Combining atom transfer radical polymerization and disulfide/thiol redox chemistry: A route to well-defined (bio)degradable polymeric materials

Article abstract of DOI:10.1021/ma050020r

Linear well-defined degradable polymethacrylates with internal disulfide link were prepared by atom transfer radical polymerization (ATRP) of methyl, terf-butyl, and benzyl methacrylate using bis[2-(2-bromoisobutyryloxy)ethyl] disulfide as the initiator and CuBr/2,2'-bipyridine as the catalyst at 50°C. The disulfide bond was cleaved to thiol by reduction with tributylphosphine, yielding polymers of half the molecular weight of the starting materials. Degradable gels were prepared by the copolymerization of methyl methacrylate and a disulfide-containing difunctional methacrylate, bis(2-methacryloyloxyethyl) disulfide, using similar reaction conditions. The produced gels were reduced with tributylphosphine to form soluble, low molecular weight linear polydnethyl methacrylate) fragments containing thiol groups at the chain end and along the backbone, originating from the disulfide difunctional initiator and monomer, respectively. The disulfide-cross-linked gels were further used as "supennacroinitiators" for the bulk ATRP of styrene at 90°C, employing CuBr/N,N,N'N'',N''-pentamethyldiethylenetriamine as the catalyst. The length of the polystyrene pendant chains could be controlled by varying the reaction time. The prepared gels with segmented structure swelled more than the starting polymethacrylate gels in both THF and toluene. Degradation experiments confirmed the high degree of chain-end bromine functionalization of the "supermacroinitiators".

Full text of DOI:10.1021/ma050020r

Macromolecules 2005, 38, 3087-3092
3087
Combining Atom Transfer Radical Polymerization and Disulfide/Thiol
Redox Chemistry: A Route to Well-Defined (Bio)degradable Polymeric
Materials
Nicolay V. Tsarevsky and Krzysztof Matyjaszewski*
Department of Chemistry, Carnegie Mellon University, 4400 Fifth Avenue,
Pittsburgh, Pennsylvania 15213
Received January 5, 2005; Revised Manuscript Received February 24, 2005
ABSTRACT: Linear well-defined degradable polymethacrylates with internal disulfide link were prepared
by atom transfer radical polymerization (ATRP) of methyl, tert-butyl, and benzyl methacrylate using
bis[2-(2-bromoisobutyryloxy)ethyl] disulfide as the initiator and CuBr/2,2′-bipyridine as the catalyst at
5
0 °C. The disulfide bond was cleaved to thiol by reduction with tributylphosphine, yielding polymers of
half the molecular weight of the starting materials. Degradable gels were prepared by the copolymerization
of methyl methacrylate and a disulfide-containing difunctional methacrylate, bis(2-methacryloyloxyethyl)
disulfide, using similar reaction conditions. The produced gels were reduced with tributylphosphine to
form soluble, low molecular weight linear poly(methyl methacrylate) fragments containing thiol groups
at the chain end and along the backbone, originating from the disulfide difunctional initiator and monomer,
respectively. The disulfide-cross-linked gels were further used as “supermacroinitiators” for the bulk ATRP
of styrene at 90 °C, employing CuBr/N,N,N′,N′′,N′′-pentamethyldiethylenetriamine as the catalyst. The
length of the polystyrene pendant chains could be controlled by varying the reaction time. The prepared
gels with segmented structure swelled more than the starting polymethacrylate gels in both THF and
toluene. Degradation experiments confirmed the high degree of chain-end bromine functionalization of
the “supermacroinitiators”.
Introduction
ization have only become accessible with the develop-
ment of the various methods for controlled/“living”
radical polymerization (CRP) that rely upon an equi-
The development of “green” methods is an ongoing
effort in chemistry, materials science, and industry. The
term “green” implies the use of environmentally friendly
6-10
librium between active (radicals) and dormant species.
The past decade has witnessed the flourishing of several
methods of CRP, among which atom transfer radical
(
nontoxic and reusable) reagents and solvents in the
processes, or the development of active catalysts, and
11-14
polymerization (ATRP),
reversible addition-frag-
1
technologies consuming less energy. In polymer syn-
15,16
mentation chain transfer (RAFT),
nitroxide-medi-
thesis, the preparation of recyclable and (bio)degradable
materials is particularly important for prevention of
environmental pollution. Such polymeric materials
17,18
ated polymerization,
and degenerative transfer with
19
alkyl iodides are the most widely applicable. This is
due to the simple experimental setup, the use of
inexpensive or easy to prepare and purify reagents, in
addition to the typical for the radical polymerization
tolerance toward functional groups, solvents and impu-
rities. ATRP has been successfully used to prepare a
wide variety of well-defined polymeric materials includ-
2
contain, as part of their backbones, weak chemical links
which can be easily cleaved chemically or photochemi-
cally at ambient conditions. The produced lower molec-
ular weight polymeric fragments can be further de-
graded by microorganisms. Degradable polymers are
also of significant interest in soil treatment, tissue
engineering, and (drug) delivery, which has further
2
0
21
ing functional polymers, gradient, and segmented
copolymers22 as well as hybrid materials. This CRP
technique was recently employed to synthesize well-
defined degradable polymers by the incorporation of
hydrolytically, photochemically,24 or electrochemically
labile chemical bonds in the polymer backbone.
23
3
-5
stimulated the research in the field.
Cleavable links
such as ester, amide, polysulfide, etc., can be generated
in the backbone during the polymerization, which is
typical for polymers prepared by polycondensation
processes. Radical polymerization, which has wide ap-
plication in industry, can also be used to synthesize
degradable polymers. The incorporation of the cleavable
functional group can be achieved by the use of functional
initiators or monomers. However, because of fast ir-
reversible chain-breaking reactions, such as radical
coupling or disproportionation and/or transfer, conven-
tional radical polymerization is not suitable for the
preparation of well-defined structures.
25
The disulfide group is an example of (bio)degradable
group, which can be cleaved in the presence of reducing
2
6,27
28,29
agents,
nucleophiles, electrophiles,
or photo-
chemically.3
0,31
Since the redox potential of the disulfide
(
R-S-S-R′)/thiol couple depends on the nature of the
substituents R and R′ and the reaction medium com-
position (solvent polarity, pH, presence of complex-
forming ions, etc.),2
7,32
a polymeric disulfide can be
designed in such a way that the reductive scission of
the sulfur-sulfur bridge will occur at sufficient rate only
in a given environment. Copious amount of work has
been published on the disulfide/thiol interchange2
due to its relevance to various phenomena occurring in
living cells including protein structure stabilization,35
Materials produced by radical polymerization with
controlled molecular weight, narrow molecular weight
distribution, and high degree of chain-end functional-
7,33,34
*
Corresponding author. E-mail: km3b@andrew.cmu.edu.
1
0.1021/ma050020r CCC: $30.25 © 2005 American Chemical Society
Published on Web 03/24/2005

3088 Tsarevsky and Matyjaszewski
Macromolecules, Vol. 38, No. 8, 2005
enzyme catalytic activity, and redox cycles.27,36,37 Of
special interest is the fact that tumors are often hypoxic,
and polymeric materials that degrade in reductive
environment can be envisioned to degrade therein,
releasing a preliminarily incorporated drug, which
provides an opportunity for cancer tissue-selective
viscous oil (86% yield) was analyzed by NMR (acetone-d
ppm): 4.46 (t, 2H, CH OOC), 3.09 (t, 2H, CH S), and 1.94 (s,
H, (CH C). 2-3% of unreacted hydroxy groups were present
in the product. 1 mL of the oil weighs approximately 1.48 g.
Prior to polymerization experiments, this initiator was deoxy-
genated by bubbling with nitrogen for 2-3 h.
6
; δ,
2
2
6
3 2
)
3
8
2 2
b. Synthesis of Disulfide Monomer (MAOE) S . The
therapy.
diester was prepared from the corresponding diol, BHEDS, and
methacryloyl chloride in the presence of pyridine since the
Disulfide groups can be introduced in a polymer using
an appropriate initiator or monomer. A disulfide-based
ATRP initiator densely attached or patterned to a gold
surface was used to graft several methacrylate mono-
mers from the surface in controlled fashion.39 The
preparation of degradable well-defined polystyrene by
ATRP was recently reported in which the disulfide/thiol
reversible interconversion was utilized to obtain lower-
48
previously reported procedure; namely, the reaction of 2-chlo-
roethyl methacrylate with sodium disulfide is more laborious,
and the overall monomer yield is low. In a 500 mL round-
bottomed flask, cooled in ice-water bath, 29 mL (0.3 mol) of
methacryloyl chloride was dissolved in 200 mL of methylene
chloride dried over sodium sulfate. 0.06 g of hydroquinone was
added, followed by 24.3 mL of pyridine, dried over sodium
sulfate. A heterogeneous mixture was thus obtained, to which,
upon stirring, 15.4 g (0.1 mol) of BHEDS was added over a
period of 10 min. The mixture was stirred in the cooling bath
for another 30 min and then at room temperature for 17 h.
The methylene chloride solution was extracted with three 150
mL portions of water, twice with 150 mL of 10% solution of
sodium carbonate in water, and again with 3 portions of water.
The solution was then dried over sodium sulfate, and the
solvent was evaporated. 13.62 g of crude product was thus
obtained. To remove the excess of methacrylic acid, the product
was dissolved in 200 mL of ether, and the solution was passed
through a column filled with basic alumina, covered with a
25
or higher-molecular-weight polymers. Poly(2-hydroxy-
ethyl methacrylate) containing 2-pyridyl disulfide end
group was synthesized by ATRP and was used to modify
4
0
proteins having free thiol groups. Because of its
attractiveness, the reversible reductive degradation of
polymeric materials containing one or more disulfide
groups has been studied and exploited, although by no
means extensively. Some examples of materials include
4
1-43
disulfide-cross-linked cellulose (modified cotton),
polyoxazolines,44 and linear polymers with one or more
2
5,45
di- or polysulfide links.
1
-2 cm layer of sodium carbonate. The absorbent was washed
Herein, we report the ATRP of methyl, tert-butyl, and
benzyl methacrylate (MMA, tBuMA, and BnMA, re-
spectively) using bis[2-(2-bromoisobutyryloxy)ethyl] di-
sulfide ((BiBOE)2S2) as a difunctional initiator contain-
ing the cleavable disulfide link. Degradable gels with
disulfide bridge cross-links were synthesized as well
using the same initiator and a mixture of MMA and
disulfide-containing dimethacrylate (bis(2-methacryloyl-
oxyethyl) disulfide (MAOE)2S2). The modification of the
gels by chain-extension reactions with styrene (Sty), i.e.,
their use as ATRP “supermacroinitiators”, is also de-
scribed. Finally, the reversible redox cleavage of the
internal disulfide bond of the synthesized polymeric
materials is demonstrated.
with 30-40 mL of ether, and the solvent was removed from
the combined solution. 11.0 g (38%) of product was thus
obtained as a yellowish oil. The NMR spectrum in acetone-d
6
consists of the following signals: 6.09 ppm (d, 1H, dCH), 5.65
ppm (d, 1H, dCH), 4.42 ppm (t, 2H, CH OOC), 3.08 ppm (t,
2H, CH S), and 1.92 ppm (s, 3H, CH Cd). On the basis of NMR
2
2
3
and IR spectral analysis, the product thus obtained contained
no unreacted methacrylic acid or alcohol.
c. Preparation of Degradable Linear Polymethacryl-
ates by ATRP. MMA (5 mL, 0.0467 mol) was mixed with 3
2
mL of acetone and 0.2 mL of Ph O (internal standard for GC).
The mixture was degassed by six freeze-pump-thaw cycles,
and the flask was filled with nitrogen. CuBr (0.0666 g, 0.464
mmol) and bpy (0.1449 g, 0.929 mmol) were then added to the
frozen mixture, and the flask was closed, evacuated, and
backfilled with nitrogen. This vacuum-nitrogen cycle was
repeated twice, and the mixture was warmed to let it thaw.
The reaction flask was heated to 50 °C, and the deoxygenated
Experimental Section
Materials. Prior to use, the neat monomer (MMA, tBuMA,
BnMA, or Sty) was passed through a column filled with basic
alumina in order to remove the polymerization inhibitor. CuBr
2 2
initiator, (BiBOE) S (99 µL, 0.32 mmol, 1/145 vs monomer),
was injected. Samples were taken out periodically to check the
conversion and molecular weights. The same conditions were
used for the polymerization of tBuMA and BnMA.
(
98%, Aldrich) was purified by a modified literature proce-
46
dure: washing with glacial acetic acid followed by 2-propanol.
The conventional radical initiator V-70 (Wako) was recrystal-
lized from methanol. All other reagents (bis(2-hydroxyethyl)
disulfide (BHEDS; 98%, TCI), dicyclohexylcarbodiimide (DCC),
d. Preparation of Degradable Gels with Disulfide
Groups. MMA (5 mL, 0.0467 mol) and the disulfide-containing
2 2
dimethacrylate (MAOE) S (0.15 mL, 0.57 mmol) were dis-
4
-(N,N-dimethylamino)pyridine (4-DMAP), 2-bromoisobutyric
acid, methacryloyl chloride, 2,2′-bipyridine (bpy), tributylphos-
phine (Bu P)) and the solvents were used as received.
N,N,N′,N′′,N′′-Pentamethyldiethylenetriamine (PMDETA)
solved in 2 mL of acetone, and the mixture was degassed as
described above. The catalyst consisted of 0.0334 g (0.233
mmol) of CuBr and 0.0727 g (0.4667 mmol) of bpy. The reaction
mixture was heated to 50 °C, and 50 µL (0.164 mmol, 1/285
vs MMA) of deoxygenated (BiBOE) S was added. Gel was
3
4
7
was deoxygenated prior to the experiments by nitrogen bub-
bling for 2-3 h.
2
2
formed after ca. 250 min (ca. 80% monomer conversion,
determined by gravimetry). The obtained gel was washed
repeatedly with acetone (4-5 times with 500 mL portions,
keeping the gel in the solvent for ca. 12 h) to remove any free
polymer. In another experiment, the amount of the initiator
Synthetic Procedures. a. Synthesis of Disulfide Initia-
2 2
tor (BiBOE) S . 20.09 g (0.13 mol) of BHEDS was dissolved
in 350 mL of THF. A solution of 43.4 g (0.26 mol) of
-bromoisobutyric acid in 50 mL of THF was added, and the
2
solution was cooled in an ice-water bath. A solution of 53.65
g (0.26 mol) of DCC in 50 mL of THF was added upon stirring
followed by a solution of 3.2 g of 4-DMAP in 50 mL of THF.
The reaction mixture was kept in the ice-water bath for 5
min and then for 18 h at room temperature. The precipitated
dicyclohexylcarbamide was filtered off and washed with 50 mL
of THF on the filter. The solvent was evaporated, and the
formed suspension was kept in refrigerator for several hours
and then at room temperature for 3 days. The impurities
crystallized and were removed by filtration. The obtained
2 2
(BiBOE) S was increased 3-fold (to 0.491 mmol, i.e., 1/95 vs
MMA), while keeping the amounts of the other reagents
constant, to check the influence of the monomer-to-initiator
ratio on the kinetics of the polymerization. Gelation was
observed in ca. 150 min (93% monomer conversion). In a
control experiment, a mixture of 5 mL (0.0467 mol) of MMA
2 2
and 0.15 mL (0.57 mmol) of (MAOE) S in 2 mL of acetone
was copolymerized at 50 °C (after deoxygenation) using 0.04
g (0.12 mmol) of V-70. Gelation occurred after 43-45 min at
47% monomer conversion.

Macromolecules, Vol. 38, No. 8, 2005
(Bio)degradable Polymeric Materials 3089
Figure 1. Synthesis and reductive degradation of polymethacrylates with internal disulfide link (R ) methyl, tert-butyl, or
benzyl).
e. Chain Extension of the Disulfide-Containing PolyM-
MA-Based “Supermacroinitiator” Gel with Sty. 0.3 g of
the dried gel described above was mixed with 8 mL (0.070 mol)
of Sty, and the mixture was kept in a refrigerator overnight
and then at room temperature for 2 h to allow for sufficient
gel swelling. The mixture was degassed as described above,
and 0.0286 g (0.20 mmol) of CuBr was added, followed by
injection of 42 µL (0.20 mmol) of deoxygenated PMDETA. The
reaction was carried out for 2.5 h at 90 °C. The product was
washed repeatedly with THF to remove any free polymer. To
obtain a gel with higher molecular weight of the pendant
polySty chains, the reaction time was increased to 5 h.
f. Reductive Degradation of the Disulfide-Containing
Linear Polymers and Gels. 0.04 g of the linear polymer was
dissolved in 1 mL of 50 mM solution of LiBr in DMF (same
solution as the eluent for SEC) containing 0.05 mL of Ph
2
O
(
SEC standard), and 0.05 mL of Bu P was added. The
3
degradation was complete within several minutes. The gels
were degraded in similar fashion: 0.04 g of the gel was kept
in 6 mL of THF containing 0.10 mL of Ph
2
O for 1 h to let it
swell, and 0.10 mL of Bu P was added. The degradation
3
accompanied by complete dissolution took several hours to
days depending on the cross-link density.
Analyses. NMR spectra were recorded on a Bruker instru-
ment operating at 300 MHz. Monomer conversions were
determined on a Shimadzu GC-14A gas chromatograph
equipped with a flame ionization detector and a capillary
column (30 m × 0.53 mm × 1.0 µm CEC-Wax column, Chrom
Expert Co.) using diphenyl ether as the standard or by
gravimetry. Molecular weight distributions were determined
5
3
by SEC using a series of Styrogel columns (10 Å, 10 Å, 100
Å, PSS) and THF (30 °C) or DMF containing 50 mM LiBr (50
°
C) as the eluent and polyMMA calibration using diphenyl
Figure 2. Kinetics (a) and molecular weight evolution (b) for
ether as internal standard. The swelling ratios of gels were
determined by immersing the gels in a solvent (THF or
toluene) and keeping them in closed vials at room temperature
for 3-4 days. The swollen material was taken out, quickly
dried with filter paper, and weighed. Then, it was dried at 60-
the ATRP of MMA, tBuMA, and BnMA in acetone (5:3 by
2 2
volume) initiated by (BiBOE) S at 50 °C using CuBr/bpy as
2 2
the catalyst. [Monomer]/[(BiBOE) S ]/[CuBr]/[bpy] ) 145:1:1.5:
3.
6
5 °C under vacuum to constant weight and weighed again.
The swelling is expressed as the mass of solvent absorbed by
g of dry gel.
initiator concentration differed in the three studied
systems, causing unequal polymerization rates. The
ratio of polymerization rate to the sum of concentrations
of catalyst and initiator was the highest for BnMA. This
was most likely due to the highest value of the propaga-
tion rate constant of this monomer (kp(BnMA, 50 °C) )
1
Results and Discussion
Synthesis of Disulfide-Containing Linear Poly-
methacrylates. The preparation of degradable linear
polySty with one or more disulfide groups by ATRP and
its reversible redox cleavage/coupling was recently
described. The Sty ATRP was carried out in bulk at 90
-
1
-1
1
224-1510 L mol
s
, while kp(MMA, 50 °C) ) 648 L
-
1
-1 49
mol
s ). In all three cases, the molecular weights
increased with conversion in a linear fashion, and the
polydispersities remained relatively low (Mw/Mn < 1.4),
indicating the controlled/“living” nature of the poly-
merization.
°
C and was initiated by the 2-bromopropionate ester of
2
5
BHEDS and catalyzed by CuBr/PMDETA.
For the ATRP of methacrylates, a 2-bromoisobutyrate
initiator was used (Figure 1). The kinetics and the
evolution of the molecular weight distributions with
conversion for the solution ATRP of three methacryl-
ates, MMA, tBuMA, and BnMA, initiated by (BiBOE)2S2
are shown in Figure 2. The first-order kinetic plots were
practically linear, indicating a constant radical concen-
tration throughout the polymerization. The volume of
the reaction mixture and the targeted degree of poly-
merization at complete monomer conversion were kept
constant, but due to the different molecular weights and
densities of the three monomers, the catalyst and
Reductive Cleavage of the Disulfide-Containing
Linear Polymers. The produced polymers contained
a disulfide link in the middle of the chain, which could
be cleaved either reversibly (by reduction to thiol that
can be reoxidized to disulfide) or irreversibly (i.e., by
oxidation with performic acid to the corresponding
50
sulfonic acid ). Numerous methods for the chemical
reduction of disulfides to thiols are known and used in
biochemistry, mostly to cleave the cystine disulfide
bridge in polypeptides and proteins.26 Since the redox
potential of the thiol/disulfide couple depends on the

3090 Tsarevsky and Matyjaszewski
Macromolecules, Vol. 38, No. 8, 2005
3
Figure 3. Reductive degradation of disulfide-containing (a) polyMMA, (b) polytBuMA, and (c) polyBnMA with Bu P in DMF at
room temperature for 1 h. The SEC traces of the starting and the cleaved polymer are shown with solid and dashed lines,
respectively.
Figure 4. Preparation of degradable polyMMA-based gels by ATRP and their use as “supermacroinitiators”. The disulfide and
thiol groups originating from the functional initiator are shown in italics and the ones from the functional monomer in regular
font. PolyMMA and polySty chains are represented with solid and dotted lines, respectively.
polarity and composition of the reaction medium, the
decomposition rate of the polymers can be controlled by
changes in the medium. In addition, the nature and
polarity of the polymeric backbone should also influence
the degradation rate.27,32 In our previous work, the
disulfide bond in polystyrene prepared by ATRP was
cleaved to mercapto groups using dithiothreitol (DTT)
in THF or DMF under a nitrogen atmosphere to avoid
air oxidation of both the polymeric thiol and DTT. The
reaction in DMF was faster and more efficient than in
THF but was still relatively slow: 50 h at 60 °C was
required to fully reduce the disulfide bonds in the
Preparation of Degradable Polymethacrylate
Gels and Their Use as “Supermacroinitiators” for
Further Chain Extension. The ATRP of a mixture of
MMA and a difunctional monomer containing a disulfide
bond, (MAOE)2S2 (1.2 molar % vs MMA), initiated by
the disulfide initiator (BiBOE)2S2, yielded degradable
gels (see the left-hand side of Figure 4). Both the
initiator and the difunctional monomer served as sources
of degradable disulfide groups in the gels.
25
Several kinetic samples were withdrawn from the
reaction mixture during the synthesis, and conversion
was determined by gravimetry. The gravimetric samples
were then extracted with THF for 24 h, the solutions
were filtered through a 0.2 µm PTFE membrane filter,
and the molecular weights of the soluble polymer
fractions were determined by SEC. The results from two
experiments using different amounts of ATRP initiator
(i.e., different numbers of propagating chains) are
presented in Figure 5. With the higher [MMA]/[(Bi-
BOE)2S2] ratio (100/0.35 ) 285; experiment MMA285-
gel) the reaction was slower, and complete gelation
occurred at ca. 80% monomer conversion. When this
ratio was decreased 3-fold (to 100/1.05 ) 95), as ex-
pected, the polymerization rate increased (higher initia-
tor concentration), and the reaction mixture gelled at
around 93% monomer conversion. The differences in the
behavior of the two studied systems are due to the
different average numbers of difunctional monomer
units per chain, which is determined by the ratio of
[(MAOE)2S2] to [(BiBOE)2S2]. In experiment MMA285-
gel, the average number of difunctional monomer per
chain was 3.5, and therefore the gel point was reached
earlier than in experiment MMA95-gel, in which only
about 1.2 (on average) cross-linking units were incor-
porated in each propagating chain. In the latter case,
the formation of chains with more than one dimethacryl-
ate units made the gelation possible. In conventional
radical polymerization, the incorporation of the difunc-
51
polymer. Phosphines such as triphenylphosphine and
52
especially Bu3P in the presence of water (or moisture)
reduce the disulfide group significantly more efficiently.
Bu3P transforms disulfides to thiols very rapidly and
has been widely used in the study of proteins.53 Its
major advantages (as opposed to DTT) are relative
stability toward autooxidation and high affinity to
disulfide groups, meaning that large excess of this
reagent is not needed for complete reduction.26 More-
over, Bu3P does not interfere with reagents typically
used to bind to the formed thiol groups, which is
especially important in protein analysis. It can be used,
5
4
for instance, in conjunction with 1,3-propane sultone
or ω-toluene sultone,55 which trap very effectively the
formed thiol groups by alkylation, thus preventing back-
oxidation to disulfide after exposure to air.
In the current study, Bu3P was used to cleave the
disulfide-containing polymethacrylates converting them
to thiol-terminated polymers of lower molecular weight.
The reduction (Figures 1 and 3) was carried out at room
temperature in DMF or THF under ambient atmosphere
and was complete in several minutes. The number-
averaged molecular weight of the products of degrada-
tion was approximately twice lower than the starting
materials, since the labile disulfide link was in the
middle of the polymer chains.

Macromolecules, Vol. 38, No. 8, 2005
(Bio)degradable Polymeric Materials 3091
Table 1. Properties of Degradable Gels: PolyMMA “Supermacroinitiators” and the Products of Their Chain Extension
with Stya
c
swelling in
b
Mw/Mnb
degradable gel
chain extension reaction time, h
Mn, kg/mol
THF
toluene
MMA285-gel
“supermacroinitiator”
14.9
66.4
119.3
10.0
45.0
1.60
1.38
1.70
1.52
1.30
9.6
23.4
24
16.5
30.3
5.7
22.3
23.4
13.1
28.4
MMA285-Sty1-gel
MMA285-Sty2-gel
MMA95-gel
2.5
5
“supermacroinitiator”
2.5
MMA95-Sty1-gel
a
Conditions for the chain extension: [Sty]:[CuBr]:[PMDETA] ) 350:1:1, disulfide-cross-linked gels as macroinitiators (0.3 g/8 mL of
b
Sty), 90 °C, bulk. SEC analysis of the products of reductive degradation with Bu3P in THF for 25 h. No changes were observed if the
reduction was carried out for an additional 40 h. Expressed as grams of solvent absorbed by a gram of dry gel.
c
Figure 6. SEC traces of the products of degradation of
Figure 5. Kinetics of formation of polyMMA-based disulfide-
cross-linked gels by ATRP and evolution of molecular weights
of the soluble polymer fraction extracted from the gels with
MMA285-gel and two gels prepared from this “supermacro-
initiator” by chain extension with Sty. The notation and
reaction conditions are explained in Table 1.
2 2 2 2
reaction time. Conditions: [MMA]/[(MAOE) S ]/[(BiBOE) S ]/
[
CuBr]/[bpy] ) 100:1.22:0.35:0.5:1 (experiment MMA285-gel)
infra). Chain extension reaction of polyMMA-based gels
was performed using Sty as the second monomer and
CuBr/PMDETA as the catalyst at 90 °C. The “super-
macroinitiator” had been repeatedly washed prior to the
experiment to remove any free polyMMA chains that
could also initiate the polymerization of Sty. Two
different polyMMA gels were studied, namely, the final
products from the reactions presented in Figure 5
or 100:1.22:1.05:0.5:1 (MMA95-gel), 50 °C in acetone (2:5 by
volume vs monomer).
tional monomer is far less uniform, and gel point is
reached at markedly lower conversion than in ATRP.
For instance, a polymerization mixture of MMA with
1
.2 mol % of (MAOE)2S2, containing V-70 as radical
initiator (used at a concentration close to the concentra-
tion of ATRP initiator in experiment MMA285-gel, with
the same amounts of monomers and solvent and at the
same temperature), gelled already at 47% monomer
conversion. Similar differences were previously observed
in the gelation of mixtures of Sty and 4,4′-divinylbiphen-
yl using nitroxide-mediated and conventional radical
(
MMA285-gel and MMA95-gel). Schematically, the block
formation and the degradation of the gels are sketched
in Figure 4. The physical properties such as swellability
of the gels with “blocky” structure differed significantly
from those of the parent “supermacroinitiators”. Table
1
lists the swelling ratios of the two polyMMA-
homopolymer degradable gels and the gels derived
therefrom by chain extension in both THF and toluene.
Demonstration of the Degree of Functionaliza-
tion of PolyMMA-Based Gels by Reductive Deg-
radation of Gels with Segmented Structure Pre-
pared Therefrom. The polyMMA-based gels were
successfully degraded in THF using Bu3P as the disul-
fide reducing agent, forming linear soluble polyMMA
chains containing at least one thiol end group originat-
ing from the disulfide initiator and potentially one or
more attached to the backbone originating from the
disulfide-containing cross-linker (MAOE)2S2 (Figure 4).
The soluble polymers formed by the reduction were
analyzed by SEC. After the chain extension, the gel with
pendant polymeric chains was washed repeatedly with
THF to remove any free polySty, generated by thermal
initiation, and degraded using Bu3P. The formed block
copolymer was analyzed by SEC. The results from the
chain extension experiments are summarized in Table
1. The molecular weights of the products of reductive
degradation of the gels, given in Table 1, demonstrate
the efficient initiation from the polyMMA-based “su-
5
6
polymerization.
The molecular weights of the soluble polymer frac-
tions increased with the reaction time due to both the
living nature of the polymerization and the formation
of branched structures via the incorporation of the
dimethacrylate monomer in the backbone. The latter
process was also reflected in the broad molecular weight
distribution of the extractable soluble fraction (Mw/Mn
≈
1.5-4.9). The final products from the two reactions
were isolated, thoroughly washed with acetone, and
used for further experiments.
ATRP has an important advantage for the prepara-
tion of degradable gels compared to conventional radical
polymerization: the bromine atoms are preserved in the
product, and therefore the gel can be functionalized by
attachment of various functional groups or more com-
plex molecules such as dyes, drugs, etc. A simple way
to demonstrate the high chain-end functionality of the
gels prepared by ATRP is to use them as “supermacro-
initiators” in ATRP chain extension reactions with other
monomers followed by analysis of the products (vide

3092 Tsarevsky and Matyjaszewski
Macromolecules, Vol. 38, No. 8, 2005
permacroinitiators”. This is further verified from the
symmetrical shift observed in the SEC traces of the
soluble linear polymers formed after the reduction of
the gels (Figure 6).
Figure 6 shows that no significant amount of ho-
mopolymer of MMA was observed in the products of
degradation of the gels with segmented structures,
indicating the high degree of functionalization of the gel
prepared by ATRP.
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and benzyl methacrylate, catalyzed by CuBr/2,2′-bipy-
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(
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(
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Acknowledgment. The authors are grateful to the
members of the ATRP/CRP consortia at Carnegie Mel-
lon University, NSF (Grant DMR 0090409), and EPA
(
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(
Grant R82958001) for funding. N.V.T. acknowledges
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financial support from the Harrison Legacy Dissertation
Fellowship (Carnegie Mellon University).
(
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