Multifactor Control of Vinyl Monomer Sequence, Molecular Weight, and Tacticity via Iterative Radical Additions and Olefin Metathesis Reactions

Masato Miyajima, Kotaro Satoh, Takahiro Horibe, Kazuaki Ishihara, and Masami Kamigaito*

Article

Multifactor Control of Vinyl Monomer Sequence, Molecular Weight,

and Tacticity via Iterative Radical Additions and Oleﬁn Metathesis

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ABSTRACT: Monomer sequence control in terms of a single monomer unit, particularly in vinyl polymers, is one of the largest

challenges in polymer chemistry. Furthermore, multifactor control of monomer sequence, molecular weight, and stereoregularity is

an ultimate goal. In this work, we propose a strategy to prepare C−C main-chain sequence-regulated polymers with controlled

molecular weights from vinyl monomers via a combination of iterative atom transfer radical additions and oleﬁn metathesis

reactions. This strategy enabled the synthesis of sequence-regulated polymers with exact styrene−acrylate−styrene sequences in the

C−C main chains, controlled molecular weights of up to 10 , and stereoregularities varying with syndiotacticity, isotacticity, and

heterotacticity. The utility of this strategy is further demonstrated by formation of block copolymers consisting of sequence-regulated

vinyl polymer segments by combining living ROMP of norbornene derivatives.

INTRODUCTION

functional materials, which have properties quite diﬀerent from

those of homopolymers and random copolymers. However,

precise monomer sequence control in terms of a single

monomer unit is in principle impossible for vinyl polymers,

which are generally prepared by chain-growth copolymerization

■

An ultimate goal in polymer synthesis is multifactor control of

molecular weight, stereochemistry, and monomer sequence

because excellent properties and unique functions are expected,

as in natural macromolecules such as proteins, which possess

statistically proceeding for the comonomers.

perfectly controlled structures. In particular, precise monomer

Another eﬃcient carbon−carbon bond-forming reaction for

sequence control is one of the largest challenges and will lead to

further developments of synthetic polymers for next-generation

polymer synthesis is oleﬁn metathesis, which is applicable to

−14

functional materials.

both chain- and step-growth polymerizations, such as ring-

23,24

Among various synthetic polymers, vinyl polymers constitute

one of the largest families and are prepared by repetitive C−C

bond-forming reactions via chain-growth mechanisms between

propagating chain ends, such as radical, anion, cation, and

organometallic species, and vinyl monomers with diverse

opening metathesis polymerization (ROMP)

and acyclic

diene metathesis (ADMET) polymerization, respectively. The

latter polymerizes telechelic diene via intermolecular reactions

between monomers, oligomers, and polymers, while the former

is eﬀective for cyclic oleﬁns mainly with ring strain that react

eﬃciently with metal carbene species at the propagating polymer

chain end. Both polymerizations result in polymers linked by

substituents on the vinyl carbons. The main chain of all

vinyl polymers thus consists of only stable C−C bonds, whereas

the polymer properties vary widely with the chemical structure

of the substituents and can be tuned by the comonomer

composition, which is particularly eﬀective for radical polymer-

ization due to a wide variety of polymerizable monomers by

radical intermediates. The vinyl monomer sequence is also

expected to aﬀect polymer properties and functions. In terms of

longer range monomer sequences, diblock, triblock, and even

Received: August 29, 2020

6−20

multiblock

copolymers have been prepared and are used as

XXXX American Chemical Society

J. Am. Chem. Soc. XXXX, XXX, XXX−XXX

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Article

CC bonds, which can be subsequently hydrogenated into the

more stable saturated C−C bonds. Indeed, hydrogenated

cyclooleﬁn polymers prepared by ROMP of substituted

norbornenes and subsequent hydrogenation possess excellent

thermal and optical properties, which are diﬃcult to attain by

Scheme 1. Multifactor Control of Vinyl Monomer Sequence,

Molecular Weight, and Tacticity by Iterative Atom Transfer

Radical Additions (ATRAs), Allylation, Ring-Closing

Metathesis (RCM), Entropy-Driven Ring-Opening

Metathesis Polymerization (ED-ROMP), and

Hydrogenation

direct polymerization of vinyl monomers. In addition, linear

periodically functionalized polyethylene mimics can be obtained

7−29

by ROMP of substituted cyclooctene

or ADMET polymer-

0−32

ization of functionalized linear telechelic diene

followed by

hydrogenation. Furthermore, living ROMP enables control of

the molecular weight of the resulting polymer. A judicious use of

metathesis reactions is thus eﬀective for the synthesis of novel

C−C main-chain polymers that are not directly accessible by

polymerization of vinyl monomers. More recently, macrocyclic

oleﬁn monomers possessing sequenced ester units have been

synthesized and polymerized by ROMP to generate sequence-

,11,13

regulated polyesters.

One of the most precise sequence controls of vinyl monomers

is iterative single-unit monomer addition or insertion (SUMI) of

33−51

vinyl monomers to the chain end of an oligomer.

This

approach is particularly eﬀective for radical addition, which

results in stable dormant species and enables isolation of the

products at each step. Iterative radical addition is achieved using

an initiating system similar to that for controlled/living radical

polymerization or reversible deactivation radical polymerization

(

RDRP), such as atom transfer radical polymerization (ATRP)

and reversible addition−fragmentation chain transfer (RAFT)

polymerization, in which stable halides and thioesters are

employed as the isolable dormant species. Although the

iterative single-monomer addition accomplishes perfect se-

quence control for various vinyl monomers, precise synthesis

becomes harder with an increase in the degree of polymerization

due to the iterative processes.

To precisely multiply a short monomer sequence into a long

polymer chain, controlled polymerization of the resulting

sequence-regulated oligomers is suitable. Therefore, after

iterative atom transfer radical additions (ATRAs), we

introduced an unconjugated vinyl group and a reactive

carbon−chlorine bond at each chain end of the sequence-

regulated vinyl oligomers and subsequently polymerized them

via metal-catalyzed step-growth radical polymerization to form a

main-chain C−C bond along with a pendent C−Cl bond, which

heterotactic sequence-regulated cyclic oleﬁns were isolated by

selective recrystallization and polymerized into multifactor-

controlled vinyl polymer mimics with perfectly regulated

monomer sequences, controlled molecular weights, and stereo-

regularity.

36,37

RESULTS AND DISCUSSION

is an equivalent structure to the vinyl chloride unit.

This

■

method has thus constructed perfectly sequence-regulated vinyl

polymer structures, but molecular weight control as well as a

high molecular weight polymer have not been attained due to

the slow radical addition to the unconjugated CC bond and

step-growth mechanism.

Herein, we propose a novel strategy to achieve precisely

sequence-regulated vinyl polymers with controlled molecular

weights via a combination of iterative ATRAs and ROMP

Synthesis of Sequence-Regulated Cyclic Oleﬁns via

Iterative ATRAs, Allylation, and RCM. The sequence-

regulated telechelic diene oligomer (M1), which has a

symmetrical sequence (OSA SO) of one butyl acrylate (A )

and two styrene (S) units between the terminal oleﬁns (O), was

synthesized by iterative ATRAs and subsequent allylation. The

ﬁrst ATRA of styrene to butyl dichloroacetate (ClA Cl) was

conducted using CuCl in the presence of N,N,N′,N′′,N′′-

(Scheme 1). This method enables the synthesis of perfectly

pentamethyldiethylenetriamine (PMDETA) to form a dimer

sequence-regulated polymer mimics with controlled high

molecular weights and perfect tacticity from vinyl monomers

as starting materials. We thus prepared sequence-regulated

trimers using ATRAs twice and then placed oleﬁns at both chain

ends by allylation. We were able to then transform the sequence-

regulated telechelic diene into the sequence-regulated cyclic

oleﬁn via ring-closing metathesis (RCM) and successfully

synthesized C−C main-chain sequence-regulated polymers

(ClSA Cl), which was puriﬁed by column chromatography and

distillation. Then the second ATRA of styrene to the dimer using

the same catalyst under a slight excess of ClSA Cl over S

selectively resulted in a trimer (ClSA SCl) because the C−Cl

bond adjacent to the A unit had a higher reactivity than that

adjacent to the S unit and was preferentially activated. The crude

product was treated with allyltrimethylsilane in the presence of

TiCl to yield the sequence-regulated telechelic diene oligomer

with controlled molecular weights greater than 10 via ROMP

(OSA SO; M1) and a byproduct, OSA Cl, which was generated

of the cyclic oleﬁn followed by hydrogenation of the resulting

internal oleﬁn. Furthermore, isotactic, syndiotactic, and

by allylation of the remaining ClSA Cl in the crude product. The

byproduct (OSA Cl) was easily removed by column chroma-

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Article

tography after being converted to a more polar compound by

During the puriﬁcation process, we found that some CD1 was

recrystallized. X-ray crystallographic analysis of the single crystal

showed that the recrystallized part was indeed the 18-membered

cyclic compound, which was a completely sequence-regulated

syndiotactic styrene−butyl acrylate−styrene triad linked via

selective amidation of the activated A unit attached to the

electron-withdrawing chloride terminal group with 2-amino-

ethanol, which does not react with an internal A unit in M1

(

OSA SO). Further puriﬁcation by distillation resulted in pure

M1 composed of diastereomers and enantiomers (Figure 1A)

trans internal oleﬁns (Figure 3A). All H NMR peaks of

those of diastereomeric mixtures (Figure 1 B).

total yield 14%).

syndiotactic CD1 were very sharp (Figure 4A) in comparison to

Figure 1. H NMR spectra (CDCl , 25 °C) of M1 (A) and CD1 (B).

To synthesize the sequence-regulated cyclic oligomer, RCM

of the telechelic diene oligomer (M1) was performed using a

second-generation Grubbs catalyst (G2) under high dilution of

M1 in toluene at 20 °C ([M1] /[G2] = 5.0/0.05 mM). The

terminal oleﬁn reacted smoothly, and the conversion reached

2% in 20 h. However, contrary to our expectations for the

Figure 3. ORTEP diagrams of syndiotactic CD1 (A), syndiotactic CD2

(B), heterotactic CD2 (C), and isotactic CD2 (D).

formation of the monomeric cyclic product, the size-exclusion

chromatography (SEC) curve of the product shifted to a higher

molecular weight while maintaining the unimodal peak with

slight tailing (Figure 2 A). The main product puriﬁed by

We similarly prepared another sequence-regulated telechelic

diene oligomer consisting of a styrene−methyl acrylate−styrene

sequence (OSA SO; M2 ) and conducted RCM under similar

Figure 2. SEC curves (A) and MALDI-TOF-MS spectra (B) of M1 and

products obtained by RCM of M1 ([M1] /[G2] = 5.0/0.05 mM) in

toluene at 20 °C before and after puriﬁcation by preparative SEC.

preparative SEC showed a narrow SEC curve without tailing and

only one MALDI-TOF mass peak at 776.9, which is almost

identical to the mass (776.2) of the 18-membered cyclic dimer

(

CD1) obtained via oleﬁn-metathesis dimerization of M1

followed by RCM of the dimer (Figure 2B) (yield 32%).

Selective formation of CD1 is most likely due to the high ring

strain of the medium-sized 9-membered cyclic compound. In

the H NMR spectrum, disappearance of the terminal oleﬁn and

appearance of the internal oleﬁn were conﬁrmed, although all of

the peaks of CD1 were complicated in comparison to those of

M1 due to the diastereomeric mixture of the cyclic products

Figure 4. H NMR spectra (CDCl , 25 °C) of syndiotactic CD1 (A),

(Figure 1B).

syndiotactic CD2 (B), heterotactic CD2 (C), and isotactic CD2 (D).

Journal of the American Chemical Society

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Figure 5. Entropy-driven ring-opening metathesis polymerization (ED-ROMP) of sequence-regulated cyclic oligomer (CD1) ([CD1] /[G2] = 100/

.0 or 400/20 mM) in toluene at 20 °C. (A) Monomer conversion and remaining monomer concentration vs time plots. (B) M and M /M vs

n w n

monomer conversion plots. (C) SEC curves of products obtained at [CD1] /[G2 ] = 400/20 mM.

high-dilution conditions. The obtained products were similarly

diastereomeric mixtures of the 18-membered cyclic dimer

(CD2) of M2. Due to the lower solubility of the methyl ester

unit in nonpolar organic solvents, the diastereomers were

separated into several fractions by silica-gel column chromatog-

raphy followed by selective recrystallization under diﬀerent

conditions. The three diﬀerent single crystals obtained were

determined to be 18-membered cyclic compounds with

syndiotactic, isotactic, and heterotactic sequence-regulated

styrene−methyl acrylate−styrene and trans internal oleﬁns

(

Figure 3B−D). In addition, all peaks in the H NMR spectra

were sharp and diﬀerent from each other due to the diﬀerent

tacticity (Figure 4B−D). The sequence-regulated 18-membered

cyclic oleﬁns were thus prepared via a combination of iterative

ATRAs and RCM and could be separated into stereoregular

isomers by selective recrystallization.

Entropy-Driven ROMP of Sequence-Regulated 18-

Membered Cyclic Oleﬁns. ROMP of the diastereomeric

mixture of sequence-regulated 18-memblered cyclic oleﬁns-

Figure 6. H NMR spectra (CDCl , 55 °C) of poly(M1) (M = 20 700,

M /M = 1.62) (A) and poly(M1)-H (M = 23 000, M /M = 1.63)

(B).

(

CD1) was performed using G2 in toluene at 20 °C. Although

there was almost no ring strain in CD1, ROMP occurred (Figure

). At a lower concentration of CD1 ([CD1] = 100 mM),

those of the sequence-regulated linear telechelic diene oligomer

M1 in Figure 1A) than those of the cyclic oligomer (CD1 in

(

Figure 1B) except for the oleﬁn protons, indicating that the

cyclic oleﬁn was polymerized via ROMP to result in linear

sequence-regulated polymers with internal oleﬁns. Thus, ED-

ROMP of sequence-regulated 18-memblered cyclic oleﬁns

enables the synthesis of sequence-regulated polymers with

styrene−acrylate−styrene sequences and controlled molecular

weights.

polymerization stopped at approximately 55%, whereas the

^c^oⁿ^v^e^r^sⁱ^oⁿ^r^e^a^c^h^e^d^o^v^e^r⁹⁰^%^a^t^a^hⁱ^g^h^e^r^c^oⁿ^c^eⁿ^t^r^a^tⁱ^oⁿ⁽^[^C^D¹^]0

both conditions were almost the same, approximately 40 mM,

indicating that the polymerization reached equilibrium.

Polymerization of CD1 thus proceeded via an entropy-driven

400 mM). The ﬁnal residual monomer concentrations under

11,13

ROMP (ED-ROMP) mechanism.

Furthermore, ROMP of a series of three stereoregular

sequence-regulated 18-membered cyclic oleﬁns (CD1) with a

syndiotactic, isotactic, and heterotactic styrene−butyl acrylate−

styrene sequence (Figures S4 and S5) was investigated. Isotactic

and heterotactic CD1s were prepared by transesteriﬁcation of

isotactic and heterotactic CD2s, respectively, with butanol. The

ROMP of these stereoregular CD1s was conducted under the

same conditions ([CD1] /[G2] = 400/8.0 mM) except for

The number-average molecular weight (M ) of the polymers

obtained at a higher monomer concentration ([CD1] = 400

mM) increased in direct proportion to monomer conversion

and agreed well with the calculated value assuming that one

molecule of the catalyst generates one polymer chain. In

addition, the unimodal SEC curves shifted to higher molecular

weights, although the molecular weight distribution (MWD)

was slightly broad. To obtain a high molecular weight polymer,

the feed ratio of monomer to catalyst was varied from 20 to 50 by

decreasing the concentration of G2 while holding that of CD1

syndiotactic CD1, which was polymerized under a lower

monomer concentration ([CD1] /[G2] = 220/4.4 mM) due

to the low solubility in CH Cl . The isotactic and heterotactic

constant. The ED-ROMP also proceeded smoothly to result in a

CD2s were polymerized at high conversions (≥80%) in 24 h to

high molecular weight polymer with M greater than 2.5 × 10

result in high molecular weight polymers (M ≥ 2.5 × 10 )

(Figure S6).

(Figure S7), whereas polymerization of syndiotactic CD2s was

Figure 6A shows the H NMR spectrum of the obtained

polymer. The shapes of almost all of the peaks were closer to

slow (conversion = 31% in 24 h) to give relatively low molecular

weight polymers (M = 5.8 × 10 ) due to the low concentrations

J. Am. Chem. Soc. XXXX, XXX, XXX−XXX

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resulting polymers showed sharp peaks (Figure 7 ) in

Article

of the monomer and catalyst. All of the H NMR spectra of the

reaction (Figure S9). The polymer obtained after hydrogenation

thus possesses the completely regulated styrene−butyl acryl-

ate−styrene sequence linked by the additional ethylene−

methylene sequence. The isotactic and heterotactic polymers

were also successfully hydrogenated.

The thermal properties of the polymers were evaluated by

diﬀerential scanning calorimetry (DSC). The glass transition

temperatures (T ) of the atactic polymers before and after

hydrogenation (M = 2.1 × 10 and 2.3 × 10 ) were 14 and 13

C, respectively (Figure S10). These values were lower than that

of the 2:1 random copolymer of styrene and butyl acrylate with a

similar molecular weight (T = 40 °C, M = 2.6 × 10 ) prepared

by RAFT copolymerization, probably due to the presence of a

relatively ﬂexible ethylene−methylene sequence in the repeating

units in the sequence-regulated polymers. The eﬀects of tacticity

on the thermal properties were evaluated for atactic, isotactic,

and heterotactic polymers, which have similar molecular weights

of approximately 3.2−3.5 × 10 because the molecular weight of

the syndiotactic polymer was low (T = 2 °C, M = 6.4 × 10 ).

The T of the isotactic polymer was slightly lower than that of

the atactic polymer (10 vs 13 °C), while the heterotactic

polymer showed a slightly higher T (17 °C) before hydro-

genation. However, no additional transitions originating from

the stereoregularity were observed for these stereoregular

Figure 7. H NMR spectra (CDCl , 55 °C) of syndiotactic poly(M1)

(

M = 6400, M /M = 1.95) (A), heterotactic poly(M1) (M = 35 100,

M /M = 1.95) (B), and isotactic poly(M1) (M = 33 100, M /M =

polymers. Similar relationships between the T values were

.70) (C).

also observed for the hydrogenated polymers (Figure S10).

Almost no signiﬁcant dependence of the thermal properties on

the tacticity can be attributed to the stereoregular styrene−butyl

acrylate−styrene triad sequence being isolated by the ﬂexible

ethylene−methylene sequence.

comparison to those obtained from diastereomeric mixtures,

indicating that stereoregularity was retained during ROMP to

give polymers with controlled monomer sequences, molecular

weights, and high stereoregularity.

Block Copolymerization. Block copolymerization of exo-

N-phenylnorbornene-5,6-dicarboximide (NB1) and CD1,

which are strained and strainless monomers, respectively, was

examined to synthesize the block copolymer with a sequence-

regulated vinyl polymer structure (Figure 8A). We ﬁrst

polymerized NB1 with a third-generation Grubbs catalyst

Hydrogenation to Mimic Sequence-Regulated Vinyl

Polymer Structures with Saturated Main C−C Chains.

Hydrogenation of internal oleﬁns in the sequence-regulated

polymers was examined to mimic the structure of sequence-

regulated vinyl polymers, the main chain of which consists of

only C−C bonds. Herein, chemical hydrogenation was carried

out using p-toluenesulfonyl hydrazide in o-xylene at 135 °C. As

shown in Figure 6B, the oleﬁnic protons at 4.9−5.2 ppm

completely disappeared, while only slight changes were

observed in the other peaks, indicating nearly complete

hydrogenation (>99%). In addition, the SEC curve was almost

unchanged, indicating that no chain scission occurred during the

(

G3), which is eﬀective for fast initiation of ROMP, to obtain

a polymer with controlled molecular weights and narrow MWDs

(Figure 8B). When NB1 was completely consumed, atactic CD1

was added as the second monomer. The second polymerization

also proceeded to induce a shift of the SEC curve to a higher

molecular weight while maintaining the unimodal and narrow

MWDs.

Figure 8. Block copolymerization of norbornene derivative (NB1) and sequence-regulated cyclic oligomer (CD1) ([NB1] /[CD1]_a_d_d/[G3] = 200/

00/20 mM) in CH Cl at 20 °C. (A) Scheme. (B) SEC curves of the obtained products. (C) DSC curves of poly(NB1), poly(NB1-b-M1), and

2 2

poly(M1).

J. Am. Chem. Soc. XXXX, XXX, XXX−XXX

Journal of the American Chemical Society

orcid.org/0000-0002-3105-4592

Article

Furthermore, the ¹H NMR spectrum of the obtained

polymers showed characteristic peaks originating from both

NB1 and CD1 (Figure S11). The number-average degree of

Authors

Masato Miyajima − Department of Molecular and

Macromolecular Chemistry, Graduate School of Engineering,

Nagoya University, Nagoya 464-8603, Japan

polymerization (DP (NMR)) of each monomer unit was

calculated from the peak intensity ratios of the monomer units

to the initiating phenylene terminal group originating from G3.

The DP (NMR) value was close to DP (calcd), which was

calculated from the feed ratio of each monomer to G3 and

monomer conversion. The living ROMP chain end of NB1 thus

eﬃciently initiates ED-ROMP of CD1 to result in a block

copolymer consisting of norbornene derivative segments and

sequence-regulated vinyl polymer segments. The DSC of the

Kotaro Satoh − Department of Molecular and Macromolecular

Chemistry, Graduate School of Engineering, Nagoya University,

Nagoya 464-8603, Japan; Department of Chemical Science and

Engineering, School of Materials and Chemical Technology,

Tokyo Institute of Technology, Tokyo 152-8550, Japan;

Takahiro Horibe − Department of Molecular and

Macromolecular Chemistry, Graduate School of Engineering,

Nagoya University, Nagoya 464-8603, Japan; orcid.org/

0000-0002-4692-4642

block copolymer showed two T values at 10 and 153 °C (Figure

C), which correspond to those of poly(M1) and poly(NB1),

respectively, suggesting that microphase separation occurred

between the soft and the hard segments.

Kazuaki Ishihara − Department of Molecular and

Macromolecular Chemistry, Graduate School of Engineering,

Nagoya University, Nagoya 464-8603, Japan; orcid.org/

0000-0003-4191-3845

CONCLUSIONS

■

We developed a novel strategy to prepare precisely sequence-

regulated polymers which consist of only C−C main chains and

mimic vinyl polymer structures by iterative ATRAs of vinyl

monomer, allylation, RCM, ROMP, and hydrogenation. The

obtained polymers thus have controlled molecular weights

Complete contact information is available at:

https://pubs.acs.org/10.1021/jacs.0c09289

Notes

The authors declare no competing ﬁnancial interest.

greater than 10 and can possess stereoregularities varying with

isotacticity, syndiotacticity, and heterotacticity. In particular,

RCM of the sequence-regulated telechelic diene with styrene−

acrylate−styrene sequences under high dilution selectively

results in an 18-memebered cyclic dimer of the telechelic

diene. This sequence-regulated 18-memebered cyclic oleﬁn

undergoes ED-ROMP to aﬀord sequence-regulated polymers

with controlled molecular weights and styrene−acrylate−

styrene sequences in the main chain. Subsequent hydrogenation

results in perfectly sequence-regulated vinyl polymers consisting

of styrene−acrylate−styrene−ethylene−methylene sequences.

The sequence-regulated polymer segment can be introduced

into a block copolymer with norbornene derivatives using

sequential monomer addition in living ROMP. This strategy is

applicable to the synthesis of precisely sequence-regulated

polymers from various vinyl monomers due to the wide

applicability of ATRA as well as the robustness of ruthenium-

catalyzed ROMP. This method can be used to achieve precise

and periodic placement of functional groups in vinyl polymers

and will lead to next-generation vinyl polymer materials with

excellent properties and unique functions.

ACKNOWLEDGMENTS

■

This work was partly supported by a Grant-in-Aid for Scientiﬁc

Research (A) (No. JP18H03917) for M.K. by the Japan Society

for the Promotion of Science and the Program for Leading

Graduate Schools “Integrative Graduate School and Research

Program in Green Natural Sciences”. This paper is dedicated to

Professor Ilhyong Ryu on the occasion of his 70th birthday.

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AUTHOR INFORMATION

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Masami Kamigaito − Department of Molecular and

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