Achieving Ultrahigh Molecular Weights with Diverse Architectures for Unconjugated Monomers through Oxygen-Tolerant Photoenzymatic RAFT Polymerization

Article abstract of DOI:10.1002/anie.202010722

Achieving well-defined polymers with ultrahigh molecular weight (UHMW) is an enduring pursuit in the field of reversible deactivation radical polymerization. Synthetic protocols have been successfully developed to achieve UHMWs with low dispersities exclusively from conjugated monomers while no polymerization of unconjugated monomers has provided the same level of control. Herein, an oxygen-tolerant photoenzymatic RAFT (reversible addition-fragmentation chain transfer) polymerization was exploited to tackle this challenge for unconjugated monomers at 10 °C, enabling facile synthesis of well-defined, linear and star polymers with near-quantitative conversions, unprecedented UHMWs and low dispersities. The exquisite level of control over composition, MW and architecture, coupled with operational ease, mild conditions and environmental friendliness, broadens the monomer scope to include unconjugated monomers, and to achieve previously inaccessible low-dispersity UHMWs.

Full text of DOI:10.1002/anie.202010722

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Accepted Article
Title: Achieving Ultrahigh Molecular Weights with Diverse Architectures
for Unconjugated Monomers through Oxygen-tolerant
Photoenzymatic RAFT Polymerization
Authors: Zesheng An and Ruoyu Li
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10.1002/anie.202010722
Angewandte Chemie International Edition
RESEARCH ARTICLE
Achieving Ultrahigh Molecular Weights with Diverse Architectures
for Unconjugated Monomers through Oxygen-tolerant
Photoenzymatic RAFT Polymerization
Ruoyu Li,[a] and Zesheng An*[b]
[a]
R. Li
Institute of Nanochemistry and Nanobiology
College of Environmental and Chemical Engineering
Shanghai University, Shanghai 200444, China
Prof. Z. An
[b]
State Key Laboratory of Supramolecular Structure and Materials
College of Chemistry
Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education
School of Life Sciences
Jilin University, Changchun 130012, China
E-mail: anzesheng@jlu.edu.cn
Supporting information for this article is given via a link at the end of the document.
Abstract: Achieving well-defined polymers with ultrahigh molecular
weight (UHMW) is an enduring pursuit in the field of reversible
deactivation radical polymerization. Synthetic protocols have been
successfully developed to achieve UHMWs with low dispersities
exclusively from conjugated monomers while no polymerization of
unconjugated monomers has provided the same level of control.
Herein, an oxygen-tolerant photoenzymatic RAFT polymerization is
exploited to tackle this challenge for unconjugated monomers at 10
oC, enabling facile synthesis of well-defined, linear and star polymers
with near-quantitative conversions, unprecedented UHMWs and low
dispersities. The exquisite level of control over composition, MW and
architecture, coupled with the operational ease, mild conditions and
environmental friendliness, broadens the monomer scope to include
unconjugated monomers to achieve previously inaccessible low-
dispersity UHMWs.
polymerization, has been successfully employed to control radical
polymerization of unconjugated monomers,[4] typically low MWs
are achieved with one or more problems of incomplete conversion,
relatively high dispersity and moderate end-group fidelity.
Significantly, these challenges become deteriorated when
complex architectures such as star polymers are concerned due
to steric congestion, enhanced termination between neighbor
propagating radicals within the same star, and star-linear/star-star
coupling reactions.[5]
Some unconjugated monomers, as represented by N-vinyl
pyrrolidone (NVP), are additionally plagued by potential loss of
chain end-group at high temperature and monomer hydrolysis
when polymerized in water.[6] Although narrow-dispersity poly(N-
vinyl pyrrolidone)s (PNVPs) have been successfully synthesized
in aqueous solution through redox initiation at ambient
temperature, the MWs are smaller than 20 kg/mol.[7]
Green and sustainable synthesis of precision polymers is a
highly valued concept in contemporary polymer chemistry.[8]
Increasing attention has focused on improving RDRP livingness,
polymerization efficiency and environmental friendliness through
organic and enzymatic catalysis, high-throughput screening, the
use of clean energy (e.g. visible light and electricity) and green
solvents for controlled polymer synthesis.[9] In this regard, we
have developed RAFT polymerization initiated by enzyme
catalysis and more recently, inspired by DNA photolyase, a new
Introduction
Precision polymers with ultrahigh molecular weights (UHMWs,
Mn ≥ 106 g/mol) provide an opportunity to explore polymer
properties in previously inaccessible MW regime. There exists
strong interest in pursuit of UHMW polymers for use in high-
performance elastomers, low-concentration hydrogels, photonic
materials, durable coatings, and flocculants.[1] Advances in
reversible deactivation radical polymerization (RDRP) and
synthetic strategies that can maximize the Rp/(Rt + Rtr) ratio have
enabled access to UHMWs from various vinyl monomers.[2]
However, current examples of low-dispersity UHMWs are
exclusively limited to conjugated monomers and those based on
unconjugated monomers have yet to be achieved.
Unconjugated monomers, in which the vinyl group is attached
to a heteroatom, form highly active, unstabilized propagating
radicals. They have limited regioselectivity toward addition to an
incoming double bond and are also susceptible to termination and
transfer, making radical polymerization of unconjugated
monomers difficult to control.[3] Although RDRP, predominantly
reversible addition-fragmentation chain transfer (RAFT)
photoenzymatic radical polymerization for controlled synthesis of
10]
various polymers in water.[1i,
We envisioned that
photoenzymatic generation of stable, low-concentration radicals
under mild conditions could enable previously inaccessible low-
dispersity (Đ < 1.5) UHMWs to be achieved for unconjugated
monomers. Herein, we report our study on oxygen-tolerant,
photoenzymatic RAFT polymerization of unconjugated monomers
using xanthates as chain transfer agents (CTAs) in aqueous
solution, leading to near-quantitative conversions and
unprecedented UHMWs for well-defined linear homopolymers,
statistical copolymers, block copolymers and star-shaped
(co)polymers (Scheme 1).
1
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Accumulated light exposure resulted in pseudo-first order
polymerization kinetics, linear evolution of predicted MWs and
narrow MW distributions.
Figure 1. Comparison of photoenzymatic RAFT polymerizations of NVP with N2
deoxygenation, GOx prior deoxygenation and no prior deoxygenation. [NVP] =
10% w/v, [NVP]/[XAN1] = 200/1, [glucose] = 3 mM, [GOx] = 1.5 µM, PBS buffer
(20 mM, pH 7), room temperature. (A) plots of ln([M]0/[M]) vs time, (B) plots of
oxygen concentration during polymerization, (C) plots of molecular weight and
dispersity vs conversion, and (D) GPC traces of the final products.
Scheme 1. (A) Schematic representation of oxygen-tolerant photoenzymatic
RAFT polymerization of unconjugated monomers to achieve low-dispersity
UHMWs with architecture control. (B) chemical structures of xanthates and
monomers used in this study.
Next, the effect of oxygen on polymerization rate and the
possibility of conducting oxygen-tolerant, photoenzymatic RAFT
polymerization of NVP was explored. These experiments were
conducted in vials fully filled with polymerization solution (no
headspace): one vial was degassed with N2 prior to addition of
GOx and light irradiation (vial#1, N2 deoxygenation), the second
vial containing all the necessary components was not degassed
with N2 but allowed to stir for 15 min prior to light irradiation (vial#2,
GOx deoxygenation), while the third vial also containing all the
necessary components was directly subjected to light irradiation
(vial#3, no prior deoxygenation). As shown in Figure 1, the
apparent polymerization rate constant kpapp decreased from vial#1
to vial#3 (0.17, 0.13, 0.12 h-1, respectively), suggesting oxygen
concentration was different in the polymerization solution via
different degassing mode. Thus, the oxygen concentration in the
polymerization solution was followed by using an optical fiber
oxygen sensor (Pyroscience FS).[14] The oxygen concentration in
vial#1 was maintained at a low level (1.83 μM) starting from the
commencement of polymerization. For vial#2 and vial#3, the
oxygen concentration was lowered from 64.4 and 242.6 μM to the
same level as in vial#1 within 20 and 30 min, respectively.
Considering the polymerization of NVP was conducted for 24 h in
this study, the time needed to consume oxygen dissolved in the
polymerization solution was comparably short and thus was not
expected to significantly affect the outcome of polymerization.
Regardless the deoxygenation mode, all three polymerizations
reached near-quantitative conversions and similar MWs with low
Đ values. Thus, leveraging on the ability of GOx to simultaneously
consume oxygen and photo-control RAFT polymerization, for the
rest of this study, polymerizations were directly conducted without
prior deoxygenation in vials (2 mL or 50 mL) with no headspace
unless otherwise stated.
Results and Discussion
Glucose oxidase (GOx) is a common flavin-containing enzyme
catalyzing oxidation of glucose with oxygen.[11] Upon glucose
binding, the flavin adenine dinucleotide (FAD) cofactor is reduced
to FADH¯, which can be employed as a highly reducing
photocatalyst to initiate radical polymerization via photoinduced
electron transfer (PET) in a way analogous to DNA photolyase.[10d]
Similar photoenzymatic radical mechanisms have also been
demonstrated in other flavoenzymes for stereocontrolled radical
transformations.[12] GOx can scavenge oxygen and this natural
function has been used to deoxygenate solution in RDRP.[1i, 9f-h,
10a, 10b, 13] In this study, we exploit the unique dual function of GOx
for oxygen-tolerant, visible-light-controlled RAFT polymerization
of unconjugated monomers in aqueous solution, aiming to
achieve UHMWs in an environmentally benign manner.
Polymerization experiments using GOx/glucose as the
photocatalyst were conducted using NVP as the monomer to
elucidate the role of each component first under N2 protection at
room temperature (Tables S2-S3). High monomer conversions
were observed for both RAFT and free-radical polymerizations in
the presence or absence of XAN1, confirming the highly reducing
nature of (FADH¯)* and its efficiency for PET to either XAN1 or
NVP, though both of which are less electron-accepting than the
trithiocarbonate CTAs and conjugated monomers used in our
previous study.[10d] In the absence of GOx, glucose or light, no
NVP conversion was observed, further confirming the
photocatalytic role of GOx/glucose and discounting the possibility
of direct photolysis[1g] of XAN1 for initiating NVP polymerization
under the conditions used in this work. Further evidence for
photocatalytic radical generation to control NVP polymerization
was provided by dynamic modulation of polymerization kinetics in
light on/off experiments (Figure S6) with the expected
polymerization activation/deactivation periods being observed.
2
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10.1002/anie.202010722
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RESEARCH ARTICLE
9[b]
200
500
XAN2
XAN2
XAN2
XAN2
XAN2
XAN2
XAN4
XAN4
XAN4
XAN4
XAN4
XAN4
XAN4
90
96
98
90
94
92
92
91
93
90
92
90
98
20.4
53.8
24.8
55.1
1.16
1.17
1.20
1.29
1.30
1.34
1.19
1.21
1.16
1.17
1.17
1.30
1.35
10[b]
11[b]
12[b]
13[c]
14[c]
15[c]
16[c]
17[c]
18[c]
19[c]
20[b]
21[d]
1000
2000
5000
10000
100
109.3
200.5
522.8
1022.9
11.1
101.5
213.9
568.4
1047.6
12.3
200
21.1
24.2
Figure 2. GPC traces of PNVPs synthesized at two different temperatures
under conditions: no headspace, no prior deoxygenation, [NVP] = 20% w/v,
[NVP]/[XAN1] = 10000/1, [glucose] = 3 mM, [GOx] = 1.5 μM, PBS buffer (20 mM,
pH 7), violet LED light (11.5 W, 405 nm), 24 h.
500
52.5
50.1
1000
2000
5000
10000
100.9
205.3
501.0
1090.0
107.9
217.8
600.3
1109.7
In attempts to achieve high MWs for PNVP, polymerizations
targeting DPs of 5000 and 10000 were conducted using XAN1 at
40 oC, a temperature that we previously used for conjugated
monomers.[10d] Despite high NVP conversions were achieved, the
dispersities (Đ ~ 1.4) were relatively high. We hypothesized that
the high reactivity of PNVP propagating radical could be mitigated
by lowering polymerization temperature, with the hope to reduce
side reactions such as chain transfer, which typically requires a
lower activation energy than propagation and termination. To this
end, polymerizations were conducted in the temperature range -
[a] Polymerization conditions: no headspace, no prior deoxygenation, [NVP] =
20% w/v, [glucose] = 3 mM, GOx =1.5 μM, violet LED light (11.5 W, 405 nm),
10 oC, 24 h. [b] PBS buffer (20 mM, pH 7). [c] PBS buffer (20 mM, pH
7)/acetonitrile = 9:1 (v/v). [d] PBS buffer (20 mM, pH 7)/acetonitrile = 8:2 (v/v).
[e] Monomer conversion determined by 1H NMR spectroscopy in D2O. [f]
Theoretical molecular weight calculated by monomer conversion. [g] Molecular
weight and dispersity determined by GPC equipped with a LS detector.
o
5 to 40 C (Table S4 and Figures S8-S9), taking advantage of
photocatalysis being less affected by temperature in comparison
with thermal activation. As polymerization temperature was
reduced, MW distribution became narrower. Remarkably, at 10 oC
a low-dispersity PVNP with a predicted UHMW (Mn = 1058.7
kg/mol, Đ = 1.27) was successfully obtained at 90% conversion
(Figure 2). 1H NMR spectroscopy analysis indicated that products
due to NVP hydrolysis or coupling side reactions were not formed
(Supporting Information). After overall consideration of
polymerization rate, monomer conversion and polymerization
control, 10 oC was selected for subsequent polymerizations. This
easily accessible sub-room-temperature affords both operational
convenience and excellent polymerization control for
unconjugated monomers, especially toward achieving UHMWs.
Table 1. Summary of PNVPs synthesized using different CTAs
via oxygen-tolerant photoenzymatic RAFT polymerization. [a]
entry
target
DP
CTA
conv.
(%)[e]
Mn,th
(kg/mol)[f]
Mn,GPC
(kg/mol) [g]
Ð [g]
1[b]
2[b]
3[b]
4[b]
5[b]
6[b]
7[b]
8[b]
100
200
XAN1
XAN1
XAN1
XAN1
XAN1
XAN1
XAN1
XAN2
92
92
91
93
96
92
90
96
10.4
20.7
11.3
22.5
1.10
1.13
1.26
1.11
1.30
1.27
1.27
1.14
500
50.8
48.6
1000
2000
5000
10000
100
103.6
213.6
511.5
1000.5
11.1
120.1
236.4
503.1
1058.7
14.6
Figure 3. GPC traces (A) and dependence of molecular weight and dispersity
on degree of polymerization (B) for linear PNVPs synthesized using XAN1: no
headspace, no prior deoxygenation, PBS buffer (20 mM, pH 7), [NVP] = 20%
w/v, [glucose] = 3 mM, GOx =1.5 μM, violet LED light (11.5 W, 405 nm), 10 oC,
24 h.
3
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Encouraged by its visible-light modulation, oxygen-tolerance
and the ability to synthesize low-dispersity PNVPs of UHMWs, we
carried out photoenzymatic RAFT polymerizations systematically
targeting a wide range of DPs (100-10000), using CTAs of
different structures, namely XAN1, XAN2 and XAN4 (Table 1).
While both XAN1 and XAN2 led to the formation of linear PNVPs,
the latter installed a xanthate group at both chain ends, which
could be used for facile generation of triblock copolymers via one-
step chain extension. XAN4 bearing four xanthate groups led to
the generation of 4-arm star polymers. While most
polymerizations were conducted directly in PBS buffer,
acetonitrile[13] was added in some polymerizations to aid
dissolution of XAN2 and XAN4. Exceptionally, all polymerizations
reached high conversions (≥ 90%) without scarifying the control
over MW and MW distribution. These PNVPs all possessed MWs
close to their theoretical values and the dispersities (Đ ≤ 1.35)
were generally low in all cases (Figure 3 and Figure S10). It is
worth noting that UHMWs were obtained using all three types of
CTAs, though dispersity slightly increased for polymerizations
using XAN2 and XAN4 with more xanthate groups. This is the first
time that low-dispersity UHMWs have been achieved for well-
defined polymers, even with a star architecture, synthesized from
controlled radical polymerization of unconjugated monomers.
methylene groups from the NVP (b) and NVCL (g) units gave a
composition ratio of 9:1, which was close to the feed ratio of 10:1.
Figure 5. UHMW linear and star block copolymers synthesized via
photoenzymatic RAFT polymerization using [GOx]0 = 1.5 µM at 10 oC. [a]
[glucose]0 = 30 mM, [polymer] = 10% w/v, PBS buffer (20 mM, pH 7), violet LED
light (11.5 W, 405 nm), no prior deoxygenation, [b] [glucose]0 = 3 mM, [NVP] =
20% w/v, [NVCL] = 10% w/v, PBS buffer (20 mM, pH 7)/acetonitrile = 8:2 (v/v),
violet LED light (50 W, 405 nm), no prior deoxygenation, [c] [glucose]0 = 3 mM,
[polymer] = 10% w/v, PBS buffer (20 mM, pH 7), violet LED light (11.5 W, 405
nm), N2 deoxygenation.
To further demonstrate the high livingness and polymerization
efficiency as well as to extend the scope of polymer architecture
that can be accessed using this photoenzymatic RAFT
polymerization, a one-pot sequential polymerization protocol was
used to synthesize various linear and star block copolymers
(Figure 5 and Figures S14-S15). This protocol can speed up block
copolymer synthesis by avoiding polymer purification and
isolation but requires high conversion and livingness. To
showcase this synthetic capacity, NVP was first polymerized to
93% conversion, affording a PNVP4650 macro-CTA with a Mn of
489.2 kg/mol and a Đ of 1.32. Addition of more NVP for chain
extension resulted in the synthesis of a well-defined PNVP4650-b-
PNVP4600 with 92% conversion and an UHMW of 1058.7 kg/mol
(Đ = 1.30). Polymerization of NVP using bifunctional XAN2
provided an UHMW PNVP9700 (Mn = 998.7 kg/mol, Đ = 1.33)
bearing xanthate groups at both chain ends, from which one-step
chain extension using NVCL as the second monomer provided a
triblock PNVCL250-b-PNVP9700-b-PNVCL250 (Mn = 1106.5 kg/mol,
Đ = 1.39) consisting of two different unconjugated monomers.
Figure 4. 1H NMR spectroscopy analysis of UHMW statistical P(NVP10000-co-
NVCL1000) copolymer synthesized via photoenzymatic RAFT polymerization
using XAN1 under conditions: [M] = 20% w/v, [GOx] = 1.5 µM, [glucose] = 3 mM,
PBS buffer (20 mM, pH 7)/acetonitrile = 8:2 (v/v), violet LED light (50 W, 405
nm), 10 oC, 30 h.
It is also possible to synthesize UHMW statistical copolymers
of NVP with other unconjugated monomers via oxygen-tolerant
photoenzymatic RAFT copolymerization. This is exemplified by
copolymerization of NVP with NVCL. Since NVCL is poorly
soluble in water, 20% acetonitrile was added to aid its dissolution.
The monomers were completely consumed after polymerization
at 10 oC for 30 h, resulting in the formation of P(NVP10000-co-
NVCL1000) statistical copolymer with an UHMW (Mn = 1089.4
kg/mol, Đ = 1.38). 1H NMR spectrum showed the expected signals
from both NVP and NVCL units (Figure 4). Analysis using the
backbone methine group from the NVCL units (f) and the
Xanthates are also suitable CTAs to control RAFT polymerization
4b]
of acrylamido monomers,[1g,
providing an opportunity to
synthesize well-defined block copolymers consisting of
conjugated and unconjugated monomers. Thus, diblock
a
PDMA5000-b-PNVP4700 (Mn = 998.2 kg/mol, Đ = 1.35), a triblock
PNVP2250-b-PDMA5000-b-PNVP2250 (Mn = 978.5 kg/mol, Đ = 1.35),
and a 4-arm star-(PDMA1250-b-PNVP1163)4 (Mn = 1081.0 kg/mol, Đ
= 1.39) block copolymer were similarly synthesized via one-pot
4
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10.1002/anie.202010722
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RESEARCH ARTICLE
procedures. To the best of our knowledge, this extraordinary level
of MW and architecture control is unprecedented in the literature
for unconjugated monomers.
Finally, the linear and star series of PNVPs with MWs spanning
two orders of magnitude provide a unique opportunity to
investigate the dependence of physical properties such as glass
transition temperature, Tg, on MW and architecture. As shown in
Figure 7, Tg first quickly scales up with MW until a plateau is
reached, as expected. Linear PNVPs show higher Tg than those
with a star architecture over the whole MW range but as MW
approaches the UHMW regime their Tg values become close to
o
o
each other, 179.2 C for linear PNVP9000 and 178.5 C for star-
PNVP8400, respectively. These Tg values are consistent with the
178.5 oC reported for a BASF PNVP K90 with a Mw of 1250
kg/mol.[15] Of the same MW, a 4-arm star polymer has 4 chain
ends, doubling that for a linear polymer and this gives rise to a
higher free volume and thus a lower Tg for the former architecture
according to the free volume theory. At the UHMW regime, the
free volume of chain ends becomes negligible and thus similar Tg
values are observed for both architectures. For MWs higher than
20 kg/mol, the dependence of Tg on MW can be approximated by
Figure 6. (A) Photograph of polymerization vials and (B) GPC traces of linear
and star PNVPs synthesized using XAN1 and XAN4 under conditions: 50 mL,
no head space, no prior deoxygenation, [NVP] = 20% w/v, [GOx] = 1.5 µM,
[glucose] = 3 mM, PBS buffer (20 mM, pH 7), violet LED light (11.5 W, 405 nm),
10 oC, 36 h.
the Flory-Fox equation[16]
:
Tg = Tg, － K/Mn
in which Tg, is the Tg at infinite MW and K the Flory-Fox constant.
Similar Tg, was obtained for linear (178.9 oC) and star (178.7 oC)
Most of the photoenzymatic RAFT polymerizations were
conducted in 2 mL vials with no headspace, which provided a
convenient setup to achieve UHMWs for unconjugated monomers.
In order to demonstrate the capacity for multi-gram synthesis, we
scaled up the polymerization volume from 2 to 50 mL such that
10 grams of UHMW PNVP could be produced in the latter case,
also without prior deoxygenation and at 10 oC (Figure 6). UHMW
linear (Mn = 1005.9 kg/mol, Đ = 1.36) and star (Mn = 1102.8 kg/mol,
Đ = 1.32) PNVPs with near-quantitative conversions were
successfully produced, thus validating the potential of
photoenzymatic RAFT polymerization for facile production of well-
defined UHMW polymers on a large scale.
polymers, while smaller K was obtained for linear (3.21  105 o
g/mol) than star (10.85  105 oC g/mol) polymers.
C
Conclusion
Photoenzymatic RAFT polymerization has been successfully
exploited to achieve UHMWs with architecture control for
unconjugated monomers. The dual function of GOx enables
oxygen-tolerance and visible-light control of RAFT polymerization
of unconjugated monomers using different xanthate structures.
Key to the extraordinary control of MW and architecture in the
UHMW regime is the catalytic nature of GOx as a photoenzyme
o
and the use of a conveniently low temperature (10 C). UHMW
polymer solution is highly viscous, which also helps reduce
termination due to reduced diffusion rate of high MW propagating
radicals. The ability to scale up the polymerization to multi-grams
holds potential for routine laboratory synthesis of such well-
defined polymers as useful materials. The unprecedented access
to low-dispersity linear and star PNVPs over a wide MW range
enables Tg to be studied as a function of MW and architecture.
This mild, green and facie polymerization approach allows
previously inaccessible UHMWs to be achieved for unconjugated
monomers, opening up new possibilities for RDRP to prepare new
materials for various applications.
Acknowledgements
Financial support from the National Natural Science Foundation
of China (21871175) and the Fundamental Research Funds for
the Central Universities is thanked. We thank Profs. Yixin Chen
(Fudan Univ.), Zhigang Wang (Univ. of Science and Technology
of China) and Dongshan Zhou (Nanjing Univ.) for discussions on
Tg.
Keywords: controlled radical polymerization • enzyme • RAFT •
unconjugated monomer • ultrahigh molecular weight
Figure 7. Plots of MW dependence of Tg of linear and star PNVPs.
5
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10.1002/anie.202010722
Angewandte Chemie International Edition
RESEARCH ARTICLE
Entry for the Table of Contents
o
Photoenzymatic RAFT polymerization enables ultrahigh molecular weights to be achieved for unconjugated monomers at 10 C in
aqueous solution without prior deoxygenation.
7
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