Dynamic covalent diblock copolymers prepared from RAFT generated aldehyde and alkoxyamine end-functionalized Polymers

Article abstract of DOI:10.1021/ma902291a

Aldehyde- or alkoxyamine-containing trithiocarbonate chain transfer agents were prepared and used to mediate the synthesis of a series of polymers end-functionlized with either aldehyde or alkoxyamines functions, utilizing reversible addition-fragmentation polymerization techniques. Aldehyde end-functionalized polymers were shown to link through reversible oxime bond formation with alkoxyamine end-funtionalized polymers forming diblock copolymers. The dynamic nature of the oxime bond linking these polymer blocks together was demonstrated through a simple exchange reaction with a small molecule alkoxyamine. A diblock copolymer prepared from the self-assembly of an aldehyde end-functionalized polyisoprene with an alkoxyamine end-functionalized polystyrene was shown to undergo further hierarchical self-assembly into micellar aggregates in DMF. It was shown that the addition of an excess of a small molecule alkoxyamine triggered the disassembly of these micelles.

Full text of DOI:10.1021/ma902291a

Macromolecules 2010, 43, 1069–1075 1069
DOI: 10.1021/ma902291a
Dynamic Covalent Diblock Copolymers Prepared from RAFT Generated
Aldehyde and Alkoxyamine End-Functionalized Polymers
Alexander W. Jackson and David A. Fulton*
Chemical Nanoscience Laboratory, School of Chemistry, Bedson Building, Newcastle University,
Newcastle upon Tyne NE1 7RU, U.K.
Received October 15, 2009; Revised Manuscript Received November 13, 2009
ABSTRACT: Aldehyde- or alkoxyamine-containing trithiocarbonate chain transfer agents were prepared
and used to mediate the synthesis of a series of polymers end-functionlized with either aldehyde or
alkoxyamines functions, utilizing reversible addition-fragmentation polymerization techniques. Aldehyde
end-functionalized polymers were shown to link through reversible oxime bond formation with alkoxyamine
end-funtionalized polymers forming diblock copolymers. The dynamic nature of the oxime bond linking
these polymer blocks together was demonstrated through a simple exchange reaction with a small molecule
alkoxyamine. A diblock copolymer prepared from the self-assembly of an aldehyde end-functionalized
polyisoprene with an alkoxyamine end-functionalized polystyrene was shown to undergo further hierarchical
self-assembly into micellar aggregates in DMF. It was shown that the addition of an excess of a small molecule
alkoxyamine triggered the disassembly of these micelles.
Introduction
or material properties. Furthermore, the strength of the covalent
bond ensures product assemblies possess chemical robustness,
Block copolymers are building blocks for a large variety of
important self-assembled nanoscale objects such as micelles and
vesicles in solution or ordered copolymer morphologies such as
lamellae in bulk.1 In the drive toward the development of new
“smart” polymer-based systems possessing responsive and adap-
table properties, chemists have incorporated dynamic and rever-
sible supramolecular interactions such as H-bonding,2 metal-
ligand interactions,3 or a combination of both4 to link polymer
blocks together. Recent advances have also seen the utilization of
the macrocyclic host cucurbit[8]uril as a supramolcular “hand-
cuff” to link polymer chains into supramolecular diblock copoly-
mers in water,5 and pseudorotaxane formation has also been
utilized6 to link polymer blocks end-functionalized with either
crown ethers or secondary ammonium salts. In addition to
facilitating self-assembly, supramolecular interactions can impart
dynamic behaviors into the resultant block copolymer assemblies
which are also incorporated into supramolecular aggregates
formed from their block copolymer components.
We became intrigued by the possibility of using ideas from the
field of dynamic covalent chemistry (DCC)7 to develop new
advanced materials with responsive and adaptive properties.
DCC uses reversible covalent bond formation to link organic
building blocks into larger structures. In addition to facilitating
self-assembly, the reversible nature of the dynamic covalent
linkages enables product assemblies to modify their constitutions
by exchanging and reshuffling their building blocks. Equilibrium
perturbations, such as changes in concentration, temperature, or
the addition of other molecules, can result in constitutional
alterations as the product assemblies re-equilibrate.8 The rever-
sible nature of the dynamic covalent link instils the “intelligent”
virtues of controlled assembly, adaptability, and self-repair into
the resultant nanostructures. In effect, dynamic covalent inter-
actions could provide a mechanism for a polymer-based assembly
to reconfigure its covalent structure and therefore its functional
and as reversible covalent reactions are usually performed with
the help of a suitable catalyst to aid kinetics, the option exists to
halt these reversible processes and kinetically “fix” the products
simply by quenching the catalyst.
The groups of Otsuka, Takahara, and Lehn have pioneered the
use of reversible covalent reactions in polymer chemistry. Otsuka
and Takahara have focused9 on thermally reversible bonds based
on alkoxyamines, using this motif to link monomers into polymer
chains or graft components onto preformed polymer scaffolds.
Work by Lehn’s group on their hydrazone-based systems has
demonstrated9a,10 how the dynamic nature of the linkages can
impart adaptive behaviors into polymers or affect their optical or
mechanical properties. Recent work by the groups of Sumerlin11
12
€
and Jakle has focused on polymer blocks terminated with
boronic acids and their dynamic covalent self-assembly through
boronate ester formation into three-arm star polymers. Here, we
report the results of our preliminary studies on the synthesis and
supramolecular aggregation of diblock copolymers where the
polymer blocks are joined through a single dynamic covalent bond
and their subsequent aggregation into micellar assemblies. There
has been recent impressive work describing micellization of
dynamic covalent surfactants;13 however, to the best of our
knowledge this work describes the first examples of dynamic
covalent block copolymers of a truly polymeric nature.
Experimental Section
All chemicals were purchased from Sigma-Aldrich or Alfa
Aesar and were used as received without further purification. 1H
and 13C NMR spectra were recorded on a Bruker Avance 300
spectrometer at 300 and 75 MHz, respectively, with the residual
solvent signal as an internal standard. FTIR spectroscopy
was performed on a Varian 800 FTIR instrument (Varian Inc.).
High-resolution mass spectrometry was performed on a Waters
LCT premier mass spectrometer (Waters Inc.). Gel permeation
chromatography (GPC) was conducted on a Varian ProStar
*Corresponding author. E-mail: d.a.fulton@ncl.ac.uk.
r 2009 American Chemical Society
Published on Web 12/28/2009
pubs.acs.org/Macromolecules

1070 Macromolecules, Vol. 43, No. 2, 2010
Jackson and Fulton
instrument (Varian Inc.) equipped with a Varian 325 UV-vis
dual wavelength detector (254 nm), a Viscotek 3580 differential
RI detector, and a pair of PL gel 5 μm Mixed D 300 ꢀ 7.5 mm
columns with guard column (Polymer Laboratories Inc.) in
series. Near monodisperse polystyrene standards (Polymer
Laboratories) were used for calibration. Data collection was
performed with Galaxie software (Varian Inc.) and chromato-
grams analyzed with the Cirrus software (Varian Inc.). Dynamic
and static light scattering was performed on a Dawn Heleos II
instrument (Wyatt Technology Corp.), and data collection and
analysis were performed with Astra software (Wyatt Technology
Corp.).
(O-H), 3230 (N-H), 2981 (C-H, alkyl), 1716 (CdO). HRMSþ
C11H23NO3K: Theoretical: 256.1525. Actual: 256.1529.
Alkoxyamine-Functionalized Chain Transfer Agent (2). A
solution of S-1-dodecyl-S0-(R,R-dimethyl-R00-acetic acid)-
trithiocarbonate (DDMAT, 0.78 g, 2.14 mmol) and N-Boc-6-
aminoxy hexan-1-ol (0.50 g, 2.14 mmol) in CH2Cl2 (20 mL) was
cooled to 0 °C in an ice bath while stirring under a nitrogen
atmosphere. A solution of EDC (0.452 g, 2.35 mmol) and
DMAP (0.29 g, 2.35 mmol) in CH2Cl2 (10 mL) was added
dropwise, and the reaction mixture was stirred overnight at
room temperature. The reaction mixture was evaporated to
dryness, and the crude yellow oil was purified by column
chromatography [SiO2, hexane-EtOAc (9:1)] to yield the Boc-
protected oxylamine chain transfer agent as a yellow oil (0.707 g,
57%). 1H NMR (CDCl3): δ 0.87 (t, 3H, J = 7.0 Hz), 1.36 (m,
18H), 1.48 (s, 9H), 1.64 (m, 16H), 3.26 (t, 2H, J = 7.5 Hz), 3.83
2-[2-(2-Hydroxyethoxy)ethoxy]ethyl-4-formylbenzoate. A so-
lution of NEt3 (6.0 g, 0.059 mol) and triethylene glycol (31.1 g,
0.207 mol) in CH2Cl2 (40 mL) was cooled to 0 °C in an ice bath
while stirring under a nitrogen atmosphere. To this solution
4-formylbenzoyl chloride (4.99 g, 0.0296 mol) in CH2Cl2
(50 mL) was added dropwise over 30 min, and the reaction
was left to stir overnight at room temperature. The reaction
mixture was evaporated to dryness, and the residue was dis-
solved in EtOAc (50 mL) and washed with saturated NaHCO3
solution. The organic layer was dried over MgSO4, filtered, and
evaporated to dryness to obtain crude oil which was purified by
column chromatography [SiO2, EtOAc-hexane (3:1)] to yield
(t, 2H, J = 6.0 Hz), 4.08 (t, 2H, J = 6.5 Hz), 7.10 (s, 1H). 13
C
NMR (CDCl3): δ 14.2, 22.9, 25.8, 25.9, 26.1, 28.3, 28.6, 28.7,
29.2, 29.4, 29.6, 29.7, 29.8, 29.9, 31.8, 32.2, 37.3, 56.5, 66.2, 77.7,
81.7, 157.1, 173.1. FT-IR (wavenumber, cm-1): 2981 (C-H,
alkyl), 2925 (C-H, alkyl), 1733 (CdO).
Boc-protected oxylamine chain transfer agent (0.350 g, 0.60
mmol) was dissolved in CH2Cl2 (3 mL) and TFA (3 mL). The
reaction mixture was left to stir at room temperature for 30 min,
and the solution was evaporated to dryness to afford a yellow
oil. The crude product was purified by column chromatography
[SiO2, hexane-EtOAc (4:1)] to yield the title product as a yellow
oil (0.158 g, 55%). 1H NMR (CDCl3): δ 0.87 (t, 3H, J = 6.5 Hz),
1.25 (m, 18H), 1.68 (m, 16H), 3.26 (t, 2H, J = 7.5 Hz), 3.64 (t,
2H, J = 6.5 Hz), 4.08 (t, 2H, J = 6 Hz), 5.35 (s, 2H). 13C NMR
(CDCl3): δ 14.2, 22.9, 25.8, 26.0, 26.2, 28.2, 28.7, 28.8, 29.2, 29.4,
29.6, 29.7, 29.8, 29.9, 32.2, 37.3, 56.5, 66.2, 76.2, 173.1. HRMSþ
C23H45S3O3N: Theoretical: 480.2640. Actual: 480.2646.
1
the title product as a pale yellow oil (4.68 g, 50%). H NMR
(CDCl3): δ 3.57 (m, 2H), 3.67 (m, 6H), 3.82 (m, 2H), 4.49 (m,
2H), 7.91 (d, 2H, J = 8.0 Hz), 8.18 (d, 2H, J = 8.0 Hz), 10.06
(s, 1H). 13C NMR (CDCl3): δ 62.1, 64.8, 69.5, 70.8, 71.1, 72.9,
129.7, 130.2, 135.5, 139.8, 165.8, 191.6. FT-IR (wavenumber,
cm-1): 3490 (O-H), 2920 (C-H, alkyl), 2855 (C-H, alkyl),
1702 (CdO), 1453 (CdC, aromatic), 1385 (CdC, aromatic),
1202 (C-H, aromatic). HRMSþ C14H18O6: Theoretical:
283.1182. Actual: 283.1189.
Aldehyde-Functionalized Chain Transfer Agent (1). A solution
of S-1-dodecyl-S0-(R,R-dimethyl-R00-acetic acid)trithiocarbo-
nate (DDMAT, 0.63 g, 1.73 mmol) and 2-[2-(2-hydroxyethoxy)-
ethoxy]ethyl-4-formylbenzoate (0.49 g, 1.73 mmol) in CH2Cl2
(20 mL) was cooled to 0 °C in an ice bath while stirring under a
nitrogen atmosphere. A solution of EDC (0.37 g, 1.91 mmol)
and DMAP (0.23 g, 1.91 mmol) in CH2Cl2 (10 mL) was added
dropwise. The reaction mixture was stirred overnight at room
temperature and then evaporated to dryness to afford a crude
yellow oil which was purified by column chromatography [SiO2,
hexane-EtOAc (3:1)] to yield the title product as a yellow oil
(0.65 g, 59%). 1H NMR (CDCl3): δ 0.86 (t, 3H, J = 7 Hz), 1.25
(m, 18H), 1.68 (m, 8H), 3.24 (t, 2H, J = 7.5 Hz), 3.66 (t, 6H),
3.85 (t, 2H, J = 5.0 Hz), 4.24 (t, 2H, J = 5.0 Hz), 4.50 (t, 2H, J =
5.0 Hz), 7.95 (d, 2H, J = 9.0 Hz), 8.21 (d, 2H, 9.0 Hz), 10.10 (s,
1H). 13C NMR (CDCl3): δ 14.2, 22.9, 25.5, 25.7, 28.3, 29.2, 29.4,
29.6, 29.7, 29.8, 29.9, 30.9, 32.2, 37.3, 56.4, 64.9, 65.3, 69.3, 69.5,
71.1, 129.7, 130.6, 135.6, 139.8, 165.8, 172.9, 191.4, 206.1. FT-IR
(wavenumber, cm-1): 2981 (C-H, alkyl), 2923 (C-H, alkyl),
1726 (CdO), 1463 (CdC, aromatic), 1383 (CdC, aromatic),
1270 (C-H, aromatic). HRMSþ C31H48O7S3Na: Theoretical:
651.2460. Actual: 651.2463.
N-Boc-6-aminoxyhexan-1-ol. 1,8-Diazabicyclo[5.4.0]undec-
7-ene (0.677 mL, 4.52 mmol) was added dropwise over 10 min
to a solution of N-Boc-hydroxylamine (0.50 g, 3.75 mmol) and
6-bromohexan-1-ol (0.819 g, 4.52 mmol) in CH2Cl2 (20 mL).
The reaction mixture was left to stir overnight at room tem-
perature, then transferred into a separating funnel, and CH2Cl2
(100 mL) added. The organic layer was washed with 1 M HCl
(50 mL) and saturated NaCl(aq) (50 mL) and then dried over
MgSO4, filtered, and evaporated to dryness to afford a yellow
oil which was purified by column chromatography [SiO2, hex-
ane-EtOAc (3:2)] to yield the title product as a pale yellow oil
(0.565 g, 64%). 1H NMR (CDCl3): δ 1.38 (m, 4H), 1.45 (s, 9H),
1.57 (m, 4H), 3.61 (t, 2H, J = 6.5 Hz), 3.83 (t, 2H, J = 6.5 Hz),
7.28 (s, 1H). 13C NMR (CDCl3): δ 25.3, 28.3, 28.8, 33.1, 60.6,
63.1, 81.8, 157.2, 171.2. FT-IR (wavenumber, cm-1): 3450
Aldehyde End-Functionalized Poly(styrene) (P1a-d). To a
small Schlenk tube the chain transfer agent 1 (1 equiv) and
AIBN (0.1-0.2 equiv) was added. Styrene (100-200 equiv) was
then added followed by DMF (200 equiv). The reaction mixture
was degassed five times, and then the vessel was backfilled with
nitrogen, purged with N2, and allowed to warm to room
temperature. The reaction mixture was placed in an oil bath at
70 °C. The polymerization was quenched after a predetermined
time, and solvent was removed on the rotary evaporator. The
resulting yellow oil was dissolved in a minimal amount of THF
and added dropwise to ice cold methanol. The polymer pre-
cipitate was then isolated by filtration and dried under high
vacuum. Polymers P1a-d were obtained as pale yellow solids
with yields typically between 60 and 80%. 1H NMR (CDCl3): δ
0.88-1.01 (br, dodecyl of the chain terminus), 1.45 (br, CHCH2,
polymer backbone), 1.88 (br, CHCH2, polymer backbone), 3.29
(br, SCH2, of the chain terminus) 6.59 (br, Ar, polymer back-
bone), 7.06 (br, Ar, polymer backbone), 7.95 (d, Ar, of the chain
terminus), 8.21 (d, Ar, of the chain terminus), 10.12 (s, CHO, of
the chain terminus).
Alkoxyamine End-Functionalized Poly(styrene) (P5a-c). To a
small Schlenk tube the chain transfer agent 2 (1 equiv) and
AIBN (0.1-0.2 equiv) was added. Styrene (100-200 equiv) was
then added followed by DMF (200 equiv). The reaction mixture
was degassed five times, then the vessel was backfilled with
nitrogen, purged with N2, and allowed to warm to room
temperature. The reaction mixture was placed in an oil bath at
70 °C. The polymerization was quenched after a predetermined
time, and solvent was removed on the rotary evaporator. The
resulting yellow oil was dissolved in minimal amount of THF
and added dropwise to ice cold methanol. The polymer pre-
cipitate was then isolated by filtration and dried under high
vacuum. Polymers P5a-c were obtained as pale yellow solids
with yields typically between 70 and 80%. 1H NMR (CDCl3): δ
0.88-1.01 (br, dodecyl of the chain terminus), 1.45 (br, CHCH2,
polymer backbone), 1.88 (br, CHCH2, polymer backbone), 3.29
(br, SCH2, of the chain terminus), 5.35 (br, CH2ONH2, of the

Article
Macromolecules, Vol. 43, No. 2, 2010 1071
chain terminus) 6.59 (br, Ar, polymer backbone), 7.06 (br, Ar,
polymer backbone).
Scheme 1. Synthesis of Modified CTA Agents 1 and 2
Aldehyde-End-Functionalized Poly(methyl methacrylate)
(P2). The chain transfer agent 1 (118 mg, 0.188 mmol) and
AIBN (3.08 mg, 18.8 μmol) were added to a small Schlenk tube.
Methyl methacrylate (1.88 g, 18.8 mmol) was then added
followed by DMF (1.9 mL). The reaction mixture was degassed
five times, and then the vessel was backfilled with nitrogen,
purged with N2, and allowed to warm to room temperature. The
reaction mixture was placed in an oil bath at 70 °C. The
polymerization was quenched after 16 h, and solvent was
removed on the rotary evaporator. The resulting yellow oil
was dissolved in minimal amount of THF and added dropwise
to ice cold hexane. The polymer precipitate was then isolated by
filtration and dried under high vacuum. Polymer P2 was
obtained as pale yellow solid in a yield of 81%. 1H NMR
(CDCl3): δ 0.92 (br, 3H, CH2C(CH3)C, polymer backbone),
1.80 (br, 2H, CH2C(CH3)C, polymer backbone), 3.59 (br, 3H,
C(O)OCH3, polymer backbone), 8.01 (d, Ar, of the chain
terminus), 8.21 (d, Ar, of the chain terminus), 10.11 (s, CHO,
of the chain terminus).
Micellization of Dynamic Covalent Diblock Copolymer (P3-
Dynb-P5b). P3 poly(isoprene) (78.8 mg, 1 equiv) and P5b poly-
(styrene) (64.7 mg, 1 equiv) were dissolved in CH2Cl2 (2 mL),
and TFA (0.25 μL, 0.75 equiv) was added. The reaction mixture
was left to stir at room temperature for 24 h. After this time
DMF (8 mL) was added dropwise over 10 min. 2 mL of this
stock solution (0.4 mM) was filtered through 0.45 μm nylon
syringe filter and diluted in DMF to prepare a range of solutions
(0.2 mM-4 μM) for DLS and GPC analysis.
Aldehyde-End-Functionalized Poly(isoprene) (P3). The chain
transfer agent 1 (94 mg, 0.15 mmol) and tert-butyl peroxide (4.4
mg, 0.03 mmol) were placed in a small Schlenk tube fitted with a
Young’s tap. Isoprene (5.09 g, 0.0748 mol) was then added, the
reaction mixture was degassed five times, and the vessel was
backfilled with nitrogen, purged with N2, and allowed to warm
to room temperature. The system was then sealed and placed in
an oil bath at 125 °C. The polymerization was quenched after
45 h, and the reaction mixture was evaporated to dryness on the
rotary evaporator. The resulting yellow oil was dissolved in a
minimal amount of CH2Cl2 and added dropwise to ice cold
methanol. Evaporation to dryness and further drying under
high vacuum afforded polymer P3 as a yellow oil in a yield of
Results and Discussion
Chain Transfer Agent Syntheses. Oxime exchange was
chosen as our dynamic covalent reaction to link preformed
polymer blocks into diblock copolymers, as it is a well-
studied and successful reaction in dynamic covalent chemis-
try7,8b and one with which we had also gained experience in
our own research laboratory from previous projects. To
prepare polymer chains end-functionalized with either
alkoxyamine or aldehyde groups, we utilized reversible
addition-fragmentation transfer (RAFT) polymerization
techniques.14 RAFT is a living radical polymerization tech-
nique which allows access to a range of well-defined polymer
structures possessing high levels of end-group fidelity and is
mediated by a chain transfer agent (CTA) typically based
on dithioesters or trithiocarbonates. The use of modified
CTAs allows the preparation of polymers end-functionalized
with a specific functional group and overcomes the limita-
tions of postpolymerization strategies.15 Thus, the aldehyde-
containing CTA 1 was prepared (Scheme 1) in a yield of 59% via
a carbodiimide-mediated coupling between the chain transfer
agent (S-1-dodecyl-S0-(R,R0-dimethyl-R00-acetic acid)trithio-
carbonate)16 (DDMAT) and 2-[2-(2-hydroxyethoxy)ethoxy]-
ethyl-4-formylbenzoate. Likewise, the alkoxyamine-contain-
ing CTA 2was prepared from a similar carbodiimide-mediated
coupling between DDMAT and N-Boc-6-aminoxyhexan-1-ol
followed by acid-catalyzed removal of the Boc protecting
group, reactions which proceeded in yields of 57% and 55%,
respectively. 1H NMR (see Supporting Information) and
FTIR spectroscopies and mass spectrometry confirmed the
identity of both modified CTAs 1 and 2.
RAFT Polymerizations. Polymerizations of styrene, iso-
prene, and methyl methacrylate mediated by RAFT CTAs 1
and 2 afforded a range of formyl or alkoxyamine-termi-
nated17 polymers (Scheme 2, Table 1). The RAFT polymeri-
zations of styrene were performed in DMF at 70 °C using a
range of reagent stiochiometries (Table 1, entries P1a-P1d
and P5a-c) yielding well-defined polymers in all cases.
Pseudo-first-order rate plots and plots of molecular weight
versus conversion for styrene mediated by CTAs 1 and 2 were
performed. The plots obtained (Supporting Information)
from this brief kinetic study were linear, suggesting a con-
stant concentration of radicals during the polymerizations.
The polymerization of methyl methacrylate to afford P2 was
performed in DMF at 70 °C under near identical conditions
to those used for polystyrene P1. The RAFT polymerization
of isoprene to afford P3 was performed using the method of
1
83%. H NMR (CDCl3): δ 0.8-1.0 (br, dodecyl of the chain
terminus), 1.60 (br, CH3, polymer backbone), 2.00 (br, CH2,
polymer backbone), 3.35 (br, SCH2, of the chain terminus),
4.0-4.1 (br, CH, polymer backbone), 4.6-4.8 (br, 3,4-C-
(CH3)-CH2, polymer backbone), 4.8-5.1 (br, 1,2-CHdCH2,
polymer backbone), 5.1-5.3 (br, 1,4-CH2-C(CH3)-CH-CH2,
polymer backbone) 5.70-5.85 (1,2-CHdCH2, polymer back-
bone), 7.95 (d, Ar, of the chain terminus), 8.22 (d, Ar, of the
chain terminus) 10.12 (s, CHO, of the chain terminus). 1H NMR
spectroscopic analysis confirmed the distribution of monomers
units to be 10:19:230 for the 1,2-, 3,4-, and 1,4- conformations,
respectively.
Aldehyde-End-Functionalized Poly(ethylene glycol) (P4).
Poly(ethylene glycol) monomethyl ether Mw = 5000 g mol-1
(Sigma-Aldrich) (3.65 g, 0.731 mmol) was dissolved in CH2Cl2
(50 mL). 4-Carboxybenzaldehyde (0.548 g, 3.65 mmol), DMAP
(0.464 g, 3.80 mmol), and EDC (0.728 g, 3.80 mmol) were added,
and the reaction mixture was stirred at room temperature
for 72 h and then evaporated to dryness. The crude product
was dissolved in CH2Cl2 (10 mL), and this solution was
added dropwise to ice cold diethyl ether. The precipitated solids
were isolated by filtration, the precipitation procedure was
repeated another two times, and the product was dried
under high vacuum. Polymer P4 was obtained as a white solid
in a 20% yield. 1H NMR (CDCl3): δ 3.61 (br, 4H, CH2-CH2O,
polymer backbone), 7.95 (d, Ar, of the chain terminus), 8.21 (d,
Ar, of the chain terminus), 10.10 (s, CHO, of the chain
terminus).
General Procedure for Dynamic Covalent Diblock Copoly-
mers. The appropriate aldehyde-terminated polymer (P1a-d,
P2, P3, P4) and alkoxyamine-terminated polymer (P5a,c) were
1
dissolved in DMF-d7 (5 mM of each polymer) for H NMR
spectroscopic analysis or THF (5 mM of each polymer) for GPC
analysis. To each solution TFA (10-20 mol %) was added.
Samples were analyzed at regular intervals during the dimeriza-
tion process after predetermined times.

1072 Macromolecules, Vol. 43, No. 2, 2010
Jackson and Fulton
Wooley and co-workers18 using tert-butyl peroxide as ini-
tiator at 125 °C in the absence of solvent. All RAFT
polymers were characterized by GPC analysis, indicating
unimolecular weight distributions and low polydispersities
in all cases. The DP values calculated from NMR matched
well those found by GPC. Polymer P4 was prepared by
EDC-mediated esterification of commercially available
poly(ethylene glycol) monomethyl ether (Mw =∼5000 Da)
with 4-formylbenzoic acid. The presence of the formyl or
alkoxyamine end groups in polymers P1-P5 was confirmed
by 1H NMR spectroscopy. Polymers possessing formyl end
groups (P1-P4) each displayed singlets at 10.10-10.12 ppm,
corresponding to the formyl proton, and triplets at 3.29 ppm,
corresponding to the SCH2 group. Those polymers possess-
ing alkoxyamine end-groups (P5a-c) each displayed signals
at 5.34 ppm corresponding to CH2ONH2 and triplets
at 3.29 ppm corresponding to SCH2 group. The degree of
end-functionalization of all RAFT polymers (P1-P3, P5)
was estimated from 1H NMR spectroscopy to be ∼80-90%
and the degree of end-functionalization of polymer P4 to
be ∼95%.
the modified CTAs 1 and 2 to form the oxime-linked dimer 3
(Scheme 3). TFA catalyst (20 mol %) was added to a 1:1
mixture of 1 and 2 (c = 30 mM of each component) in CDCl3
and the solution allowed to come to equilibrium (<30 min).
1H NMR spectroscopy showed (Figure 1a) a significant
reduction in the intensity of the signal corresponding to the
formyl proton (Ha) of 1 and the appearance of a trans-oxime
(Ha ) signal at 8.14 ppm.19 These changes were accompanied
0
by a reduction in intensity of the aromatic signals (Hc) of 1 at
8.21 and 7.95 ppm and the appearance of signals correspond-
0
ing to the aromatic moiety of oxime 3 (Hc ) at 8.03 and 7.66
ppm. Further evidence for the formation of 3 was obtained
from electrospray mass spectrometry of this solution, which
showed a signal at m/z = 1090.51, indicating the presence of
the oxime-linked dimer 3 at equilibrium. To demonstrate the
dynamic nature of oxime 3, 4 equiv of 2-aminooxymethy-
napthalene 4 was added (Scheme 3), and the solution was
left to re-equilibrate. 1H NMR spectroscopic analysis
(Figure 1b) shows the appearance of a signal at 5.41 ppm,
0
corresponding to the CH2ON protons of oxime 5 (He ) and
an equal increase in the intensity of the signal corresponding
to the CH2ONH2 protons of 2 (Hf,g). This observation
indicates the presence of oxime 5 and confirms the dynamic
nature of the oxime bond.20 These same experiments were
repeated in DMF-d7 with essentially identical outcomes,
and the equilibrium constant in this solvent for the formation
of oxime 3 from starting materials 1 and 2 was determined
from 1H NMR spectroscopy to be 361.21
Formation and Characterization of Dynamic Covalent Di-
block Copolymers. As a first step toward dynamic covalent
diblock copolymers, we studied initially the dimerization of
Scheme 2. Structures of Aldehyde- or Alkoxyamine-End-Functiona-
lized Polymers P1-P5
To investigate the formation of a dynamic covalent block
copolymer, P1b (Mn = 4800 Da) and P5a (Mn = 6200 Da)
weremixedinDMF-d7 (5mMeach) andTFAadded(10mol%),
Scheme 3. Dimerization of Modified CTAs 1 and 2 To Form Oxime 3
and Subsequent Re-equilibration upon the Addition of 1-Aminooxy-
methylnapthalene into Oxime 5
Table 1. Selection of Aldehyde- or Alkoxyamine-End-Functionalized Polymers P1-P5
PDIb
(Mw/Mn)
a
b
b
chain transfer
agent
Mn
temp (°C) time (h) (g mol-1
Mn
(g mol-1
Mw
(g mol-1
polymer
monomer
initiator
)
)
)
P1a
P1b
P1c
P1d
P2
1 (1 equiv)
1 (1 equiv)
1 (1 equiv)
1 (1 equiv)
1 (1 equiv)
1 (1 equiv)
styrene (100 equiv)
styrene (100 equiv)
styrene (100 equiv)
styrene (200 equiv)
methyl methacrylate (200 equiv) AIBN (0.1eq)
isoprene (500 equiv)
AIBN (0.2 equiv)
AIBN (0.1 equiv)
AIBN (0.2 equiv)
AIBN (0.1 equiv)
70
70
70
70
70
125
3
14
24
26
24
45
1750
5100
6250
9800
13550
18300
5000
6350
10750
5050
1950
4800
6100
2100
5050
6600
10700
16000c
19100
5450c
6400
1.08
1.05
1.08
1.19
1.35
1.31
1.11
1.03
1.18
1.04
9000
11850c
14 600
4900c
6200
P3
P4
t-BP (0.2 equiv)
P5a
P5b
P5c
2 (1 equiv)
2 (1 equiv)
2 (1 equiv)
styrene (100 equiv)
styrene (300 equiv)
styrene (200 equiv)
AIBN (0.2 equiv)
AIBN (0.2 equiv)
AIBN (0.1 equiv)
70
70
70
21
23
16
12700
5450
14950
5650
a As determined by 1H NMR spectroscopy. b As determined by gel permeation chromatography in THF. c Calculated by multiangle light scattering.
AIBN: azobis(isobutyronitrile); tBP: tert-butyl peroxide.

Article
Macromolecules, Vol. 43, No. 2, 2010 1073
Figure 1. (a) Partial 1H NMR spectra (300 MHz, 298 K, CDCl3) displaying dimerization between modified chain transfer agents 1 þ 2 to afford dimer
3 linked via oxime formation. (b) Partial 1H NMR spectra (300 MHz, 298 K, CDCl3) displaying the re-equilibration of oxime 3 to oxime 5 upon the
addition of alkoxyamine 4.
Figure 2. Partial 1H NMR spectra (300 MHz, 298 K, DMF-d7)
Figure 3. Gel permeation chromatography (THF, 1 mL/min) traces of
the dimerization process of P1b and P5a into P1b-Dynb-P5a at t = 0, 3,
8, and 24 h. Traces were recorded on a UV detector at 254 nm.
displaying dimerization between P1b and P5a to afford oxime-linked
dynamic covalent diblock copolymer P1b-Dynb-P5a.
and the reaction was allowed to reach equilibrium. The
solution was analyzed by H NMR spectroscopy (Figure 2),
Table 2. Preparation of a Selection of Homo- and Heterodynamic
Covalent Diblock Copolymers (5 mM of Each Block)
1
which displayed the appearance of a signal at 8.35 ppm
corresponding to the oxime linkage of P1b-Dynb-P5a22
(Mn = 11 000 Da) and a reduction in the intensity of the
signal at 10.21 ppm corresponding to the formyl proton in
P1b. Under these conditions, equilibrium was reached in
∼24 h. Dimerization of P1b and P5a to form P1b-Dynb-P5a
was also investigated by GPC (Figure 3), which shows
the appearance of a peak at 14.29 min, corresponding to
the block copolymer P1b-Dynb-P5a and the reduction in
area of the peak at 15.01 min corresponding to both P1b and
P5a. To demonstrate the dynamic and reversible nature of
the oxime linkage, excess 1-aminooxyhexane (10 equiv) was
added to a solution of P1b-Dynb-P5a at equilibrium with its
component polymer blocks in the presence of TFA. GPC
analysis displayed the complete disappearance of the peak at
14.29 min and an increase in the area of the peak at 15.01
min, a process which took 4 days to reach completion. This
observation suggests that 1-aminooxyhexane competes with
the alkoxyamine end group of P5a to form an oxime linkage
with P1b, resulting in the re-equilibration of the diblock
copolymer P1b-Dynb-P5a into P5a and hexyloxime-
capped P1b. The results of the 1H NMR spectroscopic
and GPC analysis suggest that polymer chains can be
linked through a dynamic covalent bond to form a diblock
copolymer which displays dynamic behavior.
theoretical Mn (Da) association
constant
polymer blocks block copolymers of block copolymera
P1b þ P5a
P1d þ P5b
P2 þ P5b
P3 þ P5b
P4 þ P5a
P1b-Dynb-P5a
P1c-Dynb-P5b
P2-Dynb-P5b
P3-Dynb-P5b
P4-Dynb-P5a
11 000
21 700
24 550
27 300
11 100
5.44b
2.45b
2.66b
2.07c
6.61c
a Calculated by addition of the Mn values (as determined by GPC or
multiangled light scattering) of each polymer block. b Calculated in
DMF-d7. c Calculated in THF-d8.
1
blocks were determined from H NMR spectroscopy and
were found to be considerably lower than those for the
dimerization of 1 þ 2. This significant reduction in equili-
brium constant is presumably on account of the steric bulk
of the polymer blocks hindering the linking of the chain
ends and the fact that not all polymer chains contain the
desired end-groups as a consequence of less than 100% end-
group fidelity in the RAFT process.
Self-Assembly of Micelles. To investigate the potential of
dynamic covalent diblock copolymers to form micellar
aggregates, we focused on the P3-Dynb-P5b system formed
at equilibrium from the dimerization of the polystyrene
block P5b and the polyisoprene block P3 in DMF, which
is a selective solvent for the polystyrene block. The self-
assembly into micelles of polystyrene-b-polyisoprene di-
block copolymers in organic solvents which are selective
for one of the blocks is well-known,23 and this aggregation
process is thought to be enthalpy-driven.23b Under the
A series of end-functionalized polymer building blocks
were reacted to form dynamic covalent diblock copolymers
and characterized under equilibrium conditions (Table 2).
The equilibrium constants for the dimerization of all polymer

1074 Macromolecules, Vol. 43, No. 2, 2010
Jackson and Fulton
of the system to 65-70 nm. Furthermore, even after several
days no precipitation of the polyisoprene cores was ob-
served. These observations suggest the formation of meta-
stable aggregates of collapsed polyisoprene cores in DMF,
which is a poor solvent for polyisoprene, formed when the
individual polystyrene and polyisoprene blocks begin to
phase separate,25 and support the hypothesis26 that the
addition of the small molecule alkoxyamine 4 has indeed
triggered the decomposition of the micelles.
Summary
In summary, we have utilized RAFT polymerization techni-
ques to prepare a series of polymer building blocks possessing
either aldehyde or alkoxyamine functions as end-groups. We
have demonstrated that these polymers can link together through
dynamic covalent oxime bonds to form dynamic covalent diblock
copolymers and highlighted the dynamic nature of these species.
The ability of a dynamic covalent diblock copolymer formed
from polystyrene and polyisoprene blocks to aggregate into
higher order micellar structures has been demonstrated, and we
have shown how its disassembly can be triggered by the addition
of a small molecule alkoxyamine. We believe that the utilization
of dynamic covalent linkages between polymer blocks may lead
to the development of new dynamic functional materials and
complements alternative systems2-6 that utilize noncovalent or
metal-ligand interactions to link polymer chains together. In
particular, our approach may allow for the preparation of
kinetically stable micelles which possess the ability to alter the
polymer block composition of their coronal polymer chains while
their core polymer chains remain within the core.
Figure 4. Regularization analysis of DLS data of micelles formed from
P3-Dynb-P5b in DMF.
Acknowledgment. Research Councils UK (fellowship to
D.A.F.), Newcastle University (Studentship to A.W.J.), and
One North East are gratefully thanked for support.
Figure 5. Gel permeation chromatographic traces of the micellar
aggregates formed from dynamic covalent diblock copolymer P3-
Dynb-P5b (dotted line) and trace of the decomposition products
(solid line). GPC was performed in DMF at 1 mL/min at 40 °C and
recorded using a light scattering detector measuring the scattered light
at 90°.
Supporting Information Available: 1H NMR spectra of the
modified chain transfer agents 1 and 2 and kinetic plots demon-
strating the controlled nature of the polymerization of styrene
mediated by these chain transfer agents. This material is avail-
able free of charge via the Internet at http://pubs.acs.org.
conditions studied, any micelles formed should possess
polyisoprene chains at their core surrounded by a corona
of polystyrene chains. On account of the poor solubility of
P3 in DMF, both P3 and P5b were dissolved in CH2Cl2
(concentration of each block = 2 mM) and TFA was added
(10 mol %). DMF was added, and a portion of this stock
solution was filtered and further diluted in DMF
(concentration of each block ∼4 μM). Dynamic light scatter-
ing measurements indicated the formation of a tertiary
structure with a calculated hydrodynamic radius of 29.6 (
1.8 nm (by cumulants analysis). Regularization analysis of
the light scattering data displays (Figure 4) a narrow mono-
modal particle size distribution. Control experiments using
THF, which is selective for both blocks, revealed a hydro-
dynamic radius which indicates only the presence of non-
aggregated polymer mono- and diblocks. Further evidence
for the formation of a tertiary structure was obtained from
GPC analysis (Figure 5) at 25 °C, which displayed a peak at
11.04 min, corresponding to a very high molecular weight
aggregate. The spreading after the micelle peak may be
attributable to the effects of dilution on the micelle/free
chain equilibrium and/or the lack of micelle stability.
References and Notes
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polystyrene standards of masses up to 6.3 MDa (retention time
9.20 min) affords a linear calibration curve. The observed decom-
position product (retention time 9.00 min) is therefore probably
of even higher mass, although it is not known with certainty
whether this measurement is within the exclusion limits of our
GPC setup.
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formation of micelles, a solution of polystyrene and polyisoprene
blocks of very similar size which do not contain reactive end-
functional group was prepared and analyzed by DLS and GPC.
This sample was found to display the same GPC characteristics as
the sample prepared by the small molecule-induced decomposition
of P3-dynb-P5b. The same situation was observed when the
procedure was repeated with polyisoprene P3 on its own.
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stable trans-isomer.
(20) The NMR spectroscopic and mass spectrometry studies also
indicate that the trithiocarbonate moieties of all species in solution