Synthesis and chemical degradation of branched vinyl polymers prepared via ATRP: Use of a cleavable disulfide-based branching agent

Article abstract of DOI:10.1021/ma051121s

Highly branched poly(2-hydroxypropyl methacrylate) has been prepared by atom transfer radical polymerization (ATRP) in methanol at 20°C using a disulfide-based dimethacrylate (DSDMA) branching agent. The mean degree of polymerization of the primary chains was fixed at 50; since ATRP has reasonably good living character, the molecular weight distribution of these primary chains is relatively narrow, which allows significantly better control than conventional radical polymerization. Varying the proportion of the DSDMA produced a series of soluble branched polymers, provided that there was on average less than one branching agent per primary chain. However, higher levels of DSDMA lead to macrogelation, as expected. The soluble branched polymers were characterized using triple detector gel permeation chromatography (GPC). The most highly branched copolymers had weight-average molecular weights of up to 540 000, with polydispersities of around 8.0 and Mark-Houwink a parameters as low as 0.21 being obtained. ¹H NMR spectroscopy confirmed that very high monomer conversions were obtained (>99%), and the final branched copolymers contained little or no unreacted pendent vinyl groups. The disulfide bond in the DSDMA branching agent was readily cleaved using either dithiothreitol or benzoyl peroxide. GPC studies confirmed the progressive decrease in molecular weight and polydispersity during the chemical degradation of one of the branched copolymers with reaction time. Eventually, the final polydispersity of this degraded branched copolymer was comparable to that of linear poly(2-hydroxypropyl methacrylate) prepared in the absence of any disulfide-based dimethacrylate branching agent. Thus, all the disulfide bonds had been cleaved, reducing the branched copolymer to its near-monodisperse primary chains.

Full text of DOI:10.1021/ma051121s

Macromolecules 2005, 38, 8155-8162
8155
Synthesis and Chemical Degradation of Branched Vinyl Polymers
Prepared via ATRP: Use of a Cleavable Disulfide-Based Branching
Agent
Yuting Li and Steven P. Armes*
Department of Chemistry, Dainton Building, University of Sheffield, Brook Hill,
Sheffield, S3 7HF, United Kingdom
Received May 31, 2005; Revised Manuscript Received July 22, 2005
ABSTRACT: Highly branched poly(2-hydroxypropyl methacrylate) has been prepared by atom transfer
radical polymerization (ATRP) in methanol at 20 °C using a disulfide-based dimethacrylate (DSDMA)
branching agent. The mean degree of polymerization of the primary chains was fixed at 50; since ATRP
has reasonably good living character, the molecular weight distribution of these primary chains is relatively
narrow, which allows significantly better control than conventional radical polymerization. Varying the
proportion of the DSDMA produced a series of soluble branched polymers, provided that there was on
average less than one branching agent per primary chain. However, higher levels of DSDMA lead to
macrogelation, as expected. The soluble branched polymers were characterized using triple detector gel
permeation chromatography (GPC). The most highly branched copolymers had weight-average molecular
weights of up to 540 000, with polydispersities of around 8.0 and Mark-Houwink R parameters as low
as 0.21 being obtained. 1H NMR spectroscopy confirmed that very high monomer conversions were obtained
(>99%), and the final branched copolymers contained little or no unreacted pendent vinyl groups. The
disulfide bond in the DSDMA branching agent was readily cleaved using either dithiothreitol or benzoyl
peroxide. GPC studies confirmed the progressive decrease in molecular weight and polydispersity during
the chemical degradation of one of the branched copolymers with reaction time. Eventually, the final
polydispersity of this degraded branched copolymer was comparable to that of linear poly(2-hydroxypropyl
methacrylate) prepared in the absence of any disulfide-based dimethacrylate branching agent. Thus, all
the disulfide bonds had been cleaved, reducing the branched copolymer to its near-monodisperse primary
chains.
Introduction
termination and allows relatively good control over the
molecular weight distribution. Typically, copper(I) ha-
lide is used in conjunction with a nitrogen-based com-
plexing ligand,24,25 and ATRP is usually conducted in
organic solvents.21 Elevated temperatures are often
selected for styrenic25 or methacrylic monomers26 so as
to offset their relatively sluggish rates of polymerization,
although the choice of suitable ligands can sometimes
alleviate this problem. Alternatively, Armes and co-
workers have recently shown that ATRP can be used
to polymerize a wide range of hydrophilic methacrylates
with good control under surprisingly mild conditions,
provided that protic solvents such as lower alcohols (e.g.,
methanol) are selected.27-31 The most relevant example
in the context of the present study is that low polydis-
persity linear poly(2-hydroxypropyl methacrylate) can
be obtained in very high yield within a few hours at
ambient temperature via methanolic ATRP.32
Branched polymers have recently received much
attention due to their interesting solution properties and
their ease of preparation as compared to dendrimers.1
Branched polymers can be prepared by condensation
polymerization,2 ring-opening polymerization,3 free radi-
cal polymerization,4,5 nitroxide-mediated radical polym-
erization,6 atom transfer radical polymerization
(ATRP),7-11 reversible addition fragmentation chain
transfer (RAFT) polymerization,12 oxyanionic polymer-
ization,13 and group transfer polymerization.14 The
synthesis of branched vinyl polymers can be achieved
by self-condensing vinyl polymerization (SCVP) reported
by Frechet and co-workers15 or by the bifunctional vinyl
comonomer route favored by Sherrington and co-
workers.4,5,16-18 One advantage of the latter route is that
syntheses can be carried out using cheap, readily
available monomers and branching agents, whereas the
former route usually requires the prior synthesis of
monomer-initiator precursors or related adducts.
ATRP is a type of living radical polymerization that
was independently developed by Wang and Matyjasze-
wski and also by Sawamoto and co-workers in 1995.19,20
ATRP involves an alkyl halide initiator and a transition
metal catalyst; the latter complex is used to add or
remove terminal halogen atoms from the polymer chain
ends.21-23 This rapid, reversible capping leads to sup-
pression of the instantaneous concentration of propa-
gating polymer radicals, which in turn minimizes
In principle, the pseudo-living character of ATRP
offers a number of advantages for the synthesis of
branched polymers via the Sherrington route. First, the
primary chain length is readily controlled by adjusting
the monomer/initiator molar ratio. Second, relatively
narrow polydispersities are obtained (typically Mw/Mn
< 1.30). This means that the probability of unwanted
macrogelation due to cross-linking caused by a minor
population of higher molecular weight chains is signifi-
cantly reduced. Thus, it is of considerable interest to
evaluate the use of ATRP for the synthesis of branched
vinyl polymers, and indeed, preliminary results have
been very encouraging.33
* To whom correspondence should be addressed. E-mail:
s.p.armes@sheffield.ac.uk.
10.1021/ma051121s CCC: $30.25 © 2005 American Chemical Society
Published on Web 08/26/2005

8156 Li and Armes
Macromolecules, Vol. 38, No. 20, 2005
Figure 1. Schematic representation of the synthesis of branched poly(2-hydroxpropyl methacrylate) via methanolic ATRP at 20
°C using a disulfide-based dimethacrylate branching agent (DSDMA).
ice bath, and methacryloyl chloride (21.0 g, 200 mmol, 4.0
equiv) was added dropwise to the stirred THF solution. The
resulting heterogeneous mixture was stirred at 20 °C for 24 h
and then filtered to remove the triethylamine hydrochloride
byproduct. The solvent was removed by evaporation, and the
crude product was dissolved in chloroform. This solution was
washed three times with an aqueous solution of 0.1 M Na2-
CO3, followed by three washings with water. The purified
organic solution was dried using anhydrous MgSO4, and the
chloroform was removed under reduced pressure. The final
disulfide-based dimethacrylate (DSDMA) product was obtained
as a slightly yellow liquid (10.0 g, 69%) and was stored in a
freezer under nitrogen in the absence of light prior to use. 1H
NMR spectroscopy indicated a mean degree of esterification
of at least 97%. 1H NMR: δ 5.6 and 6.2 ppm (4 H, singlet,
CH2C(CH3)COO); 4.4 ppm (4 H, triplet, CH2C(CH3)COOCH2-
CH2); 3.0 ppm (4 H, triplet, COOCH2CH2SS); 1.95 ppm (6 H,
In 2002, Tsarevsky and Matyjaszewski reported the
synthesis of a bifunctional ATRP initiator derived from
bis(2-hydroxyethyl) disulfide.34 This initiator was used
to prepare low polydispersity polystyrene containing a
disulfide bond located in the middle of the chain. This
disulfide unit was cleaved using excess dithiothreitol
(DTT) in THF at 60 °C to produce thiol-terminated
polystyrene chains with half the molecular weight of the
original polymer. In the present study, we have used
the same bis(2-hydroxyethyl) disulfide starting material
to prepare a model disulfide-based branching agent that
is readily cleavable under mild conditions. A similar
approach has been used to prepare hydrogels that can
be degraded to produce soluble polymers.35-37 In one
recent proof-of-concept study, various hydrogels were
successfully reconstructed from the soluble thiol-func-
tionalized polymer products obtained by degradation of
the original hydrogel.35 Inspired by this work, we
designed a disulfide-based dimethacrylate (DSDMA, see
Figure 1) to learn more about the nature of the branched
vinyl polymers that are obtained using the approach
described by Sherrington and co-workers.18 In their
original paper, the Strathclyde group used an ozone-
cleavable cross-linker to gain insight into the nature of
branched poly(methyl methacrylate) prepared by con-
ventional radical polymerization.18 In contrast, the
present study is devoted to understanding the nature
of a branched vinyl polymer, poly(2-hydroxyethyl meth-
acrylate), that is synthesized by controlled radical
polymerization, namely, ATRP.
1
singlet, CH2C(CH3)COO). An assigned H NMR spectrum of
this compound is shown in the Supporting Information.
Homopolymerization of 2-Hydroxypropyl Methacry-
late Using Conventional Free Radical Chemistry. The
HPMA monomer (5.04 g, 35 mmol) was introduced into a dry
100 mL Schlenk flask containing 6.0 mL of THF and a
magnetic stir bar. After purging with nitrogen for 30 min, the
AIBN initiator (0.05 g) was added to this flask under nitrogen.
The flask was then immersed in a preheated (60 °C) oil bath.
After approximately 60 min, 1H NMR analysis indicated that
about 40% of the HPMA had been polymerized (the vinyl
signals between δ 5.5 and 6.0 were compared to that of the
CH3 group of the methacrylate backbone at δ 0.5-1.5). The
crude homopolymer was then dissolved in a small amount of
THF and precipitated into a large excess of water to remove
the unreacted monomer. The purified HPMA homopolymer
was dried under vacuum to remove traces of solvent and finally
isolated in 33% yield.
Experimental Procedures
Materials. 2-Hydroxypropyl methacrylate (HPMA, 97%)
was kindly donated by Cognis Performance Chemicals (Hythe,
UK). Benzoyl peroxide (BPO, 97%), bis(2-hydroxyethyl) disul-
fide (technical grade), methacryloyl chloride (97%), dithio-
threitol (DTT; 99%), Cu(I)Br (99.999%), 2,2′-bipyridine (bpy,
99%), and methanol (99%) were purchased from Aldrich and
used as received. The ME-Br initiator was synthesized by
esterification of 4-(2-hydroxyethyl)morpholine (ME) with 2-bro-
moisobutyryl bromide, as described previously.38 Water was
deionized and doubly distilled prior to use. The silica used for
removal of the ATRP copper catalyst was column chromatog-
raphy grade silica gel 60 (0.063-0.200 mm) purchased from
E. Merck (Darmstadt, Germany).
ATRP of 2-Hydroxypropyl Methacrylate in the Pres-
ence of the DSDMA Branching Agent. A typical protocol
for the synthesis of branched HPMA-based copolymers via
methanolic ATRP using the DSDMA branching agent was as
follows. ME-Br (0.1939 g, 0.70 mmol, 1.0 equiv), DSDMA
(0.0903 g, 0.35 mmol, 0.50 equiv), and HPMA (5.04 g, 35 mmol,
50.0 equiv) were codissolved in methanol (6.0 mL). After
purging with nitrogen for 30 min, the Cu(I)Br catalyst (0.1001
g, 0.70 mmol, 1.0 equiv) and the bpy ligand (0.2184 g, 1.4
mmol, 2.0 equiv) were added to this stirred solution under
nitrogen. The reaction mixture immediately became dark
brown and progressively more viscous, indicating the onset of
1
polymerization. After approximately 16 h, H NMR analysis
Synthesis of the Disulfide-Based Dimethacrylate
Branching Agent. Bis(2-hydroxyethyl) disulfide (BHEDS,
7.70 g, 50 mmol, 1.0 equiv) and triethylamine (50 mL, 40
mmol, 8.0 equiv) were dissolved in 150 mL of anhydrous THF.
The flask containing the solution was then immersed in an
indicated that more than 99% of the HPMA had been polym-
erized (disappearance of vinyl signals between δ 5.5 and 6.0).
The reaction solution was diluted with methanol and turned
blue on exposure to air, indicating aerial oxidation of the Cu-
(I) catalyst. The resulting branched HPMA-DSDMA copolymer

Macromolecules, Vol. 38, No. 20, 2005
Branched Vinyl Polymers Prepared via ATRP 8157
was passed through a silica column to remove the spent ATRP
catalyst. The resulting colorless solution was dried under
vacuum to remove the solvent to obtain a white copolymer
(isolated yield ) 85%).
Cleavage of the Disulfide-Containing Branched Poly-
mers by Reduction with Dithiothreitol. In a typical
procedure, the disulfide-containing ME-HPMA50-DSDMA0.95
branched copolymer (0.100 g, 0.0164 mmol of disulfide units)
was dissolved in 6 mL of deoxygenated THF solvent, and
dithiothreitol (DTT; 0.0192 g, 0.125 mmol) was added. The
reaction mixture was stirred under nitrogen at 40 °C. Samples
were periodically withdrawn, diluted with THF at ambient
temperature, and analyzed by THF GPC immediately to
determine the extent of cleavage of the disulfide branch sites
in the copolymer.
Cleavage of the Disulfide-Containing Branched Poly-
mers by Oxidation with Benzoyl Peroxide. In a typical
procedure, the disulfide-containing ME-HPMA50-DSDMA0.95
branched copolymer (0.100 g, 0.0164 mmol of disulfide units)
was dissolved in 6 mL of deoxygenated THF solvent, and
benzoyl peroxide (BPO; 0.121 g, 0.50 mmol) was added. The
reaction mixture was stirred under nitrogen at 60 °C. Samples
were periodically withdrawn, diluted with THF at ambient
temperature, and analyzed by THF GPC immediately to
determine the extent of cleavage of the disulfide branch sites
in the copolymer.
Copolymer Characterization. All 1H NMR spectra were
recorded using a Bruker AC 250 MHz spectrometer. A Polymer
Laboratories PL-GPC50 integrated GPC system was used to
analyze the branched polymers. Linear and branched HPMA-
based polymers were characterized by GPC using THF (con-
taining 2% triethylamine) as an eluent at a flow rate of 1.0
mL min-1 at 30 °C equipped with two 5 µm (30 cm) mixed C
columns, a WellChrom K-2301 refractive index detector oper-
ating at 950 ( 30 nm, a Precision detector PD 2020 light
scattering detector (at scattering angles of 90 and 15 °C), and
a BV400RT viscosity detector. Molecular weights of the
branched copolymers were determined by the triple detection
method using PL Cirrus Multi online software (version 2.0)
supplied by Polymer Laboratories. A series of near-monodis-
perse linear PMMA standards (purchased from Polymer Labs)
was used to construct the calibration curve. The refractive
index increments (dn/dc) of the branched copolymers were
determined in THF using an Optilab differential refractometer
operating at 633 nm. One reviewer has pointed out that it is
possible that our branched copolymers may contain microgel
fractions. All GPC samples were analyzed directly from the
polymerizing solution after ultrafiltration (i.e., silica was not
used to remove the ATRP catalyst from these aliquots). In most
cases, the recovery of the branched copolymer after silica
treatment was fairly efficient. However, significant loss of
copolymer was observed during silica treatment of the ME-
HPMA50-DSDMA0.95 branched copolymer, which may indicate
the presence of a microgel fraction in this particular sample.
Figure 2. GPC traces recorded using (a) the refractive index
detector and (b) the light scattering detector for the series of
branched copolymers obtained by ATRP of HPMA in the
presence of increasing amounts (mol %) of the disulfide-based
dimethacrylate (DSDMA) branching agent. See Table 1 for
detailed polymerization conditions.
Choice of Branching Agent. In their first paper
describing the synthesis of branched vinyl copolymers,
Sherrington and co-workers used ozonolysis at -78 °C
to chemically degrade branched poly(methyl methacry-
late).4 These conditions led to efficient cleavage of the
double bond in the but-2-ene-1,4-diacrylate branching
agent. However, the workup of the ozonolyzed copolymer
was acknowledged to be difficult and time-consuming.
Moreover, it involved a precipitation step in methanol,
which is a marginal solvent for low molecular weight
poly(methyl methacrylate).41 Thus, although discounted
by Sherrington et al., it seems likely that some frac-
tionation most likely occurred during workup: this
would account for the relatively low isolated yields of
copolymer (only 20-50%) and also would explain why
the polydispersity of one of the ozonolyzed copolymers
is lower than the theoretical minimum value of 1.50
expected for materials prepared by conventional free
radical copolymerization. In view of these perceived
difficulties, we decided to explore the use of an alterna-
tive disulfide-based branching agent since it is well-
known that disulfide bonds can be readily and selec-
tively cleaved using various reagents.34-37
Copolymer Characterization. GPC chromato-
grams obtained for the branched HPMA copolymers
using varying levels of the DSDMA branching agent are
shown in Figure 2. GPC curves recorded using the
refractive index detector (Figure 2a) show pronounced
tailing to shorter retention times (higher molecular
weights) with increasing DSDMA, but the main peak
is not significantly shifted from that of the linear HPMA
homopolymer prepared in the absence of any DSDMA.
On the other hand, the light scattering detector (Figure
2b) is significantly more sensitive to the presence of
Results and Discussion
Choice of Monomer. 2-Hydroxypropyl methacrylate
(HPMA) was chosen as the monomer in this study for
several reasons. First, Save et al. had already studied
the kinetics of polymerization of this monomer via ATRP
and shown that very high conversions could be obtained
within a few hours at ambient temperature.32 Second,
poly(2-hydroxypropyl methacrylate) is sufficiently hy-
drophobic to be soluble in THF, which is the preferred
eluent for our triple detection GPC system. Third,
although not a feature of the present study, the second-
ary hydroxyl groups in HPMA polymers can be readily
esterified by reaction with excess succinic anhydride to
produce well-defined polyacids.39 In this context, it is
noteworthy that Sherrington and co-workers recently
reported that branched architectures can lead to very
interesting aqueous solution properties, such as the
suppression of the well-known polyelectrolyte effect.40

8158 Li and Armes
Macromolecules, Vol. 38, No. 20, 2005
Table 1. Summary of the Reaction Conditions for the Methanolic ATRP of HPMA in the Presence of the Disulfide-Based
Dimethacrylate Brancher (DSDMA) at 20 °C
target copolymer structure
(subscripts refer to Dp)
entry no.
DSDMA (mol %)
time (h)
conversion (%)
Mn
Mw
Mw/Mn
R
1
2
3
4
5
6
7
AIBN-initiated PHPMA
HPMA50 homopolymer
HPMA50/DSDMA0.20
HPMA50/DSDMA0.50
HPMA50/DSDMA0.80
HPMA50/DSDMA0.95
HPMA50/DSDMA1.05
0.0
0.0
0.4
1.0
1.6
1.9
2.1
1.0
16.0
16.0
16.0
16.0
16.0
16.0
40
301 000
14 100
19 100
22 600
30 400
67 300
489 700
17 300
27 100
46 400
91 400
540 000
1.63
1.23
1.42
2.05
3.01
8.03
0.80
0.79
0.45
0.29
0.25
0.21
100
>99.9
>99
>99
>99
macrogelation
higher molecular weight chains. With this latter detec-
tor, the GPC peak maxima, and indeed each molecular
weight distribution, are systematically shifted to lower
retention times with increasing levels of DSDMA. The
molecular weight and polydispersity data shown in
Table 1 are those calculated from the light scattering
detector analyses. For a fixed target degree of polym-
erization of 50, the DSDMA content of 1.9 mol % (see
entry 6 of Table 1) corresponds to just less than one
DSDMA brancher per chain. Under these conditions, a
high molecular weight, relatively polydisperse branched
HPMA-DSDMA copolymer is obtained (Mw ) 540 000
and Mw/Mn ) 8.03). According to Sherrington’s hypoth-
esis, these conditions correspond to just below the gel
point.33 This simple approximation appears to be correct
because increasing the DSDMA content to 2.1% causes
macrogelation due to cross-linking (see entry 7 in Table
1). Mark-Houwink R values for this series of branched
copolymers are also summarized in Table 1. These R
values decrease monotonically from 0.80 for the linear
polydisperse HPMA homopolymer (prepared as a refer-
ence material by conventional free radical polymeriza-
tion using an AIBN initiator) to less than 0.30 for
branched copolymers with the highest DSDMA contents.
A very high conversion (typically >99%) was obtained
in each copolymerization, which is due to the facile
nature of the ATRP of HPMA in methanol under these
conditions. Such high conversions are very important
in living polymerizations because the target degree of
polymerization (which is dictated by the monomer/
initiator molar ratio) is only achieved at the end of the
polymerization. This is a fundamentally different situ-
ation to that found for conventional free radical polym-
erization, where high molecular weight chains are
generated even at low conversions. This means that, if
conversions are incomplete, soluble branched copoly-
mers can be obtained from living radical polymerization
formulations that might otherwise be expected to form
chemical gels. Thus, in the event of incomplete polym-
erization, we believe that the precise monomer conver-
sion should be cited as an important caveat for soluble
branched copolymers prepared by living radical polym-
erization. It is noteworthy that other workers have also
expressed this opinion, albeit in the context of insoluble
copolymer gels rather than soluble branched copoly-
mers.36,42
this approach is flawed for branched polymers since
refractive index detection significantly underestimates
Mw and hence Mw/Mn. Moreover, Perrier and co-workers
reported final monomer conversions of around 96%.
Although these values are relatively high, this still
leaves open the possibility that their formulations would
have gelled if they had been allowed to attain their final
target degrees of polymerization. In this context, it is
unfortunate that Perrier et al. chose not to carry out
any control experiments in the absence of any bifunc-
tional comonomer (in their case, ethylene glycol dimeth-
acrylate), so it was not possible to assess the initiator
efficiencies in their syntheses. We also note that these
RAFT syntheses of branched copolymers required rela-
tively long reaction times (40-60 h) and elevated
temperatures (60 °C), even for incomplete monomer
conversions. Nevertheless, we acknowledge that RAFT
polymerization is an important, and perhaps potentially
more attractive, route to soluble branched copolymers
using the Sherrington approach.
It is well-known that branched polymers have more
compact structures in solution as compared to linear
polymers of the same molecular weight since higher
levels of branching lead to smaller hydrodynamic vol-
umes. GPC analysis is only sensitive to changes in
hydrodynamic volume. This means that linear polymer
chains of a given molecular weight cannot be distin-
guished from higher molecular weight branched chains
since in principle these species could elute at the same
retention volume. Figure 3 shows the relationship
between log (molecular weight) and retention volume
for the branched HPMA-DSDMA statistical copolymers
prepared by ATRP. For a given retention volume, each
of the branched copolymers has higher molecular weights
than the polydisperse linear HPMA homopolymer refer-
ence prepared using the AIBN initiator (entry 1 in Table
Recently, Perrier and co-workers reported the syn-
thesis of soluble branched poly(methyl methacrylate)
using RAFT polymerization.12 The Leeds group claimed
that RAFT is superior to ATRP for such vinyl branched
polymer syntheses since significantly lower polydisper-
sities were obtained. This work can be criticized on two
counts. First, it is not possible to make a meaningful
comparison between the GPC data reported by Perrier
and co-workers and that reported by the Sherrington/
Armes groups since the Leeds group only used a
refractive index detector. On the basis of the previous
discussion regarding Figure 2, it is absolutely clear that
Figure 3. Relationship between log (molecular weight) and
retention volume for the branched copolymers obtained by the
ATRP of 2-hydroxypropyl methacrylate in the presence of
increasing levels (mol %) of the DSDMA branching agent.

Macromolecules, Vol. 38, No. 20, 2005
Branched Vinyl Polymers Prepared via ATRP 8159
Table 2. Evolution of the Molecular Weight and
Polydispersity Determined Using the Triple Detection
Method during the Methanolic ATRP Synthesis of the
Branched ME-HPMA50-DSDMA0.50 Statistical Copolymer
at 20 °Ca
time
entry no. (min) conversion (%)
Mn
Mw
Mw/Mn
R
1
2
3
4
5
6
7
8
9
5
10
14
3 500 3 900 1.10
b
23
5 000 6 000 1.19 0.58
7 300 8 800 1.20 0.50
10 800 13 100 1.21 0.44
16 200 21 200 1.31 0.43
21 000 29 700 1.41 0.36
21 300 35 900 1.68 0.35
23 100 43 600 1.89 0.33
24 400 51 700 2.12 0.29
20
31
40
80
140
260
430
1320
55
76
91
97
99
>99.9
a Conditions: 5.04 g of HPMA and 6.0 mL of methanol; ME-
Br/CuBr/Bpy ) 1:1:2; target copolymer structure was ME-HPMA50
/
Figure 4. Mark-Houwink plot and light scattering signal
obtained for the branched ME-HPMA50-DSDMA0.95 copolymer
obtained by ATRP (see entry 6 in Table 1).
DSDMA0.5.
b The molecular weight was too low (and the molecular
weight distribution was too narrow) to allow reliable calculation
of R in this case.
grow at 0.8-2.2 ppm. There is little or no evidence for
any semi-reacted pendent vinyl groups at high conver-
sion (>99%). GPC analyses were also carried out on the
same aliquots that were extracted for the NMR studies,
and these results are summarized in Table 2. The
polydispersities and Mw values remain relatively low up
to 50% conversion, with extensive branching only be-
coming evident in the latter stages. There is a progres-
sive reduction in R with increasing conversion, with a
final R value of 0.29 being attained under these par-
ticular conditions. The evolution of the molecular weight
distribution with reaction time recorded using the
refractive index detector during the synthesis of the
same branched copolymer (entry 4 in Table 1) is shown
in Figure 6. Under these conditions, the whole molecular
weight distribution curve shifted progressively to higher
molecular weight and remained more or less unimodal.
Table 2 summarizes the GPC data obtained for the same
copolymer calculated using the triple detection method.
It is worth emphasizing that the Mw and polydispersity
data change most noticeably in the latter stages of the
polymerization, with significant differences being ob-
served between 97 and 99.9% conversion. This observa-
tion supports our criticism of the RAFT syntheses of
branched copolymers recently reported by Perrier et al.12
Chemical Degradation Using Dithiothreitol. Di-
sulfide bonds can be readily cleaved using a well-known
exchange reaction with dithiol compounds such as
dithiothreitol (DTT)34 or tributylphosphine.36 This pro-
cess is illustrated schematically in Figure 7. In principle,
if all the disulfide bonds are cleaved, the branched
HPMA-DSDMA statistical copolymer will be reduced to
its primary chains (containing, on average, one or fewer
randomly located thiol groups). First, we carried out a
control experiment to confirm that no degradation of
HPMA homopolymer occurs under the conditions used
to cleave the disulfide bonds. Thus, the linear, polydis-
perse HPMA homopolymer prepared using the AIBN
initiator was subjected to an excess of DTT in THF at
elevated temperature. After DTT treatment, this HPMA
homopolymer had an Mn of 307 000, an Mw of 491 000,
and an Mw/Mn of 1.60, which is almost identical to that
obtained for the HPMA precursor (see entry 1 in Table
1). Thus these conditions cause no discernible chemical
degradation of HPMA homopolymer, as expected. In
contrast, DTT treatment of the HPMA50-DSDMA0.95
statistical copolymers leads to substantial chain scission
and a concomitant reduction in both molecular weight
Figure 5. Evolution of 1H NMR spectra recorded during the
synthesis of the ME-HPMA50-DSDMA0.50 branched copolymer
(entry 4 in Table 1) by ATRP in d4-methanol at 20 °C.
Conditions: 5.04 g of HPMA and 6.0 mL of methanol; relative
molar ratios of initiator, catalyst, and ligand (ME-Br/CuBr/
bpy) are 1:1:2.
1). Moreover, the molecular weight increases monotoni-
cally with increasing DSDMA brancher content. These
results strongly suggest a systematic increase in the
degree of branching of these HPMA-DSDMA copolymers
with increasing DSDMA content.
A double log plot of intrinsic viscosity versus molec-
ular weight is shown in Figure 4 for the HPMA-DSDMA
statistical copolymer prepared at the highest level of
DSDMA branching agent that did not cause macroge-
lation (entry 6 in Table 1). The GPC curve obtained for
the same copolymer using the light scattering detector
is also shown. The Mark-Houwink R value calculated
for this copolymer is 0.21, which indicates a heavily
branched architecture and is significantly lower than
the R values of 0.50-0.56 reported by Sherrington and
co-workers.4,5
1H NMR spectroscopy was used (i) to determine
monomer conversions by periodically sampling the
polymerizing solutions and (ii) to assess the presence
(or absence) of semi-reacted DSDMA pendent groups in
1
the final isolated branched copolymers. A series of H
NMR spectra is depicted in Figure 5 for the HPMA50/
DSDMA0.50 branched copolymer (entry 4 in Table 1). The
vinyl signals due to the HPMA monomer at 5.4-6.3 ppm
decrease progressively with time as the polymer signals

8160 Li and Armes
Macromolecules, Vol. 38, No. 20, 2005
Table 3. Progressive Reduction in the Molecular Weight
and Polydispersity Determined Using the Triple
Detection Method for the Branched
ME-HPMA50-DSDMA0.95 Statistical Copolymer on
Treatment with Excess Dithiothreitol in THF at 40 °C
entry no.
time (min)
Mn
Mw
Mw/Mn
R
1
2
3
4
5
6
7
8
0
67 300
63 100
57 200
41 700
24 200
16 500
16 400
14 100
540 000
332 500
196 000
93 000
35 600
21 800
20 800
17 300
8.03
5.27
3.43
2.23
1.47
1.32
1.27
1.23
0.21
0.28
0.34
0.42
0.58
0.72
0.78
0.79
5
10
20
40
140
240
N/A
In contrast, the light scattering GPC data indicate
somewhat different results (see Figure 8b; only selected
curves are shown for clarity). Although the original
molecular weight distribution curve has changed sig-
nificantly, a prominent molecular weight peak remains
after DTT-induced chemical degradation at 40 °C for 4
h. This disparity simply reflects the much greater
sensitivity of the light scattering detector toward higher
molecular weight fractions. Once we recognized that
degradation was incomplete, the same copolymer was
treated for 4 h at 60 °C. At this higher temperature,
the chemical degradation was much more efficient, and
the high molecular weight feature disappeared (see
Figure 8b). The light scattering GPC curve of the
degraded copolymer corresponded closely to that of the
linear HPMA homopolymer prepared in the absence of
the DSDMA branching agent (see Figure 8b and Table
3). Thus, DTT can be used for the efficient cleavage of
the disulfide bonds in the original ME-HPMA50-DS-
DMA0.95 branched copolymer, and the light scattering
GPC detector is preferred for monitoring this degrada-
tion process.
It is perhaps also noteworthy that Mn and Mw data
reported in Table 3 for the linear, near-monodisperse
HPMA homopolymer prepared via ATRP in the absence
of any DSDMA (see entry 8 in Table 3) are significantly
higher than that reported by Save et al. under the same
conditions.32 These apparent differences are primarily
due to the type of GPC detector used. For example, entry
8 in Table 3 was analyzed using the light scattering
detector. Reexamination of this same homopolymer
using the refractive index detector gave an Mn of 9200
and an Mw of 11 500. These latter results are much
closer to those reported by Save et al.,32 who used a
refractive index detector exclusively in their work.
Reanalysis of the chemically degraded HPMA ho-
mopolymer (entry 7 in Table 3) using the refractive
index detector gave very similar data (Mn ) 9100 and
Figure 6. GPC chromatograms using (a) the refractive index
detector and (b) the light scattering detector obtained after
various polymerization times during the methanolic ATRP of
the ME-HPMA50-DSDMA0.50 branched copolymer (entry 4 in
Table 1) at 20 °C. Conditions: 5.04 g of HPMA and 6.0 mL
methanol; relative molar ratios of initiator, catalyst, and ligand
(ME-Br/CuBr/bpy) are 1:1:2.
and polydispersity. This chemical degradation is con-
veniently monitored by GPC: typical data obtained for
the DTT treatment of the ME-HPMA50-DSDMA0.95
statistical copolymer are summarized in Table 3. Peri-
odic sampling of the DTT-treated ME-HPMA50-DS-
DMA0.95 copolymer solution indicated a dramatic re-
duction in the molecular weight (particularly Mw) and
polydispersity, while the R value of the degraded
copolymer increased monotonically up to 0.78 after 4 h
at 40 °C, which is characteristic of a linear, rather than
branched, polymer. According to the refractive index
detector (see Figure 8a), the GPC curve for the final
degraded copolymer has an almost identical appearance
to that of a linear HPMA homopolymer (target degree
of polymerization ) 50) prepared via ATRP in the
absence of any DSDMA. This suggests that the original
ME-HPMA50-DSDMA0.95 statistical copolymer has been
degraded to its constituent primary chains (i.e., that
every disulfide bond has been cleaved).
Figure 7. Schematic representation of the reduction of branched poly(2-hydroxypropyl methacrylate) using dithiothreitol (DTT).
Cleavage of all the disulfide bonds in the DSDMA branching comonomer generates linear, thiol-functionalized primary chains of
poly(2-hydroxypropyl methacrylate).

Macromolecules, Vol. 38, No. 20, 2005
Branched Vinyl Polymers Prepared via ATRP 8161
Figure 8. GPC traces recorded after various reaction times
using (a) the refractive index detector and (b) the light
scattering detector during the reductive degradation of the
ME-HPMA50-DSDMA0.95 branched copolymer (entry 6 in Table
1) with DTT. Conditions: 0.10 g of branched ME-HPMA50-
DSDMA0.95 statistical copolymer (1 disulfide equiv) and 0.0192
g of DTT (7.6 dithiol equiv) in 6 mL of THF at 40 °C (all
refractive index curves) and either 40 or 60 °C (light scattering
curves; see label on curve). The GPC curve obtained for linear,
near-monodisperse poly(2-hydroxypropyl methacrylate) pre-
pared via ATRP with a target degree of polymerization of 50
is included as a reference.
Figure 9. GPC traces recorded after various reaction times
using (a) the refractive index detector and (b) the light
scattering detector during the oxidative degradation of the ME-
HPMA50-DSDMA0.95 branched copolymer (entry 6 in Table 1)
using benzyl peroxide at 60 °C. Conditions: 0.1 g (1 disulfide
equiv) of branched ME-HPMA50-DSDMA0.95 copolymer and
0.121 g (30.5 peroxide equiv) of benzoyl peroxide in 6 mL of
THF. Only selected light scattering curves are shown for
clarity. The GPC curve obtained for linear, near-monodisperse
poly(2-hydroxypropyl methacrylate) prepared via ATRP with
a target degree of polymerization of 50 is included as a
reference.
Mw ) 11 700), thus providing further evidence that the
original branched copolymer had been efficiently con-
verted into its primary chains, as intended. Moreover,
since chemical degradation yields the primary chains
almost exclusively, the chain transfer to polymer must
be negligible during the ATRP synthesis of these
branched copolymers. One of the reviewers of this
manuscript has suggested that termination by coupling
should be expected in the final stages of the ATRP
copolymerization (i.e., under monomer-starved condi-
tions). The effect of this side reaction would be to double
the Mw, but of course this cannot be readily distin-
guished from the random branching processes that are
occurring. Moreover, there is no evidence for significant
coupling during the linear homopolymerization of HPMA
carried out under the same ATRP conditions.
disulfides is complex: a range of functional groups,
including sulfoxides and sulfonic acids, can be generated
depending on the precise conditions.45 Thus we explored
the use of benzoyl peroxide to cleave the disulfide bonds
in the DSDMA branch sites. Our THF GPC results
obtained using this reagent at 60 °C under a nitrogen
atmosphere are summarized in Table 4 and Figure 9
(only selected curves are shown for clarity). Under these
conditions, complete chemical degradation is also readily
achieved within 160 min, as evidenced by the light
scattering GPC curves shown in Figure 9.
In principle, it should be possible to reconstitute the
original branched ME-HPMA50-DSDMA0.95 copolymer
from the degraded primary chains by reacting the
pendent thiol groups with a disulfide compound such
as bis(2-hydroxyethyl) disulfide. This possibility will be
explored in future work. However, such reconstruction
will most likely not be possible if benzoyl peroxide is
Chemical Degradation Using Benzoyl Peroxide.
DTT is a relatively expensive reagent. However, it is
well-documented that alkyl disulfides can also be ef-
ficiently cleaved under oxidative conditions using re-
agents such as peroxides, hydroperoxides, or peroxyac-
ids.43,44 According to Allen and Book, the oxidation of

8162 Li and Armes
Macromolecules, Vol. 38, No. 20, 2005
Table 4. Progressive Reduction in the Molecular Weight
and Polydispersity Determined Using the Triple
Detection Method for the Branched
ME-HPMA50-DSDMA0.95 Statistical Copolymer on
Treatment with Excess Benzoyl Peroxide in THF at 60 °C
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entry no.
time (min)
Mn
Mw
Mw/Mn
R
1
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0
67 300
61 100
41 200
31 600
14 200
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branching agent has been used to gain considerable
insight into the nature of branched vinyl polymers
obtained using the Sherrington route via methanolic
ATRP of 2-hydroxypropyl methacrylate under mild
conditions. The disulfide bonds can be efficiently cleaved
either under reducing conditions using dithiothreitol or
under oxidizing conditions using benzoyl peroxide. In
both cases, GPC analyses confirm that fully degraded
poly(2-hydroxypropyl methacrylate) has almost the
same molecular weight distribution as a linear poly(2-
hydroxypropyl methacrylate) sample synthesized by
ATRP under the same conditions in the absence of any
disulfide-based dimethacrylate branching agent. Thus,
the primary chains of these branched copolymers are
well-defined and have Mn and Mw values predicted for
a well-controlled ATRP synthesis. Moreover, incorpora-
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agent is clearly the sole reason for the high molecular
weights and degrees of branching observed for these
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Acknowledgment. EPSRC is thanked for a Plat-
form grant to support YTL (GR/S25845). The University
of Sheffield is thanked for start-up funds to purchase
the triple detector GPC equipment. S.P.A. is the recipi-
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award. We thank the reviewers of this manuscript for
their helpful and constructive comments.
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1
Supporting Information Available: Assigned H NMR
spectrum of the disulfide-based dimethacrylate (DSDMA)
branching agent. This material is available free of charge at
the Internet at http://pubs.acs.org.
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MA051121S