Unprecedented Sequence Control and Sequence-Driven Properties in a Series of AB-Alternating Copolymers Consisting Solely of Acrylamide Units

Article abstract of DOI:10.1002/anie.201915075

Herein, we report a method to synthesize a series of alternating copolymers that consist exclusively of acrylamide units. Crucial to realizing this polymer synthesis is the design of a divinyl monomer that contains acrylate and acrylamide moieties connected by two activated ester bonds. This design, which is based on the reactivity ratio of the embedded vinyl groups, allows a “selective” cyclopolymerization, wherein the intramolecular and intermolecular propagation are repeated alternately under dilute conditions. The addition of an amine to the resulting cyclopolymers afforded two different acryl amide units, i.e., an amine-substituted acryl amide and a 2-hydroxy-ethyl-substituted acryl amide in alternating sequence. Using this method, we could furnish ten types of alternating copolymers; some of these exhibit unique properties in solution and in the bulk, which are different from those of the corresponding random copolymers, and we attributed the differences to the alternating sequence.

Full text of DOI:10.1002/anie.201915075

A Journal of the Gesellschaft Deutscher Chemiker
Angewandte
Chemie
International Edition
www.angewandte.org
Accepted Article
Title: Unprecedented Sequence Control and Sequence-Driven
Properties in A Series of AB-Alternating Copolymers Consisting
Solely of Acrylamide Units
Authors: Makoto Ouchi, Yuki Kametani, Mitsuo Sawamoto, and
Francois Genès Tournilhac
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To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.201915075
Angew. Chem. 10.1002/ange.201915075
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10.1002/anie.201915075
Angewandte Chemie International Edition
RESEARCH ARTICLE
Unprecedented Sequence Control and Sequence-Driven
Properties in A Series of AB-Alternating Copolymers Consisting
Solely of Acrylamide Units
Yuki Kametani, [a] François Tournilhac, [b] Mitsuo Sawamoto, [c] and Makoto Ouchi*[a]
Abstract: In this article, we report a method to synthesize a series of
alternating copolymers that consist exclusively of acrylamide units.
Crucial to realizing the unprecedented polymer synthesis is the design
of a divinyl monomer that contains acrylate and acrylamide moieties
connected via two activated ester bonds. This elaborate design, which
is based on the reactivity ratio of the embedded vinyl groups, allows
a “selective” cyclopolymerization, wherein the intramolecular and
intermolecular propagation are repeated alternately under dilute
conditions. The addition of an amine to the resulting cyclopolymers
afforded two different acryl amide units, i.e., an amine-substituted
in the absence of irreversible deactivation, which offers a way to
control the molecular weight, the chain-end structure, and the
architecture.7-9 One issue that remains to be addressed in this
context is the precision of the synthesis of polymers with a well-
defined sequence and sequence-oriented properties/functions,
which could potentially lead to a ground-breaking paradigm shift
for the synthesis of polymer materials.
Copolymerizations have been widely used for the synthesis
of polymer materials with practical applications, and especially
radical copolymerizations have been particularly useful due to the
robustness of the process and the wide variety of applicable
comonomers, which include polar and functional derivatives. The
composition or sequence of the comonomer units in the resulting
chains can be discussed, to a certain extent, in terms of the
reactivity ratios. For example, totally random copolymers are
synthesized via the so-called ideal copolymerization of two
comonomers with the same reactivity (Figure 1, right, r1 = r2 = 1).
This is mostly the case using the same type of monomer, whereby
derivatives differ only with respect to the pendant groups as in e.g.
styrenes, (meth)acrylates, or acrylamides. On the other hand,
perfectly alternating copolymerization occurs when two
comonomers that show cross-over propagation (r1 = r2 = 0) are
used, e.g. a combination of vinyl ethers and maleic anhydrides.10-
acryl amide and
a 2-hydroxy-ethyl-substituted acryl amide in
alternating sequence. Using this method, we were able to furnish ten
types of alternating copolymers; some of these exhibit unique
properties in solution and in the bulk, which are clearly different from
those of the corresponding random copolymers, and we attributed the
observed differences to the alternating sequence.
Introduction
The “sequence” in polymer science, which can be defined
as the order of the pendant groups that are attached to the repeat
units in the polymer backbone or main chain. in e.g. proteins and
DNA, it is arguably the most crucial structural factor for natural
polymers, as it determines the higher-order structures that lead to
smart functions. These natural macromolecules are copolymers
that consist of one type of monomer, i.e., amino acids or
nucleotides, and various substituents on the side chains are
combined to realize cooperative functions due to the well-defined
sequence. Although comonomers of the same type usually exhibit
similar reactivity, the sequence-programmed propagation is
12
Alternating propagation is caused by a large difference in
electron density between the two monomers,13-19 or by addition of
a Lewis acid to an electron-poor comonomer in order to further
deplete electron density.20,21 It is thus easy to understand that
achieving genuine sequence control in the copolymerization of
one type of monomer with different pendants is very challenging.
Indeed, even control of simple periodic sequences such as AB
alternating made of one type of repeating unit remains
unprecedented in the long history of polymer science (Figure 1,
left).
perfectly controlled on account of
a
template system.
Unfortunately, in the context of synthetic macromolecules such a
template-based sequence control is currently beyond our reach,
even though the synthesis of sequence-defined macromolecules
has attracted substantial attention from polymer chemists and
physicists.1-6 Recent progress in the area of the reversible
deactivation radical polymerization (or living/controlled radical
polymerization) has allowed regulating the initiation/propagation
[a]
[b]
[c]
Mr. Yuki. Kametani, Prof. Dr. Makoto Ouchi
Department of Polymer Chemistry, Graduate School of Engineering,
Kyoto University, Nishikyo-ku, Kyoto 615-8510, Japan.
E-mail: ouchi@living.polym.kyoto-u.ac.jp
Dr. François Tournilhac
Molecular, Macromolecular Chemistry, and Materials, CNRS,
ESPCI-Paris, PSL Research University, 10 rue Vauquelin, 75005
Paris, France.
Prof. Dr Mitsuo Sawamoto
Institute of Science and Technology Research, Chubu University,
1200 Matsumoto-cho, Kasugai, Aichi 487-8501, Japan.
Figure 1. An alternating copolymer (left) that consists only of one type of
repeating unit (acryl amide) with different substituents in comparison with the
corresponding random copolymer (right).
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10.1002/anie.201915075
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RESEARCH ARTICLE
We have recently developed a method to control the
alternating sequence in copolymers via selective radical
cyclopolymerization and the cleavage of the cyclo-spacer in the
resulting repeat units.22-26 The spacer of the divinyl monomer can
either be cleaved or transformed, and the design determines the
pendant groups in the resulting alternating sequence. For
instance, one design is based on two types of cleavable bonds,
tertiary ester and activated ester bonds, which have been
embedded in the spacer between methacrylate and acrylate vinyl
groups. We obtained alternating copolymer of methacrylic acid
and N-isopropyl acrylamide via selective cyclopolymerization and
side-chain cleavage of the designed divinylmonomer. The
alternating copolymer showed sequence-specific properties: the
thermal and pH responses in aqueous solution were different from
those of the corresponding random copolymers.26
substituents on the original acrylate unit via a transformation into
the acryl amide analogue by a reaction with the amine under
concomitant cleavage of the spacer and liberation of another
HEAm unit.
Even though these studies on the cyclopolymerization
approach for sequence control are very promising, the applicable
types of repeat units in the resulting copolymers remain limited.
Moreover, since this method partially depends on the reactivity
ratio of the embedded monomers, controlling the sequence of
copolymers that consist of identical repeat units remains
challenging. Against this background, we designed a new divinyl
monomer that could provide an AB-alternating sequence while
consisting of only acrylamide repeat units. The resulting
alternating copolymers showed sequence-specific features that
are different from those of the corresponding 1:1 random
copolymers. Examples on such sequence control of pendant
groups for identical repeat units have not yet been reported, and
this research provides a step toward synthetic polymers that show
sequence-oriented functions similar to natural polymers.
Figure 2. (A) selective cyclopolymerization of 1 and transformation by addition
of an amine; (B) selective cyclopolymerization; (C) cleavage of the activated
esters in side-chain of the cyclo-units.
A preliminary study of the radical cyclopolymerization of 1
revealed that the resulting polymer was insoluble in most common
solvents, but soluble in DMF; a small portion of the spacer in
Results and Discussion
cyclopolymer derived from
1 was damaged during the
We designed a new divinyl monomer and scheme that was
expected to furnish AB-alternating copolymers that consist of the
same type of repeat unit after the spacer transformation (Figure
2A). This divinyl monomer (1) consists of an electron-deficient
acrylate and an acrylamide, and the two vinyl monomers are
connected by two ester bonds that can be cleaved by a reaction
with amines. The different reactivity of two monomers allows
selective cyclopolymerization consisting of intramolecular
cyclopropagations that rely on the neighboring effect under dilute
conditions and selective intermolecular propagations based on
the inherent reactivity of the embedded vinyl comonomers (Figure
2B). The obtained polymer is AB alternating sequence embedded
cyclopolymer. The vinyl group in the electron-deficient acrylate is
an acrylate with a 4-nitrophenyl ester substituent intended for a
subsequent transformation into an acrylamide through the
reaction with the amine due to the reactivity of the activated
ester.27,28 Moreover, 2-hydroxyethyl acrylamide (HEAm) was
connected to the phenyl ring of the electron-poor acrylate via an
ester bond. The ester bond would be also activated thanks to the
electron-withdrawing substituent (–NO2), albeit that the
orientation of the ester bond is in opposing direction in order to
permit the generation of different types of substituents (Figure 2C).
The spacer design should allow incorporating various
polymerization in DMF, probably due to the very high polarity of
the solvent. Therefore, we tuned the polarity of the solvent for the
polymerization by mixing DMF with dioxane (dioxane/DMF = 8/2;
v/v) to balance the solubility of the obtained polymer and the
stability of the spacer. First, the cyclopolymerization proceeded
readily to afford a soluble polymer via a free radical polymerization
similar to the RAFT system ([1]0 = 100 mM; [AIBN]0 = 2 mM). Both
conversions of the vinyl groups were identical (Table S1, Entry 1).
Thus, we tried to control the polymerization with various
conditions of reversible deactivation radical polymerization. First,
ATRP conditions were applied to the cyclopolymerization of 1
under dilute conditions ([1]0 = 100 mM; [initiator]0 = 2.0 mM),
which are similar to those of the cyclopolymerization of the
methacrylate-acrylate divinyl monomer in our previous study.24,26
However, the conversion of the vinyl groups in 1 reached a
plateau less than 50% during the early stages of the reaction,
affording low molecular weight polymers with any ligands and
additives, even if iron and copper catalysts were used (Table S1,
entry 2-9). This could be reasonably interpreted in terms of
catalyst poison by the nitro group.29
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10.1002/anie.201915075
Angewandte Chemie International Edition
RESEARCH ARTICLE
A
B
a-amide
O
NH
O
acryl
100
75
50
25
0
Time
Mn
(Mw/Mn)
In order to realize the alternating sequence, it is also crucial
to exercise control over the selectivity of the intermolecular
propagation process, which depends on the reactivity ratio of the
two vinyl monomers26. The reactivity ratios were estimated by the
Fineman-Ross method31 via the free radical copolymerizations of
p-nitrophenoxy acrylate (NPA) and n-butyl acrylamide (BuAm) as
the model comonomers, which afforded the following values: r1 =
1.1, r2 = 0.11 (M1: NPA; M2: BuAm) (Figure 3D). In general, a
combination of common acrylate (M1) and acrylamide (M2) gives
higher r2 value [e.g., r1 = 1.2, r2 = 0.26 for methyl acrylate (M1) and
n-propyl acrylamide (M2)32]. Thus, the lower r2 value is most likely
due to the electron-withdrawing substituent of NPA and helpful in
enhancing the selectivity of the intermolecular propagation that
leads to a highly alternating sequence.
O
O
O
12 h
7800
(1.62)
p Acrylate
24 h
9100
(1.68)
q Acrylamide
NO2
6 h
6300
(1.53)
0.7 %
–0.6 %
48 h
9800
(1.72)
–0.6 %
0.3 %
Conv.acryl – Conv.a-amide
105
104
MW (PMMA)
103
0
12
24
Time, h
36
48
C
DMF DMSO
=
= =
dangling ~ 3%
DMF
=
To permit a transformation of the resulting cyclopolymer into
an alternating copolymer, the quantitative cleavage of the two
activated ester bonds in the cyclic units is required. Thus, the
cleavage characteristics of the spacer in divinyl monomer 1 were
evaluated using model compound 2, which exhibits a similar
chemical structure without the vinyl groups, as the vinyl groups
engage in Michael addition reactions with the primary amines. For
that purpose, an excess of n-butylamine was added to a DMSO-
d6 solution of 2 and the reaction was monitored by 1H NMR
spectroscopy (Figure 4). Soon after the addition, the phenoxy
ester bond was cleaved to form phenol and amide moieties, which
was supported by the up-field shift of the aromatic protons (b, c,
d  b’, c’, d’) and the emergence of peaks derived from the amide
compound (a’, f’). After several days, another ester bond in the
phenol compound was cleaved to afford ethanol and amide
moieties, which was supported by the emergence of peaks
attributed to the methylene moiety of ethanol (e’’) and another
type of methylene moiety adjacent to the amide (f’’). Importantly,
all these peaks were detected with reasonable integration ratios,
which supports the notion of a quantitative transformation.
ppm
1.0
9.0
8.0
7.0
6.0
5.0
4.0
3.0
2.0
D
1
Model Monomers of 1
O
NH
O
O
HN
O
O
O
O
0.5
O
r1 = 1.1, r2 = 0.11
NO2
NO2
n-BuAm
(M2)
NPA
(M1)
1
0
0
0.5
Monomer composition
f = [M1]0/([M1]0 + [M2]0)
1
Figure 3. Cyclopolymerization of 1 using a RAFT system: [1]0/[CPDTC]0/[AIBN]0
= 100/2/2 mM in dioxane/DMF (8/2; v/v) at 60 ˚C. (A) Plots of conversions of the
two vinyl groups against polymerization time; (b) SEC curves of the
cyclopolymers; (C) 1H NMR spectrum of obtained cyclopolymer obtained in 48
hours; (D) monomer reactivity ratio of the model monomers. CPDTC: 2-Cyano-
2-propyl dodecyl trithiocarbonate.
Then, we used a RAFT polymerization technique30 to
control the cyclopolymerization (Table 1, entry 10-13, Figure 3A).
RAFT polymerization with CPDTC gave high conversion and
narrow molecular weight distribution. The two vinyl groups were
consumed at an almost identical rate, i.e., the difference was less
than 1%. The SEC curves of the obtained polymer shifted to
higher molecular weight, while retaining their unimodal shape,
albeit that the molecular weight distribution was slightly broad
(Mw/Mn ~ 1.7, Figure 3B). When the concentration was increased
([1]0/[chain transfer agent]0 = 200/4 or 500/10 mM), the difference
between the conversions of the two vinyl groups increased, and a
small shoulder peak at higher molecular weight was observed and
molecular weight distribution becomes latger at longer reaction
time, indicating an uncontrolled cyclopropagation and thereby
cross-linking reaction (Table 1, entry 12,13 and Figure S2). These
results suggest that dilute conditions (e.g. 100 mM of the divinyl
monomer) are required to control the cyclopolymerization. Figure
3C shows the 1H NMR spectrum of the product of the
polymerization of 1. The spectrum is very broad, most likely due
to the rigid cyclic structure. Very small peaks from the dangling
olefinic protons caused by non-cyclopropagation were observed
at 5.4-7.3 ppm, and the integral ratio indicates the error was about
3% relative to the whole number of repeat units (Figure S19).
These results suggest the intramolecular reaction was well
controlled under such a dilute condition.
a
A
a
e
O
O
O
b
d
e
b
O
c
d
2
c
DMSO
Model
NO2
compound
H2
O
10 eq.
NH2
a’
B
e’
b’
a’
d’
OH
O
O
NH
e’
b’
c’
O
f’
f’
d’
NO2
c’
C
a’
e’’
a’
e’’
f’’
O
NH
HO
b’’
f’
d’’
f’’
f’
OH
O
c’’
b’’
c’’
N
H
d’’
NO2
ppm
2.0
8.0
7.0
6.0
5.0
4.0
3.0
Figure 4. 1H NMR study on the quantitative transformation of the two ester
bonds in model compound 2 upon addition of n-BuNH2: [2]0/[n-BuNH2]0 =
100/1000 mM in DMSO-d6 at room temperature.
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RESEARCH ARTICLE
A
B
Copolymer from 1
Copolymer from 1
Cyclopolymn.
m
n
n-BuNH2
HN
O
HN
O
1
MeOH
=
OH
g
Random
Random
a
h
b
i
f
d, k, l
Copolymn.
e
m
O
j
c
n
O
HN
O
HN
O
a, b, h, i
HN
HN
MeOH
=
R
d
k
e
l
OH
OH
g
f
4.0
3.0
Copolymer from 1
10/10
2.0
1.0
ppm
C
D
m/n
9/10
10/11
Copolymer from 1
11/12
11/11
10/9
12/11
11/10
MeOH
=
g
8/14
7/15
Random
Random
9/13
f
6/16
5/17
4/18
3/19
e
10/12
11/11
d
b, i, k
l
c, j
MeOH
=
b,i
ppm
2400
2500
2600
2700
2800
2900
m/z
180
170
60
50
40
30
20
Figure 5. Comparison of the alternating copolymer and random copolymer of BuAm and HEAm (A) Scheme for the synthesis of the alternating and the
corresponding random copolymers; (B) 1H NMR spectra of the copolymers; (C) 13C NMR spectra of the copolymers; (D) MALDI-TOF MS spectra of the
copolymers. The m/z peaks were detected as Na+ adduct of copolymer.
molecular-weight intervals that correspond to the BuAm and
HEAm units. The molecular weight was corresponding to
Thus, we studied conversion of the cyclopolymer into
alternating copolymer or a polymer with only one sequence error.
alternating copolymer. At first, we used n-butylamine to
This result also shows the terminal group was well controlled like
synthesize BuAm-HEAm alternating copolymer. an excess amine
Scheme S7. RAFT end group was eliminated via aminolysis and
(~ 20 eq.) was directly added to the polymerization solution and
the thiol reacts with residue monomer (thiol-ene reaction) during
the solution was stirred at room temperature for 2 days in order to
the side chain transformation. Given the results of the reactivity
ensure a quantitative cleavage of the two ester bonds. As the
ratios of the model comonomers, the cyclopolymerization without
expected product was an alternating copolymer of BuAm and
cross-linking, the 1:1 composition established by the 1H NMR
HEAm, the corresponding 1:1 random copolymer was also
analysis, and MALDI-TOF-MS analysis, it is feasible to attribute
synthesized via RAFT copolymerization of the two acrylamide
an alternating sequence to the obtained copolymer.
1
monomers (Figure 6A). Figure 6B shows the H NMR spectrum
of the product after the treatment with n-BuNH2 and
corresponding random copolymer. The spectrum is quite similar
to that of the 1:1 random copolymer, and an analysis of the peak
integration ratios indicated a 1:1 ratio of the two units. In addition,
Figure 5C shows 13C NMR of the obtained copolymer in
comparison with the random copolymer, and the spectra exhibit
almost identical shapes and peak-splitting patterns. Peculiar
peaks specifically due to the alternating sequence were not
observed though 13C NMR of alternating copolymer was different
from random ones, and it clarified the sequence in previous works
of sequence control.23,24,26,33
As the cyclopolymerization proceeds via an iterative intra-
and intermolecular propagation, the tacticity of the resulting
polymer after the cleavage could be different from that obtained
via a conventional propagation process.36,37 As the tacticity could
affect the physical properties, its characterization is important in
order to study the sequence-dependent properties. Therefore, we
examined the tacticity of the resulting polymer via the conversion
into HEAm homopolymers using 2-amino ethanol for the cleavage
reaction, considering that it is difficult to characterize the tacticity
of copolymers. Figure S4 shows the 13C NMR spectra of the
product (top) in comparison with poly(HEAm) synthesized via the
radical polymerization of HEAm (bottom). Although some slight
differences were observed, the peak shapes were almost
identical, indicating similar tacticity to the polymer obtained via
general propagation. The little change in tacticity is likely due to
that the spacer is not so rigid as our previous design with
naphthalene leading to heterotactic-rich tacticity. Thus, it is
feasible to conclude that influence of the tacticity is negligible.
On the other hand, we recorded quite different MALDI-TOF
mass spectra34 from the product after cleavage with n-butylamine
to the random copolymer (Figure 5D). The random copolymer of
BuAm and HEAm showed a series of distributed peaks similar to
those of typical random copolymers.35 In sharp contrast, the
copolymer obtained after cyclopolymerization and cleavage
showed
a different peak series, consisting of alternating
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10.1002/anie.201915075
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RESEARCH ARTICLE
remove any low-molecular-weight compounds (Figure S20-S31).
Some peaks characteristic for the substituents of the added
amines were unequivocally observed with reasonable chemical
shifts and integration ratios.
Subsequently, we studied the solubility of the series of acryl-
amide-based alternating copolymers in H2O and CHCl3 (Figure
7A). The propyl-based copolymers showed similar solubility,
regardless of the branch structure (normal vs. iso), i.e., they were
soluble in H2O but not in CHCl3. The latter, obtained from N-
isopropyl acrylamide (NIPAM), showed no thermal response,
unlike the corresponding homopolymer.38 This behavior is most
likely due to the hydrophilicity of the HEAm units. However, when
the pendant was increased by one carbon atom to butyl, the
copolymer showed thermal response in H2O, i.e., the copolymer
was soluble in H2O at ambient temperature but insoluble at higher
temperature. The thermal response was further investigated by
variable-temperature UV-vis transmittance measurements in
comparison with the copolymers obtained 1:1 radical
copolymerization of the corresponding comonomers, i.e., n-butyl
acrylamide and HEAm (Figure 7B; 10 mg/mL; 1 ˚C/min;  = 670
nm). Sequence of the copolymer for comparison should be
random, as both comonomers exhibit almost identical reactivity.
Figure 6. Side chain cleavage into a series of alternating copolymers. (A)
Scheme for alternating copolymers; (B) List of alternating copolymers
Once the cyclopolymer is synthesized, various alternating
copolymers can be generated by selecting different amines for the
cleavage, which is a particular advantage of this method. Thus, a
variety of amine derivatives was directly added after the
cyclopolymerization to incorporate the corresponding substituents
on one of acrylamide units in the alternating sequence. For all the
amine compounds studied in this work, the addition led to a quick
and quantitative cleavage of the 4-nitrophenyl ester bonds. As
already confirmed by the model reaction (vide supra), the 3-
nitrobenzoate esters undergo cleavage after the transformation of
the nitrophenyl ester bonds (Figure 6, path A). However, some
amines, such as isopropyl amine, stearylamine, benzylamine,
picorylamine, morpholine, and histamine, were not capable of
effectively cleaving the 3-nitrobenzoate ester bonds. In these
cases, a post addition of n-butyl amine quantitatively cleaved the
nitrobenzoate ester bonds (Figure 6, path B). In the case of
stearylamine, higher temperature was needed due to the solubility.
Secondary amine, morpholin also needs higher temperature to
complete the conversion of 4-nitrophenyl ester. The structures of
Figure 7. Solution properties of the alternating copolymers. Variable-
temperature transmittance measurements with butyl- and benzyl-based
alternating copolymers in H2O and CHCl3 (10 mg/mL; heating; 1 ˚C/min)
1
the series of alternating copolymers were confirmed by H NMR
analysis after purification (dialysis or reprecipitation) in order to
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RESEARCH ARTICLE
The alternating copolymer showed a sharp response, i.e., the
width of the transmittance decreased from 90% to 10% within 2
˚C. On the other hand, the solution of the random copolymer
became gradually cloudy and the response was less sharp (90%
to 10% within 5 ˚C). The average composition of the random
copolymer is 1:1, i.e., identical to the alternating copolymer, but
vital differences were observed between the two copolymers. The
same trend was also observed during the cooling process, albeit
that some hysteresis processes were observed (Figure S5). This
difference should be attributed to the presence of mixtures of
polymer chains with various compositions that afford on average
a 1:1 ratio. In the distributed mixture, the BuAm-rich copolymers
would be expected to show poorer solubility at lower temperature
to afford aggregates that partially scatter light. On the other hand,
the HEAm-rich copolymer, which is more hydrophilic, forms
aggregates at higher temperature. The sharp thermal response of
the alternating copolymer truly indicates that the copolymer
exhibits a uniform sequence. Dynamic light scattering (DLS)
measurements corroborated these results by revealing that for
the random copolymers, the size of the aggregates increased
gradually, while the size of the alternating copolymer increased
more sharply (Figure S6).
average of the two homopolymers. Interestingly, another
endothermic peak was observed at higher temperature (181.3 ˚C),
which was not observed for the random copolymer and the
homopolymers. Similar trends were observed during the cooling
process (Figure S8). These results suggest that the alternating
copolymer chains crystallize faster and more tightly than their
random analogues or the corresponding homopolymers, and that
some specific phase transition occurs at high temperature.
A
Tg
94.2 ˚C
Ti
n
O
181.3 ˚C
HN O HN
C18H37
Tm
31.2 ˚C
Alternating
OH
93.5 ˚C
19.7 ˚C
n
m
HN
O
HN
O
Random
C18H37
OH
74.8 ˚C
n
C18Am
Homo
HN
O
31.2 ˚C
C18H37
115.6 ˚C
When the number of the carbon atoms in the alkyl chain was
further increased to pentyl and octadecyl, the copolymers became
hydrophobic. Interestingly, the copolymer containing benzyl acryl
amide units showed thermal response in CHCl3. The CHCl3
solvent in this study contains EtOH as stabilizer (0.3 – 1.0%),
which might affect the thermal response.39 Anyway, the thermal
response was different from the corresponding random
copolymer, similar to the case with the butyl group in H2O, i.e., the
response was sharper than for the random copolymer, and similar
trends were observed during the cooling process (Figure S7). The
difference is also likely due to an absence of any composition
distribution among the chains. The dimethyl-amine-embedded
alternating copolymer is amphiphilic, whereas the pyridine-based
alternating copolymer is insoluble in both solvents. The
alternating copolymer that carries imidazole pendants is
hydrophilic. These amine-containing alternating copolymers
might find applications in catalysis and bio-related materials,
which is currently under investigation in our laboratory.
n
O
Heating
HEAm
Homo
HN
-40
0
40
80
120 160 200
Temperature, ˚C
OH
Alternating
B
20 ˚C
80 ˚C
180 ˚C
200 µm
200 µm
200 µm
20 ˚C
80 ˚C
189 ˚C
200 µm
200 µm
200 µm
Random
140 ˚C
20 ˚C
20 ˚C
Finally, the crystalline behaviour of the alternating
copolymer that contains octadecyl acryl amide40 was evaluated
by DSC measurements. A sharp endothermic peak derived from
melting was observed at 31.2 ˚C (Tm), which is similar to the
homopolymer of octadecyl acryl amide. In such virtually atactic
copolymers, the crystallization is solely due to the presence of
crystallizable C18 side chains. The melting enthalpy (Hm = 35 J/g)
relative to the weight fraction of the octadecyl substituent (74%)
is comparable to that of the homopolymer (53 J/g). Moreover, the
peak was sharper, as evident from the half-width values
(alternating copolymer: 10 ˚C; homopolymer: 15 ˚C). On the other
hand, the corresponding random copolymer exhibited lower
enthalpy and a much broader melting peak at lower temperature
(Tm = 19.7 ˚C; half-width= 21 ˚C; Hm = 29 J/g). A shift of the base
line derived from the glass transition was observed, albeit that the
glass transition temperature (Tg) was identical to that of the
random copolymer, and that the value was almost equal to the
200 µm
200 µm
200 µm
Fig 8. Solid phase transitions of the alternating copolymer of C18Am and HEAm:
(A) DSC profiles of the alternating copolymer of C18Am and HEAm in
comparison with the random copolymer and the polyC18Am and polyHEAm
homopolymers. Samples were heated from -50 ˚C to 210 ˚C at 10 ˚C/min (2nd
heating); (B) POM image of the alternating copolymer of C18Am and HEAm.
Samples were pressed at 140°C between glass slides and cooled to RT.
Textures are recorded on second heating/cooling cycle. For further information
on the details of the measurements, see the Supporting Information.
To clarify the event, the phase transition was observed by
polarizing optical microscopy (POM). Below 130°C, both
copolymers behaved as solid powders (Figure S9). When heated
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10.1002/anie.201915075
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Figure 9. X-ray diffraction of alternating copolymer of C18Am and HEAm alternating (A,B) and random copolymers (C,D); (E) predicted structure of the
alternating copolymer. For further information on the details of the measurements, see the Supporting Information.
to 140˚C, i.e., well above the glass transition revealed by DSC,
the random copolymer became a fluid that easily filled the gap
between the glass slide and the coverslip driven by capillary
forces. Viewed between crossed polarizers, the sample appeared
black, i.e., this fluid is an optically isotropic liquid, and the black
texture remained down to room temperature and during the next
heating/cooling cycle (Figure 8B). The alternating counterpart
also liquified at 140˚C, but showed birefringence colors between
crossed polarizers, and birefringence disappeared only above
180˚C (clearing point) (Figure S9). The clearing point was well
corresponding to that of the specific endothermic peak on the
DSC measurement and thus, the peak can be assigned to the
phase transition from anisotropic liquid to isotropic liquid (Ti). It
that this latter is the overlap of a single Bragg peak at 1.54 Å-1 and
a halo with maximum at q = 1.39 Å-1. These features indicate a
semicrystalline morphology and the lack of any long-range order
of this polymer at room temperature. The pattern is similar to the
one recorded for the homo-C18 homopolymer in the same
conditions but with lower crystallinity and smaller size of
crystallites in the random copolymer. The characteristic feature of
the random copolymer is precisely that it contains more or less
important fragments of homopolymer. Thus, the pristine sample
contains areas of microphase separated short homo-C18
fragments that reproduce crystalline features of the homopolymer.
At 80°C small Bragg peaks are detected at q = 0.146 Å-1 and q =
0.294 Å-1 but thus disappear and 120°C and then do not reappear
anymore. The cooling cycle is shown in figure 9D, where the
random copolymer appears essentially amorphous at any
temperature.
was concluded that the alternating copolymer shows
a
mesomorphic state between melting and clearing points, whereas
the random copolymer merely shows an ordinary liquid phase as
soon as the sample is liquefied. The nature of the mesophase
exhibited by the alternating copolymer was identified from its
optical textures: when the sample was carefully cooled across the
clearing point, birefringence appeared in the form of "bâtonnets"41
that gradually extend within the whole sample to form the classical
"focal conics" texture. After cooling, the focal conics texture
survived until room temperature, but an increase of birefringence
was observed when passing the crystallization point. During the
next heating cycle, illustrated in figure 8B, the same sequence of
images was observed and the resulting texture between Tm and
Tiso was the same as before.
In the case of alternating copolymer, it showed quite
different result. The first heating cycle is illustrated in Figure 9A.
Contrarily to its random counterpart, the alternating copolymer
becomes more ordered upon thermal annealing. Thus in the low-
q region, whereas broad features are scarcely detected in the
pristine sample, heating reveals the presence of Bragg peaks
which are then constantly observed during further cycles up to
about 180°C where the pattern becomes essentially amorphous.
The temperature variations of crystalline parameters are reported
in table S2. At room temperature, low q signals are indexed as
001 and 002 reflections of a layered structure with a layer spacing
of about 37.2 Å. These reflections are sharp thus indicating that
once annealed, this layer structure has a long-range ordering. At
large q the presence of a single Bragg peak indicates a 2D
hexagonal ordering with a spacing of 4.2 Å (hexagonal parameter
4.2 × 2/√3 = 4.8 Å). This value is typical of alkyl chains in a
hexagonal arrangement (e.g. structure of soaps). This phase is
X-ray diffraction data were recorded to clarify the structure.
The X-ray pattern of the random copolymer sample evaporated
from dichloromethane solution at 25°C is plotted in Figure 9C. At
low q, a series of broad reflexions with maxima at about q = 0.2,
0.4, 0.6 Å-1 is detected. At large q, another broad complex signal
is detected around q = 1.5 Å-1. The temperature evolution reveals
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10.1002/anie.201915075
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In a round bottom flask was placed divinylmonomer 1 (3.63 g, 10.8 mmol)
and AIBN (35.7 mg, 0.216 mmol) under argon. Then, degassed anhydride
dioxane (83.1 mL), DMF (20.8 mL), and CTA (0.89 mL of 244 mM stock
solution in toluene, 0.216 mmol) were added sequentially in this order at
room temperature under dry argon; the total volume was 109 mL. For
recognized as smectic B. Between 25°C and 80°C, a phase
transition is detected: both low q signals and the large q signal
show a discontinuity. Furthermore, the ratio of intensities I002/I001
drops from about 0.07 to 0.01, indicating much larger thermal
fluctuations in the higher temperature phase. Nevertheless both
001 and 002 signals remain sharp, indicating that long range layer
order is still present. At large q, the Bragg peak is no longer
detected but a halo with maximum at about 4.6 Å is observed
indicating a 2D liquid-like order inside the layers. At 80°C, the layer
spacing is of about 39.5 Å i.e. larger than at 25°C but upon further
heating, the interlayer spacing gradually decreases whereas the
intralayer spacing gradually increases thus accounting for the
shortening of the end-to-end distance of the alkyl chains. Such
features are typical of the smectic A phase where elongated
molecules are packed perpendicular to the layer planes. This
second mesophase is stable up to about 180°C, whereupon
transition to the isotropic liquid is observed. Appearance of
reversible smectic B and smectic A phases, with long range
positional ordering in a large range of temperature is the specific
feature of the alternating copolymer. The formation of such
mesophases is due to the controlled sequence of hydrophobic
and hydrophilic groups, conducive to a layered arrangement with
regular alternation of well-defined octadecyl and hydroxyethyl
sublayers. Self-assembly in the bulk through segregation of short
incompatible fragments is well known for small mesogenic
molecules,43 but was also observed in random44 and alternating45
copolymers. The interesting fact in this work is that the formation
of layers is inhibited in the random copolymer and specific to the
alternating sequence.
immediately after mixing, the flask was placed in an oil bath kept at 60 ̊C
for 48 h. The reaction was terminated by cooling the solution to –78 ˚C. To
5 mL polymerization solution (monomer unit 0.5 mmol) was directly added
butylamine (0.988 mL, 10 mmol). The reaction mixture was stirred at
ambient temperature for 48 hours. Then, the reaction mixture was purified
by dialysis with MeOH (about 12 hours stirring; 4 times replacement of the
solvent). Mn and Mw/Mn were measured by GPC (Mn = 7600 Mw/Mn = 1.37).
Acknowledgements
The authors would like to thank Dr. Takaya Terashima (Kyoto
University) for fruitful discussions, Karin Nishimura (Kyoto
University) for MALDI-TOF-MS measurements and Dr. Antoine
Tissot (ENS, Paris) for help in X-ray measurements. This work
was partially supported by the Strategic International
Collaborative Research Program (SICORP) from The French
National Research Agency (ANR) and the Japanese Science and
Technology Agency (JST), the ANR-15-JTIC-0004 grant, as well
as by JSPS KAKENHI grants 17H06453 and 19H00911.
Keywords: alternating copolymers • cyclopolymerization •
radical polymerization • sequence • polyacrylamides
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RESEARCH ARTICLE
RESEARCH ARTICLE
This article deals with a series of
alternating copolymers that consist
exclusively of acrylamide units.
Crucial to realizing the unprecedented
polymer synthesis is the design of a
Yuki Kametani, François Tournilhac,
Mitsuo Sawamoto, and Makoto Ouchi*
Alternating Copolyacrylamides
O
NH
O
O
O
O
2-hydroxyethyl acrylamide (–OH)
and
>10 seriesof acrylamide (–R)
Page No. – Page No.
NO2
HN
O
O
O
HN
O
O
HN
O
O
O
HN
HN
HN
O
HN
O
O
O
HN
HN
HN
O
HN
O
O
O
HN
HN
HN
O
HN
O
O
O
HN
HN
HN
O
HN
O
O
O
HN
HN
HN
O
Unprecedented Sequence Control
and Sequence-Driven Properties in A
Series of AB-Alternating Copolymers
Consisting Solely of Acrylamide
Units
R
R
R
R
R
R
divinyl
monomer
carrying
two
OH
OH
OH
OH
OH
OH
activated ester bonds to allow
“selective” cyclopolymerization and
the post aminolysis reactions. Some
HN
HN
HN
HN
O
HN
O
HN
O
HN
O
HN
O
R
R
R
R
R
R
OH
OH
OH
OH
OH
OH
HN
O
HN
O
HN
O
HN
O
HN
O
HN
O
R
R
R
R
R
R
of
resultant
alternating
OH
OH
OH
OH
OH
OH
copolyacrylamides exhibit unique
properties to the regulated sequence
in solution and in the bulk state.
Unique Properties
toAlternatingSequence
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