Molecular weight and functional end group control by RAFT polymerization of a bisubstituted acrylamide derivative

Article abstract of DOI:10.1021/ma025646l

Controlled radical polymerization of the bisubstituted acrylamide derivative N-acryloyl-morpholine (NAM) has the potential to yield telechelic polymers, one end of which can subsequently be grafted to latex particles. Once grafted, the other chain end of the polymer can be used as an immobilization site for species with applications in molecular biology and biomedicine. The controlled polymerization of NAM using reversible addition-fragmentation chain transfer (RAFT) is performed using two new chain transfer agents S = C(Z)-SR bearing the same functional propanoic acid group (R) and two different Z groups, benzyl (CTA 1) and phenyl (CTA 2). RAFT polymerization of NAM mediated by CTA 1 is very fast (>80% conversion in less than half an hour at 65 °C). The linear evolution of M_n and the low polydispersity indices (M_w/M_n < 1.2) are in accord with the expected characteristics of a living polymerization. CTA 2 leads to broader M_w/M_n's (< 1.4). The resulting CTA-capped polymers were further used to yield an amphiphilic polyNAM-block-polystyrene. These α,ω-functionalized polyNAM chains were characterized by ¹H NMR and MALDI-ToF mass spectrometry.

Full text of DOI:10.1021/ma025646l

Macromolecules 2003, 36, 621-629
621
Molecular Weight and Functional End Group Control by RAFT
Polymerization of a Bisubstituted Acrylamide Derivative
F r a n ck D’Agosto,† Rober t Hu gh es, Ma r ie-Th e´ r e` se Ch a r r eyr e,
,§
†
‡
‡
,†
Ch r istia n P ich ot, a n d Rober t G. Gilber t*
Key Centre for Polymer Colloids-Chemistry School F11, University of Sydney NSW 2006, Australia,
and Unit e´ Mixte CNRS-bioM e´ rieux, EÄ cole Normale Sup e´ rieure de Lyon, 46 all e´ e d’Italie,
6
9364 Lyon Cedex 07, France
Received September 5, 2002; Revised Manuscript Received November 17, 2002
ABSTRACT: Controlled radical polymerization of the bisubstituted acrylamide derivative N-acryloyl-
morpholine (NAM) has the potential to yield telechelic polymers, one end of which can subsequently be
grafted to latex particles. Once grafted, the other chain end of the polymer can be used as an immobilization
site for species with applications in molecular biology and biomedicine. The controlled polymerization of
NAM using reversible addition-fragmentation chain transfer (RAFT) is performed using two new chain
transfer agents SdC(Z)-SR bearing the same functional propanoic acid group (R) and two different Z
groups, benzyl (CTA 1) and phenyl (CTA 2). RAFT polymerization of NAM mediated by CTA 1 is very
fast (>80% conversion in less than half an hour at 65 °C). The linear evolution of Mh
polydispersity indices ( Mh / Mh < 1.2) are in accord with the expected characteristics of a living
polymerization. CTA 2 leads to broader Mh
n
and the low
w
n
w
/ Mh ’s (<1.4). The resulting CTA-capped polymers were further
n
used to yield an amphiphilic polyNAM-block-polystyrene. These R,ω-functionalized polyNAM chains were
1
characterized by H NMR and MALDI-ToF mass spectrometry.
In tr od u ction
Sch em e 1
N-Acryloylmorpholine (NAM) is a bisubstituted acryl-
amide derivative (Scheme 1) whose corresponding poly-
1
,2
mer can be used in molecular biology and biomedicine.
The polymer has a number of useful properties,
3
-6
including solubility in water and other polar and low-
polarity solvents. N-Acryloylmorpholine has been used
1
,2,7-11
•
for many years in biological applications
and in
eliminating R , which is able to reinitiate the poly-
merization. The polymerization is controlled by the
transfer of the CTAs between dormant and active
chains. Molecular weight control can be adjusted by the
relative amount of reagents involved in the polymeri-
zation; the end-functionality of the resulting chains is
controlled by the nature of the substituents Z and R on
the CTA. Earlier work on RAFT-mediated polymer-
ization of NAM has been performed using four differ-
ent CTAs: tert-butyldithiobenzoate, carboxymethyl-
dithiobenzoate, (1-(4-methylcyclohexan-2-onyl)-1-meth-
yl)ethyldithiobenzoate, and 1,3-bis(2-(thiobenzoylthio)-
prop-2-yl)benzene; in each case, except for carboxy-
methyldithiobenzoate, this showed that the RAFT tech-
nique can produce well-controlled NAM polymer chains.22
However, the R groups introduced at the chain ends
were not always functional.
photocurable products such as inks.12 Previous work by
some of the present authors studied the conventional
free-radical homopolymerization13 of NAM and its co-
1
4
polymerization with an activated-ester monomer.
The present paper shows that controlled radical
polymerization can be used for this process, thereby
opening up a range of potential biomedical applications
for the resulting polymers. For example, one could
synthesize R,ω-functionalized polymer chains, one end
of which can subsequently react with appropriate
functional groups introduced at the surface of the
1
5
latex. The other chain end could be used for the
immobilization of single-stranded DNA fragment probes.
The other chain end could also be functionalized by a
sugar, which would lead to polymers with application
in carbohydrate-protein recognition.1
6-18
Controlled radical polymerization using reversible
The reactive function introduced on the CTA must be
compatible with the RAFT dithioester function. The
present paper uses a carboxylic acid group as the
reactive function on the CTA; it fulfills the compatibility
requirement and can easily be activated into a highly
1
9-21
addition-fragmentation chain transfer (RAFT)
is
applicable to a wide range of monomers and can be
performed in a wide variety of solvents under a broad
range of conditions. In this process, a dithioester chain
transfer agent (CTA), SdC(Z)-SR, reacts with either
the primary radical derived from an initiator or a
23
reactive ester. Hitherto, only a few CTAs bearing a
carboxylic acid group as a R group have been used in
RAFT polymerizations,
•
propagating polymer chain (P ), forming a new CTA and
24-27
and in all cases the R
leaving group was a primary radical which is not very
favorable for an efficient fragmentation.
In the present paper, we investigate the syntheses of
two new CTAs (Scheme 2) bearing the same functional
R group, namely a propanoic acid group, which gives
rise to secondary reinitiating radicals. We introduce two
†
University of Sydney.
ENS Lyon.
Present address: LCPP CPE/CNRS, B aˆ t 308 F, 43 Blvd du
‡
§
1
1 Novembre 1918, BP 2077, 69616 Villeurbanne Cedex, France.
Corresponding author: e-mail gilbert@chem.usyd.edu.au, phone
61-2-9351 3366.
*
+
1
0.1021/ma025646l CCC: $25.00 © 2003 American Chemical Society
Published on Web 01/08/2003

6
22 D’Agosto et al.
Macromolecules, Vol. 36, No. 3, 2003
Sch em e 2
232.66. νmax: 3384-2411, 1708, 1289, 1211, 1132, 1074, 986,
-
1
8
55, 698 cm .
Syn th esis of 2-[[2-P h en yl-1-th ioxo]th io]pr opan oic Acid
CTA 2). Bromobenzene (2.68 mL, 4 g, 25 mmol) in dry
(
tetrahydrofuran (10 mL) was added dropwise to magnesium
turnings (607 mg, 25 mmol) in tetrahydrofuran (20 mL) with
stirring under nitrogen. After the magnesium had finished
reacting the solution was cooled to 0 °C and carbon disulfide
(2.2 mL, 2.855 g, 37.5 mmol) was added. After 1 h, 2-bromo-
propanoic acid (2.249 mL, 3.824 g, 25 mmol) was added and
the mixture left for 48 h. The mixture was then acidified with
2
M hydrochloric acid (40 mL) and extracted with ethyl acetate
(
2 × 100 mL). The combined organic extracts were dried with
magnesium sulfate and evaporated to dryness. The excess
bromopropanoic acid was removed by kugerol distillation at
1
20 °C and 0.5 Torr. Purification by silica chromatography
different Z groups, a phenyl and a benzyl group, since
previous studies28 have reported a dependence of retar-
gave two fractions, the first eluting with 15% ethyl acetate/
light petroleum and the second eluting with 60% ethyl acetate/
light petroleum gave the desired compound (1.57 g, 30%) as
red crystals (mp 55 °C). H NMR (CDCl
d, J 7.39 Hz, 3H, CH
dation on the nature of the Z group. Their use in the
RAFT polymerization of NAM is then evaluated by
performing kinetic measurements and following the
evolutions of molecular weight distribution and poly-
dispersities as a function of conversion. The living
character of the process is further investigated by
polymerizing styrene in the presence of polyNAM used
as “macroCTA”, which should lead to the formation of
polyNAM-block-polystyrene. Polymers in all cases are
1
3
, 200 MHz): δ 1.72,
3
; 4.90, q, J 7.41 Hz, 1H, CH; 7.39, t, J
7
.73 Hz, 2H, Ar-H3′; 7.52, q, J 7.14 Hz, 1H, Ar-H4′; 8.00, d,
13
J 7.25 Hz, 2H, Ar-H2′; 10.2-10.4, br s, 1H, COOH. C NMR
(50 MHz): δ 16.30, 48.14, 126.94, 128.39, 132.78, 144.06,
177.13, 225.40. νmax: 3270-2463, 1698, 1284, 1211, 1038, 876,
-
1
755, 677 cm
.
The excess 2-bromopropanoic acid could not be removed
from the resulting CTAs by chromatographic methods and thus
was removed by distillation under reduced pressure. Recrys-
tallizing the CTAs so obtained did not result in the complete
removal of impurities. However, H and C NMR character-
izations showed the purity of both CTAs to be higher than 97%.
1
analyzed by H NMR and MALDI-ToF mass spectrom-
etry.
1
13
Exp er im en ta l Section
N-Acryloylmorpholine (NAM, 99% from Polysciences, Inc.)
and styrene (99% from Aldrich) were purified by distillation
under reduced pressure. Azobis(isobutyronitrile) (AIBN, 98%
from Merck) as initiator was purified by recrystallization in
ethanol. Dioxane (99.8% from Aldrich) was distilled over
P olym er iza tion P r oced u r e a n d Kin etics. Polymeriza-
tions were performed in a round-bottom flask capped with a
septum. The reaction vessel was loaded with dioxane, mono-
mer (∼2 M), trioxane (molar ratio NAM/trioxane ) 6:1), CTA,
and AIBN in a 10:1 CTA:AIBN molar ratio. As described by
d’Agosto et al.,13 trioxane was used as an internal reference
for the determination of the conversion using NMR, by
comparison with the vinyl protons of NAM, since trioxane gives
a clean peak at 5.1 ppm. For accuracy, the area of this peak
should be about the same as that of a NAM vinylic proton. As
there are six protons in trioxane, the molar ratio of NAM/
trioxane was chosen as 6:1. The mixture was purged with
nitrogen for 15 min at 20 °C. The temperature was then raised
to 65 or 85 °C using a thermostated oil bath. Polymerizations
were carried out under a nitrogen atmosphere. The experi-
mental conditions used in the different experiments are listed
in Table 1.
4
LiAlH under reduced pressure. Tetrahydrofuran (99.8% from
Lab-Scan) was distilled over sodium metal under nitrogen.
Bromobenzene (95%, Ajax Chemicals) was distilled over
calcium hydride. Carbon disulfide (Merck, 99.5%) was distilled
over calcium hydride under nitrogen. Benzylmagnesium bro-
mide (1 M in ether from Aldrich) was used as obtained.
2
-Bromopropanoic acid (Merck, 98%) was distilled under
reduced pressure before use.
The syntheses of both CTA 1 and CTA 2 were performed
using methods analogous to those described by Rizzardo et
2
9,30
al.
Syn th esis of 2-[[2-P h en yl-1-th ioxoeth yl]th io]p r op a n -
Samples were withdrawn from the polymerization mixture
at different reaction times and introduced into vials containing
hydroquinone (inhibitor), placed in ice to stop polymerization,
then stored at -20 °C. Monomer consumption was followed
oic Acid (CTA 1). Carbon disulfide (4 mL, 66 mmol) and dry
tetrahydrofuran (40 mL) were cooled in an ice bath under
nitrogen. 1 M Benzylmagnesium bromide in ether (40 mL, 40
mmol) was added slowly with stirring. After 30 min, 2-bromo-
propanoic acid (3.6 mL, 6.18 g, 40 mmol) was added slowly.
After 48 h, the mixture was poured into ethyl acetate (200 mL)
and washed with water (3 × 100 mL) and saturated sodium
chloride (100 mL). The organic extract was dried with mag-
nesium sulfate and then evaporated under reduced pressure
to dryness. The excess bromopropanoic acid was removed by
kugerol distillation at 120 °C and 0.5 Torr. The residue was
then dissolved in ether (200 mL) and extracted with a 50:50
mixture of saturated sodium hydrogencarbonate/water (4 ×
1
1
by H NMR analysis of each sample. H NMR analysis was
performed without evaporation of the polymerization solvent
3
by mixing 0.2 mL of each sample with CDCl (1:3 v/v).
Monomer conversion was determined by comparison of the
vinyl protons of NAM with the protons of trioxane as reference
(Figure 1).
P olym er Ch a r a cter iza tion . Molecular weights and mo-
lecular weight distribution were determined by size-exclusion
chromatography with THF as eluent (flow rate ) 1 mL/min)
at 25 °C using three Styragel columns (HR2, HR3, and HR4
5
0 mL). The combined aqueous extracts were washed with
2
3
4
ether (100 mL) and acidified carefully to pH < 1 with 2 M
hydrochloric acid. The solution was extracted with ethyl
acetate (2 × 100 mL), and the combined organic extracts were
washed with water (2 × 50 mL), saturated sodium chloride
with pore sizes 10 , 10 , and 10 Å, respectively) and a
refractometric detector (Shimadzu RID 10A), using polystyrene
standards for calibration. The theoretical number-average
molecular weight was obtained using
(50 mL), and then dried with magnesium sulfate. Evaporation
of the solvent gave the title compound (3.73 g, 39%) as a red
liquid which slowly solidified on standing (mp 36 °C). H NMR
[
NAM]
1
Mh (theor) ) M
+
CTA
MNAMxNAM
(1)
n
[
CTA]
(
CDCl
3
, 200 MHz): δ 1.54, d, J 7.40 Hz, 3H, CH
3
; 4.28, s, 2H,
CH ; 4.59, q, J 7.40 Hz, 1H, CH; 7.22-7.34, m, 5H, Ar-H;
1
1
2
1
3
0.8-11.0, br s, 1H, COOH. C NMR (CDCl
6.05, 47.65, 57.31, 127.35, 128.56, 129.05, 136.28, 177.16,
3
, 50 MHz): δ
where MCTA and MNAM are the molecular weights of RAFT
agent and NAM and xNAM is the fraction conversion. The

Macromolecules, Vol. 36, No. 3, 2003
RAFT Polymerization of an Acrylamide Derivative 623
Ta ble 1. Exp er im en ta l Con d ition s
run
CTA
CTA 1
CTA 2
CTA 1
“macroCTA 1”
CTA 1
“macroCTA 1”
[CTA]/mM
[monomer]/M
[styrene]/M
dioxane/mL
temperature/°C
A
B
C
D
E
F
10.7
11.4
5.3
7.8
14.7
6.6
2
2
2
1.25
5
5
7.5
2.5
5
65
85
65
65
85
85
a
2.7
2
a
2.5
a
4
Obtained by RAFT CTA1 mediated polymerization of NAM, theoretical Mh n ) 2.17 × 10 , Mh w/ Mh n ) 1.2, [CTA]/[AIBN] ) 10.
F igu r e 1. 1H NMR spectrum of the reaction mixture during polymerization A (300 MHz, CDCl
).
3
contribution of the molecular weight of the chains initiated
by AIBN was neglected because of the high CTA:AIBN ratio
used here.
1
For analyses by H NMR spectrometry (Bruker Avance 300,
3
3
00 MHz, CDCl or DMSO as deuterated solvents), polymers
were precipitated out with diethyl ether, recovered by filtra-
tion, washed several times with the same solvent, and finally
dried under vacuum until constant weight was attained.
MALDI-ToF mass spectrometry of the polymers was per-
formed with sodium R-cyano-4-hydroxycinnamate as matrix.
The ratio of polymer to matrix was 1:100. Spectra were
recorded with a Micromass TOFSPEC E spectrometer, equipped
with a 337 nm N
reflectron mode.
2
laser and 20 kV acceleration voltage, in
Resu lts a n d Discu ssion
P r elim in a r y Com p a r ison of CTA 1 a n d CTA 2.
NAM was first polymerized in dioxane using CTA 1
F igu r e 2. Conversion as a function of time for polymerization
of NAM with CTA 1 (65 °C) for runs A (10.7 mM RAFT) and
C (5.3 mM RAFT); see Table 1.
(
6
10.7 mM) and AIBN as initiator. The temperature was
5 °C, and a NAM:CTA 1 ratio was chosen such that
Mh n(theor) after complete conversion should be 2.65 ×
4
1
0 (entry A, Table 1). Samples were withdrawn from
rapid: ∼80% conversion is reached within half an hour.
The conversion dependences of Mh n values (which are
relative to polystyrene standards and hence “apparent”
Mh n) and of polydispersity (obtained by DRI-SEC analy-
sis of the untreated samples) are given in Figure 3.
Within experimental uncertainty, the apparent Mh n
values are linear with conversion, consistent with
polymerization proceeding in a controlled fashion. Now,
the apparent Mh n values are not in agreement with those
the polymerization mixture at different times. Each
1
sample was analyzed by H NMR to determine conver-
sion. The time dependence of conversion is given in
Figure 2 (for later reference, this also shows data for
5
.3 mM CTA); note that the data in Figure 2 at low
conversions (e5%) are subject to the highest uncer-
tainty, inherent in the measurement technique. The
polymerization of NAM under these conditions is

6
24 D’Agosto et al.
Macromolecules, Vol. 36, No. 3, 2003
F igu r e 3. Points: experimental Mh
functions of conversion for polymerization of NAM with CTA
(theor); full line,
. Molecular weights are relative to
n
and polydispersity as
F igu r e 6. Points: experimental Mh
n
and polydispersity as
functions of conversion for polymerization of NAM with CTA
1
at 65 °C (run A, Table 1). Broken line: Mh
n
best fit to experimental Mh
n
1
at 65 °C (run C, Table 1). Full line, best fit to experimental
. Molecular weights are relative to styrene standards.
styrene standards.
Mh
n
F igu r e 4. Conversion as a function of time for polymerization
of NAM with 10.2 mM CTA 2 (85 °C) for run B (Table 1).
F igu r e 7. SEC chromatograms (GPC distributions as a
function of elution time) for a starting CTA-capped polyNAM
(
“macroCTA 1”) and for the species resulting after second-stage
polymerization of this with NAM.
F igu r e 5. Points: experimental Mh
functions of conversion for polymerization of NAM with 11.4
(theor); full line, best fit
. Molecular weights are relative to styrene
n
and polydispersity as
mM CTA 2 at 85 °C. Broken line: Mh
n
to experimental Mh
n
standards.
n
F igu r e 8. Points: experimental Mh and polydispersity as
functions of conversion for polymerization of NAM with CTA
expected from eq 1; this may be an artifact arising from
the use of polystyrene standards to obtain these appar-
ent Mh n values. The polydispersity, which never exceeds
1
n
at 85 °C (run E, Table 1). Broken line: Mh (theor).
dithiobenzoate (Z ) phenyl, R ) cumyl) to cumyl
phenyldithioacetate (Z ) benzyl, R ) cumyl). Fukuda
1
.2, may increase slightly with conversion. However,
this is not a firm conclusion, because Mh n is rather
32
and co-workers have suggested that retardation, in the
sensitive to baseline subtractions, etc.; a number of
case of a styrene/dithiobenzoate system, could be ad-
ditionally explained by the formation of stars arising
from reversible or irreversible termination reactions of
the intermediate radicals. Although molecular weight
control in the present CTA 2 system seems adequate,
as suggested by the almost linear increase of Mh n with
conversion, polydispersities (Mw/Mn e 1.4) are higher
than those observed with CTA 1. Again, Mh n values
calculated on the basis of a polystyrene calibration are
not in agreement with the theoretical values.
It is interesting to compare the experimental Mn
values from SEC measurements obtained for CTA 1 and
CTA 2. These should be the same for a given conversion
regardless of the calibration; however, those for CTA 2
are consistently ∼20% higher than for CTA 1. This
result may arise from different amounts and types of
impurities in the CTAs (see above remarks) or from the
degradation of CTA 2 at the reaction temperature (85
workers1
9,26,31
have previously reported an increasing
Mh w/ Mh n for several monomers such as N-isopropylacryl-
amide and other acrylamide-based monomers.
NAM was polymerized in the presence of CTA 2 under
the same conditions as for CTA 1, such that Mh n(theor)
4
after complete conversion should be 2.49 × 10 (entry
B, Table 1). Polymerization with CTA 2 was much
slower than with CTA 1: at 65 °C, only a few percent
conversion was reached after 5 h. At 85 °C, 80%
conversion was obtained after just over 2 h, as shown
in Figure 4; Mh n and polydispersities are shown in Figure
5
1
. The observed difference between the behaviors of CTA
and CTA 2 could be related to the nature of their Z
group, benzyl and phenyl respectively, as suggested by
Barner-Kowollik et al.,28 who reported a significant
decrease in “macroCTA” radical lifetimes in the RAFT
polymerization of styrene when going from cumyl

Macromolecules, Vol. 36, No. 3, 2003
RAFT Polymerization of an Acrylamide Derivative 625
F igu r e 9. 1H NMR analysis of the block polymer from run F, recovered after precipitating twice from methanol (300 MHz,
CDCl ).
3
Ta ble 2. Solu bilities of P olym er s in Differ en t Solven ts
methanol
ether
water
“
macroCTA 1” (polyNAM capped with CTA 1)
soluble
insoluble
insoluble
insoluble
swollen
insoluble
soluble
insoluble
insoluble
polyNAM-block-polystyrene capped with CTA 1
polystyrene
4
°
C for several hours instead of 65 °C for less than an
1” ( Mh n ) 2.17 × 10 ; Mh w/ Mh n ) 1.2), obtained by RAFT
polymerization of NAM mediated by CTA 1. This
homopolymer second growth was undertaken because
its molecular weight analysis avoids difficulties that can
arise in the determination of the molecular weight
distribution of a block copolymer, discussed later. The
polymerization was performed at 65 °C, and the ratio
NAM/“macroCTA 1” was such as the expected chain
hour for CTA 1). The amount of actual CTA 2 available
for polymerization would then be overestimated, and
consequently Mh n(theor) will be higher (eq 1). The high
Mh w/ Mh n values can be explained in the same way.
Deta iled Stu d y of CTA 1. As the RAFT polymeri-
zation with CTA 1 exhibited several advantages over
that with CTA 2 (lower polydispersity, higher poly-
merization rate), this system was investigated further.
With lower [CTA] (run C, Table 1; Figure 2), the rate is
extension should approximately double the original Mh n
4
(
i.e., Mh n(theo, extension) ) 2.27 × 10 ). After 3 h, the
conversion was 89%. The polymer was recovered by
precipitation in diethyl ether. Comparison of SEC
chromatograms of the starting polyNAM and the second-
growth polymer shows that the extension was successful
(Figure 7). However, a small amount of residual low
molecular weight dead chains remains in the final
product. Also, a small shoulder appears at high molec-
ular weight, probably corresponding to bimolecular
termination by combination.
faster and closer to that of the corresponding system in
the absence of CTA.13 In a pure RAFT process, the
polymerization rate should be independent of the CTA
concentration, but retardation may occur and originate
from different factors such as a too low fragmentation
rate or a too slow reinitiation.33 Polydispersities are
much larger with lower [CTA] (Figure 6). No meaningful
comparison can be made between the observed and
theoretical Mh n because of the lack of absolute molecular
weights. (Because of possible mass bias in ablation,
MALDI-ToF cannot be used reliably to find Mh n in these
systems with relatively high molecular weights and
moderate polydispersity.)
P olyNAM Used a s a “Ma cr oCTA”. An important
criterion of true living character is the successful
extension of chains or the synthesis of a block copolymer
using preformed polymer chains as a “macroCTA”;
linear increase of the molecular weight should
ensue. To investigate this point, we first performed
the polymerization of NAM mediated by a polyNAM
Gr ow in g a Block Cop olym er . As mentioned in the
Introduction, as a part of a program to synthesize latex
particles with “hair” (i.e., grafted layer) of controlled
chain length and functionality, obtaining block copoly-
mers of NAM and styrene is of importance, e.g., when
considering their use as surfactants in emulsion poly-
merization. On the basis of the previous result, the
synthesis of a block copolymer was investigated by
polymerizing styrene in the presence of the same
“macroCTA 1”. One requirement for forming a narrow
polydispersity AB block copolymer is that the first-
formed polymeric CTA should have a high transfer
“macroCTA” (run D, Table 1), referred to as “macroCTA

6
26 D’Agosto et al.
Macromolecules, Vol. 36, No. 3, 2003
low (Figure 8), consistent with controlled polymeriza-
tion. The fast polymerization rate observed for CTA 1
mediated polymerization of NAM is consistent with
supposing a higher apparent propagation rate coefficient
of acrylamide derivatives (e.g., the propagation rate
coefficient for N-isopropylacrylamide in water at 65 °C
3
5
4
-1 -1
is ∼8 × 10 M
s ) combined with a lower termina-
tion rate coefficient for NAM arising from steric hin-
drance provided by the bulky morpholine group.13
The polymerization of styrene using “macroCTA 1”
to form polyNAM-block-polystyrene was then under-
taken (run F, Table 1), with the ratio styrene/
“
macroCTA 1” chosen so that Mh n(theor) of the poly-
4
styrene block was 3.1 × 10 after 100% conversion.
F igu r e 10. SEC chromatograms of the parent “macroCTA 1”
and of the block copolymer obtained after polymerization with
styrene (run F, Table 1).
Conversion leveled off at 40% after 10 h.
Solubilities in various solvents of this supposedly
block copolymer and of the parent “macroCTA 1” are
given in Table 2. The final polymer was recovered by
precipitation in methanol. Whereas “macroCTA 1” is
precipitated out in diethyl ether, the supposedly block
copolymer was only swollen by the same solvent. On the
other hand, it precipitated out in methanol wherein
“macroCTA 1” is soluble. These solubility results are
consistent with the formation of a block copolymer.
constant in the subsequent polymerization step to give
the B block. This requires that the leaving-group ability
of propagating radical A is comparable to or greater
than that of the propagating radical of B. We could have
chosen to form the polystyrene block first; however, with
a view to introducing our R group at the end of the
hydrophilic part, we decided to start with a polyNAM
1
“macroCTA 1”.
Figure 9 shows the H NMR spectrum of the suppos-
Prior to the synthesis of this block copolymer, the
polymerization of styrene mediated by CTA 1 was
investigated (run E, Table 1). As is expected that styrene
would be slower to polymerize than NAM (styrene
having a low propagation rate coefficient ), a temper-
ature of 85 °C was chosen to avoid long polymerization
times (noting however that the half-life of AIBN is ∼15
min at this temperature). After polymerization for 10
h, 35% conversion was obtained, and conversion leveled
off at this value. Experimental Mh n values agreed very
well with the theoretical ones and polydispersities were
edly block copolymer, purified by two successive pre-
cipitations in methanol. One sees the presence of peaks
corresponding to polystyrene and polyNAM. Integration
under the appropriate peaks (in which the contributions
of residual solvents, dioxane at 3.7 ppm and methanol
at 3.4 ppm, and of CDCl3, are neglected) gives a
composition of 44% styrene and 56% NAM. This is in
agreement with the theoretical composition, 47% sty-
rene and 53% NAM, calculated at the conversion where
polymerization was stopped. Taking into account these
compositions and the molecular weight of “macroCTA
3
4
F igu r e 11. 1H NMR spectrum (256 scans) of polyNAM synthesized in the presence of CTA 1 (300 MHz, DMSO).

Macromolecules, Vol. 36, No. 3, 2003
RAFT Polymerization of an Acrylamide Derivative 627
F igu r e 12. MALDI-ToF mass spectrum (reflectron mode) of polyNAM over the range 1200-4000 Da and enlargement of the
+
region from 1500 to 1710 Da. Matrix: R-cyano-4-hydroxycinnamate; cationization agent: Na .
4
1
”, a Mh n(exp) of 1.25 × 10 for the polystyrene block was
Ch a r a ct er iza t ion of t h e P olym er Ch a in -E n d
F u n ction a liza tion . The RAFT process was chosen to
produce polyNAM chains of controlled chain length and
end functionality. Given the structure of CTA 1 and the
living behavior evidenced above, each polyNAM chain
should be R- and ω-functionalized by a propanoic acid
group and a phenyldithioacetate group, respectively.
This last part of this study aims at characterizing the
presence of these two end groups using two independent
techniques: NMR and MALDI-ToF mass spectrometry.
obtained ( Mh n(theor) at this conversion being calcu-
4
lated to be 1.24 × 10 ). SEC analysis of the starting
“
1
macroCTA 1” and the block copolymer given in Figure
0 shows a shift of the distribution toward higher
molecular weights. However, termination reactions
seem to occur more readily, as evidenced by the shape
of the chromatogram and the larger polydispersity
(
1.60). More detailed information as to the microstruc-
ture of the formed polymer (e.g., the presence of any
residual polyNAM homopolymer) would require more
sophisticated techniques such as two-dimensional poly-
mer chromatography.36
1
The H NMR spectrum of polyNAM obtained using
CTA 1 is presented in Figure 11. A comparison of this
spectrum with that of CTA 1 (not shown) enabled the

6
28 D’Agosto et al.
Macromolecules, Vol. 36, No. 3, 2003
Sch em e 3
trometer after fragmentation of the -CH2-S- bond
under the laser beam can abstract a hydrogen from the
matrix and give rise to P4. In this case, no unsaturated
chains would be produced, and the only population
present is P4. However,because of the intensity and the
resolution of the peaks under consideration, it is difficult
to discriminate between the two possible phenomena.
Note that the proportion of population P4 corresponding
to dead chains tends to be higher at low molecular
weight (see starred peaks in Figure 12). In addition, we
were unable to assign P2 and P3, for which there are
many possibilities. The MALDI-ToF spectrum did not
show significant peaks corresponding to chains initiated
by a radical coming from the initiator, which suggests
an efficient functionalization.
different protons of the Z group (protons 1-5 at 7.4 ppm
and proton 6 at 4.9 ppm) and the -CH of the R group
proton 7 at 4.4 ppm) to be assigned, as shown in Figure
1. Peaks corresponding to the vinylic protons between
.6 and 6.9 ppm are evidence for the presence of a very
(
1
5
small amount of residual monomer. The carboxylic
function provided by the R group is visible (proton 8
around 12.5 ppm) but broadened by the unavoidable
presence of water in DMSO, while the peak of the
methyl group (proton 9), at around 1.6 ppm in CTA 1,
is probably shifted downfield in the polymer and may
correspond to the very small peaks around 1.1 ppm.
This NMR technique could in principle be used to
determine the absolute molecular weight of the chains,
by comparing the integrals of peaks for the chain-end
protons to those of the main-chain protons. However,
this cannot be realized in the present system because
of the overlap of peaks from the deuterated solvent and
water with those of the main polymer chain. To over-
Con clu sion s
Two new RAFT chain transfer agents bearing the
same functional propanoic acid group R and two differ-
ent Z groups were synthesized: a benzyl (CTA 1) and a
phenyl group (CTA 2). The kinetics of RAFT polymer-
ization of NAM mediated by CTA 1 were fast and
showed good molecular weight control, but those with
CTA 2 were much slower and gave poorer control of
molecular weight.
The living character of the process mediated by CTA
1 was confirmed by polymerizing both NAM and styrene
in the presence of polyNAM, previously synthesized
using CTA 1, used as a macro chain transfer agent.
Second-stage polymerization with the parent NAM
monomer gave the desired chain extension. The polymer
synthesized by second-stage polymerization with sty-
rene showed all the characteristics of a polyNAM-block-
1
come this drawback, H NMR analysis of the same
polymer was carried out in D2O, and comparison of
integrations of the benzylic chain-end protons and of the
CH of the main chain gave Mh n ) 26 500, in good
-
agreement with the theoretical value of 21 700.
MALDI ToF Ma ss Sp ectr om etr y An a lyses. Char-
acterization of the chain structure of a short-chain
polyNAM was performed by MALDI-ToF mass spec-
1
polystyrene amphiphilic block copolymer. H NMR and
MALDI-ToF mass spectrometry analyses of the R,ω-
functionalized polyNAM chains were consistent with the
conventionally accepted mechanism for RAFT poly-
merization.
The techniques developed here have application in the
synthesis of functionalized latex particles.
trometry; three other RAFT MALDI spectra have also
appeared in the literature.3
1,37,38
The spectrum (reflec-
tron mode) is given in Figure 12.
The molecular weight difference between two con-
secutive peaks in the MALDI-ToF mass spectrum is
41.2, which corresponds to a single NAM monomer
1
unit. The degree of polymerization (DP) for each peak
is found by taking into account the Z and R groups of
the CTA 1 and the attached Na . This analysis confirms
that each polyNAM chain is R- and ω-functionalized by
a propanoic acid R group and a phenyldithioacetate Z
group, respectively.
Ack n ow led gm en t. We gratefully acknowledge the
support of the Australian Research Council’s Research
Infrastructure Equipment and Facilities Scheme, Dulux
Australia, bioM e´ rieux S.A France, the ARC Strategic
Partnerships with Industry-Research and Training
Scheme (R.H.), and the International Research and
Development and Technology Access Activities compo-
nent of the Innovation Access Program of AusIndustry.
We also thank J elica Strauch and Dr. Christopher
Ferguson (Key Centre for Polymer Colloids, University
of Sydney) for the SEC analyses, Dr. Christopher
Barner-Kowollik (Centre for Advanced Macromolecular
Design, University of New South Wales, Australia), and
Dr. Keith Fisher (School of Chemistry, University of
Sydney) for MALDI-ToF mass spectrometry analyses.
The Key Centre for Polymer Colloids is established and
supported under the Australian Research Council’s
Research Centres Program.
+
Figure 12 also shows an enlarged part of the spec-
trum, corresponding to the chain population centered
on 1533.6 (DP ) 9). The main population, P0, is that
expected from the widely accepted mechanistic scheme
for RAFT polymerization. Thus, the peak at 1533.6
corresponds to a DP ) 9, with the Z and R groups from
+
CTA 1 and an Na . Four populations of low intensity,
denoted P1, P2, P3, and P4, are present and centered
respectively on 1549.4, 1587.5, 1625.7, and 1649.7. P1
can readily be assigned to a side cationization by K+
often observed in MALDI. Population P4 is consistent
with the structure displayed in Scheme 3. These chains,
with DP ) 11, may be formed from termination reac-
tions. Two possible explanations for the formation of
these chains are events (i) in the polymerization me-
dium or (ii) in the spectrometer. In the polymerization
medium, the macroradical can undergo termination by
disproportionation, giving rise to an ω-unsaturated and
an ω-saturated chain. Both chain populations should
then be observable in the mass spectrum; however, this
is not the case. The macroradical formed in the spec-
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