃ1
ꢃ1
1.11
1.45
0.29(þ)
0.31
0.36
1.00
1.05
0.85(ꢂ)
0.87(þ)
1.45
1.00
1.95(þ)
Column: 25 cm ꢁ 0.20 cm ID. Flow rate: 0.1 mL/min. Eluent: hexane/2-propanol (95/5). The signs in parentheses represent the optical rotation of
the first-eluted enantiomer.
which was coated with THF showed lower chiral recognition
than the other three CSPs coated with DMF or MeOH or
MeOH/CHCl3. Only racemate 4 was effectively resolved on
CSP-poly-2a-1, while more racemates were resolved and
higher chiral recognition was attained on the other three
CSPs of poly-2a, especially CSPs coated with MeOH or
MeOH/CHCl3. The effects of coating solvents on the chiral
recognition of poly-2a may be due to the different conforma-
tion of poly-2a induced by the coating solvents.
cal conformation in DMF, MeOH, MeOH/CHCl3 (3/7, v/v),
and CHCl3. These CD data are well correlated with the reso-
lution results, and the helical conformation induced by
changing the coating solvents really made a valuable contri-
bution to the chiral recognition abilities of poly-2a. The heli-
cal poly(phenylacetylene) derivatives with the regular
arrangement of chiral side chains can show high chiral rec-
ognition for some racemates.23–25,37
To investigate the influence of the mixture of MeOH/CHCl3
on the structure of poly-2a, the 1H NMR spectra of poly-2a
were measured in deuterated methanol/chloroform mixtures
(Fig. 7). The spectrum in chloroform was broad, possibly due
to the association of the polymer chains in the nonpolar sol-
vent through intrachain and interchain hydrogen bonding.
The poor resolution of the spectrum made it difficult to
assign the signals. Addition of a protonic solvent (methanol,
20 vol %) to the chloroform solution improved the spectral
resolution, and the amide resonance was identified at 8.09
ppm. Further addition of methanol progressively shifted the
resonance peak of the amide proton to a lower field. When
the volume proportion of methanol increased to 80%, the
proton signal of the amide group shifted to 8.35 ppm.
Figure 6 shows the UV–vis and CD spectra of poly-2a in
THF, DMF, MeOH, MeOH/CHCl3 (3/7, v/v), and CHCl3 at
room temperature. It was found that poly-2a exhibited a
very weak UV–vis absorption and no Cotton effect in THF in
the range from 300 to 500 nm. The weak UV–vis absorption
in THF demonstrates the absence of a helical conformation
of poly-2a as discussed before. This may be the reason why
CSP-poly-2a-1 coated with THF showed a lower chiral recog-
nition. In clear contrast, distinctive Cotton effects in DMF,
MeOH, MeOH/CHCl3 (3/7, v/v), and CHCl3 were observed in
the UV–vis wavelength ranging from 300 to 500 nm, where
the p-conjugation of the polymer backbone typically appears.
This indicates that poly-2a has a prevailing one-handed heli-
FIGURE 5 Chromatograms for the resolution of (a) rac-4 and (b) rac-10 on CSP-poly-2a-4 with hexane/2-propanol (95/5) as eluent.
2276
JOURNAL OF POLYMER SCIENCE, PART A: POLYMER CHEMISTRY 2013, 51, 2271–2278

JOURNAL OF
POLYMER SCIENCE
ARTICLE
WWW.POLYMERCHEMISTRY.ORG
FIGURE 6 UV–vis (lower) and CD (upper) spectra of poly-2a in
variable solvents (c ¼ 1 mg/mL) at 25 ꢀC.
FIGURE 8 UV–vis (lower) and CD (upper) spectra of poly-2b in
MeOH and CHCl3 (c ¼ 1 mg/mL) at 25 ꢀC.
Clearly, hydrogen bond formation between the hydroxyl
groups of methanol and the amide groups of the polymer
pendants resulted in the change in helical conformation and
chiral recognition abilities of poly-2a.
same as those coated with DMF or MeOH. These results
suggest that the chiral pendants play the main role in chiral
recognition and that the helical conformation of the poly-2
chain can adjust its chiral recognition.
Moreover, the Cotton effects of poly-2a in a mixture of
MeOH/CHCl3 (3/7, v/v) are opposite to those in DMF or
MeOH, while the elution orders of the enantiomers on the
CSP-poly-2-4 coated with MeOH/CHCl3 (3/7, v/v) are the
Chiral Recognition of Poly-2b
To investigate the influence of main chain regularity of poly-
(phenylacetylene) derivatives on their chiral recognition abil-
ities, solid-state thermal polymerization of 2 was carried out
ꢀ
under a nitrogen atmosphere at 140 C for 3 days to obtain
a stereoirregular polymer poly-2b. As shown in Figure 1, the
1H NMR spectrum of poly-2a demonstrates a peak at 5.98
ppm, indicating the propensity of the cis-configuration in the
main chain,29 whereas the 1H NMR spectrum of poly-2b
showed no signal due to cis-poly(phenylacetylene) or trans-
poly(phenylacetylene), suggesting that poly-2b must be a
stereoirregular polymer. Although poly-2a and poly-2b were
polymerized from the same monomer, the stereoregularities
of poly-2a and poly-2b are different.
Figure 8 shows the CD and UV–vis spectra of poly-2b in
CHCl3 and MeOH at room temperature. As predicted, poly-
2b exhibited a very weak UV–vis absorption and no Cotton
effect in these solvents in the range from 300 to 500 nm,
indicating that poly-2b does not possess
a
helical
conformation.
CSP-poly-2b was prepared by coating poly-2b on silica gel
using a MeOH/CHCl3 (3/7, v/v) mixture as the coating sol-
vent. The chiral recognition of CSP-poly-2b was evaluated
with the eight racemates 3-10 by HPLC, and the resolution
FIGURE 7 1H NMR spectra of poly-2a in CD3OD/CDCl3 ¼ 20/80
– 80/20 (v/v).
WWW.MATERIALSVIEWS.COM
JOURNAL OF POLYMER SCIENCE, PART A: POLYMER CHEMISTRY 2013, 51, 2271–2278
2277

JOURNAL OF
POLYMER SCIENCE
ARTICLE
WWW.POLYMERCHEMISTRY.ORG
TABLE 3 Resolution of Racemates on CSP-poly-2ba
6 C. Ravelet, E. Peyrin, J. Sep. Sci. 2006, 29, 1322–1331.
7 V. A. Davankov, J. Chromatogr. A 2003, 1000, 891–915.
8 Y. Okamoto, T. Ikai, Chem. Soc. Rev. 2008, 37, 2593–2608.
9 H. Pirkle, T. C. Pochapsky, Chem. Rev. 1989, 89, 347–362.
10 M. H. Hyun, Bull. Korean Chem. Soc. 2005, 26, 1153–1163.
3
4
5
7
8
9
10
0
k1
0.27(ꢂ)
ꢃ1
0.33
1.00
0.27
1.00
0.18
1.00
1.63
1.00
1.32(þ)
ꢃ1
0.64
1.00
a
11 Y. Okamoto, T. Ikai, J. Shen, Isr. J. Chem. 2011, 51,
1096–1106.
a
Column: 25 cm ꢁ 0.20 cm ID. Coating solvent: MeOH. Flow rate: 0.1
mL/min. Eluent: hexane/2-propanol (99/1). The signs in parentheses rep-
resent the optical rotation of the first-eluted enantiomer.
12 J. Shen, S. Liu, P. Li, X. Shen, Y. Okamoto, J. Chromatogr.
A 2012, 1246, 137–144.
13 T. Ikai, C. Yamamoto, M. Kamigaito, Y. Okamoto, J. Chro-
matogr. A 2007, 1157, 151–158.
results are summarized in Table 3. CSP-poly-2b exhibited
much lower chiral recognition than CSP-poly-2a-4 and showed
very low chiral recognition only for 3 and 9. These results
indicate that irregular arrangements of chiral side chains can
show only low chiral recognition and that their regular
arrangement is essential to attain high chiral recognition.
14 P. Mobian, C. Nicolas, E. Francotte, T. Burgi, J. Lacour, J.
Am. Chem. Soc. 2008, 130, 6507–6514.
15 T. Nakano, J. Chromatogr. A 2001, 906, 205–225.
16 C. Yamamoto, Y. Okamoto, Bull. Chem. Soc. Jpn. 2004, 77,
227–257.
17 Y. Okamoto, S. Honda, I. Okamoto, H. Yuki, S. Murata, R.
Noyori, H. Tanaka, J. Am. Chem. Soc. 1981, 103, 6971–6973.
CONCLUSIONS
18 G. Blaschke, Angew. Chem. Int. Ed. Engl. 1980, 19, 13–24.
Helical and nonhelical poly(phenylacetylene) derivatives
bearing L-leucine ethyl ester pendants (poly-1, poly-2a, and
poly-2b) were synthesized and coated on silica gel using
various solvents to evaluate their chiral recognition abilities
as CSPs for HPLC. Both helical poly-1 and poly-2a exhibited
chiral recognition ability. The linkage groups between the
poly(phenylacetylene) main chains and L-leucine ethyl ester
pendants played an important role in chiral recognition, and
poly-2a with a shorter amide linkage showed higher chiral
recognition than poly-1 with a longer urea linkage. Coating
solvents also played an important role in chiral recognition
because different conformations of helical poly(phenylacety-
lene) derivatives were induced by changing the coating sol-
vents. Non-helical poly-2b exhibited much lower chiral rec-
ognition than the corresponding helical poly-2a, suggesting
that the regular structure the of poly(phenylacetylene) main
chains is essential for high chiral recognition.
19 K. Morioka, Y. Suito, Y. Isobe, S. Habaue, Y. Okamoto, J.
Polym. Sci. Part A: Polym. Chem. 2003, 41, 3354–3360.
20 A. Yamagishi, I. Tanaka, M. Taniguchi, M. Takahashi, J.
Chem. Soc. Chem. Commun. 1994, 6, 1113–1114.
21 K. Tamura, T. Miyabe, H. Iida, E. Yashima, Polym. Chem.
2011, 2, 91–98.
22 T. Miyabe, H. Iida, A. Ohnishi, E. Yashima, Chem. Sci. 2012,
3, 863–867.
23 E. Yashima, S. Huang, Y. Okamoto, J. Chem. Soc. Chem.
Commun. 1994, 6, 1811–1812.
24 E. Yashima, T. Matsushima, T. Nimura, Y. Okamoto, Korea
Polym. J. 1996, 4, 139–146.
25 Y. Naito, Z. Tang, H. Iida, T. Miyabe, E. Yashima, Chem.
Lett. 2012, 41, 809–811.
26 K. Saigo, Y. Chen, N. Yonezawa, K. Tachibana, T. Kanoe, M.
Hasegawa, Chem. Lett. 1985, 1891–1894.
27 R. Kakuchi, S. Nagata, R. Sakai, I. Otsuka, H. Nakade, T.
Satoh, T. Kakuchi, Chem. Eur. J. 2008, 14, 10259–10266.
ACKNOWLEDGMENTS
28 R. Kakuchi, S. Nagata, Y. Tago, R. Sakai, I. Otsuka, H.
Nakade, T. Satoh, T. Kakuchi, Macromolecules 2009, 42,
1476–1481.
This work was supported by the Natural Science Foundation of
Heilongjiang Province (Grant No. B201013), the Scientific
Research Foundation for the Returned Overseas Chinese Schol-
ars, State Education Ministry (20111568), the Special Fund for
Scientific and Technological Innovative Talents in Harbin City
(Grant No. 2012RFLXG001), and the Fundamental Research
Funds for the Central Universities, China (Grant No.
HEUCF201210011 and HEUCF201310009). This work was
also partially supported by Daicel Corporation (Tokyo, Japan).
The authors are grateful for the support.
29 R. Sakai, S. Okade, E. B. Barasa, R. Kakuchi, M. Ziabka, S.
Umeda, K. Tsuda, T. Satoh, T. Kakuchi, T. Macromolecules
2010, 43, 7406–7411.
30 R. Kakuchi, R. Shimada, Y. Tago, R. Sakai, T. Satoh, T. Kaku-
chi, J. Polym. Sci. Part A: Polym. Chem. 2010, 48, 1683–1689.
31 R. Sakai, N. Sakai, T. Satoh, W. Li, A. Zhang, T. Kakuchi,
Macromolecules 2011, 44, 4249–4257.
32 Y. Kishimoto, M. Itou, T. Miyatake, T. Ikariya, R. Noyori,
Macromolecules 1995, 28, 6662–6666.
33 M. N. Jeffrey, J. S. Daniel, Y. Lin, J. F. Bruce, Macromole-
cules 2005, 38, 7645–7652.
REFERENCES AND NOTES
34 Y. Okamoto, M. Kawashima, K. Hatada, J. Chromatogr.
1986, 363, 173–186.
1 B. Kasprzyk-Hordern, Chem. Soc. Rev. 2010, 39, 4466–4503.
€
35 H. Koller, K. H. Rimbock, A. Mannschrek, J. Chromatogr.
1983, 282, 89–94.
2 J. Zhang, Q. Tian, S. Y. Chan, S. C. Li, S. F. Zhou, W. Duan,
Y. Z. Zhu, Drug Metab. Rev. 2005, 37, 611–703.
36 Y. Okamoto, R. Aburatani, T. Fukumoto, K. Hatada, Chem.
Lett. 1987, 1857–1860.
3 Y. Zhang, S. Yao, H. Zeng, H. Song, Curr. Pharm. Anal. 2010,
6, 114–130.
37 L. Liu, Y. Zang, S. Hadano, T. Aoki, M. Teraguchi, T. Kaneko,
T. Namikoshi, Macromolecules 2010, 43, 9268–9276.
4 T. Ikai, Y. Okamoto, Chem. Rev. 2009, 109, 6077–6101.
5 E. Francotte, J. Chromatogr. A 2001, 906, 379–397.
2278
JOURNAL OF POLYMER SCIENCE, PART A: POLYMER CHEMISTRY 2013, 51, 2271–2278