Alternating Ring-Opening Metathesis Polymerization Provides Easy Access to Functional and Fully Degradable Polymers

Access to Functional and Fully Degradable Polymers

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Alternating Ring-Opening Metathesis Polymerization Provides Easy

Francis O. Boadi, Jingling Zhang, Xiaoxi Yu, Surita R. Bhatia, and Nicole S. Sampson*

Cite This: https://dx.doi.org/10.1021/acs.macromol.0c01051

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sı Supporting Information

ABSTRACT: Polymers with hydrolyzable groups in their back-

bones have numerous potential applications in biomedicine,

lithography, energy storage, and electronics. In this study, acetal

and ester functionalities were incorporated into the backbones of

copolymers by means of alternating ring-opening metathesis

polymerization catalyzed by the third-generation Grubbs ruthe-

nium catalyst. Speciﬁcally, combining large-ring (7−10 atoms)

cyclic acetal or lactone monomers with bicyclo[4.2.0]oct-1(8)-ene-

-carboxamide monomers provided perfectly alternating copoly-

mers with acetal or ester functionality in the backbones and low to

moderate molecular weight distribution (D = 1.2−1.6).

Copolymers containing ester and acetal backbones hydrolyzed to signiﬁcant extent under basic conditions (pH 13) and acidic

conditions (pH ≤ 5), respectively, to yield the expected byproducts within 30 h at moderate temperature. Unlike the copolymer with

an all-carbon backbone, copolymers with a heteroatom-containing backbone exhibited the viscoelastic behavior with crossover

frequency, which decreases as the size of the R group on the acetal increases. In contrast, the glass transition temperature (T_g)

decreases as the size of the R group decreases. The rate of hydrolysis of the acetal copolymers was also dependent on the R group.

Thus, ruthenium-catalyzed alternating ring-opening metathesis copolymerization provides heterofunctional copolymers whose

degradation rates, glass transition temperatures, and viscoelastic moduli can be controlled.

INTRODUCTION

In the last three decades, ROMP has been championed for a

wide range of applications in the life and materials sciences

because the ruthenium catalysts used for ROMP exhibit

■

Degradable polymers with hydrolyzable groups, such as esters

and acetals, in their backbones have numerous applications in

15,16

−4

5,6

excellent tolerance to many functional groups,

and, most

biomedicine,

tronics.

lithography,

energy storage, and elec-

−9

important, the method provides good control over the

However, simultaneously controlling the installa-

17−19

molecular weight.

These features of ROMP have led to

tion of appropriate functional units on the backbone and the

sequential placement of the hydrolyzable groups by means of

conventional polymerization methods is challenging. Poly-

condensation and transacetalation methods are widely utilized

to synthesize polyacetal polymers,

and ring-opening polymerization are commonly used to

synthesize ester-based polymers. However, many polycon-

densation methods often yield low-molecular-weight polymers

that lack important mechanical properties needed for certain

applications; the metal alkoxide catalysts that are commonly

employed for ring-opening polymerization have limited

functional group tolerance. Other conventional polymer-

ization methods such as Suzuki polycondensation and cationic

copolymerization of vinyl ethers and conjugated aldehydes

show promise for providing access to degradable acetal

polymers. In addition, ionic polymerization, atom transfer

radical polymerization, reversible addition fragmentation chain

transfer polymerization, and ring-opening metathesis polymer-

ization (ROMP) are also robust techniques that provide

control over polymer molecular weight and dispersity.

the development of diverse and useful material architec-

0,21

tures.

However, owing to the heavy reliance on

norbornene and norbornene derivatives as ROMP monomers,

2−30

,10

progress on the use of this method to prepare degradable

and polycondensation

3,25

and sequence-deﬁned polymers has been limited.

The

32,33

research groups of Grubbs, Kilbinger,

and O’Reilly

have reported that commercially available acetal-based cyclic

oleﬁns (dioxepins) can be used in ROMP systems to

potentiate polymer degradation. However, their eﬀorts were

met with limited success because these cyclic oleﬁns do not

31,35

undergo controlled homopolymerization

or perfectly cross

or alternating copolymerization with monomers such as

13,14

Received: May 3, 2020

Revised: June 25, 2020

XXXX American Chemical Society

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Chart 1. Monomers and Catalyst Used for Alternating Copolymer and Diblock Copolymer Synthesis

Monomers 1, 2, and 3 were used for alternating copolymer synthesis, and monomer 4 was used for block copolymer synthesis. Third-generation

Grubbs catalyst 5 was used for all the metathesis polymerization reactions. Monomer 6 was used to prepare 1a-alt-6, an all carbon-backbone

copolymer, for comparison.

31,34

cyclooctadiene and norbornene.

Even when used in excess,

the dioxepins are scarcely incorporated. Utilization of func-

tional dioxepins in ROMP does not give access to fully

degradable polymers, although when a single monomer is

added to a ROMP polymer chain, the dioxepin can be

sacriﬁced to yield a chain-end functional group that serves as a

35−37

handle for postpolymerization chain extension.

Recent work on alternating ring-opening metathesis

polymerization (AROMP) in which high-ring-strain and low-

ring-strain oleﬁn monomers undergo perfect alternating

38,39

polymerization to yield long controlled polymers

inspired

us to consider the use of heterocycles for the synthesis of

degradable polymers. Our discovery that bicyclo[4.2.0]oct-

(8)-ene-8-carboxamides undergo AROMP with large cyclo-

alkenes (10−12 carbon atoms) suggested that large

heterocyclic rings containing hydrolyzable linkages would

also work in the new system (Chart 1). Contemporaneously,

Xia and co-workers demonstrated the eﬃcient incorporation

of dioxepins into copolymer backbones using their novel

cyclopropene monomers in AROMP. Herein, we report the

eﬃcient synthesis of alternating, readily degradable ester and

acetal copolymers by means of cyclobutene-based AROMP

(Figure 1) with thermal properties and interfacial elasticity that

are signiﬁcantly diﬀerent from the all-carbon backbone

AROMP copolymers.

RESULTS

■

Monomer Preparation. Monomer 1a was synthesized by

coupling bicyclo[4.2.0]oct-1(8)-ene-8-carboxylic acid with N-

propylamine according to the literature procedure. Column

chromatography and recrystallization aﬀorded 1a in good

isolated yield (>70%) and excellent purity (>95%, as indicated

Figure 1. Synthesis of alternating and diblock copolymers. (A)

Cartoon representation of alternating copolymer synthesis, (B)

poly(1-alt-2)_msynthesis where 1a or 1b was used together with 2a

or 2b to form copolymers with 5 (10 mM), (C) poly(1a-alt-3)_m

synthesis with 5 (10 mM), and (D) cartoon representation of

poly(4) -b-poly(1a-alt-3) synthesis with 5 (25 mM) and subsequent

by H NMR spectroscopy). Monomer 1b was prepared

analogously as previously described with N-hexylamine in

good yield (>65%) with excellent purity (>95%, as indicated

by H NMR spectroscopy). Monomer 2a was obtained by

means of the procedure described by Conrad et al. Monomer

a was a mixture of cis and trans isomers and contained 10%

hydrolytic degradation to aﬀord poly(4) with a functional end-group

(green ball). n and m represent the repeat units.

oleﬁn regioisomer that was inseparable from 2a. Monomer 2b

was synthesized by the ring-closing metathesis of prop-2-enyl

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Table 1. Average Molecular Weights and Molecular Weight Distributions (Đ ) of Ester and Acetal Alternating Copolymers

Prepared by AROMP

entry

copolymer

[1]/[2,3]/[5] ratio

conv (%)

time (h)

% 2/3

M_w_,_t_h_e_o(kDa)

M_n(kDa)

M_w(kDa)

Đ_M

M_n(kDa)

(1a-alt-2a)₁₀

(1a-alt-2a)₅₀

(1a-alt-2b)₁₀

(1a-alt-2b)₅₀

(1b-alt-2a)₁₀

(1b-alt-2b)₁₀

(1b-alt-2b)₅₀

(1a-alt-3a)₂₀

(1a-alt-3a)₅₀

(1a-alt-3a)₁₀₀

(1a-alt-3b)₂₀

(1a-alt-3b)₅₀

(1a-alt-3b)₁₀₀

(1a-alt-3c)₂₀

(1a-alt-3c)₅₀

10:10:1

50:50:1

10:10:1

50:50:1

10:10:1

50:50:1

20:20:1

50:50:1

100:100:1

20:40:1

50:100:1

100:200:1

20:20:1

50:90:1

100

3.50

17.3

3.30

16.6

3.90

3.80

18.8

5.89

14.6

4.80

20.8

5.10

12.7

4.30

6.00

16.2

6.92

12.5

15.5

7.49

11.9

13.2

4.38

5.37

7.40

27.7

7.60

20.2

6.60

9.80

24.7

10.1

15.6

24.2

9.32

17.2

20.3

5.88

8.06

1.5

1.3

1.5

1.6

1.5

1.6

1.5

1.2

1.6

1.2

1.4

1.5

1.3

1.5

4.2

24.0

7.4

22.6

5.9

5.7

1.5

2.5

19.9

6.16

17.0

29.1

7.39

12.2

18.5

6.76

18.4

24.9

8.78

12.0

20.3

6.14

15.4

2.5

AROMP was performed with catalyst 5 (10 mM) at 40 °C in CH Cl or CHCl . Conversion was determined by the integration of the cyclohexyl

peak at 2.8 ppm in the H NMR spectrum. Percent composition of lactone 2 or dioxepin 3 in copolymers. Theoretical molecular weight was

calculated from the monomer/catalyst feed ratio. Number average molecular weight (M ) was determined by GPC with polystyrene standard

calibration. Weight average molecular weight (M ) was determined by GPC with polystyrene standard calibration. Polymers were analyzed by

GPC on a Phenogel 5 μm 10E4A LC column (300 × 7.8 mm, 5−500 kDa MW) with THF as the eluent at a ﬂow rate of 0.7 mL/min at 30 °C.

Theoretical molecular weight after adjustment for conversion. Determined by phenyl end-group analysis by means of H NMR spectroscopy.

hept-6-enoate; the complete consumption of the starting

contained an oleﬁn regioisomer that also polymerizes with

monomer 1. Thus, a complex polymeric backbone structure

was formed. Three copolymers with 2a were synthesized

(Table 1, entries 1, 2 and 5) demonstrating that the

regioisomer does not impede AROMP and 2a forms

alternating copolymers at least 50 repeating 1-alt-2a units

long. Monomer 1a was slightly more reactive than 1b; we infer

that the shorter side chain decreased steric hindrance in the

metathesis reaction.

material was conﬁrmed by the disappearance of the alkene

proton signals at 5.3−4.9 ppm in the H NMR spectrum

(Figures S1 and S2 ). The product was a 70:30 mixture of cis

and trans isomers. Dioxepin monomer 3a was purchased from

Sigma-Aldrich and used as received. Monomers 3b and 3c

were synthesized from cis-2-butene-1,4-diol and benzaldehyde

or acetaldehyde, respectively, as described in the literature

and were microdistilled to give the desired products in >98%

purity (as indicated by H NMR spectroscopy, Figures S3 and

Two regioisomeric structures are proposed for alternating

S4 ) and in good yield (80%). Monomer 4 was synthesized in

copolymer poly(1b-alt-2b) and poly(1b-alt-2b)′ on the

3% isolated yield by coupling exo-5-norbornenecarboxylic

basis of analysis by H− H COSY (Figure 2 ), H, C and

HSQC NMR spectroscopy (Figures S9 −S11 ). COSY

indicated that H4 and H5 were neighbors and that H1′ was

coupled to H5′. No correlation was seen between H4′ and H5′

or between H1 and H5. Taken together, these results indicate

acid with N-hexylamine.

Test for Monomer Homopolymerization. Monomers 1

do not undergo homopolymerization (ROMP) in the presence

of third-generation Grubbs catalyst 5 (Chart 1). We

hypothesized that they would undergo AROMP with a cyclic

oleﬁn that has low ring strain and does not undergo 5-

catalyzed ROMP, or does so extremely slowly. To evaluate this

hypothesis, we subjected solutions of 2 (125 mM) and 3 (250

mM) to catalyst 5 (12.5 mM) at temperatures of 30−40 °C. As

that poly(1b-alt-2b) accounted for approximately two-thirds

of the polymer backbone structure and poly(1b-alt-2b)′

accounted for approximately one-third. Poly(1a-alt-2b)

exhibited regioisomerism in its backbone because 2b could

ring open and coordinate with Ru alkylidene in two diﬀerent

ways.

observed by H NMR spectroscopy, 2 did not homopoly-

merize over 24 h (Figure S5), nor did monomer 3. However,

Alternating copolymers poly(1a-alt-3a)_mwere synthesized

a and 3c underwent oleﬁn isomerization; speciﬁcally, double

from equimolar mixtures of 1a and 3a with catalysis by 5 (10

bond migration generated thermodynamically more stable

cyclic vinyl ether products 3a′ and 3c′ (Figures S6 and S7).

Isomerization of monomer 3b was much slower or barely

occurred (Figure S8).

Preparation of Ester and Acetal Alternating Copoly-

mers by AROMP of Monomers 1 with Monomers 2 or 3.

When monomer 1a or 1b was allowed to react with 2a or 2b at

mM, Table 1, entries 8−10). However, poly(1a-alt-3b)

copolymers with near theoretical molecular weights were

obtained using a twofold excess of monomer 3b with respect to

1a (Table 1, entries 11−13). We noted a slight decomposition

of 3b during the reaction, evident by the appearance of

aldehyde peak at 10 ppm in the H NMR spectrum of the

reaction mixture; the use of excess 3b compensated for the

molar loss due to decomposition. The reaction between

monomers 3b and 1a was relatively slow; the preparation of

higher-molecular-weight polymers required longer reaction

time (19 h), and monomer conversion was only slightly higher

than 50% (Table 1, entries 12 & 13). Poly(1a-alt-3c)_m

copolymers were synthesized following a protocol similar to

0 °C in the presence of catalyst 5 (10 mM), all combinations

resulted in the formation of linear alternating copolymers

poly(1-alt-2)_mwith ester linkages in the polymer backbone

(

Table 1, entries 1−7). The reactions of both 1a and 1b were

robust enough to form long chains (50 repeating 1-alt-2), and

molecular weight distributions were acceptable. Monomer 2a

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hydrolysis in aqueous solution at several pH values. Poly(1-

alt-2a) was not included in the degradation studies because of

its complex backbone structure introduced by regioisomers in

the monomer 2a. Copolymers, poly(1-alt-2b)_mwere readily

hydrolyzed under strongly basic conditions; at pH 13, 78% of

poly(1a-alt-2b) and 26% of poly(1b-alt-2b) were degraded

within 8 h (Figure S17 ). However, under mildly acidic

conditions or mildly basic conditions, these 2b-based

copolymers exhibited slow to no degradation. The alkaline

degradation products, which were soluble in the aqueous

phase, were puriﬁed by high-performance liquid chromatog-

raphy (HPLC); the eluates were analyzed by mass

spectrometry and the expected hydroxy acid degradation

product was observed (Figure S17). The mass spectrum did

not reveal evidence of homoaddition of 1 to form dimer or

trimer. Copolymers containing propyl amide side chain, 1a had

a much faster degradation rate than 1b, which has the hexyl

amide. This result is expected because the lower hydro-

phobicity of 1a allows for better solvation of its copolymers.

Therefore, 1a-containing copolymers were used for all

subsequent degradation testing.

For acetal alternating copolymers, poly(1a-alt-3) , we began

by exploring hydrolysis under mildly acidic conditions (sodium

phosphate buﬀer, pH 5). Under these conditions, the poly(1a-

alt-3a)₂₀copolymer was inert to hydrolytic degradation, even

^a^f^t^e^r^s^e^v^e^r^a^l^d^a^y^s⁽^F ⁱ ^g ^u ^r ^e ^S ¹ ⁸⁾^.^H^o^w^e^v^e^r^,^p^o^l^y⁽¹^a^-^a^l^t^-³^b⁾20

underwent signi ﬁ cant hydrolysis and the time scale was hours

Figure 2. (A) Proposed structures of poly(1b-alt-2b) (left) and

poly(1b-alt-2b)′ (right), (B) partial H− H COSY NMR spectrum

of a mixture of the two regioisomers.

Figures 3 ; S19 ). When the degraded crude mixture of

that used for poly(1a-alt-3a) (Table 1, entries 14−15). The

molecular weights and distributions of the copolymers were

determined by gel permeation chromatography (GPC) and H

NMR endgroup analysis. For higher degrees of polymerization

(

DP), especially DP ≥ 50, only MWs measured by H NMR

were similar to the theoretical molecular weights. DP refers to

the total number of alternating AB pairs in the polymer. All the

synthesized copolymers had moderate molecular weight

distributions (Đ ), with Đ values ranging from 1.2 to 1.6

and near stoichiometric incorporation of the comonomers

suggesting eﬃcient alternation (Table 1). In the matrix-assisted

laser desorption ionization time-of-ﬂight (MALDI-TOF) mass

spectrum of the 1a-alt-3a copolymer (Figure S12) there is an

absence of mass shifts corresponding to 3a−3a diads,

consistent with the clear alternation of 1a and 3a in the

copolymer.

We examined the kinetics of AROMP versus isomerization

by H NMR spectroscopy. The half-lives of 3a and 1a for

AROMP were 20 and 23 min, respectively, which indicates

that both 1a and 3a are incorporated into the copolymer at

almost equal rates during copolymerization (Figure S13 );

whereas the half-life of 3a isomerization was 203 min (Figure

S14). To suppress 3a ′ formation, 1,4-benzoquinone was used

as an additive (Figure S15). Moreover, AROMP reaction

involving 1a and 3a in the presence of 1,4-benzoquinone

Figure 3. Poly(1a-alt-3b)20 underwent complete degradation within

0 h at pH 5. (A) Acetal copolymer degradation reaction scheme, (B)

acetal hydrolysis and benzaldehyde formation at 37 °C, pH 5.

yielded a copolymer, which had identical H and HSQC NMR

spectra as the copolymer prepared without the additive

poly(1a-alt-3b)₂₀was analyzed by mass spectroscopy, peaks:

m/z = 107.0 [M + H] , corresponding to benzaldehyde (exact

Figures S16 ), which is consistent with poly(1a-alt-3a) rather

mass = 106.4 g/mol), and m/z = 305.1−308.2 [M + Na + H] ,

than poly(1a-alt-3a′) .

which we attributed to diallyl alcohol (exact masses = 281.20

and 283.21 g/mol for OH and OD, respectively) were

observed (Figure S20 ). Similar to 1−2-based copolymers,

there was no evidence of homoaddition of 1a in the 5-

catalyzed reaction of 1a and 3 monomers, which conﬁrms that

eﬃcient alternation occurs.

Hydrolytic Degradation of Ester and Acetal Alternat-

ing Copolymers. Surprisingly, the ester and acetal copoly-

mers exhibited diﬀerent solubility proﬁles; hence, diﬀerent

hydrolysis protocols were applied for these two categories of

polymers. Ester-alternating copolymers were subjected to

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, entry 8). This diblock copolymer was treated under two

Article

Preparation and Hydrolytic Degradation of Diblock

Copolymers. A nondegradable norbornene polymer block,

poly(4) , was extended with a degradable poly(1a-alt-3)

block to aﬀord poly(4) -b-poly(1a-alt-3) (Scheme 1). Upon

Scheme 1. Synthesis of Poly(4) -b-poly(1a-alt-3) and

Hydrolytic Degradation of the Poly(1a-alt-3) Blocks at pH

≤

Figure 5. GPC analysis of block copolymer poly(4) -b-(1a-alt-3b)

before and after hydrolytic degradation under diﬀerent acidic

conditions. Installation of poly(1a-alt-3b)₁₀onto poly(4)₂₀(black

line) yields diblock copolymer poly(4) -b-(1a-alt-3b) (red line).

Partial degradation (60%) of the (1a-alt-3b)₁₀block at pH 5 for 68 h

dashed green line), and the complete degradation of (1a-alt-3b)₁₀

(

block at pH 1 for 46 h (dashed blue line). Horizontal arrows

represent an increase (solid) or a decrease (dotted) in the MW.

diﬀerent acidic conditions (thus pH 1 & 5) at 37 °C.

Incubation of this diblock copolymer in sodium phosphate

buﬀer (pH 5) for 68 h resulted in a nearly 60% loss of the

poly(1a-alt-3b)₁₀block (Table 2, entry 9). At pH 1 (TFA

condition), the poly(1a-alt-3b)₁₀block is completely hydro-

lyzed within 46 h to yield a new poly(4) , as indicated by

extension of the chain with the second block, the molecular

weight of the polymer increased (Figures 4 and 5). According

to the number average molecular weight determined by GPC

GPC (Figure 5; Table 2, entry 10) and H NMR spectroscopy

(

Figure S21 ).

(Table 2, entry 2) approximately 12 units of (1a-alt-3a) were

Inspired by the degradation rates observed for the diblock

installed onto poly(4)₂₀to yield the diblock copolymer,

poly(4) -b-poly(1a-alt-3a) (Figure 4A). (1a-alt-3a) copoly-

copolymers containing poly(1a-alt-3a/b) , we explored

substituent eﬀects on the degradation rate. We anticipated

mer is hydrolytically inert at pH 5, so we employed relatively

stronger acidic conditions to induce degradation; the diblock

copolymer was treated with aqueous triﬂuoroacetic acid (TFA,

pH 1) at 37 °C for ∼7 days. This treatment resulted in a loss of

that acetaldehyde-derived copolymer poly(1a-alt-3c) would

hydrolyze faster than the formaldehyde-derived poly(1a-alt-

a) . Therefore, we prepared diblock copolymer poly(4) -b-

m 20

poly(1a-alt-3c)₁₀(Figure 4B; Table 2, entry 4). Notably, the

installation of poly(1a-alt-3c) (R = Me) onto poly(4)₂₀was

much faster than the installation of poly(1a-alt-3b) (R = Ph),

but not as fast as that of poly(1a-alt-3a) (R = H); this trend is

consistent with the relative sizes of the R groups. Poly(4) -b-

∼

⁶⁷^%^o^f^t^h^eⁱⁿ^s^t^a^l^l^e^d^p^o^l^y⁽¹^a^-^a^l^t^-³^a⁾¹2 block (Figure 4A;

Table 2, entry 3). Partial degradation of the (1a-alt-3a) block

of the diblock copolymer was hardly detected by H NMR

spectroscopy (Figure S21).

We next explored the hydrolysis rate of the (1a-alt-3b)

copolymer in a diblock copolymer system. A block of (1a-alt-

poly(1a-alt-3c)₁₀was subjected to hydrolytic degradation

under two diﬀerent sets of acidic conditions (pHs 1 & 5).

Interestingly, when this diblock copolymer was treated with

sodium phosphate buﬀer (pH 5), only 50% of the poly(1a-alt-

b)₁₀was successfully installed onto poly(4)₂₀to form a

diblock copolymer poly(4) -b-(1a-alt-3b) (Figure 5; Table

3c ) block was hydrolyzed within 68 h (Figure 4B; Table 2,

Figure 4. GPC analysis of MW shifts associated with the assembly and hydrolysis of block copolymers, 10−12 units of (1a-alt-3) were successfully

installed onto poly(4) (black line) to form a diblock copolymer (A) poly(4) -b-poly(1a-alt-3a) (red line) or (B) poly(4) -b-poly(1a-alt-3c)

(

red line). After treatment of the diblock copolymers with aqueous TFA (pH 1) at 37 °C (dashed blue line) (A) for 161 h, (1a-alt-3a) unit is

partially hydrolyzed to yield poly(4)₂₀with a new end group, (B) 46 h, (1a-alt-3c) unit degrades completely. At pH 5 only (1a-alt-3c) degrades

(

dashed green line). Horizontal arrows represent an increase (solid) or decrease (dotted) in the MW.

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Table 2. Molecular Weights of Poly(4)₂₀and Diblock

Copolymers Consisting of Poly(4) and Poly(1a-alt-3)_m

a b

before and after Hydrolysis

pH & time

entry treatment

polymer

poly(4)₂₀block

poly(4) -b-(1a-alt-3a)

(kDa) (kDa)

Đ_M

N/A

4.48

8.04

5.50

11.51

1.23

1.43

before hydrolysis

1.0 (161 h) poly(4) -b-(1a-alt-3a)

5.64

7.58

5.92

4.27

7.47

11.3

8.17

5.21

1.33

1.49

1.38

1.22

after hydrolysis

N/A

poly(4) -b-(1a-alt-3c)

before hydrolysis

5.0 (68 h)

1.0 (46 h)

poly(4) -b-(1a-alt-3c)

after hydrolysis

poly(4) -b-(1a-alt-3c)

after hydrolysis

N/A

poly(4)₂₀

3.89

7.86

5.45

11.6

1.40

1.48

poly(4) -b-(1a-alt-3b)

before hydrolysis

Figure 6. Interfacial rheology comparing the viscous and elastic

properties of interfacial ﬁlms of poly(1a-alt-3)50 and poly(1a-alt-6)50.

5.0 (68 h)

1.0 (46 h)

poly(4) -b-(1a-alt-3b)

5.89

4.15

8.10

5.72

1.38

after hydrolysis

The cyclohexene-based copolymer (A) displays a gel-like behavior

with G′ > G″ over the measurable frequency range, whereas the

dioxepin-based copolymers (B−D) are viscoelastic with a crossover of

G′ and G′ at intermediate frequencies of 3−60 rad/s, indicating

timescales for the stress relaxation of the interface of 0.1−2 s,

depending upon the R group. Solid lines, storage modulus (G′):

dotted lines, loss modulus (G″).

poly(4) -b-(1a-alt-3b)

after hydrolysis

Values were determined using polystyrene standards and combined

columns: a Phenogel 5 μm linear (2) LC column (300 × 7.8 mm,

00−10,000 kDa MW) and a Phenogel 5 μm, 50 Å LC column (300

4.6 nm, 100 Da to 3 kDa MW) with THF as the eluent at a ﬂow

rate of 0.7 mL/min at 30 °C (entries 1−6; Figure 4). Values were

determined using polystyrene standards and Phenogel 5 μm linear (2)

LC column (300 × 7.8 mm, 100−10,000 kDa MW) with THF as the

eluent at a ﬂow rate of 0.7 mL/min at 30 °C (entries 7−10; Figure 5).

equilibrium before oscillatory shear experiments were

performed. Interfacial rheology, rather than bulk solution

rheology, is the appropriate technique to explore this

phenomenon. Additionally, as noted below, interfacial

viscoelasticity is important to a number of applications,

N/A: not applicable.

entry 5); whereas the treatment with aqueous TFA (pH 1)

resulted in complete degradation within 46 h (Table 2, entry 6;

Figures 4B & S21 ).

The GPC data clearly indicate that the AROMP acetal

copolymer prepared from 3c hydrolyzed much faster than 3a,

but slightly slower than that of 3b. Unlike poly(1a-alt-3a)_m,

poly(1a-alt-3b)_mand poly(1a-alt-3c)_mhydrolyzed to a

considerable extent under mildly acidic conditions, and

completely at pH 1. The hydrolysis rates paralleled the

including the stability of multiphase formulations. We

found that acetal copolymers poly(1a-alt-3)₅₀exhibited the

viscoelastic behavior, with a crossover between the loss

modulus G″ (indicative of viscous character) and the storage

modulus G′ (indicative of elastic character) as frequency was

increased. Moreover, the crossover frequency for the 3a

copolymer was near the upper limit of the measurements at

∼60 rad/s, while the 3c and 3b copolymers displayed

crossovers at ∼10 and ∼3 rad/s, respectively (Figure 6). The

poly(1a-alt-6) , which has an all-carbon backbone, was

stabilities of the carboxonium-like ion intermediates formed

during hydrolysis with formaldehyde (3a) < acetaldehyde (3c)

dominated by the elastic behavior, with G′ > G″ over the

measurable frequency range. Ester-based copolymers (1a-alt-

2) exhibited a ﬂow behavior that is similar to the acetal

copolymers and displayed a crossover at higher frequencies.

Among the copolymers, poly(1a-alt-6)₅₀had a higher G′ and

G″ than its acetal-based counterparts. Although the moduli are

frequency-dependent, as would be expected for viscoelastic

interfaces, over nearly all of the measurable frequency range,

the storage modulus G′ of the acetal copolymers increased as

the size of the R group on the acetal carbon increased. That is,

poly(1a-alt-3b) , which has a phenyl substituent, had the

benzaldehyde (3b).

Thermal Properties and Interfacial Elasticity of

AROMP Polymers. We assessed copolymers comprising

approximately 50 repeating comonomer units. We used

diﬀerential scanning calorimetry (Figure S22 ), thermogravi-

metric analysis (Figure S23 ), and interfacial rheology (Figures

, S24, and S25 ) to evaluate the processing properties and

potential applications including the stability of the multiphase

formulation of these copolymers. To elucidate the eﬀects of the

backbone heteroatoms, we compared the current generation of

copolymers (those shown in Figure 1C) with one of our ﬁrst-

highest G′, whereas poly(1a-alt-3a) with hydrogen sub-

generation copolymers, poly(1a-alt-6), where 6 is cyclo-

stituent has the lowest G′ over the measurable frequency range.

It was not possible to obtain the high-frequency plateau

modulus because of instrument inertia eﬀects. We also could

not obtain data at lower frequencies to characterize the

terminal regime, as data taken in this regime were below the

limit of the torque transducer on the rheometer.

hexene. Interfacial rheology was utilized because previous

studies of related polymers indicated an interesting behavior

in the water-polymer ﬁlm contact angle. This suggests a

possible formation of self-assembled structures at the air−

water interface during the drying of ﬁlms. Data from strain

amplitude sweeps (Figure S24 ) and time-dependent measure-

ments (Figure S25 ) demonstrate that the samples are in the

linear viscoelastic regime and the interfaces have come to

Copolymer with poly(1a-alt-6)₅₀has the highest glass

transition temperature T and decomposition temperature

T_d_e_c. Of the acetal copolymers, 3a-containing copolymer had

Macromolecules XXXX, XXX, XXX−XXX

Macromolecules

Article

the lowest T (7.7 °C), yet the most thermally stable (T

and at pH 13, these polymers were degraded completely within

dec

∼

237 °C). Interestingly, there appeared to be a direct

24 h as expected. In contrast, they were almost completely

inert under mildly acidic conditions (pH 5). The acetal-based

copolymers degraded substantially under acidic conditions

correlation between moduli and T . Thus, as the T increased,

the modulus increased with 6 > 3b > 3c > 3a.

,52

(

pH ≤ 5).

Because copolymers containing 3 had more

DISCUSSION

regular backbones, we focused the remainder of our work on

the dioxepin-derived copolymer series.

■

Reactivity of Heteroatom-Containing Large Rings, 2

and 3, with Catalyst 5. Monomers 2 and 3 are excellent

substrates for AROMP with monomer 1. We recognized that

some of these monomers undergo competing reactions or

contained inseparable regioisomers. Therefore, we undertook

investigation of their reactivity and characterization of the ﬁnal

copolymer structures to determine the best copolymer

candidates for exploring degradation and material properties.

Because of the structural complexity associated with 2a

copolymers (Figures S26 and S27), arising from the presence

of the inseparable 9-hydroxy-7-nonenoic acid lactone impurity,

we devised monomer 2b in the hope that the close proximity

of the alkene to the ester functional group would increase steric

hindrance and suppress oleﬁn isomerization. However, 2b

contained cis/trans-isomeric mixtures, both of which undergo

AROMP to yield regioisomerically complex copolymers

^T^h^e^kⁱⁿ^e^tⁱ^c^s^o^f^p^o^l^y⁽¹^a^-^a^l^t^-³^b⁾20 hydrolysis revealed a

constant rate of benzaldehyde release (Figure 3B). This feature

makes this copolymer a candidate for applications, in which

controlled-sustained release of a cargo is desired. The clean-

readable mass spectrum of the degraded mixture also suggests

that hydrolytic degradation has potential utility as a tool for

sequencing nontemplated sequence-controlled copolymers.

We prepared blocks of degradable and nondegradable

polymers to more readily characterize the process of

hydrolysis. At pH ≤ 5, free poly(1a-alt-3b) degraded twice

as fast as poly(1a-alt-3b) in the diblock copolymer. The

diblock copolymer may undergo phase separation because of

^t^h^e^dⁱ^ﬀ^e^r^eⁿ^c^eⁱⁿ^t^h^e^h^y^d^r^o^p^h^o^bⁱ^cⁱ^tⁱ^e^s^o^f^t^h^e^p^o^l^y⁽⁴⁾20 block

(

hydrophobic) and the poly(1a-alt-3b) block (more hydro-

philic), which could be expected to decrease the interaction

of the poly(1a-alt-3b) block with the aqueous acidic medium

(Figure 2). Hence, we did not pursue further extensive studies

and hamper its hydrolysis.

with monomers 2.

Diblock copolymer design revealed another important

physical characteristic of the hetero-atom AROMP block

We then moved to the exploration of the dioxepin

monomers 3. Because of their symmetrical structures, we

anticipated they would yield structurally regular copolymers.

However, 3a and 3c readily form 3a′ and 3c′ in the presence of

(

¹^a^-^a^l^t^-³⁾^.^W^eⁿ^o^t^e^d^t^h^a^t^p^o^l^y⁽⁴⁾20 was not readily soluble in

tetrahydrofuran (THF). However, when the chain was

extended with poly(1a-alt-3) , the resulting polymer dissolved

. This isomerization process is most likely catalyzed by a

readily. This result suggests that the copolymers with

heteroatom-containing backbones act not only as degradable

blocks but also as solubilizing units.

ruthenium hydride species generated by catalyst decomposi-

tion. Because of the twist boat conformation of dioxepins,₄

intramolecular aryl-vinyl π-stacking interactions in 3b

sterically hinder oleﬁn isomerization. We were concerned

that the copolymer microstructure would be irregular should

the isomerization products participate in AROMP. Alter-

natively, 3′ are vinyl ethers and could act as terminating agents

to quench the polymerization prematurely. Fortunately, the

rate of isomerization of 3a to 3a′ was approximately 1/10 the

rate of consumption of 3a in AROMP. This rate diﬀerence

suggests that AROMP of 3a competes eﬀectively with

isomerization to 3a’. To conﬁrm the reactivity ratios, we

Thermal Properties and Interfacial Elasticity of

Carbon and Acetal Backbone Copolymers. Our interfacial

rheology data show that all acetal copolymer ﬁlms display the

viscoelastic behavior with a crossover frequency that is

dependent on the R group and increases as 3a > 3c > 3b,

indicating the fastest dynamics for R = H, followed by R = Me

and R = Ph. Because timescales for the relaxation of

mechanical stress are inversely proportional to the crossover

frequency, this indicates that the timescale for mechanical

relaxation increases with the size of the R group, which is

physically reasonable. We note that, although these samples

have varying molecular weights, the interfacial rheology

experiments are all conducted on polymers with 50 backbone

repeat units. So, any diﬀerences in the polymer molecular

weight are due to diﬀerences in the molecular weight of the

substituent groups, and impacts on the rheology can be

attributed to size of the R groups. As the stability of multiphase

formulations is directly impacted by interfacial rheology, the

variation in G′ and crossover frequency that we observe may

serve as a useful means of tuning release in applications such as

emulsion-based injectables. By contrast, the relaxation of the

added 1,4-benzoquinone to suppress ruthenium hydride

Figure S15 ). There was no structural diﬀerence as detected by

NMR spectroscopy and we concluded that monomers 3 can be

used eﬀectively in AROMP.

In most cases, a degree of polymerization (DP ) ≈100 was

achieved. Molecular weights determined using GPC with

polystyrene standards were signiﬁcantly diﬀerent than

molecular weights determined by H NMR endgroup analysis.

The latter gave MW values that were comparable with the

theoretical MW, and consistent with complete monomer

consumption. Because our polymers are linear with backbones

signiﬁcantly diﬀerent from the polystyrene standards, the MW

may be underestimated by GPC, except in the case of

cyclohexene-based copolymer poly (1-alt-6) was dominated

poly(1a-alt-3b) , which contains aromatic rings similar to the

by the elastic response over the accessible frequency range. We

believe the elasticity in the acetal copolymers arises from

calibration standards. The complete monomer consumptions

during the copolymerization of 2, 3a, and 3c, further suggests

MWs may be underestimated by GPC.

56,57

interchain hydrogen boding

owing to the oxygen atoms.

Copolymers with higher T , particularly those containing 6 and

Hydrolytic Degradation of Ester and Acetal Copoly-

mers. Hydrolytic degradation experiments were conducted

over a wide pH range. Poly(1a-alt-2)_mand poly(1b-alt-2)_m

underwent degradation under basic conditions, but degrada-

tion was relatively slow. Extreme pH-accelerated degradation,

3b, also tend to have higher moduli, which is indicative of a

less-ﬂexible backbone. Although the 3a (R = H) acetal

copolymer is least susceptible to hydrolytic degradation, it has

signiﬁcantly higher thermal stability. Moreover, as a polyoxy-

methylene-like material, 3a-polymer can be used as a polymer

Macromolecules XXXX, XXX, XXX−XXX

Macromolecules

Article

blend with polylactide to increase its ﬂexural strength and

modulus.

ments Q Series software). Heat ﬂow (Tzero) calibration was

performed with sapphire standards, and the temperature (cell

constant) was calibrated using indium at a scan rate of 10 °C/min.

All discrete scanning calorimetry measurements were performed

CONCLUSIONS

■

under a N ﬂow (50 mL/min) using S5 Tzero aluminum pans and

hermetic lids. The sample weights ranged from 3 to 8 mg. Polymer

samples were ﬁrst heated from −50 to 200 °C at a rate of 10 °C/min

to erase thermal history. The samples were then cooled back to −50

A polymer’s thermal properties, such as glass transition

temperature (T ) and decomposition temperature (T ), are

dec

crucial for material processing, and its interfacial rheological

properties are important for applications such as coatings and

multiphase formulations. We have developed a new class of

functional alternating copolymers that demonstrate the

versatility of the AROMP method to eﬃciently incorporate

oxygen functionality into the copolymer backbone. Substitu-

C at 10 °C/min and reheated to 200 °C at 5 °C/min. The second

ramp was used for the thermal analysis of the polymers.

Thermogravimetric analysis was performed with a TA Instruments

Q50 Thermogravimetric Analyzer equipped with a platinum pan. The

sample sizes ranged from 5 to 15 mg. Weight loss data were collected

from 25 to 600 °C at 10 °C/min under a N ﬂow (60 mL/min).

tion at the 2-position in poly(1-alt-3b) and poly(1-alt-3c)_m

Interfacial Rheology Characterization of Polymers. Inter-

facial rheological properties of polymer solutions were measured by

using a double wall ring (DWR) ﬁxture on a TA Instruments DHR-III

rheometer. The DWR trough was loaded with 20 mL of water. The

upper DWR ﬁxture was lowered until it made initial contact with the

water, as determined by the visual observation of the water surface.

Then, 60 μL of a solution containing 1.0 wt % of the copolymer in

chloroform was applied dropwise to the surface of the trough. A

freshly prepared copolymer solution was used for each run. The

solution was allowed to evaporate for 300 s. To ensure the formation

of a stable polymer interface, G′ and G″ were measured at a stress of

0.1% and a frequency of 1 rad/s as a function of time. Samples

typically took 20 min to reach equilibrium. After this time, stress

sweeps and frequency sweeps were performed. Before each copolymer

system was tested, amplitude sweep tests were performed at a

constant frequency, but at variable amplitudes to ensure the frequency

sweep tests were performed within the linear viscoelastic regime. All

tests were performed at 25 °C.

allows control of the stereochemistry of the double bonds in

the polymer backbone, the rate of hydrolytic degradation, ﬁne-

tuning of physical properties such as T_gand T , and

dec

interfacial rheology. Thus, the processing of ﬁlms and coatings

and stability of multiphase formulations can be adjusted. In

addition, the precise incorporation of hydrolyzable monomeric

units in the polymer backbone allows for controlled

degradation that will be useful for reading sequence and

analyzing precision in nontemplated copolymers. We anticipate

polymers based on these copolymer structures will ﬁnd

applications in data and energy storage and the circular

economy of polymers.

EXPERIMENTAL SECTION

Materials and General Methods. All air-sensitive reactions were

■

performed under N by means of standard Schlenk or glove box

Preparation of Monomers. N-Propyl bicyclo[4.2.0]oct-1(8)-

ene-8-carboxamide (1a). A modiﬁed version of the procedure

techniques. All metathesis reactions were performed under N₂.

Solvents for ring-opening reactions and deuterated solvents for NMR

spectroscopy were degassed and ﬁltered through basic alumina before

use. Poly(styrene) standards and Cl (H IMes)(PCy )RuCHPh, 7,

reported in the literature was used. Speciﬁcally, bicyclo[4.2.0]oct-

(8)-ene-8 carboxylic acid (750 mg, 4.93 mmol) and (1-cyano-2-

ethoxy-2-oxoethylidenaminooxy)dimethylamino-morpholino-carbe-

nium hexaﬂuorophosphate (2.1 g, 4.93 mmol) were dissolved in 25.0

were purchased from Aldrich. The synthesis of (3-Br-

mL of dimethylformamide, the mixture was purged with N for 15

Pyr) Cl (H IMes)RuCHPh (5) was performed according to the

min, and then N,N-diisopropylethylamine (1.8 mL, 9.86 mmol) was

added. Upon the addition of the amine, the colorless mixture instantly

procedure reported by Love et al. Dry, oxygen-free CH Cl , THF,

and DMF were obtained with a Pure Process Technology solvent

puriﬁcation system. Mallinckrodt silica gel-60 (230−400 mesh) was

used for column chromatography. Analytical thin-layer chromatog-

raphy was performed on precoated silica gel plates (60F254), and

Combi-Flash chromatography on RediSep normal-phase silica

columns (silica gel-60, 230−400 mesh). Bruker Nanobay 400,

AVANCE III 500 MHz, and AVANCE III 700 MHz instruments

were used for NMR spectroscopy. Chemical shifts (δ, ppm) are

relative to the peaks of residual undeuterated solvents: δ 7.28 and

became bright orange. After the mixture was purged with N for an

additional 10 min, N-propylamine (0.40 mL, 4.93 mmol) was added,

and the mixture was stirred vigorously under N2 for 48 h. The

resulting dark orange mixture was diluted with 60 mL of CH Cl ,

2 2

sequentially washed with 1 M HCl (2 × 35 mL), saturated sodium

bicarbonate (3 × 45 mL), and distilled water (2 × 45 mL). The

organic layer was dried over anhydrous sodium sulfate and ﬁltered,

and the ﬁltrate was concentrated in vacuo to aﬀord an oﬀ-white solid.

Column chromatography (CombiFlash) on silica gel with a solvent

7.22, respectively, for H and C spectra in CDCl ; δ 1.96 for H

spectra in d -acetonitrile, and δ 118.26 and 1.79 for C spectra in d₃-

gradient of 0−50% ethyl acetate/hexane (R = 0.6 in 1:1 ethyl acetate/

acetonitrile.

hexane) aﬀorded 1a as a white solid (695 mg, 73). The NMR data

agreed with the literature data.

Number- and weight-average molecular weights (M and M ) and

dispersity indices (D_M

) were determined by GPC by using a Phenogel

N-Hexyl Bicyclo[4.2.0]oct-1(8)-ene-8-carboxamide (1b). The

μm 10E4A LC column (300 × 7.8 mm, 5−500 kDa MW), a

literature procedure was used.

Phenogel 5 μm linear (2) LC column (300 × 7.8 mm, 100−10,000

kDa MW), and a Phenogel 5 μm, 50 Å LC column (300 × 4.6 nm,

Non-6-eno-9-lactone (2a). Monomer 2a was prepared from but-3-

enyl hept-6-enoate by ring-closing metathesis according to the

00 Da to 3 kDa MW) with THF as the mobile phase at 30 °C.

procedure reported by Conrad et al. H NMR (700 MHz, CDCl ,

Output was detected with a Brookhaven Instruments refractive index

detector by using an eluent ﬂow rate of 0.7 mL/min and a 100 μL

injection loop.

MALDI-TOF mass spectrometry was performed on the Bruker

AutoFlex II MALDI-TOF/TOF at mass spectroscopy facility in

Chemistry Department, Stony Brook University. Sample preparation:

δ): 5.82−5.57 (m, 0.1H), 5.58−5.30 (m, 2H), 4.59−4.49 (m, 0.1H),

4.25−3.99 (m, 2H), 2.49−2.37 (m, 0.2H), 2.37−2.17 (m, 4H), 2.05

(m, 2H), 1.79−1.67 (m, 1H), 1.67−1.53 (m, 2H), 1.39 (dt, 2H, J =

14.5, 7.3 Hz), 1.34−1.18 (m, 0.1H).

Prop-2-enyl Hept-6-enoate. In a 2-neck round-bottom ﬂask, 6-

heptenoic acid (1 g, 7.80 mmol) and allyl alcohol (0.46 g, 7.93 mmol)

were dissolved in 30 mL of dry chloroform, and then p-

toluenesulfonic acid (1 mol %) was added as the catalyst. The ﬂask

was equipped with an inverse Dean−Stark trap that was partially ﬁlled

with 4 Å molecule sieves and ﬁtted with a condenser. The reaction

mixture was heated at reﬂux with stirring overnight, cooled to room

0 mg 2,5-dihydroxybenzoic acid (DHB) was dissolved in 1 mL of

methanol. 5 mg of the polymer was dissolved in 1 mL of methanol.

The sample plate was prepared using 5:1 DHB/polymer. 0.4 μL of

DHB was added onto the plate + 0.2 μL of polymer + 0.4 μL of DHB.

Thermal analysis was performed on a TA Instruments Q2000

diﬀerential scanning calorimeter with Wizard software (TA Instru-

temperature, and washed sequentially with 5% NaHCO (3×), 1 N

Macromolecules XXXX, XXX, XXX−XXX

Macromolecules

Article

HCl (3×), and brine (2×) to completely remove the p-

toluenesulfonic acid. The solvent was then removed under reduced

pressure. Silica gel column chromatography (5% ethyl acetate in

capped with a PTFE-lined septum was charged with a solution of

catalyst 5 (1 mg per 80 μL of CDCl ). Then, a solution of 1 (10 mg

per 10 μL of CDCl ) was added, and the reaction mixture was

hexane) aﬀorded pure product (1.0 g, 75% isolated yield). H NMR

incubated at 40 °C with monitoring by H NMR. When the monomer

(

400 MHz, CDCl , δ): 6.07−5.68 (m, 2H), 5.45−4.85 (m, 4H),

was fully initiated (usually 10−15 min), as indicated by the complete

disappearance of the ruthenium alkylidene proton at ∼19 ppm,

monomer 2 or 3 was added. Upon completion of the reaction (in the

case of near 100% conversion, the cyclohexyl proton at ∼2.9 ppm

disappeared) or when monomer consumption ceased, the reaction

was quenched with excess ethyl vinyl ether (at least 500-fold with

respected to 5) and stirred for 20 min. Polymers synthesized with

monomer 2 were puriﬁed through precipitation in cold diethyl ether

at least three times. Polymers synthesized with monomer 3 were

puriﬁed by precipitation with hexanes at least three times. The

precipitates were vacuum-dried.

.66−4.47 (m, 2H), 2.42−2.26 (m, 2H), 2.13−2.01 (m, 2H), 1.75−

.60 (m, 2H), 1.51−1.37 (m, 2H). C NMR (176 MHz, CDCl , δ):

73.33, 138.39, 132.31, 118.11, 114.70, 64.96, 34.08, 33.36, 28.33,

4.39.

-Hydroxy-6-octanoic Acid Lactone (2b). A solution of Grubbs

nd generation catalyst 7 (24 mg, 0.0283 mmol) in 10 mL of CH Cl

was added all at once to a solution of prop-2-enyl hept-6-enoate (100

mg, 0.595 mmol) in 250 mL of CH Cl . The resulting solution was

stirred at 22 °C for 15 min, heated at reﬂux for 5 h, and then

concentrated to a volume of ∼1 mL. Puriﬁcation by chromatography

on silica gel (5% ethyl acetate in CH Cl ) aﬀorded 2b as a mixture of

Poly(1a-alt-2a) . Amide 1a (24.5 mg, 127.6 μmol), catalyst 5

0% cis and 30% trans cis isomers (50.9 mg, 47.6% isolated yield). H

(11.3 mg, 12.8 μmol), and 2a (19.7 mg, 127.6 μmol) were mixed in

CDCl₃in an NMR tube. After 5 h, amide 1a was completely

consumed. Precipitation in cold diethyl ether yielded poly(1a-alt-

NMR (400 MHz, CDCl , δ): 5.93−5.31 (m, 2H), 4.72−4.43 (m,

H), 2.41−2.22 (m, 2H), 2.14−1.98 (m, 2H), 1.75−1.53 (m, 2H),

.41 (tt, 2H, J = 9.7, 4.9 Hz). C NMR (126 MHz, CDCl , δ):

2a) . H NMR (500 MHz, CDCl , δ): 6.28−6.04 (m, 9H), 6.03−

73.22, 135.83, 130.41, 127.46, 124.50, 77.32, 77.06, 76.81, 64.59,

3.24, 34.67, 32.04, 31.67, 28.65, 27.67, 24.77, 24.66. MS (+EI) calcd

5.59 (m, 9H), 5.42−5.20 (m, 1H), 5.04 (m, 8H), 4.72−4.55 (m, 3H),

4.31−3.88 (m, 20H), 3.36−3.12 (m, 20H), 2.69−1.91 (m, 112H),

1.81−1.20 (m, 127H), 0.94 (t, 30H, J = 7.3 Hz). Mn,theo = 3.5 kDa,

for C H O [M + H] , 141.1; found, 141.1.

-Phenyl-4,7-dihydro-1,3-dioxepin (3b). A modiﬁed literature

Mn,meas = 4.8 kDa, Mw,meas = 7.4 kDa, D̵ = 1.5.

procedure was followed. Speciﬁcally, benzaldehyde (1.05 g, 9.8

mmol), cis-2-butene-1,4-diol (1.1 g, 12.5 mmol), and p-toluenesul-

fonic acid (30 mg, 0.16 mmol) were dissolved in 20 mL of CH Cl .

Poly(1a-alt-2a)50. Amide 1a (24.5 mg, 127.6 μmol), catalyst 5 (2.2

mg, 2.6 μmol, 1 equiv), and 2a (19.7 mg, 127.6 μmol) were mixed in

CDCl in an NMR tube. After 18 h, amide 1a was completely

consumed. Precipitation in cold diethyl ether yielded poly(1a-alt-

Enough anhydrous magnesium sulfate was added to clarify the

mixture, which was then stirred at room temperature overnight,

passed through a basic alumina plug, and microdistilled to aﬀord 3b as

2a)50. H NMR (500 MHz, CDCl , δ): 6.21−6.03 (m, 45H), 5.99−

5.56 (m, 55H), 5.15 (d, 50H, J = 110.5 Hz), 4.21−4.05 (m, 100H),

3.39−3.16 (m, 100H), 2.66−1.94 (m, 550H), 1.89−1.25 (m, 650H),

0.95 (t, J = 7.3 Hz, 150H). Mn,theo = 17.3 kDa, Mn,meas = 20.8 kDa,

a colorless oil (1.38 g, 80% yield, purity >98% as indicated by H

NMR spectroscopy). H NMR (700 MHz, CDCl3, δ): 7.56 (m, 2H),

.41 (dd, 2H, J = 8.20, 6.56 Hz), 7.37 (m, 1H), 5.89 (s, 1H), 5.80 (d,

H, J = 1.83 Hz), 4.43 (dt, 2H, J = 16.2, 2.47 Hz), 4.31 (dt, 2H, J =

6.4, 2.21 Hz). ¹³C NMR (700 MHz, CDCl3, δ): 139.0, 130.1, 128.6,

w,meas = 27.7 kDa, D

= 1.3.

Poly(1a-alt-2b)10. Amide 1a (24.5 mg, 127.6 μmol), catalyst 5

(11.3 mg, 12.8 μmol), and 2b (17.9 mg, 127.6 μmol) were mixed in

CDCl in an NMR tube. After 5 h, amide 1a was completely

consumed. Precipitation in cold diethyl ether yielded poly(1a-alt-

28.4, 126.6, 102.3, 64.7. These data agree with the literature data.

-Methyl-4,7-dihydro-1,3-dioxepin (3c). A modiﬁed literature

procedure was followed. Acetaldehyde (1.57 g, 35.6 mmol), cis-2-

butene-1,4-diol (3.00 g, 34.1 mmol), and p-toluenesulfonic acid (52

mg, 0.27 mmol) were dissolved in 40 mL of 1:4 THF/CH Cl .

2b)10. H NMR (700 MHz, CDCl , δ): 6.28−6.05 (m, 10H), 6.06−

5.58 (m, 8H), 5.56−5.31 (m, 1H), 5.22 (m, 6H), 5.00 (s, mH), 4.78−

4.48 (m, 20H), 3.37−3.13 (m, 20H), 2.78−2.49 (m, 12H), 2.49−1.80

Enough anhydrous magnesium sulfate was added to clarify the

mixture, which was then stirred at room temperature overnight,

passed through a short alumina plug, concentrated, and was distilled

(m, 92H), 1.77−1.07 (m, 128H), 0.93 (t, 30H, J = 7.0 Hz). Mn,theo =

3.3 kDa, Mn,meas = 5.1 kDa, Mw,meas = 7.6 kDa, D

Poly(1a-alt-2b)50. Amide 1a (24.5 mg, 127.6 μmol), catalyst 5 (2.2

mg, 2.6 μmol), and 2b (17.9 mg, 127.6 μmol) were mixed in CDCl

= 1.5.

via the microdistillation setup to aﬀord 3c as an oil (3.1 g, 80%, purity

95% as indicated by 1H NMR spectroscopy). H NMR (700 MHz,

in an NMR tube. After 18 h, amide 1a was completely consumed.

CDCl3, δ): 5.75 (d, 2H, J = 1.8 Hz), 5.03 (q, 1H, J = 5.2 Hz), 4.41

dt, 2H, J = 16.2, 2.50 Hz), 4.20 (dt, 2H, J = 16.2, 2.22 Hz), 1.38 (d,

Precipitation in cold diethyl ether yielded poly(1a-alt-2b)50. H NMR

(

(700 MHz, CDCl , δ): 6.26−6.00 (m, 51H), 6.00−5.29 (m, 40H),

H, J = 5.2 Hz). ¹³C NMR (700 MHz, CDCl3, δ): 150.0, 101.3, 64.9,

5.23 (m, 30H), 5.01 (m, 15H), 4.76−4.46 (m, 100H), 3.34−3.14 (m,

100H), 2.73−1.86 (m, 460H), 1.84−1.09 (m, 610H), 1.02−0.86 (m,

0.2. These data agree with the literature data.

1R,2S,4R)-N-Hexylbicyclo[2.2.1]hept-5-ene-2-carboxamide (4).

(

150H). Mn,theo = 16.6 kDa, Mn,meas = 12.8 kDa, Mw,meas = 20.2 kDa, D̵

exo-5-Norbornenecarboxylic acid (300 mg, 2.17 mmol) and (1-

cyano-2-ethoxy-2-oxoethylidenaminooxy)dimethylamino-morpholi-

no-carbenium hexaﬂuorophosphate (930 mg, 2.17 mmol) were

dissolved in 20 mL of dimethylformamide followed by the addition

of N-hexylamine (284 μL, 2.17 mmol). The procedure used to

= 1.6.

Poly(1b-alt-2a)10. Amide 1b (30.0 mg, 127.6 μmol), catalyst 5

(11.3 mg, 12.8 μmol), and 2a (19.7 mg, 127.6 μmol) were mixed in

CDCl

consumed. Precipitation in cold diethyl ether yielded poly(1b-alt-

in an NMR tube. After 8 h, amide A was completely

synthesize 1a aﬀorded 4 (445 mg, 93%).

H NMR (500 MHz,

2a)10. H NMR (700 MHz, CDCl , δ): 6.19−5.99 (m, 6H), 5.95−

CDCl3, δ): 6.15−6.11 (dd, 2H, J = 15.4, 2.90 Hz), 5.51 (s, 1H), 3.27

5.59 (m, 1H), 5.58−5.45 (m, 4H), 5.45−5.32 (m, 3H), 5.12−4.93

(m, 6H), 4.18−3.98 (m, 20H), 3.41−3.15 (m, 20H), 2.69−1.87 (m,

120H), 1.76−1.17 (m, 196H), 0.94−0.88 (m, 30H). Mn,theo = 3.9

(

m, 2H), 2.92 (s, 2H), 1.95 (m, 2H), 1.74 (d, 1H, J = 8.23 Hz), 1.51

p, 2H, J = 7.23, 2.17 Hz), 1.33 (m, 8H), 0.89 (m, 3H). C NMR

500 MHz, CDCl3, δ): 175.7, 138.2, 136.2, 47.4, 46.6, 44.9, 41.8,

kDa, Mn,meas = 4.3 kDa, Mw,meas = 6.6 kDa, D = 1.5.

9.9, 31.8, 30.7, 29.9, 26.8, 22.8, 14.2. ESI-MS m/z calcd, 222.2;

Poly(1b-alt-2b)10. Amide 1b (30 mg, 127.6 μmol), catalyst 5 (11.3

mg, 12.8 μmol), and 2b (17.9 mg, 127.6 μmol) were mixed in CDCl

found, 222.1 [M + H] .

Preparation of Polymers. General Procedure for AROMP

Polymers. Reaction vessels and reagents were maintained under

oxygen-free conditions. For preliminary experiments, an NMR tube

in an NMR tube. After 8 h, amide 1b was completely consumed.

Precipitation in cold diethyl ether yielded poly(1b-alt-2b) . H NMR

(400 MHz, CDCl , δ): 6.20−5.95 (m, 9H), 5.95−5.30 (m, 6H),

Macromolecules XXXX, XXX, XXX−XXX

Macromolecules

Article

.31−5.11 (m, 6H), 5.11−4.89 (m, 3H), 4.72−4.48 (m, 16H), 3.45−

in methylene chloride (10 mg, 11 μmol) and chilled at 0 °C, and then

87 μL of monomer 4 solution (50 mg, 230 μmol) was added all at

once. After initiation for 5 min at 0 °C and then for 25 min at room

temperature, a 100 μL of aliquot was removed and quenched with

ethyl vinyl ether (100 μL); subsequent precipitation with diethyl ether

(3×) yielded poly(4)₂₀as an oﬀ-white solid. To the remaining

mixture in the vial (which contained approximately 8.8 μmol of

poly(4) -appended catalyst), 260 μL of 1a solution in CH Cl (42.2

.05 (m, 20H), 2.88−1.90 (m, 103H), 1.76−1.21 (m, 188H), 0.91−

.83 (m, 30H). M

= 3.8 kDa, M

= 6.0 kDa, M

= 9.8 kDa,

n,theo

n,meas

w,meas

D = 1.6.

Poly(1b-alt-2b) . Amide 1b (30 mg, 127.6 μmol), catalyst 5 (2.2

mg, 2.6 μmol), and 2b (17.9 mg, 127.6 μmol) were mixed in CDCl₃

in an NMR tube. After 21 h, amide 1b was completely consumed.

Precipitation in cold diethyl ether yielded poly(1b-alt-2b) . H NMR

(

400 MHz, CDCl , δ): 6.19−6.00 (m, 41H), 6.00−5.30 (m, 54H),

mg, 220 μmol) and 3a (21 μL, 22 mg, 220 μmol) were added in that

order. The mixture was incubated at 40 °C for 2 h and quenched with

ethyl vinyl ether (50 μL); precipitation with diethyl ether (3×)

yielded the diblock copolymer as an oﬀ-white solid. The polymer was

vacuum-dried overnight prior to use.

.22 (t, 26H, J = 6.1 Hz), 5.00 (t, 13H, J = 6.7 Hz), 4.75−4.39 (m,

8H), 3.38−3.12 (m, 100H), 2.68−1.83 (m, 475H), 1.80−0.90 (m,

56H), 0.89−0.82 (m, 154H). M

w,meas

Poly(1a-alt-3a)_m(m = 20, 50, and 100). For the preparation of

= 15.2 kDa, M

= 14.2 kDa,

n,theo

n,meas

= 19.6 kDa, D̵ = 1.4.

Poly(4) -b-poly(1a-alt-3b) . A 4 mL vial was charged with 400

the 20-mer, a 4 mL vial equipped with a PTFE-lined cap and a stir bar

was charged with 550 μL of a solution of 5 in chloroform (6.9 mg, 7.8

μmol), and then 300 μL of monomer 1a solution in chloroform (30

mg, 155 μmol) was added all at once. After initiation at 40 °C for 15

min, monomer 3a (16 μL, 16 mg, 155 μmol) was added to the hot

reaction mixture and stirring was continued for an additional 2 h. The

mixture was then cooled to rt and quenched with excess ethyl vinyl

ether, and the polymer was precipitated with hexanes (three times)

and vacuum-dried to give a reddish-brown solid in 70% isolated yield.

For the preparation of the 50- and 100-mers, the [5]/[1a]/[3a] ratios

were 1:50:50 and 1:100:100, respectively. Selected NMR data for the

μL of the solution of 5 in methylene chloride (10.8 mg, 12.2 μmol),

and then 180 μL of monomer 4 solution in CH Cl (53 mg, 240

μmol) was added all at once. Reaction went for 25 min at rt, a 150 μL

of aliquot was removed and quenched with ethyl vinyl ether (100

μL); precipitation with diethyl ether (3×) yielded poly(4)₂₀as an oﬀ-

white solid. To the remaining mixture in the vial (which contained

approximately 8.8 μmol of poly(4) -appended catalyst), 350 μL of 1a

solution in methylene chloride (42.7 mg, 220 μmol) and 3b (71 μL,

78 mg, 440 μmol) in that order. The mixture was incubated at 40 °C

for 19 h and quenched with ethyl vinyl ether (50 μL); precipitation

with diethyl ether (3×) yielded the diblock copolymer as an oﬀ-white

solid. The polymer was vacuum-dried overnight prior to use.

Poly(4) -b-poly(1a-alt-3c) . A 4 mL vial was charged with 200

signature region of poly(1a-alt-3a) : H NMR (500 MHz, CDCl , δ):

.18 (t, 1H, J = 6.02 Hz), 5.98 (br, 1H), 5.26 (t, 1H, J = 6.77 Hz),

.69 (s, 2H), 4.19 (d, 2H, J = 5.89 Hz), 4.08 (m, 2H), 3.26 (dq, 2H, J

μL of the solution of 5 in CH Cl (7.9 mg, 9.00 μmol) and chilled at 0

15.2 Hz, 7.71, 7.30). C NMR (500 MHz, CDCl , δ): 169.7

°C, and then 300 μL of monomer 4 solution (40 mg, 179 μmol) was

added quickly. After initiation for 5 min at 0 °C and warming to room

temperature over the course of 25 min, a 150 μL of aliquot was

removed and quenched with ethyl vinyl ether (50 μL); precipitation

with diethyl ether (3×) yielded poly(4)₂₀as an oﬀ-white solid. To the

remaining mixture in the vial (containing approximately 6.3 μmol of

poly(4) -appended catalyst), 260 μL of 1a solution (30.4 mg, 158

(

CONHR), 147.6, 139.4, 130.3, 117.0, 94.3, 93.8, 64.1, 63.5.

Poly(1a-alt-3b)_m(m = 20, 50, and 100). For the preparation of

the 20-mer, a 4 mL vial equipped with a PTFE-lined cap and a stir bar

was charged with 650 μL of a solution of 5 in chloroform (8 mg, 9.1

μmol), and then 350 μL of monomer 1a solution in chloroform (35

mg, 181 μmol) was added. After initiation at 40 °C for 15 min,

monomer 3b (57 μL, 64 mg, 363 μmol) was added to the hot reaction

mixture and stirring was continued for an additional 3 h. The mixture

was then cooled to rt before quenching with excess ethyl vinyl ether,

and the polymer was precipitated with hexanes and vacuum-dried to

yield a dark yellowish-brown solid in 75% isolated yield. For the

preparation of the 50- and 100-mers, the [5]/[1a]/[3b] ratios were

μmol) was added followed by 3c (17 μL, 158 μmol). The mixture was

incubated at 40 °C for 3 h and quenched with ethyl vinyl ether (50

μL); precipitation with diethyl ether (3×) yielded the diblock

copolymer as an oﬀ-white solid. The polymer was vacuum-dried

overnight prior to use.

Hydrolysis of Poly(1-alt-2b) . Poly(1a-alt-2b) (3 mg) and

:50:100 and 1:100:200, respectively. Selected NMR data for the

poly(1b-alt-2b)₁₀(3 mg) were each dissolved separately in 1:1

acetonitrile/CH Cl (300 μL each), owing to the limited solubility of

signature region of poly(1a-alt-3b) : H NMR (500 MHz, CDCl , δ):

.46 (m, 2H), 7.35 (dt, 3H, J = 15.9, 8.93 Hz), 6.16 (t, 1H, J = 6.31

these copolymers in water. Each solution was then treated with 1 mL

Hz), 5.90 (br s, 1H), 5.55 (1H, s), 5.22 (t, 1H, J values not

determined), 4.11 (m, 4H), 3.19 (t, 2H, J values not determined).

of 0.1 M NaOH at 40 °C with stirring. Degradation was monitored by

means of H NMR spectroscopy with tetramethylsilane as an internal

NMR (500 MHz, CDCl , δ): 169.7, 146.9, 139.1, 138.5, 130.4, 128.8,

standard. The degradation products were puriﬁed by HPLC with

0.1% formic acid in water as the aqueous solvent and acetonitrile as

the organic solvent (Luna 5 μm C18(2) 100 Å, LC Column 250 × 10

mm) Eluates were collected and tested using Mass Spec to identify

the structures of degraded polymer fragments. M = 351.2, found [M +

28.5, 126.9, 117.3, 100.9, 61.7.

Poly(1a-alt-3c)_m(m = 20, 50). For the preparation of the 20-mer,

a 4 mL vial equipped with a PTFE-lined cap and a stir bar was

charged with 650 μL of a solution of 5 in chloroform (11.5 mg, 13.0

μmol), and then 350 μL of monomer 1a solution in chloroform (50

mg, 260 μmol) was added. After initiation at 40 °C for 15 min,

monomer 3c (28 μL, 30 mg, 260 μmol) was added to the hot reaction

mixture and stirring was continued for an additional 2 h. The mixture

was then cooled to room temperature before quenching with excess

ethyl vinyl ether, and the polymer was precipitated with hexanes and

vacuum-dried to yield a dark yellowish-brown solid in 80% isolated

Na] . Samples of polymer solution were also treated with citric acid−

Na HPO buﬀer solutions at pH = 2.6, 5.0, 7.4, and Na CO −

NaHCO buﬀer solutions at pH = 10.8 at 40 °C with stirring but no

signiﬁcant degradation was seen after 5 days, which was expected as

polyesters were known to degrade slowly.

Kinetics of Poly(1a-alt-3a/3b)₂₀Hydrolysis. Polymer (5 mg, 1.4

μmol) was dissolved in 500 μL of d -acetonitrile, and the solution was

yield. Selected NMR data for the signature region of poly(1a-alt-

transferred to an NMR tube with a PTFE-lined cap. Then, 250 μL of

c) : H NMR (700 MHz, CDCl , δ): 6.18 (d, 1H, J = 5.67 Hz),

0.2 M sodium phosphate buﬀer (in D O, pH 5) was added. The

.24 (t, 1H, J = 6.81 Hz), 4.70 (q, 1H, J = 5.89 Hz) 4.11 (m, 4H),

reaction mixture was incubated at 37 °C, and the reaction progress

.25 (m, 2H). ¹³C NMR (700 MHz, CDCl , δ): 169.7, 146.4, 138.9,

was monitored by H NMR. In the case of poly(1a-alt-3a)₂₀,

30.7, 129.0, 128.6, 117.6, 99.1, 61.4. For 50 mer, the [5]/[1a]/[3c]

hexylamine was added as a scavenging agent of formaldehyde.

ratios were 1:50:90. Selected NMR data for the signature region of

Hydrolysis of poly(4) -b-poly(1a-alt-3) at pH 1. Each polymer

poly(1a-alt-3c) : H NMR (700 MHz, DMSO-d , δ): 7.90 (s, 1H,

(30 mg) was added to 1 mL of THF in a 4 mL vial capped with a

PTFE-lined septum, and then 0.3 mL of 10 mM aqueous TFA was

added. For poly(4) -b-poly(1a-alt-3a) , N-hexylamine (15 μL, 114

CONHR), 6.13 (d, 1H, J = 5.81 Hz), 5.14 (t, 1H, J = 6.78 Hz), 4.69

(

m, 1H) 4.05 (m, 4H), 3.03 (m, 2H). C NMR (700 MHz, DMSO-

d₆, δ): 168.8, 145.5, 137.9, 130.8, 129.9, 129.0, 117.8, 98.7, 61.6.

Poly(4) -b-poly(1a-alt-3a) . A 4 mL vial equipped with a PTFE-

lined cap and a stir bar was charged with 320 μL of the solution of 5

μmol) was added to scavenge-evolved formaldehyde. The hydrolysis

reaction was carried out at 37 °C, and aliquots were periodically

removed for analysis. Polymers were precipitated with diethyl ether

Macromolecules XXXX, XXX, XXX−XXX

Macromolecules

Cameron, J. F.; Thackeray, J. W. Backbone Degradable Poly(Aryl

Article

and vacuum dried. The average molecular weights of the residual

polymers were acquired by GPC.

(5) Ober, M. S.; Romer, D. R.; Etienne, J.; Thomas, P. J.; Jain, V.;

Acetal) Photoresist Polymers: Synthesis, Acid Sensitivity, and

Extreme Ultraviolet Lithography Performance. Macromolecules 2019,

Hydrolysis of poly(4) -b-poly(1a-alt-3) at pH 5. Each polymer

was dissolved in 1.0 mL of THF, and then 0.25 mL of 0.2 M sodium

phosphate buﬀer (pH 5) was added. The mixture was incubated at 37

(

2, 886−895.

C, and aliquots were removed periodically for analysis. Polymers

were precipitated from diethyl ether and analyzed by GPC.

6) Cushen, J. D.; Bates, C. M.; Rausch, E. L.; Dean, L. M.; Zhou, S.

X.; Willson, C. G.; Ellison, C. J. Thin Film Self-Assembly of

Poly(Trimethylsilylstyrene-B-D,L-Lactide) with Sub-10 nm Domains.

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ASSOCIATED CONTENT

sı Supporting Information

The Supporting Information is available free of charge at

https://pubs.acs.org/doi/10.1021/acs.macromol.0c01051.

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(7) Pal, R. K.; Kundu, S. C.; Yadavalli, V. K. Fabrication of Flexible,

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Reaction kinetic data, experimental details for strain

amplitude sweep, time-dependent modulus plots, and

spectral characterizations data (PDF)

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AUTHOR INFORMATION

Corresponding Author

Nicole S. Sampson − Department of Chemistry, Stony Brook

University, Stony Brook, New York 11794-3400, United States;

orcid.org/0000-0002-2835-7760 ;

in Degradable Electronic Devices. ACS Cent. Sci. 2018 , 4 , 337 −348.

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10) Hufendiek, A.; Lingier, S.; Du Prez, F. E. Thermoplastic

Polyacetals: Chemistry from the Past for a Sustainable Future? Polym.

Chem. 2019, 10, 9−33.

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into Synthesis, Stability and Biomedical Applications. Polym. Chem.

016, 7, 7039−7046.

12) Stukenbroeker, T. S.; Bandar, J. S.; Zhang, X.; Lambert, T. H.;

Email: nicole.sampson@stonybrook.edu

(

Authors

Waymouth, R. M. Cyclopropenimine Superbases: Competitive

Initiation Processes in Lactide Polymerization. ACS Macro Lett.

Francis O. Boadi − Department of Chemistry, Stony Brook

University, Stony Brook, New York 11794-3400, United States;

orcid.org/0000-0002-2064-5151

13) Ishido, Y.; Aburaki, R.; Kanaoka, S.; Aoshima, S. Well-Defined

015, 4, 853−856.

Jingling Zhang − Department of Materials Science and

Chemical Engineering, Stony Brook University, Stony Brook,

New York 11794-2275, United States; orcid.org/0000-

Alternating Copolymers of Benzaldehydes with Vinyl Ethers:

Precision Synthesis by Cationic Copolymerization and Quantitative

Degradation to Cinnamaldehydes. Macromolecules 2010, 43, 3141−

3144.

002-5595-0666

Xiaoxi Yu − Department of Chemistry, Stony Brook University,

Stony Brook, New York 11794-3400, United States

Surita R. Bhatia − Department of Chemistry, Stony Brook

University, Stony Brook, New York 11794-3400, United States;

orcid.org/0000-0002-5950-193X

(14) Yokota, D.; Kanazawa, A.; Aoshima, S. Alternating Degradable

Copolymers of an Ionic Liquid-Type Vinyl Ether and a Conjugated

Aldehyde: Precise Synthesis by Living Cationic Copolymerization and

Dual Rare Thermosensitive Behavior in Solution. Macromolecules

15) Ouchi, M.; Terashima, T.; Sawamoto, M. Transition Metal-

019, 52, 6241−6249.

Complete contact information is available at:

Catalyzed Living Radical Polymerization: Toward Perfection in

https://pubs.acs.org/10.1021/acs.macromol.0c01051

Catalysis and Precision Polymer Synthesis. Chem. Rev. 2009, 109,

963−5050.

Notes

(16) Bielawski, C. W.; Grubbs, R. H. Living Ring-Opening

The authors declare no competing ﬁnancial interest.

Metathesis Polymerization. Prog. Polym. Sci. 2007 , 32 , 1 −29.

(17) Gilliom, L. R.; Grubbs, R. H. Titanacyclobutanes Derived from

ACKNOWLEDGMENTS

This research is funded by the NSF CHE1609494 (N.S.S.), the

NIH R01GM097971 (N.S.S.), the NIH T32GM092714

Strained, Cyclic Olefins: The Living Polymerization of Norbornene. J.

Am. Chem. Soc. 1986 , 108 , 733 −742.

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Catalyzed by Well-Characterized Transition-Metal Alkylidene Com-

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F.O.B.), the ACS PRF 55729-ND9 (S.R.B.), and the DOE

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Contract DE-SC0012704 (the CFN at the Brookhaven

National Laboratory). Shearson Editorial Services (Cornwall,

NY, U.S.A.) provided English language editing of the text of

this paper.

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