Macromolecular helicity induction and memory in a poly(biphenylylacetylene) bearing an ester group and its application to a chiral stationary phase for high-performance liquid chromatography

Article abstract of DOI:10.1246/cl.150299

An optically inactive poly(biphenylylacetylene) bearing an ester group at the 4′-position of the pendants formed a preferred-handed helical conformation and biased axial chirality in the pendants through a noncovalent interaction with a chiral alcohol, both of which were retained (memorized) even after removal of the chiral alcohol. The chiral stationary phase for high-performance liquid chromatography, prepared by coating the polymer with macromolecular helicity memory on silica gel, showed good chiral recognition ability towards various racemates.

Full text of DOI:10.1246/cl.150299

CL-150299
Received: April 1, 2015 | Accepted: April 17, 2015 | Web Released: April 23, 2015
Macromolecular Helicity Induction and Memory in a Poly(biphenylylacetylene)
Bearing an Ester Group and Its Application to a Chiral Stationary Phase
for High-performance Liquid Chromatography
Ryoma Ishidate, Kouhei Shimomura, Tomoyuki Ikai, Shigeyoshi Kanoh, and Katsuhiro Maeda*
Graduate School of Natural Science and Technology, Kanazawa University, Kakuma-machi, Kanazawa, Ishikawa 920-1192
(E-mail: maeda@se.kanazawa-u.ac.jp)
An optically inactive poly(biphenylylacetylene) bearing an
ester group at the 4¤-position of the pendants formed a preferred-
handed helical conformation and biased axial chirality in the
pendants through a noncovalent interaction with a chiral alcohol,
both of which were retained (memorized) even after removal of
the chiral alcohol. The chiral stationary phase for high-perform-
ance liquid chromatography, prepared by coating the polymer
with macromolecular helicity memory on silica gel, showed
good chiral recognition ability towards various racemates.
However, the chiral recognition ability of poly(DOBA) was not
high. In this communication, we designed and synthesized a
novel cis-transoidal poly(biphenylylacetylene) derivative bear-
ing an ester group as an effective chiral recognition site instead
of an ether group, poly([2,2¤-bis(methoxymethoxy)-4¤-butoxy-
carbonyl-4-biphenylyl]acetylene) (poly(BCBA)) (Scheme 1),
and investigated the effects of the functional group at the 4¤-
position of the biphenyl pendant on helicity induction and
memory effect, and further the chiral recognition ability as a
CSP for HPLC.
Poly(BCBA) was synthesized by the polymerization of
the corresponding biphenylylacetylene monomer (Scheme S1)
with a rhodium catalyst ([Rh(nbd)Cl]2; nbd: norbornadiene) in
tetrahydrofuran in the presence of triethylamine in a similar
method to that previously reported (Scheme S2).7 The stereo-
regularity of the obtained polymer was confirmed to be almost
completely cis-transoidal by 1H NMR analysis (Figure S1).8,9
The number-average molecular weight and its distribution,
determined by size-exclusion chromatography, were 9.4 © 105
and 1.7, respectively. Poly(BCBA) was totally insoluble in n-
hexane, but soluble in toluene and chiral alcohol 1, whereas the
previously reported poly(DOBA) was soluble in n-hexane and
insoluble in 1. Therefore, we used toluene instead of hexane
as the solvent in the following helicity induction and memory
experiments.
The optically inactive poly(BCBA) formed a preferred-
handed helical conformation in response to the chirality of
(R)- or (S)-1, showing mirror-imaged intense-induced circular
dichroisms (ICDs) in the absorption region of the polymer
backbone (Figures 1a and 1b).10 The ICD intensity slowly
increased with time to reach an almost constant value after 24 h
at 25 °C (Figure S2). On the other hand, the previously reported
poly(DOBA) exhibited a maximum ICD after standing at 25 °C
for 1 h in the presence of optically active 1 in toluene. Therefore,
these results indicate that poly(BCBA) requires a longer time to
form a single-handed helix compared with poly(DOBA).
We then investigated if an unusual macromolecular helicity
memory, similar to that observed in poly(DOBA), could be
possible for poly(BCBA). After helicity induction in (R)-1/
toluene (20/80, v/v) at 25 °C for 48 h, the poly(BCBA) was
isolated from the solution by precipitating into an excess amount
of methanol. The complete removal of (R)-1 was confirmed by
1H NMR analysis of the isolated polymer (Figure S4). The CD
spectrum of the isolated poly(BCBA) dissolved in toluene at
¹10 °C was nearly identical to that obtained before removal
of (R)-1 (Figures 1a and 1c). This result clearly demonstrates
that the preferred-handed helical conformation induced in
poly(BCBA) was automatically memorized after complete
removal of (R)-1 (Scheme 1). Interestingly, the helical confor-
Direct enantioseparation, using chiral stationary phases
(CSPs), by high-performance liquid chromatography (HPLC)
has provided a promising method not only for performing
microanalysis of chiral compounds but also for obtaining
highly-pure enantiomers on the ton scale.1,2 Although a large
number of CSPs have been developed,3,4 it is still a challenging
issue to switch the elution order of enantiomers without using
the CSPs prepared from antipodal chiral materials despite their
advantages both in analytical and preparative modes.5,6
We recently reported that poly([2,2¤-bis(methoxymethoxy)-
4¤-dodecyloxy-4-biphenylyl]acetylene) (poly(DOBA)) forms a
preferred-handed helical conformation together with an excess
of one of the axially twisted conformations in the biphenyl
pendants, which occurs through the noncovalent interaction with
an optically active alcohol ((R)- or (S)-1) both in solution and
in the solid state.7 The induced main-chain helicity and axial
chirality can be maintained (or memorized) even after the
removal of the chiral alcohol (Scheme 1). By using this unusual
feature of poly(DOBA), we succeeded in developing a switch-
able CSP in which the elution order of the enantiomers could be
switched at will on the basis of reversible switching and the
subsequent memory of macromolecular helicity in poly(DOBA)
by sequential treatment with (R)- and (S)-1 in the solid state.
n
n
*
OH
H
O
O
H
O
O
O
O
2'
O
O
(S)- or (R)-1
1'
3'
6'
5'
4'
removal of
(S)- or (R)-1
X
X
poly(DOBA): X = OC12H25
poly(BCBA): X = CO2C4H9
helicity & axial chirality
induction and memory
Scheme 1. Schematic illustration of induction and memory of
main-chain helicity together with pendant axial chirality in
poly(biphenylylacetylene)s through noncovalent interaction with
a chiral alcohol ((S)- or (R)-1).
946 | Chem. Lett. 2015, 44, 946–948 | doi:10.1246/cl.150299
© 2015 The Chemical Society of Japan

Table 1. Resolution results of racemates 2-13 on poly(BCBA)-
based CSP prepared by the interaction with (R)-1a
20
10
0
Racemates
k1
¡
Racemates
k1
¡
2
1
0
2
3
4
5
6
7
1.04 ca. 1 (+)
8.34 ca. 1 (+)
6.80 1.08 (¹)
4.50 1.15 (+)
2.61 1.07 (+)
1.02 ca. 1 (+)
8
9
10
11
12
13
1.21 1.18 (+)
1.01 1.28 (¹)
1.40 1.31 (¹)
ε
-10
-20
(a)
(b)
(c)
1.95
1.0
0.18 ca. 1 (+)
0.27 ca. 1 (¹)
aColumn: 25 © 0.20 cm (i.d.); eluent: n-hexane/2-propanol
(97:3, v/v); flow rate: 0.2 mL min¹1; temperature: 10 °C. The
signs in parentheses represent the Cotton effect signs at 254 nm
of the first-eluted enantiomers.
300
400
Wavelength/nm
500
Figure 1. CD and absorption spectra of poly(BCBA) in the
presence of (R)-1 (a) and (S)-1 (b) (1/toluene = 20/80, v/v)
in toluene after standing at 25 °C for 48 h and the isolated
poly(BCBA) form a (c) in toluene at ¹10 °C.
Ph
HO OH Ph
HO OH
HO OCH3
HO OH
HO OH
H3C CH3
2
Br
Br
3
4
5
6
1.6
1.2
0.8
0.4
0
CH3O OCH3
Co(acac)3
Cr(acac)3
Ru(acac)3
8
9
N
O
Ph
H
C
OH
N
CF3
Ph
-0.4
-0.8
-1.2
7
10
11
12
13
In order to examine the chiral recognition ability of
poly(BCBA) with macromolecular helicity memory, we pre-
pared the CSP for HPLC as follows. After helicity induction in
poly(BCBA) in a mixture of (R)-1/toluene (20/80, v/v) for 48 h
at 25 °C, the solution was coated onto macroporous silica gel.12
The obtained packing material was packed into a stainless-steel
column (25 © 0.20 cm (i.d.))13 and then thoroughly rinsed by
flowing a mixture of n-hexane/2-propanol (97/3, v/v) as the
eluent to completely remove the remaining (R)-1. The coated
polymer was redissolved in toluene at ¹10 °C from the residual
part of the packing material, whose CD spectrum was measured
to directly confirm if the macromolecular helicity could be
maintained after coating on the silica surface (Figure S6). The
CD intensity was more than 80% of that before coating,
demonstrating that the preferred-handed helical structure can be
maintained on the silica surface and that the poly(biphenylyl-
acetylene)-based CSP can be prepared from the optically
inactive polymer using its characteristic features of helicity
induction and the memory effect.
The resolution ability of the helical poly(BCBA)-based CSP
was evaluated using the racemates 2-13 (Table 1). Figure 3
shows the representative chromatograms for the resolution of
racemic 5 and 10 on the poly(BCBA)-based CSP. As shown in
Figure 3b, the enantiomers of 10 were eluted at retention times t1
and t2 with almost baseline separation. The retention factors k1
[= (t1 ¹ t0)/t0] and k2 [= (t2 ¹ t0)/t0], where the dead time (t0)
was estimated to be 4.15 min, were determined to be 1.40 and
1.84, respectively, which led to a separation factor ¡ (= k2/k1)
of 1.31. The other resolution results on the poly(BCBA)-based
CSP are summarized in Table 1. Poly(BCBA) resolved six
racemates including axially chiral compounds 4-6 and chiral
metal complexes 8-10. It should be noted that racemic 1 was not
resolved on poly(BCBA)-based CSP (¡ = 1.0), while optically
0.6
0.4
0.2
0
1700
1500
1300
1100
900
Wavenumber/cm-1
Figure 2. VCD (top) and IR (bottom) spectra of the isolated
poly(BCBA) in toluene at ¹10 °C after helicity induction with
(R)-1 (red line) and (S)-1 (blue line).
mation memorized in poly(BCBA) was much more stable than
that of poly(DOBA) bearing an ether group instead of an ester
group. For example, the half-life period (t1/2) of poly(BCBA)
at 25 °C in toluene (ca. 4 h) was more than 20-fold longer than
that for the isolated helical poly(DOBA) (<0.2 h) (Figure S5).
This means that the macromolecular helicity memory in
poly(BCBA) can be more efficiently stabilized, probably owing
to the intramolecular dipole-dipole interaction between the
neighboring ester functional groups, than that in poly(DOBA).
The vibrational circular dichroism (VCD) spectra of iso-
lated poly(BCBA) measured in toluene at ¹10 °C exhibited
intense Cotton effects in the C-O-C stretching band region of
the methoxymethoxy (OMOM) groups at around 1010 cm
¹1
,
suggesting that the axially twisted conformation in the biphenyl
pendants was biased during the helicity induction process
through noncovalent interaction with optically active 1, as
observed for poly(DOBA) (Figure 2).7 Moreover, mirror-imaged
VCD signals were also observed in the C=O stretching band
region of the ester groups in the pendants. These results indicate
that the ester groups introduced at the 4¤-position of the biphenyl
pendants are arranged in a preferred-handed helical array along
the main-chain helicity.11
Chem. Lett. 2015, 44, 946–948 | doi:10.1246/cl.150299
© 2015 The Chemical Society of Japan | 947

(a)
(b)
R&D from Japan Science and Technology Agency (JST) (K.M.)
and a Grant-in-Aid for Young Scientists (B) (T.I.) from the Japan
Society for the Promotion of Science (JSPS) and the Nano-
technology Platform Program (Molecule and Material Synthesis)
of the Ministry of Education, Culture, Sports, Science and
Technology (MEXT), Japan.
5
10
CD254
t1
t2
Supporting Information is available electronically on J-STAGE.
UV254
19
23
27
31
8
10
12
14
References and Notes
Elution time/min
Elution time/min
1
2
3
4
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Figure 3. HPLC chromatograms for the resolutions of 5 (a)
and 10 (b) on poly(BCBA)-based CSP prepared by the
interaction with (R)-1. Eluent: hexane-2-propanol (97:3, v/v).
active 1 could induce a preferred-handed helical conformation
together with pendant axial chirality in poly(BCBA). As for
structurally similar racemates 5-7, both the k1 and ¡ values
decreased with decreasing number of hydroxy groups in the
racemates, and poly(BCBA) did not resolve 7 with two methoxy
groups instead of hydroxy groups. These results suggest that
the multiple hydrogen bonds between the carbonyl groups of
the pendants of poly(BCBA) and the hydroxy groups of the
racemates may play an important role in efficient chiral
discrimination.
In conclusion, we have demonstrated the applicability of
unique macromolecular helicity induction and memory effect
to other poly(biphenylylacetylene)s bearing functional groups,
such as ester groups, in the pendants. Moreover, we found that
the pendant ester groups can enhance not only the chiral
recognition ability but also the stability of the macromolecular
helicity memory. These findings will contribute to the develop-
ment of practically useful switchable CSPs toward various
racemates. In contrast to the previously reported poly(DOBA),
poly(BCBA) is soluble in 1, and therefore, it is difficult to
switch its enantioselectivity in the column by feeding a solution
containing (R)- or (S)-1 into the column. We believe that this
problem can be solved by immobilization of the polymer onto
silica supports through chemical linkages.14,15 This work is now
in progress.
5
6
7
8
9
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poly(DOBA) reached a maximum value in the presence of
5 vol % of (R)-1 in toluene (Figure S3).
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This work was partly supported by a grant of Adaptable and
Seamless Technology Transfer Program through Target-driven
15 J. Shen, T. Ikai, Y. Okamoto, J. Chromatogr. A 2014, 1363,
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948 | Chem. Lett. 2015, 44, 946–948 | doi:10.1246/cl.150299
© 2015 The Chemical Society of Japan