Synthesis and characterization of double hydrophilic block copolymers containing semi-rigid and flexible segments

Article abstract of DOI:10.1002/pola.27296

3-Methyl-(E)-stilbene (3MSti) and 4-(diethylamino)-(E)-stilbene (DEASti) monomers are synthesized and polymerized separately with maleic anhydride (MAn) in a strictly alternating fashion using reversible addition-fragmentation chain transfer (RAFT) polyme

Full text of DOI:10.1002/pola.27296

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Synthesis and Characterization of Double Hydrophilic Block Copolymers
Containing Semi-Rigid and Flexible Segments
This manuscript is dedicated to Prof. Jean Fr eꢀ chet on the occasion of his 70th birthday and to his extraordinary contributions to
polymer science.
Alice M. Savage, Elizabeth Ullrich, Stacey M. Chin, Zachary Kiernan,
Caitlyn Kost, S. Richard Turner
Department of Chemistry (MC0212) and Macromolecules and Interfaces Institute (MC0344), Virginia Tech, Blacksburg,
Virginia 24061
Correspondence to: S. R. Turner (E-mail: srturner@vt.edu)
Received 28 May 2014; accepted 21 June 2014; published online 16 July 2014
DOI: 10.1002/pola.27296
ABSTRACT: 3-Methyl-(E)-stilbene (3MSti) and 4-(diethylamino)-
E)-stilbene (DEASti) monomers are synthesized and polymer-
anhydride) (DEASti-alt-MAn) with pseudo-first order polymeriza-
tion kinetics. DEASti-alt-MAn is chain extended with 4-
acryloylmorpholine (ACMO) to synthesize diblock copolymers and
subsequently converted to a double hydrophilic polyampholyte
block copolymers (poly((4-(diethylamino)-(E)-stilbene)-alt-maleic
acid))-b-acryloylmorpholine) (DEASti-alt-MA)-b-ACMO) via acid
hydrolysis. The isoelectric point and dissociation behavior of these
maleic acid-containing copolymers are determined using
(
ized separately with maleic anhydride (MAn) in a strictly alter-
nating fashion using reversible addition-fragmentation chain
transfer (RAFT) polymerization techniques. The optimal RAFT
chain transfer agents (CTAs) for each copolymerization affect
the reaction kinetics and CTA compatibilities. Psuedo-
first order polymerization kinetics are demonstrated for the
synthesis of poly((3-methyl-(E)-stilbene)-alt-maleic anhydride)
f-potential and acid–base titrations, respectively. V
2014 Wiley Peri-
C
(
3MSti-alt-MAn) with
a
thiocarbonylthio CTA (methyl 2-
odicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015, 53, 219–227
(
dodecylthiocarbonothioylthio)22-methylpropionate, TTCMe).
In contrast, a dithioester CTA (cumyl dithiobenzoate, CDB) controls
KEYWORDS: reversible addition fragmentation chain transfer
the synthesis of poly((4-(diethylamino)-(E)-stilbene)-alt-maleic
(RAFT); stiffness; water-soluble polymers
INTRODUCTION The precise control over monomer sequence
tives afford a variety of copolymers and polyelectrolytes with
precise control over the alternating monomer sequence.
in synthetic copolymers attracted researchers’ interest over
1
,2
the past few decades. Random-sequenced copolymers are
often used as replacements for defined biological polymers.
Unfortunately, due to the random monomer sequences, syn-
thetic copolymers typically lack the hierarchal structure pro-
ven critical for biological activity, recognition, self-replication,
Because of a decreased solubility, Sti-alt-MAn originally
appeared to be a crosslinked copolymer but upon dissolu-
8
tion in sodium hydroxide solution, the linear topology of
9
these copolymers was confirmed. Recently, copolymers syn-
thesized from functionalized stilbene monomers resulted in
1
,3
and self-assembly.
Synthetically, it remains challenging to
linear, organic-soluble copolymers with sterically congested
control the precise sequence of monomers with conventional
radical polymerization techniques. Typically, reactivity ratios
between vinyl monomers are used to predict monomer
7,10–12
polymer backbones.
Investigation into the copolymer
rigidity revealed that these copolymers are classified as
13
semi-rigid (or semi-flexible), stemming from the sterically
4
sequence. However, unavoidable defects in monomer
crowded, 1,2-diphenylethylene structures of stilbene mono-
mers and the ring structures of MAn/maleimide comono-
sequence result in unwanted or uncontrollable conformational
and morphological changes. Nevertheless, examples of radical
mers. The semi-rigid, sterically congested copolymers show
4
–6
copolymerizations with controlled monomer sequences
12
ꢀ
no visible T
g
below 280 C.
exist like poly(stilbene-alt-maleic anhydride) (Sti-alt-MAn).
Neither comonomer self-propagates under radical polymeriza-
tion conditions and they display reactivity ratios close to
Protected, stilbene-containing, organic-soluble copolymer
precursors easily convert to semi-rigid, aqueous-soluble,
4
,7
10,14,15
zero, resulting in strictly alternating monomer sequences.
polyelectrolytes via acid or alkaline hydrolysis.
The syntheses of substituted Sti-alt-MAn copolymer deriva-
This deprotection strategy allows for molar mass
Additional Supporting Information may be found in the online version of this article.
2014 Wiley Periodicals, Inc.
V
C
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TABLE 1 THF SEC Results for the Synthesis of 3MSti-alt-MAn and DEASti-alt-MAn Using RAFT CRP Techniques
Target M
n
ꢀ
21
21
Copolymer
MSti-alt-MAn
RAFT Agent
Initiator
Temperature ( C)
[CTA]:[I]
(g mol
)
M
n
(g mol
)
PDI
Modality
3
TTCMe
TTCMe
CDB
AIBN
DCP
60
2:1
2:1
2:1
2:1
8:1
8:1
2:1
2:1
15,000
15,000
20,000
15,000
20,000
25,000
20,000
20,000
–
–
–
110
60
15,000
–
1.11
–
Unimodal
AIBN
DCP
–
CDB
110
60
–
–
–
DEASti-alt-MAn
TTCMe
TTCMe
CDB
AIBN
DCP
–
–
–
110
60
2,000
17,000
10,000
1.31
1.13
2.56
Bimodal
Unimodal
Bimodal
AIBN
DCP
CDB
110
determination of the precursors using organic solvents and
circumvents the typical difficulties in the molar mass deter-
with a choice of solvent, monomer concentration, and radical
initiator. With control over the polymer chain-end structure,
chain extension of polymers synthesized by RAFT techniques
produces well-defined block copolymers.
1
6
mination of polyelectrolytes. This strategy also allows for
1
other traditional polymer characterization: H NMR, TGA,
DSC, DLS (dynamic light scattering), and solution SAXS
1
3
To synthesize double hydrophilic block copolymers with
semi-rigid and flexible blocks, RAFT CRP techniques were
employed. RAFT was chosen as the optimal CRP technique
for these copolymers due to the mild reaction conditions
and functional group compatibilities of the RAFT polymeriza-
(
small angle X-ray scattering).
These precisely defined,
semi-rigid polyelectrolytes afford pH and salt-responsive
1
4,15
copolymers,
likely due to the semi-rigid polymer back-
bone. Semi-rigid polymers are uncommon compared to rigid
1
7
polyelectrolytes, and incorporating the stilbene-containing
copolymers into more sophisticated polymer architectures,
such as block copolymers, enables investigation into the
effects of the semi-rigid polymer segments on the polyelec-
trolyte solution properties.
2
4
tion mechanism. ATRP and NMP were not compatible CRP
techniques due to acidic monomer (MAn) incompatibilities
2
0,25
with the ATRP copper-catalyst
atures of the NMP techniques.
and high reaction temper-
2
6
Two types of RAFT agents (thiocarbonylthio and dithioben-
zoate) where chosen as possible CTAs. The choice of RAFT
agent for these copolymerizations was found to be critical
for controlling molar mass and molecular weight distribu-
tions (PDI). The effects of RAFT agent on the time depend-
ence of monomer conversion and dependence of molar mass
on monomer conversion were investigated for both copoly-
mers: 3MSti-alt-MAn (poly((3-methyl-(E)-stilbene)-alt-maleic
anhydride)) and DEASti-alt-MAn (poly((4-(diethylamino)-(E)-
stilbene)-alt-maleic anhydride)) (Fig. 1). Chain extension of
DEA-alt-MAn copolymers with a non-stimuli responsive,
Our group previously reported the synthesis of polyampho-
lyte diblock copolymers containing alternating N,N-dialkyla-
mino-substituted stilbene-MAn segments by using reversible
addition-fragmentation chain transfer (RAFT) polymerization
1
4
techniques. The asymmetric stilbene monomer synthesis
by the Wittig–Horner reaction resulted predominately in the
1
8
trans isomer. This asymmetry promoted the solubility of
both copolymers with 3-methyl-(E)-stilbene (3MSti) or 4-
(
diethylamino)-(E)-stilbene (DEASti) comonomers in organic
1
1
solvents. Also, the basic functional group (diethylamino) of
the DEASti monomer promoted copolymer solubility in aque-
ous solutions.
2
7–29
1
2,14
amphiphilic, acrylamide (4-acryloylmorpholine (ACMO))
Further investigation into polymerizing
resulted in linear, organic-soluble block copolymer precur-
sors and revealed end group control. Using acid hydrolysis,
the block copolymers were easily converted to their respec-
tive polyampholyte structures and used to measure the iso-
electric point (IEP) and dissociation behavior of the semi-
rigid, stilbene-containing segments within the double hydro-
philic block copolymers.
stilbene comonomers via RAFT polymerization techniques
proved difficult due to the steric congestion of the 1,2-diphe-
1
9,20
nylethylene structure
and the electron-donating capabil-
ities of functional groups that significantly affect the
copolymerizability with certain RAFT agents, Table 1.
1
9,21,22
Since 1998,
the number of investigations into RAFT
polymerization techniques skyrocketed with advances in
new RAFT chain transfer agents (CTAs), different monomer
compatibilities, and combining RAFT with other controlled
radical polymerization (CRP) techniques [atom transfer radi-
cal polymerization (ATRP) and nitroxide mediated polymer-
EXPERIMENTAL
Chemicals
11
Diethyl benzylphosphonate was synthesized as reported. MAn
(Aldrich, ꢁ99.0%), methyl 2-(dodecylthiocarbonothioylthio)22-
methylpropionate (TTCMe, Aldrich, 97%), hexanes (spectrum,
ACS), m-tolualdehyde (Aldrich), tetrahydrofuran (THF, Aldrich,
2
3
izations (NMP)].
With reaction conditions similar to
conventional radical polymerization techniques, RAFT pro-
vides a means to polymerize functionalized vinyl monomers
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FIGURE 1 Synthesis of stilbene-containing alternating copolymers. (a) Synthesis of 3MSti-alt-MAn copolymers with TTCMe CTA.
b) Synthesis of DEASti-alt-MAn copolymers with CDB CTA.
(
anhydrous, ꢁ99.9%), potassium tert-butoxide (1.0 M THF solu-
Zeta potential measurements were performed using a MAL-
VERN Zatasizer (Nano ZS, ZEN3600) with a He–Ne laser
tion, Aldrich), 4-(diethylamino)benzaldehyde (Aldrich, 99%),
0
dicumyl peroxide (DCP, Aldrich, 98%), and 2,2 -azobis(2-methyl-
(k 5 632.8 nm) and
a folded disposable capillary cell
propionitrile) (AIBN, Aldrich, 98%), chlorobenzene (PhCl,
(DTS1060). pH of the solutions was adjusted and measured
before each zeta potential measurement in 1 mg mL poly-
mer solutions.
21
Aldrich, anhydrous 98.8%), and calcium chloride (CaCl , Aldrich,
2
anhydrous, ꢁ93.0%) were used as received. ACMO (Aldrich,
ꢀ
9
7%) was distilled before use at 60 C and 1 mmHg of
Synthesis
Synthesis of 3MSti
pressure.
Diethyl benzylphosphonate (11.3 g, 0.050 mol), m-tolualde-
hyde (5.95 g, 0.050 mol), and dry THF (200 mL) were added
to a 500-mL round bottom flask with stir bar, septum, and
needle under argon. The reaction flask was chilled in an ice
bath for 30 min. A 1.0 M solution of potassium tert-butoxide
in THF (55 mL, 0.055 mmol) was added slowly by using a
syringe over 30 min to the reaction flask. After the addition
of potassium tert-butoxide solution was completed, green
solids began to crash out of solution. The reaction was
allowed to warm to room temperature and stirred for a total
of 24 h. The green liquid was poured into 600 mL of satu-
rated ammonium chloride solution. After 1 day, a brownish/
red solid appeared and was filtered by using vacuum filtra-
tion. The product was purified by using column chromatog-
raphy (hexanes) to yield a white solid (7.90 g, 82%). mp
Instruments
Size exclusion chromatography (SEC) determined the molar
mass of the polymers at 35 C in THF at 1 mL min flow
rate. The THF SEC system was equipped with a Waters
ꢀ
21
717plus autosampler, a Waters 515 HPLC pump, three Poly-
mer Laboratories PLGel 5 lm Mixed-C columns, multiangle
laser light scattering (MALLS) detector and a Waters 2414
differential refractive index detector. Absolute molecular
weights were obtained from the MALLS detector after deter-
mining the dn/dc offline using a Wyatt Optilab T-rEX differ-
ꢀ
ential refractometer at 658 nm and 35 C.
pH titrations were performed with a pH glass electrode in
conjunction with a pH meter at room temperature. The poly-
ampholyte concentration used for the titrations was 1.0 mg
ꢀ ꢀ
31
59.3–59.4 C; Lit. mp 48 C.
21
30
2
mL in 0.02 M CaCl solution, starting with 25 mg of poly-
1
ampholyte sample. The pH of the starting solution was
adjusted to pH 11 using 1.0 M NaOH stock solution. The
aqueous HCl titrant (0.0075 M) was delivered into the stirred
polymer solution from a 50-mL burette and pH readings were
stable and accurate to 0.01 pH unit. Dissociation behavior of
the polyampholyte was studied by using backward titration
H NMR (500 MHz, CDCl , d): 7.51 (m, 2H, Ar H), 7.34 (m,
3
4H, Ar H), 7.26 (m, 2H, Ar H), 7.08 (m, 3H, Ar H), 2.38 (s,
1
3H, -CH ). HRMS (ESI, m/z): [M1H] calcd. for C H ,
3
15 14
195.1222; found, 195.1229.
Synthesis of 4-Diethylamino- (E)-stilbene (DEASti)
1
5
Diethyl benzylphosphonate (15.0 g, 0.07 mol), 4-(diethylami-
no)benzaldehyde (11.69 g, 0.070 mol), and dry THF
(200 mL) were added to a 500-mL round bottom flask with
stir bar, septum, and needle under argon. The reaction flask
procedures (basic conditions titrated with HCl).
1
H NMR spectra were obtained on a Varian Unity 400 MHz
spectrometer in CDCl3.
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was chilled in an ice bath for 30 min. A 1.0 M solution of
potassium tert-butoxide (72 mL, 0.072 mol) was added
slowly by using a syringe over 30 min to the reaction flask.
After the addition of potassium tert-butoxide solution was
completed, red solids began to crash out of solution. The
reaction was allowed to warm to room temperature and
stirred for a total of 24 h. The orange liquid was poured into
to a 50 mL reaction flask with stir bar and septum. The flask
was purged with argon and 40 mL of anhydrous THF were
added to the flask with a syringe. The solution was purged
ꢀ
with argon for 30 min, and then stirred 4 h at 60 C. The
reaction was cooled to room temperature and the polymer
solution was precipitated into 400 mL of hexanes. The white
solid was collected by using vacuum filtration. The solid was
then redissolved in THF and precipitated into hexanes
(400 mL). The white solid was collected by using vacuum fil-
tration and dried in the vacuum oven at RT overnight
600 mL of saturated ammonium chloride solution. After 1 h,
a yellow/green solid appeared and was filtered by using vac-
uum filtration. The pail yellow solid product was purified by
recrystallization in hot hexanes. (15.70 g, 95%). mp 85.4–
2
1
(1.37 g, 40%) (M 5 45,000 g mol and PDI 5 1.25).
n
ꢀ ꢀ
32
8
6.0 C; Lit. mp 96 C.
Deprotection of (DEASti-alt-MAn)-b-ACMO and Synthesis of
Polyampholyte (DEASti-alt-MA)-b-ACMO
1
H NMR (500 MHz, CDCl , d): 7.37 (m, 6H, Ar H), 7.18 (t,
3
J 5 10 Hz, 1H, Ar H), 7.03 (d, J 5 20 Hz, 1H, ACH@CH@),
The typical procedure for deprotection and polyampholyte
synthesis was as follows. (DEASti-alt-MAn)-b-ACMO (0.50 g,
0.01 mmol), HCl (3 mL, 0.04 mol) and deionized water
(15 mL) were added to a 50-mL round bottom flask and
6.88 (d, J 5 20 Hz, 1H, ACH@CHA), 6.65 (d, J 5 10 Hz, 2H,
Ar H), 3.37 (q, 4H, J 5 10 Hz, ANACH ACH ), 6.65 (d, J 5 10
2
3
1
Hz, 2H, Ar H). HRMS (ESI, m/z): [M1H] calcd. for C H N,
1
8 22
ꢀ
252.1745; found, 252.1747.
stirred for 2 h at 50 C. The solutions were placed in cellu-
21
lose/ester membranes (MWCO 1000 g mol ), which were
placed in a beaker with water (2 L); the water was stirred
for 48 h after which time dialysis was presumed to be com-
pleted. The aqueous contents of the membranes were then
frozen in liquid nitrogen and lyophilized for 24 h to yield a
white fluffy solid. Complete conversion into the polyanion
Typical RAFT Copolymerization of DEASti and Man
2
1
(
21,000 g mol Target Mn)
DEASti (1.000 g, 4.0 mmol), MAn (0.3905 g, 4.0 mmol), CDB,
0.018 g, 0.066 mmol), and AIBN (0.005 g, 0.033 mmol)
(
were added to a 50 mL reaction flask with stir bar and sep-
tum. The flask was purged with argon and 16 mL of anhy-
drous THF were added to the flask with a syringe. The
solution was purged with argon for 30 min, and then stirred
10,14
was confirmed by FTIR.
RESULTS AND DISCUSSION
ꢀ
for 3.5 h at 60 C. The reaction was cooled to room tempera-
ture and the polymer solution was precipitated into 400 mL
of hexanes. The orange solid was collected by using vacuum
filtration. The solid was then redissolved in THF and precipi-
tated into hexanes (400 mL). The white solid was collected
by using vacuum filtration and dried in the vacuum oven at
The stilbene monomers 3MSti and DEASti were successfully
synthesized and polymerization by using controlled radial
polymerization techniques. As summarized in Table 1,
TTCMe RAFT agent was used to control the polymerization
ꢀ
3MSti with MAn at 110 C with DCP initiator and resulted in
ꢀ
21
60
C overnight (0.45 g, 30%) (M
n
5 12,000 g mol , and
unimodal SEC chromatograms with linear pseudo-first order
reaction kinetics. Whereas, CDB prevented the polymeriza-
PDI 5 1.13).
ꢀ
tion of 3MSti with MAn at 60 or 110 C. Conversely, the CDB
Typical RAFT Copolymerization of 3MSti and MAn (51,000
RAFT agent sufficiently controlled the polymerization of
DEASti with MAn at 60 C with AIBN and exhibited pseudo-
21
g mol
MSti (1.000 g, 5.1 mmol), MAn (0.505 g, 5.1 mmol), TTCMe,
0.010 g, 0.029 mmol), and DCP (0.004 g, 0.014 mmol) were
Target Mn)
ꢀ
3
(
first order reaction kinetics and TTCMe did not control this
ꢀ
polymerization at either 60 or 110 C.
added to a 50 mL reaction flask with stir bar and septum.
The flask was purged with argon and 16 mL of anhydrous
chlorobenzene were added to the flask with a syringe. The
solution was purged with argon for 30 min, and then stirred
for 24 h at 110 C. The reaction was cooled to room temper-
ature and the polymer solution was precipitated into
DEASti-alt-MAn copolymers were then chain extended with
ACMO to synthesize linear block copolymers. These organic-
soluble copolymers were then converted to polyampholytes
via acid hydrolysis. By measuring the zeta-potential of 1 mg
ml polymer solutions at different pH, the IEP of these pol-
yampholytes was observed at 4.32 pH. Acid–base titration
curves reveal multi-step dissociation behavior of double
hydrophilic block copolymers.
ꢀ
2
1
400 mL of hexanes. The white solid was collected by using
vacuum filtration. The solid was then redissolved in THF and
precipitated into hexanes (400 mL). The white solid was col-
lected by using vacuum filtration and dried in the vacuum
ꢀ
21
Monomer and CTA Ratio Calculations
oven at 60 C overnight (1.28 g, 85%) (M 5 15,000 g mol
,
n
For each reaction kinetic study, the CTA, initiator, and mono-
mer concentration ratios followed the initial conditions set
and PDI 5 1.11).
2
0
Synthesis of (DEASti-alt-MAn)-b-ACMO Block Copolymers
forth by Davies et al. It is also important to note that the
monomer conversions were based on the isolated yield of
each polymerization. Because of the semi-rigid polymer back-
2
1
with RAFT Polymerization (90,000 g mol Target M
n
)
DEASti-alt-MAn (macroRAFT agent) (0.39 g, 0.03 mmol,
2
1
13
M 5 12,000 g mol , PDI 5 1.13), ACMO (3.00 g, 11 mmol),
bone, very broad aromatic and polymer backbone peaks
n
1
and AIBN (0.003 g, 0.02 mmol, [CTA]:[I] 5 2:1) were added
appear in every H NMR spectrum of these copolymers (even
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FIGURE 2 Possible structures for the RAFT main chain equilibrium structures of stilbene-MAn RAFT copolymerizations.
at low conversion). Also, vinyl peaks from both comonomers
overlap with the polymer backbone peaks; thus, making it
impossible to calculate monomer conversion with H NMR.
tion of 3MSti and MAn but only at high temperatures
ꢀ
ꢀ
(110 C) (Table 1). 3MSti-MAn did not polymerize at 60 C
with TTCMe and AIBN. Polymerizations with TTCMe and
1
ꢀ
DCP at 110 C demonstrated linear pseudo-first order poly-
merization kinetics with a linear time dependence of mono-
mer conversion and linear dependence of molar mass on
monomer conversion (Fig. 3). At reaction times less than 6.5
h, copolymers could not be isolated by precipitation and fil-
tration; thus, monomer conversion could not be calculated.
However, copolymer molar mass could be directly measured
using SEC from reaction aliquots at shorter reaction times;
therefore, this is likely not a retardation period. PDIs
remained constant as monomer conversion increased.
Polymerization of 3MSti and MAn
Cumyl dithiobenzoate (CDB) (R-group 5 cumyl, Z-group 5 di-
thiobenzoate) was found to inhibit the copolymerization of
3MSti and MAn at either low or high temperatures. However,
styrene-alt-MAn (poly(styrene-alt-maleic anhydride)) copoly-
mers have been synthesized by RAFT CRP techniques by
using benzyl dithiobenzoate (R-group 5 benzyl, Z-group 5 di-
2
0,33
thiobenzoate).
The dithiobenzoate CTA exhibited effec-
tive molar mass control, and pseudo-first order reaction
2
0
kinetics.
As there are minimal electronic differences
3
4
between the vinyl moieties of styrene and 3MSti, the steric
congestion of 3MSti likely prevented or drastically slowed
monomer conversion with CDB. In the RAFT polymerization
mechanism, there are three possible main chain equilibrium
structures with stilbene and MAn comonomers (Fig. 2). If a
stilbene radical is the propagating radical and reacts with a
dormant RAFT adduct chain, then the steric hindrance
remains large and could potentially decrease polymerization
rates. This decreased polymerization rate also occurred with
another sterically hindered monomer, a-methylstyrene, poly-
merized with MAn copolymers compared to styrene-alt-MAn
Polymerization of DEASti and MAn
A different trend occurred with DEASti and MAn comonomer
polymerization. In the synthesis of DEASti-alt-MAn, only CDB
controlled molar mass and the reaction demonstrated linear
pseudo-first order kinetics (Fig. 4), while TTCMe polymeriza-
tions exhibited bimodal THF SEC-MALLS chromatograms and
a lack of molar mass control.
Again for TTCMe mediated copolymerizations, the polymer-
ꢀ
ization only proceeded at 110 C with the DCP initiator,
Table 1. However, probable side reactions between DCP and
3
5
2
0
the diethylamino functional group were the likely cause of
the uncontrolled molar mass and the bimodal peaks seen in
the THF SEC-MALLS chromatogram. Higher temperature
using RAFT polymerization techniques.
TTCMe (R-group 5 AC(CH ) (COOMe), Z-group 5 thiocarbo-
3
2
0
nylthio) was successfully used to control the copolymeriza-
azo-initiators like 1,1 -azobis(cyclohexanecarbonitrile) which
ꢀ
FIGURE 3 Reaction kinetics data of 3MSti-alt-MAn copolymers with AIBN and TTCMe CTA at 110 C in PhCl (Target M
n
5 15,000 g
21
mol , [Monomer] 5 0.5 M).
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ꢀ
n
FIGURE 4 Reaction kinetics data of DEASti-alt-MAn copolymers with AIBN and CDB CTA at 60 C in THF (Target M 5 10,000 g
21
mol , [Monomer] 5 0.5 M).
molar mass on monomer conversion (Table 1, Fig. 4). Possibly, the
more electron-rich vinyl moiety of DEASti (compared to 3MSti)
37
increased the reactivity of the stilbene monomer and the copoly-
merization rate (cross-propagation); thus, increasing the copoly-
merization rate with CDB. The increase in polymerization rate of
alternating copolymers where the electron-rich monomer (donor
monomer) is rendered more electron-rich and/or the electron-
poor monomer (acceptor monomer) is made more electron-
38,39
poor is well documented in the literature.
For example, the
copolymerization of p-methoxystyrene with MAn has a faster
polymerization rate than the copolymerization of styrene
and MAn.
FIGURE 5 RAFT CTA agents used to synthesize both 3MSti-alt-
MAn and DEASti-alt-MAn.
20
Like styrene homopolymerizations with dithiobenzoate CTAs,
a retardation period (2 h) appeared due to the over-stabili-
zation of the RAFT adduct arising from the dithiobenzoate Z-
group of CDB. Pseudo-first order polymerization kinetics
resumed after this period of polymerization retardation. An
increase in the PDI occurred with monomer conversions
ꢀ
36
exhibits a 10 h half-life at 88 C, were also unsuccessful
when employed with this comonomer pair.
1
9
In the polymerization of DEASti and MAn with CDB, molar
mass control was achieved along with a linear dependence of
FIGURE 6 Synthesis of (DEASti-alt-MA)-b-ACMO polyampholyte block copolymers. (a) Chain extension of DEASti-alt-MAn macro-
ꢀ
RAFT agent with ACMO in THF at 60 C. (b) Acid hydrolysis of (DEASti-alt-MAn)-b-ACMO to synthesize final polyampholyte block
copolymer.
224
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FIGURE 8 Zeta potential versus pH of block copolymer
21
(
DEASti-alt-MA)-b-ACMO at varying pH with 1 mg mL
poly-
mer concentration. The block copolymer used has an overall
2
1
n
M of 45,000 g mol (PDI of 1.25) with a DEASti-alt-MA seg-
21
ment of 12,000 g mol
.
unimodal and narrow PDIs of the THF SEC-MALLS chromato-
grams imply the absence of uncontrolled ACMO homopoly-
merization and high molar mass termination reaction
products (Table 2, Fig. 7).
FIGURE 7 THF SEC-MALLS chromatograms of (a) DEASti-alt-
MAn macroRAFT CTA copolymer and b) block copolymer
(
DEASti-alt-MAn)-b-ACMO.
Acid hydrolysis converts the organic-soluble block copoly-
mers to water-soluble polyampholytes with two acidic resi-
dues (carboxyl groups) and one basic residue (diethylamino
group) per repeat unit [Fig. 6(b)]. Acidic conditions were
chosen during the synthesis of the polyampholyte (instead of
alkaline conditions) to increase the solubility of the block
copolymer precursor in water during this ring-opening reac-
tion. The IEP of the copolymers was calculated using an
above 0.5 due to possible termination through chain-end
combination. In addition, bimodal peaks appear in the THF
SEC-MALLS chromatogram at higher monomer conversions
from these possible termination processes, which indicates a
lack of chain-end control at higher monomer conversions.
To compare R group effects and to reduce the polymeriza-
tion retardation effect with CDB, a thiocarbonylthio CTA with
4
1,42
0
acid–base equilibrium calculation
itoring the f-potential of these copolymers at different pH
Fig. 8). By using the pK ’s calculated for the maleic acid res-
idues on Sty-alt-MA (pK
and measured by mon-
a benzylic R-group (S-1-dodecyl-S -(1-phenyl ethyl)trithiocar-
4
0
bonate) (Fig. 5) was used to polymerize DEASti with MAn.
(
a
The retardation period disappeared. However, the polymer-
ization was uncontrolled and again, bimodal peaks appeared
in the THF SEC-MALLS chromatogram like copolymerizations
with TTCMe.
4
3
a
5 4 and 10), an IEP of 4.30 pH
was calculated which was in very good agreement with the
experimental IEP of 4.32 pH. Ultimately, IEP determination
serves as a reference point for further polymer solution
characterization.
(DEASti-alt-MA)-b-ACMO Polyampholyte Double
Hydrophilic Block Copolymers
Poly(ACMO) is an acrylamide homopolymer with gaining
interest due to its amphiphilic nature, and low cytotoxic-
2
7–29
ity.
Particularly, poly(ACMO) was chosen for these block
copolymers due to its non-stimuli responsive nature with
respect to pH, temperature, or salt. Conditions for the block
copolymerization of ACMO onto the DEASti-alt-MAn macro-
CTA were implemented according to similar procedures pre-
2
9
viously described (Fig. 6). THF SEC-MALLS chromatogram
confirmed an increase in molar mass of the block copolymer
with a shift to shorter elution times (Fig. 7). In addition, the
TABLE 2 THF SEC Results for the Chain Extension of
DEASti-alt-MAn with ACMO
DEASti-alt-Man
Block Copolymer
21
21
M
n
(g mol
)
PDI
M
n
(g mol
)
PDI
1
1
1
2,000
4,500
7,000
1.13
1.25
1.26
44,500
21,500
33,000
1.25
1.24
1.33
FIGURE 9 Titration curve of (DEASti-alt-MA)-b-ACMO (20 mg)
2
in CaCl solution (20 mL, 0.02 M) with excess NaOH (1.0 M, 0.6
mL). Solutions titrated with 0.0075 M HCl solution.
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The dissociation behavior of the maleic acid-containing poly-
ampholyte block copolymer was also evaluated using back-
C. Scholz, J. Kressler, Eds.; 2013; ACS Symposium Series;
American Chemical Society: Washington, DC, Vol. 1135, pp
319–330.
1
5,30
ward titration procedures.
A multi-step dissociation
4
F. M. Lewis, F. R. Mayo, J. Am. Chem. Soc. 1948, 70, 1533–
behavior was observed and consistent with previously
3
0,44
1536.
reported copolymers containing maleic acid (Fig. 9).
The
5
R. M. Davis, W. B. Russel, J. Polym. Sci. Part B: Polym. Phys.
vicinal diacids that originated from the enchained MAn
4
3
1986, 24, 511–533.
comonomer exhibit two distinct pKa’s and are responsible
6
F. M. Houlihan, T. I. Wallow, O. Nalamasu, E. Reichmanis,
for the multi-step dissociation behavior. The two pK ’s arise
a
4
5
Macromolecules 1997, 30, 6517–6524.
from the sharing of one sodium ion per pair of carboxyl
groups. This sharing/stabilization of the charged vicinal diac-
ids is only possible due to the close proximity of the neigh-
boring groups and is amplified with the addition of
7
N. T. H. Ha, Polymer 1998, 40, 1081–1086.
8
T. Wagner-Jauregg, Ber. Dtsch. Chem. Ges. B 1930, 63B,
3
213–3224.
1
5,30
9 T. Tanaka, O. Vogl, Polym. J. 1974, 6, 522–531.
0 Y. Li, M. Mao, L. E. Matolyak, S. R. Turner, ACS Macro Lett.
2012, 1, 257–260.
1 Y. Li, S. R. Turner, Eur. Polym. J. 2010, 46, 821–828.
CaCl .
1
(
Based on the pK s of the vicinal diacids (4 and
a
2
4
3
1
0) and pK ’s of the protonated dimethylaniline groups
a
4
6
5.5), we hypothesize that the protonation of the diethyla-
1
mino groups overlaps with the protonation of the second
carboxyl group between pH 4–5. The dissociation behavior
of these polyampholytes allows for more control over the
degree of ionization by simply varying the pH of the polymer
solution. This degree of ionization control becomes impera-
12 M. Mao, S. R. Turner, Polymer 2006, 47, 8101–8105.
13 Y. Li, M. Zhang, M. Mao, S. R. Turner, R. B. Moore, T. H.
Mourey, L. A. Slater, J. R. Hauenstein, Macromolecules 2012,
4
1
1
5, 1595–1601.
4
7,48
4 M. Mao, S. R. Turner, J. Am. Chem. Soc. 2007, 129, 3832–3833.
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5 Y. Li, A. M. Savage, X. Zhou, S. Richard Turner, R. M. Davis,
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CONCLUSIONS
1
6
6 R. J. Bruessau, Makromol. Chem. Macromol. Symp. 1992,
1, 199–218.
In summary, two stilbene derivatives (3MSti and DEASti)
were successfully copolymerized with MAn by RAFT CRP
techniques. Electron-donating groups like tertiary amino
groups on stilbene not only affected the increased polymer-
ization rate but also CTA compatibilities. Psuedo-first order
polymerization kinetics appeared for both 3MSti- and
DEASti-containing alternating copolymers. These RAFT poly-
merization techniques offer new pathways to synthesize pre-
cisely defined alternating copolymers and block copolymers
with semi-rigid segments. Further investigation into the solu-
tion properties and stimuli responsive nature of these
copolymers is underway and will be reported in the future.
1
7 M. Rikkou-Kalourkoti, E. Kassi, C. S. Patrickios, J. Polym.
Sci. Part A: Polym. Chem. 2012, 50, 665–674.
1
1
8 W. S. Wadsworth, Jr., W. D. Emmons, J. Am. Chem. Soc.
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1
9 G. Moad, J. Chiefari, Y. K. Chong, J. Krstina, R. T. A.
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2
2 J. Chiefari, Y. K. Chong, F. Ercole, J. Krstina, J. Jeffery, T. P.
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ACKNOWLEDGMENTS
2
3 D. Zehm, A. Laschewsky, H. Liang, J. P. Rabe, Macromole-
National Science Foundation grant numbers DMR 9905231 and
cules 2011, 44, 9635–9641.
1206409 supported fundamental studies on the synthesis,
2
4 A. B. Lowe, C. L. McCormick, Prog. Polym. Sci. 2007, 32,
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research fellowship supported by an REU grant from NSF DMR
2
83–351.
2
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5 J. Qiu, B. Charleux, K. Matyjaszewski, Prog. Polym. Sci.
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