Designing miktoarm polymers using a combination of "click" reactions in sequence with ring-opening polymerization

Article abstract of DOI:10.1021/ma100845a

The design and synthesis of a well-defined molecular building block with three orthogonal functionalities which facilitate the construction of ABC-type miktoarm star polymers via a combination of sequential Cu^I-catalyzed cycloaddition of an azi

Full text of DOI:10.1021/ma100845a

5688 Macromolecules 2010, 43, 5688–5698
DOI: 10.1021/ma100845a
Designing Miktoarm Polymers Using a Combination of “Click” Reactions
in Sequence with Ring-Opening Polymerization
Kunal Khanna,† Sunil Varshney,‡ and Ashok Kakkar*,†
†Department of Chemistry, McGill University, 801 Sherbrooke St. West, Montreal, Quebec H3A 2K6, Canada,
and ‡Polymer Source Inc., 124 Avro Street, Dorval (Montreal), Quebec H9P 2X8, Canada
Received April 20, 2010; Revised Manuscript Received May 27, 2010
ABSTRACT: The design and synthesis of a well-defined molecular building block with three orthogonal func-
tionalities which facilitate the construction of ABC-type miktoarm star polymers via a combination of sequential
CuI-catalyzed cycloaddition of an azide to an alkyne (“click”) followed by ring-opening polymerization are
reported. Using this simple and highly versatile methodology, a variety of miktoarm star polymers were prepared
which consisted of hydrophilic poly(ethylene glycol) and hydrophobic polystyrene and poly(ε-caprolactone) arms.
Their self-assembly in an aqueous medium was examined using dynamic light scattering and transmission electron
microscopy. These ABC miktoarm polymers were found to self-assemble into spherical micelles whose core size and
hydrodynamic diameter were found to be inversely proportional to the size of the PEG arm. The potential of
encapsulating small molecules into these micelles was explored using Disperse Red 1 dye. An enhancement in the
loading capacity of the micelles was observed with an increase in the length of the hydrophobic arm.
Introduction
orthogonal functionalities that facilitates performing two “click”
reactions in sequence, followed by ring-opening polymerization. We
Miktoarm polymers1 constitute an intriguing class of star-
shaped polymers whose arms can be varied in terms of their chemi-
cal identity and/or molecular weight.2 The inherent architecture of
these polymers that can be finely tuned based on the desired fea-
tures and their unique self-assembly3 has made this relatively novel
class of macromolecules very attractive for applications in a large
variety of areas, the most widely explored of which are micellization
and drug delivery.4 The challenges that were faced in the prepara-
tion of these star polymers using earlier techniques such as living
anionic polymerization and chlorosilane chemistry have led to the
development of some elegant synthetic methodologies,5 including
“arm-first”,5k “core-first”,5l “in-out”,5m and coupling,5n each with
its own merits. Despite requiring the synthesis of a unique small
molecule designated as the core of the star structure, coupling
methods have recently garnered much momentum in the field of
miktoarm star polymer synthesis because of two important factors:
the opportunity to ensure the integrity of each polymer arm before
attachment to the growing miktoarm star, and the well-defined
control that is achieved over the final structure’s number of arms
and their chemical identity. Recent addition of “click” chemistry6
to macromolecule synthesis has provided a highly useful tool to the
polymer chemist in diversifying the synthetic strategy of these star
polymers. A “click” reaction such as the CuI-catalyzed cycloaddi-
tion of an azide to an alkyne6a can be carried out with great ease in a
variety of experimental conditions without interfering with a large
variety of functionalities that may be present in the overall
structure. This reaction has been widely employed in the synthesis
of branched macromolecular structures including dendrimers6b-d
and star polymers.7
used this methodology to construct a library of ABC-type miktoarm
star polymers containing a combination of poly(ethylene glycol)
(PEG), polystyrene (PS), and poly(ε-caprolactone) (PCL). These
linear polymeric arms8 offer tunability in terms of the properties of
the corresponding miktoarm polymers.
The synthetic elaboration of these multicomponent macromole-
cules has also intrigued scientists to evaluate their self-assembly in
solution. Hadjichristidis et al. have carried out numerous studies in
which they have shown that the morphologies of the self-assembled
structures from miktoarm polymers can range from lamellar to
cylindrical structures.9 In addition, the formation of spherical mice-
lles that were pH-responsive was reported by Babin et al. using
A2B-type miktoarm polymers.10 Lodge’s group has demonstrated
that ABC-type miktoarm polymers containing poly(ethylethylene)
(PEE), poly(ethylene oxide (PEO), and poly(perfluoropropylene
oxide) (PFPO) form multicompartment micelles in aqueous solu-
tions.11 The aqueous self-assembly of these ABC star polymers was
found to be dependent on the individual lengths of the chains and
was reported to be dictated by the inherent incompatibility of the
polymeric arms. The miktoarm polymers that do not contain such
distinct partitions in interactions of their polymeric arms offer ano-
ther platform to finely tune their self-assembly behavior.12 We have
studied the aqueous self-assembly of ABC μ-miktoarm polymers
reported here that contain PEG, PS, and PCL arms, using dyna-
mic light scattering (DLS) and transmission electron microscopy
(TEM). These star polymers assemble into spherical micelles, and
our results suggest that the size of the hydrophilic corona arm
influences the hydrodynamic diameter of the micellar assemblies.
We have also evaluated loading of Disperse Red 1 dye molecules
into the self-assembled structures of these miktoarm polymers in
solution, whose loading efficiency was found to be dependent on
the length of the hydrophobic polymeric arms.
As it is well documented now, the controlled introduction of
different types of polymeric arms onto a single scaffold necessitates a
combination of synthetic methodologies in order to ensure the inte-
grity of the final structure. Thus, it is essential to design a core struc-
ture with orthogonal functional groups that will allow stitching of
polymers at different junctures throughout the synthesis. We report
here the construction of a versatile core structure with three
Results and Discussion
We first envisioned the construction of a versatile multifunc-
tional core structure on which a variety of miktoarm star
polymers (μ-stars) could be easily constructed using a desired
*Corresponding author. E-mail: ashok.kakkar@mcgill.ca.
pubs.acs.org/Macromolecules
Published on Web 06/09/2010
r 2010 American Chemical Society

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Macromolecules, Vol. 43, No. 13, 2010 5689
Scheme 1. Synthesis of the Core Compound 4 with Three Orthogonal Functionalities
Scheme 2. Synthesis of Monofunctional Azide- and Alkyne-Termi-
nated Polymers 5 and 6
variation of synthetic strategies. One of the key features required
in the design of the core structure was the introduction of ortho-
gonality because it ensures a controlled introduction of polymeric
arms. By allowing each of its specific functional groups to be
activated for the attachment or growth of an individual polymeric
arm, the final μ-star can be synthesized with relative ease and
minimal purification strategies. While many different “click” reac-
tions have now been identified,6 the most widely used to date has
been the CuI-catalyzed Huisgen [3 þ 2] cycloaddition between an
azide and an alkyne (CuAAC).6a Some of the key features of this
methodology include benign reaction conditions, high yield, rela-
tively simple purification methods, and modular applicability.
Many examples have recently surfaced throughout macromolecu-
lar chemistry where “click” chemistry has been employed as a
synthetic route6,7 and has been utilized to adjoin building blocks
together in a predictable and efficient fashion. To implement the
synthesis of ABC-type miktoarm star polymers reported here,
compound 4 (Scheme 1) was designed as a core which features (i)
a benzylic alcohol that can be used for the ring-opening polymer-
ization of ε-caprolactone and (ii) two protected alkyne groups for
“click” chemistry using CuAAC. It is well-known that the tri-
methylsilyl (TMS) moiety can be selectively cleaved from the
protected acetylene under mildly basic conditions, while the re-
maining triisopropylsilyl (TIPS) moiety is left intact. The latter
requires stronger basic conditions for deprotection of its acetylene,
thereby ensuring that these two protected acetylenes are orthogonal
to one another.13 Thus, the core structure 4 is a trifunctional
compound that can be utilized for two “click” reactions sequen-
tially, followed by ROP to construct a μ-star.
monomethyl ether was quantitatively converted to a mesyl group.
The latter is an excellent leaving group for its subsequent nucleo-
philic substitution with an azide. Polystyrene azide (PS-N3) of Mn
∼ 4300 (6b) was synthesized in a similar manner from its commer-
cially available monohydroxy form. PS with Mn ∼ 2700 (6a) was
synthesized by living anionic polymerization with sec-butyllithium
as the initiator, end-capped with ethylene oxide. Conversion to its
azide form was achieved in a similar fashion as described for 5 and
6a.16 It should be noted that 1H and 13C{1H} NMR spectra were
found to be highly useful in monitoring the conversions in these
reactions.
The synthesis of the core started with the reduction of
commercially available 3-bromo-5-iodobenzoic acid (1) to its
corresponding alcohol14 2 in high yield (Scheme 1) and was easily
1
A general procedure for the synthesis of μ-star polymers using
a combination of “click” reactions in sequence followed by ROP
is described in Scheme 3 for μ(PEG2000-PS4300-PCL4000: the
subscript corresponds to Mn). The details of this methodology
apply to the rest of μ-stars synthesized using this route. The
synthesis was begun by carrying out “click” reactions, and the
conversion of 4 to 7 was the first step for the buildup of miktoarm
polymer. Because the integration and peak position of the aryl
protons, triazole ring protons, and the acetylene proton become
diagnostic in monitoring the reaction, we decided to delay the
monitored via H NMR by the appearance of the CH2-OH
group at 4.63 ppm. The Sonogashira coupling reaction was
subsequently utilized to covalently link triisopropylsilylacetylene
with the aryl iodide group, leading to the synthesis of 3. It was
followed by the appearance of the triisopropylsilyl (TIPS) group
in the 1H NMR at 1.12 ppm. In this step, column chromatogra-
phy was found to be essential for isolation of the monosubstituted
compound from the impurities, including the disubstituted side
product. The final step in the synthesis involved another Sono-
gashira coupling reaction between trimethylsilylacetylene and the
1
1
ROP to the final step in order to facilitate this analysis via H
aryl bromide to yield 4. Once again, H NMR made it easy to
NMR. Aqueous potassium carbonate was used to deprotect the
TMS group while leaving the TIPS group completely intact, as
confirmed by 1H and 13C{1H} NMR. In the 1H NMR spectrum,
both the shift in the peak positions of the aryl protons and their
relative integration with the new acetylene peak were used to
confirm the identity of 7. The subsequent CuAAC “click”
reaction between 5b and 7 using CuBr/PMDETA as a catalyst
confirm this coupling in which the desired TMS group appeared
at 0.23 ppm. It should be noted that throughout each of these
transformations the changes in the position of the aryl protons in
the 1H and 13C{1H} NMR spectra are highly diagnostic for
determining the purity of the final compound, as the impurities
such as leftover reactants that did not undergo coupling can be
easily observed, particularly in the aryl region of the spectra.
The azide-terminated polymers used for “click” reactions with
the core were subsequently synthesized (Scheme 2). Poly(ethylene
glycol) monomethyl azide (PEG-N3) 5a or 5b was prepared starting
from commercially available poly(ethylene glycol) monomethyl
ether with Mn ∼ 775 or 2000 g/mol by adaptation of a literature
method.15 In a general procedure for the synthesis of the azide-
terminated polymers, the terminal alcohol in poly(ethylene glycol)
1
yielded compound 8. The latter reaction was monitored by H
NMR in which shifts of the core’s aryl protons, disappearance of
the alkyne proton, and appearance of the PEG chain protons and
triazole ring proton were observed. Furthermore, GPC analysis
showed a polydispersity (PDI) which was in agreement with the
precursor PEG-N3. Tetrabutylammonium fluoride (TBAF) was
subsequently used to deprotect the second acetylene to give

5690 Macromolecules, Vol. 43, No. 13, 2010
Khanna et al.
Figure 1. GPC analyses of (a) azide-terminated PEG2000, (b) PEG2000-b-PS4300 copolymer, and (c) μ(PEG2000-PS4300-PCL4000) ABC miktoarm star
terpolymer.
Scheme 3. Synthesis of ABC Miktoarm Star Polymers μ(PEG-PS-PCL) Using CuAAC “Click” Reactions in Sequence, Followed by Ring-Opening
Polymerization (ROP)
compound 9. The evidence for this conversion was obtained from
peak integration of the new acetylene peak to the aryl protons in
1H NMR, loss of the TIPS group, and the corresponding shifts in
the acetylene carbons in 13C{1H} NMR.
displayed characteristic resonances for each of the three polymeric
arms (Figure 2). The μ-star polymers synthesized using this
procedure are summarized in Table 1. The PDI of these polymers
increased in direct proportion to the desired molecular weight of the
PCL arm and is related to the ROP method employed for the
synthesis. Such an increase in PDI from the ROP of ε-caprolactone
has been reported in the literature. For example, the growth of ε-
caprolactone using the same catalyst on a diblock copolymer
precursor led to an ABC miktoarm polymer with a broad molec-
ular weight distribution (PDI 1.50).17 It should be noted that the
ROP of ε-caprolactone was conducted at 130 °C except for 14,
where it was first attempted at a more modest temperature of
100 °C. In the latter case, no change in molecular weight was
observed when polymerization reaction was performed overnight.
After subsequently increasing the reaction temperature to 130 °C,
an increase in molecular weight was observed, corresponding to
the growth of PCL. This result strongly suggests a slow ROP
initiation due to steric hindrance in the diblock miktoarm
polymer, which can simply be overcome by performing the
PEG-PS precursor 10 was synthesized by CuAAC reaction of
6b with 9. GPC analysis of the latter showed a complete shift in
the chromatogram of the growing μ-star as well as a PDI and
molecular weight consistent with both polymeric precursors 6b and
9. The macroinitiator 10 was then employed for ROP with ε-
caprolactone monomer catalyzed by stannous octoate. The pro-
duct was precipitated into cold methanol to yield the final μ-star 11
as a white solid. GPC analysis (Figure 1) showed a clear shift in the
chromatogram with an increase in molecular weight that corre-
sponded with the theoretical molecular weight based on the
monomer/initiator ratio, indicating that an ABC miktoarm star
polymer was formed (as opposed to a mixture of macroinitiator 10
and poly(ε-caprolactone) homopolymer). The 1H NMR depicted a
new set of peaks that corresponded to poly(ε-caprolactone) (PCL),
and the final 1H NMR spectrum of the miktoarm polymer

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Macromolecules, Vol. 43, No. 13, 2010 5691
Figure 2. 1H NMR spectrum (400 MHz) of the miktoarm polymer 11 in CDCl3.
Table 1. μ-Star Polymers Synthesized Using Two Sequential “Click” Reactions Followed by ROP
mean DH of
aqueous micelles
mean DH of DR1
loaded micelles
DR1 loading
(wt %)
μ-star polymera
compound
PDIb
μ(PEG2000-PS4300-PCL4000
)
11
12
13
14
15
16
1.26
1.43
1.40
1.59
1.28
1.55
185
118
224
250
212
251
217
157
198
222
164
262
1.3
N/A
1.8
2.1
0.4
1.0
μ(PEG2000-PS4300-PCL10000
μ(PEG775-PS4300-PCL4500
μ(PEG775-PS4300-PCL10000
)
)
)
μ(PEG775-PS2700-PCL3000
)
μ(PEG775-PS2700-PCL6900
)
a Numbers in subscript indicate Mn of the polymeric arm. b From GPC measurements (THF) calibrated with polystyrene standards and refractive
index detector.
polymerization reaction at higher temperature. This might ex-
plain the increase in polydispersity upon growth of PCL, as it
well-known that higher reaction temperatures in ROP generally
lead to higher polydispersities.
star polymers form well-defined assemblies with a fairly
narrow size distributions. A comparison of the DLS data for
the miktoarm polymers (Table 1) indicated that there may be
an inverse relationship between the length of the PEG arm and
the mean hydrodynamic diameter (DH), a trend similar to one
observed by other groups.11a For example, as the PEG length
decreased in going from 12 (PEG2000-PS4300-PCL10000) to 14
(PEG775-PS4300-PCL10000), the mean DH increased from 118
Self-Assembly of Miktoarm Polymers. We subsequently
examined aqueous self-assembly behavior of the library of ABC
miktoarm polymers. Aqueous micelle preparation for miktoarm
polymers 11 and 12 was carried out by either (i) direct dispersion,
i.e., by dissolving a known amount of the polymer in water, or (ii)
a dialysis method in which the polymer is dissolved in a solvent
compatible with all polymeric arms, followed by addition of
water, and finally removal of the solvent by dialysis. Direct
dispersion of the polymer into water allowed 11 to self-assemble
into micelles, while 12 precipitated out of solution and showed no
micellar behavior. On the other hand, both polymers formed
micelles in the dialysis technique and even demonstrated repro-
ducibility in the micellar sizes. Therefore, all aqueous micelles
were subsequently prepared by the dialysis method, where the
polymer was dissolved in 10 mL of a 1:9 ratio of DMF and Milli-
Q water (0.1 wt % in solution), and then dialyzed against DMF
to yield aqueous micelles. The miktoarm polymers reported here
are expected to assemble in aqueous solution so that PEG (a
hydrophilic polymeric arm) forms a corona, as it interacts with
the surrounding solvent. This protects the hydrophobic interior
that is composed of PS and PCL arms which do not interact
to 250 nm (Figure 3). Similarly in the case of 11 (PEG2000
-
PS4300-PCL4000) and 13 (PEG775-PS4300-PCL4500), DH in-
creased from 185 to 224 nm (Figure 4). We exercise caution
in the interpretation of the above results because the miktoarm
polymers reported here span a narrow spectrum of PEG
volumefractions (fPEG), andtherefore any inverse relationship
does not take into account different packing motifs that can
be observed across a wider spectrum of fPEG.
11a,d Our correla-
tion between PEG arm size and DH will need to be further
elaborated with polymers that are more hydrophilic than
those used in this study. A variety of polymeric systems are
currently being explored in numerous laboratories for che-
motherapeutic drug delivery with the eventual goal of improv-
ing passive targeting of macromolecules toward tumors. It has
been suggested20 that not only can the branched architecture
of miktoarm polymers inhibit renal filtration and promote
prolonged blood circulation, but higher molecular weight
(and, more importantly, the consequent increase in DH) can
also contribute to these beneficial effects. For the miktoarm
polymers reported here, shorter PEG arms lead to higher DH
while the overall discrete micellar structure in solution is
maintained (see Figures 5-8), suggesting that tuning the size
of the overall self-assembled miktoarm polymers may be
possible in a way that can help optimize the passive targeting
of these macromolecules into tumor tissues.
1
favorably with water. We examined this behavior using H
NMR of 11 in D2O, which confirmed this hypothesis,18,19 and
the 1H NMR showed the peaks for PEG, while the PS and PCL
signals were found to be absent due to restricted movement of
these polymer arms within the micelle core.
The sizes of aqueous μ-star were examined by dynamic light
scattering (DLS), and in general, the polydispersities of the
micelles were relatively narrow (e0.1). It suggested that these

5692 Macromolecules, Vol. 43, No. 13, 2010
Khanna et al.
Figure 3. Comparison of hydrodynamic diameter DH of 12 with 14 in aqueous solution.
Figure 4. Comparison of hydrodynamic diameter DH of 11 with 13 in aqueous solution.
Transmission electron microscopy (TEM) was subse-
quently employed to further elucidate the self-assembly of
these miktoarm polymers. In the case of star polymer 11
small, spherical micelles of 10-20 nm in size were observed
(Figure 5). One possible explanation here for the disparity
between TEM and DLS data, which had given a mean size
distribution of 185 nm, lies in the fact that DLS creates a size
distribution curve from solvated micelles where the PEG
chains, which form the corona, are spread out. On the other
hand, TEM images are acquired from dried solutions where
the PEG chains are coiled and bent. Additionally, PEG
chains will not be visible through TEM, so the sizes obtained
from TEM are more representative of the core of the
micelles, which is composed of PS and PCL and shows up
clearly in TEM.
Self-assembly of 12 in TEM yielded individual micelles
with a predominant size distribution between 50 and 100 nm
(Figure 6), while DLS had suggested a size distribution of
100-135 nm. Once again, the difference in DLS and TEM
data can be attributed to both the lack of solvation of the
hydrophilic PEG corona as well as the lack of visibility of
these chains. An interesting trend was noted while compar-
ing DLS and TEM data for 11 and 12. Polymers 11 and 12
differ in the length of the hydrophobic PCL arm which
comprises the core. It is 2.5 times larger for 12 compared to
11, and we observed a corresponding increase in the size of
micelles from 12 when examined using TEM. We expect that
a similarly proportional increase in size would be measured
by DLS, as the only difference between 11 and 12 would be
the increase in the size of the core. However, according to

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Macromolecules, Vol. 43, No. 13, 2010 5693
Figure 7. TEM image for micelles of 13. Scale bar is 500 nm.
Figure 5. TEM image for micelles of 11. Scale bar is 100 nm.
Figure 8. TEM image for micelles of 14. Scale bar is 500 nm.
Figure 6. TEM image for micelles of 12. Scale bar is 500 nm.
DLS results, the micellar size of 12 is significantly smaller
than 11. This suggests that an increased micellar core size
which results from longer hydrophobic PCL arms accom-
panies a change in the structure of the corona where the
hydrophilic PEG chains are of the same size. This could be a
result of a change in the interfacial curvature of the micelle.
In addition, an increase in polydispersity could also con-
tribute to the decrease in DH observed by DLS. An altogether
different chain packing motif could also explain this phe-
nomenon, especially when one considers the limitations that
accompany viewing aqueous micelles by TEM.
Figure 9. TEM image for micelles of 16. Scale bar is 500 nm.
(10-20 nm) and 13 (160-250 nm). It suggested that a
dramatic increase in the size of the core can be obtained
from a simple decrease in the length of the hydrophilic PEG
chain which forms the corona. Similarly, a comparison of the
sizes of 12 and 14 (Figure 8) also suggested an inverse
relationship between PEG arm length and the size of the
core. This trend corresponds with that which was observed
from DLS: that controlling the size of the hydrophilic PEG
arm allows one to control the size of the micelle. While one
may expect a similarity in the core sizes between the micelles
of these miktoarm polymers on account of their similarities
in sizes of the hydrophobic blocks, it has also been docu-
mented that morphological changes within the micellar core
can occur as the hydrophilic polymer length is varied.11a
Polymer 16 showed a rather unique assembly of micelles
that had conjoined from end to end to form an aggregate
which resembled a pearl necklace (Figure 9), composed
mostly of small micelles (∼60 nm). These individual micelles
assembled to form aggregates with sizes well over 200 nm.
The appearance of large aggregates composed of small
Miktoarm polymer 13 depicted spherical micelles in TEM
(Figure 7), ranging in size from roughly 160 to 250 nm. The
size distribution curve from DLS studies of this polymer was
found to be between 190 and 270 nm. We attribute the
observed TEM sizes to the formation of individual micelles
rather than any micellar clusters, based on the excellent base-
line fitting from DLS and reproducibility of this data. It is
expected that the difference in the size distribution between
DLS and TEM should not be as dramatic for polymers
13-16 since the PEG chain is almost 3 times shorter, in com-
parison to 11 and 12. Thus, a small increase in the micelle
size for polymers 13-16 is expected when comparing results
from TEM to those from DLS. This is confirmed above
by a modest increase in size distribution of 13 from TEM
(160-250 nm) to DLS (190-270 nm).
It was interesting to compare the micellar core size dis-
tribution obtained from TEM studies of star polymers 11

5694 Macromolecules, Vol. 43, No. 13, 2010
Khanna et al.
Figure 10. Evolution of size-distribution curve for aqueous micelles of 13, from micelle preparation through 2 weeks.
micelles helps to explain the predominant population ob-
served in DLS of structures above 200 nm.
Since we had carried out DR1 loading using the extraction
method, a change in hydrodynamic diameter observed upon
small molecule encapsulation could be misleading. For example,
in a control experiment, we evaluated the changes in micellar size
upon exposure to tert-butyl methyl ether without the addition of
DR1. The aqueous micelles from miktoarm polymers were
extracted with tert-butyl methyl ether and studied using DLS.
The hydrodynamic diameter was found to increase by about
70 nm upon exposure to tert-butyl methyl ether. The change in
hydrodynamic diameter upon loading the micelle with the dye is
of less importance than the stability of the dye-encapsulated
micelle itself, as this stability is a more salient feature in the design
of a drug delivery nanoparticle.
UV-vis spectroscopy was subsequently employed to
quantify the loading capacity of dye molecules within the
hydrophobic interior of these aqueous micelles. DR1 solu-
tions in dichloromethane were used to create a calibration
curve in order to determine the amount of DR1 that was
encapsulated within each micellar system. The calibration
curve had a correlation of 99.6%. The dye-encapsulated
micelles were lyophilized and harvested into DCM and
analyzed by UV-vis spectroscopy. Encapsulation results
obtained from this calibration curve are summarized in
Table 1, and in general a modest loading between ∼1 and
2 wt % was observed. In miktoarm polymer 12, DR1 loading
could not be determined with certainty because the DR1
peak in the UV-vis spectra was hidden by the stronger
absorption of the polymer. Miktoarm polymers 13 and 14
showed the best loading capacities, while 15 and 16 with
smaller PS and PCL chains exhibited the lowest levels of
DR1 encapsulation. The encapsulation studies suggest that
larger PS and PCL arm lengths contribute to a higher DR1
loading, and this is in agreement with the notion that the
higher volume fractions of the hydrophobic polymers facil-
itate higher loading of the hydrophobic dye DR1 within the
micelles. Another contributing factor to the encapsulation
results comes from the micelle size of DR1-loaded μ-stars.
Polymers 12 and 15 had the smallest micelle size (157 and
164 nm) compared to the rest of the miktoarm polymers and
showed either undetectable or minimal DR1 loading. On
the other hand, the rest of the polymers had sizes in excess of
Stability of the micelles is highly essential for applications
including drug delivery, catalysis, etc. To examine the stabi-
lity of the micelles formed by miktoarm polymers reported
here, DLS data were obtained over a period of 2 weeks.
During this period, aqueous micelles were stirred at room
temperature. Figure 10 shows data for a representative
miktoarm polymer 13. It showed no significant change in
the size of the micelles, suggesting that the micelles were
stable once formed in water. Any variations in sizes (within
10 nm) can be attributed to slight changes in temperature or
even statistical variations in the data. Nonetheless, the curve
for the size distributions retained the same overall shape.
Disperse Red Encapsulation. The encapsulation of small
molecules into the assemblies of the miktoarm polymers
reported here was evaluated using Disperse Red 1 (DR1).
It was considered to be a suitable candidate for this study due
to its hydrophobic nature which should facilitate its encap-
sulation within the hydrophobic core of aqueous micelles. In
addition, DR1 does not dissolve in water but has excellent
solubility in organic solvents. Thus, upon interaction with
aqueous micelles, DR1 would prefer to move into the
protected hydrophobic interior of the polymeric micelles,
where it will be shielded from unfavorable interactions with
the surrounding solvent. Encapsulation was achieved by the
extraction technique, where an aqueous polymer solution
was stirred with a concentrated solution of Disperse Red 1 in
tert-butyl methyl ether overnight at room temperature. After
allowing the solution to settle for an hour, the aqueous
fraction was withdrawn and analyzed by DLS and UV-vis
spectroscopy, and the results are presented in Table 1. tert-
Butyl methyl ether was chosen for the organic phase due to
the insolubility of the μ-stars in this solvent.
In general, the DR1-loaded micelles were found to be stable
based on the DLS results. The initial size distribution of DR1-
loaded micelles was found to be well-maintained upon prolonged
exposure to the organic dye solution (for 1 week, Figure 11).
Furthermore, this size distribution was maintained through
equilibration of the aqueous solution and even upon vigorous
stirring of the aqueous solution at room temperature for 2 weeks.

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Macromolecules, Vol. 43, No. 13, 2010 5695
Figure 11. Evolution of size-distribution curve for DR1-loaded micelles of 11, from initial DR1-loaded micelle preparation to prolonged exposure to
the dye solution as well as vigorous stirring of the aqueous dye-loaded micelles for 2 weeks.
200 nm, corresponding to the systems that encapsulated
more DR1. Finally, in predicting the loading capacity of a
small molecule from the DH in our systems, it is important to
note that comparison of DH of DR1-encapsulated polymers
is more important than that of the blank aqueous micelles
where the dye is absent. Even though our observations reveal
that polymers above 200 nm typically show relatively high
loading capacities, it is not easy to predict successful loading
of small molecules based on the blank aqueous micelles due
to changes that may take place in the micelle as it accom-
modates a small molecule within its hydrophobic interior.
under reduced pressure prior to use. Monohydroxy-terminated
polystyrene was purchased from Scientific Polymer. Triisopro-
pylsilylacetylene and trimethylsilylacetylene were purchased
from Oakwood Chemicals, and 3-bromo-5-iodobenzoic acid
was purchased from AK Scientific and used as received. Triethy-
lamine and diethylamine were dried over potassium hydroxide
and distilled prior to use. All reactions were performed under a
nitrogen atmosphere using dried and distilled solvents. All other
1
reagents were used as received. H and 13C{1H} NMR spectra
were recorded in CDCl3 at ambient temperature using either a
400 or 500 MHz Varian instrument. Gel permeation chroma-
tography (GPC) was performed in THF at 30 °C on a Viscotek
TDA model 301 triple detector array equipped with a refractive
index detector that was calibrated with polystyrene standards.
The instrument was also equipped with two PolyAnalytik
columns (PAS-103M-L and PAS-104M-M). The flow rate was
1 mL/min. Mass spectra were recorded on Thermo Scientific
Orbitrap mass analyzer (ES) and Kratos MS25 (EI) mass
spectrometers.
Conclusions
We have demonstrated that well-defined ABC-type miktoarm
star polymers can be synthesized using a highly versatile core with
three orthogonal functionalities. Using this building block, we
constructed a variety of μ-stars using a combination of highly
efficient “click” chemistry reactions with ring-opening polymer-
ization. The buildup of the ABC-type miktoarm polymers on the
core molecule is easily monitored using simple techniques includ-
ing 1H, 13C{1H} NMR, and GPC. The star polymers containing
PEG, PS, and PCL arms were found to assemble into spherical
micelles in an aqueous solution in which the hydrophobic arms
formed the core, while the hydrophilic PEG as corona interacted
with the surrounding medium. Our results suggest that one could
tailor the sizes of these aqueous micelles by varying the lengths of
the appropriate polymeric arms. For instance, decreasing the size
of the PEG arm led to an increase in both the core and the
hydrodynamic diameter of the micelle. Also, increase in the
hydrophobic PCL arm size led to increased micellar core sizes.
Disperse Red 1 dye molecules were then encapsulated into the
hydrophobic core of these micelles, and their loading capacity
seemed to be dependent on the hydrodynamic diameter of the
micelles as well as the length of the hydrophobic arms.
UV-vis spectra were obtained from a Cary 5000 spectro-
photometer in 1 cm cuvettes. First, a calibration curve was
constructed for DR1 dissolved in DCM by creating a series of
solutions of DR1 with known concentrations (3 mL). After
recording the absorbances of these solutions (in the range of 1-8
μg/mL), a line of best fit was constructed in order to model the
relationship between the concentration of DR1 in DCM and its
absorbance. The obtained calibration curve was deemed accu-
rate as the correlation coefficient r2 value was 0.996. The dye-
encapsulated polymer solutions were then lyophilized to obtain
a reddish powder. These solutions were then dissolved in 3 mL of
DCM, and their UV-vis absorbances were recorded. Using the
calibration curve, the loading level of the dye was calculated
from the following formula: wt % = (mass of DR1)/(mass of
polymer and DR1 in solution) ꢀ 100.
Dynamic light scattering (DLS) measurements were carried
out on a Brookhaven photon correlation spectrometer equipped
with a BI9000 AT digital correlator. Also on this instrument is a
compass 315M-150 laser (Coherent Technologies). Measure-
ments were taken at a wavelength of 532 nm. Measurements
were made at ∼25 °C at a 90° scattering angle. Mean hydro-
dynamic radius measurements were obtained from a Gaussian
Experimental Section
Materials and Methods. ε-Caprolactone (Sigma-Aldrich,
g99%) was dried over calcium hydride for 24 h and distilled

5696 Macromolecules, Vol. 43, No. 13, 2010
Khanna et al.
fit of the CONTIN analysis mode from five averaged measure-
ments of the dilute dispersion.
After letting the reaction mixture cool to room temperature, the
product was extracted with DCM and washed thoroughly with
water. The extract was then dried over MgSO4, and the solvent
was removed in vacuo. The residue was dissolved in THF
(25 mL) and precipitated in cold methanol (500 mL). After
vacuum filtration, the precipitate was dried under vacuum to
yield a white powder (18.05 g, 95%). 1H NMR (500 MHz,
CDCl3): δ (ppm) 1.3-2.2 (br), 2.89 (br), 6.3-7.2 (br). 13C{1H}
NMR (125 MHz, CDCl3): δ (ppm) 31.2, 40.5 (br), 44.0 (br), 49.1,
125.0 (br), 128.2 (br). GPC: Mn = 4300 g/mol, Mw/Mn = 1.040.
Synthesis of 3-(Triisopropylsilyl)-5-ethynylbenzyl Alcohol (7).
A solution of 3-(triisopropylsilylethynyl)-5-(trimethylsilylethy-
nyl)benzyl alcohol (1.69 g, 4.4 mmol) in acetone (20 mL) was
prepared and stirred for ∼15 min at room temperature. Subse-
quently, an aqueous solution of K2CO3 (10 mL; 1.4 g, 7.89
mmol) was added. The reaction mixture was left to stir overnight
at room temperature. After acetone was removed in vacuo, the
solution was extracted with DCM. The extract was dried over
MgSO4, and the solvent was removed under vacuum. The
residue was then purified by silica gel column chromatography
using an ethyl acetate/hexanes (1:4) mixture, and the solvent was
again evaporated to yield a yellowish oil (1.12 g, 81%). 1H NMR
(400 MHz, CDCl3): δ (ppm) 1.12 (s, 21H, -Si(C3H7)3), 1.78 (s,
1H, -CH2OH), 3.08 (s, 1H, -ArCCH), 4.66 (d, 2H, CH2OH),
7.30 (s, 1H, ArH), 7.45 (s, 1H, ArH), 7.53 (s, 1H, ArH). 13C{1H}
NMR (75 MHz, CDCl3): δ (ppm) 11.5, 18.8, 64.5, 78.1, 82.8,
91.9, 105.9, 122.7, 124.3, 130.3, 130.8, 134.9, and 141.4.
Transmission electron microscopy (TEM) was used to cap-
ture images of the aqueous micelles using a Phillips CM200
electron microscope equipped with an AMT 2k ꢀ 2k CCD
camera at an acceleration voltage of 80 kV. TEM samples were
prepared by adding 2-3 drops of the aqueous micelle solutions
onto a Formvar-coated 400 mesh grid stabilized with evapo-
rated carbon film. The samples were stained with OsO4. The
samples were allowed to dry overnight at room temperature.
3-Bromo-5-iodobenzyl alcohol (3a) was synthesized from its
carboxylic acid by adopting a literature procedure.14
Synthesis of 3-Bromo-5-(triisopropylsilylethynyl)benzyl Alcohol
(3). Toa solutionof3-bromo-5-iodobenzylalcohol (5 g, 16 mmol)
in diethylamine (150 mL), catalytic amounts (ca. 5 mol %)
of [Pd2Cl2(PPh3)2] and CuI were added. The solution was then
degassed by three evacuation/refill cycles and placed under
nitrogen, and triisopropylsilylacetylene (3.80 g, 20.8 mmol) was
added via syringe. The reaction mixture was stirred at room
temperature for 48 h. The solvent was then removed in vacuo,
and the residue was extracted with diethyl ether. The extract was
dried over MgSO4, and the solvent was then removed in vacuo.
The product was purified by silica gel column chromatography
using an ethyl acetate/hexanes (1:20) mixture. The solvent was
1
removed in vacuo to yield a pale yellow oil (4.64 g, 79.1%). H
NMR (400 MHz, CDCl3): δ (ppm) 1.12 (s, 21H, -Si(C3H7)3),
4.63 (d, 2H, -ArCH2OH), 7.38 (d, 1H, ArH), 7.45 (s, 1H, ArH),
7.52 (s, 1H, ArH). 13C{1H} NMR (75 MHz, CDCl3): δ (ppm)
11.5, 18.9, 64.3, 92.7, 105.4, 122.4, 125.7, 129.0, 130.0, 133.9,
and 143.1. HRMS (EI): Theoretical Mw = 366.10 g/mol. Found
Mw = 366.10 g/mol.
Typical “Click” Reaction of PEG-N3 to the Deprotected
Alkyne, Mn ≈ 2000 (8). CuBr (0.116 g, 0.807 mmol) was added
to a solution of PEG-N3 (1.366 g, 0.632 mmol) in N,N-dimethyl-
formamide (DMF) (10 mL) in a Schlenk flask. The solution was
degassed by three evacuation/refill cycles and placed under nitro-
gen, after which a second solution of 3-(triisopropylsilylethynyl)-
5-ethynylbenzyl alcohol (0.202 g, 0.645 mmol) in DMF (5 mL) was
added. Upon complete dissolution of the reactants, the flask was
further degassed by three additional evacuation/refill cycles. Nitro-
gen-purged N,N,N0,N00,N00-pentamethyldiethylenetriamine (PMD-
ETA) (0.140 g, 0.807 mmol) was then added, whereupon the
reaction mixture developed a dark green color. The solution was
stirred at room temperature for 24 h. Aliquots were periodically
removed for analysis by GPC. After the reaction, the solution was
exposed to air and DMF was removed under vacuum. Upon
dilution with DCM, the solution was passed through a silica gel
column to remove the copper catalyst and the unreacted starting
materials using a methanol/DCM (1:20) mixture as eluent. Then,
the solvent was removed, and the solution was dried under vacuum
Synthesis of 3-(Triisopropylsilylethynyl)-5-(trimethylsilylethy-
nyl)benzyl Alcohol (4). To a solution of 3-bromo-5-(triisopro-
pylsilylethynyl)benzyl alcohol (4.46 g, 12.2 mmol) in benzene
(70 mL) and triethylamine (130 mL), catalytic amounts (ca. 5
mol %) of [PdCl2(PPh3)2] and CuI were added, and the reaction
mixture was stirred to dissolution. The reaction flask was
degassed by three evacuation/refill cycles and placed under
nitrogen, after which trimethylsilylacetylene (3.58 g, 36.5 mmol)
was added via syringe. The reaction mixture was stirred under
reflux overnight. The solvent was then evaporated, and the
residue was extracted with diethyl ether. The extract was dried
over MgSO4, and the solvent was again removed in vacuo. The
product was purified by silica gel column chromatography using
an ethyl acetate/hexanes (1:20) mixture. The solvent was re-
moved under vacuum to yield a pale yellow oil (4.23 g, 90.4%).
1H NMR (300 MHz, CDCl3): δ (ppm) 0.23 (s, 9H, Si(CH3)3),
1.12 (s, 21H, -Si(C3H7)3), 4.63 (d, 2H, -ArCH2OH), 7.41 (s,
2H, ArH), 7.50 (s, 1H, ArH). 13C{1H} NMR (100 MHz, CD-
Cl3): δ (ppm) 0.1, 11.2, 18.6, 64.4, 91.5, 95.0, 103.9, 105.8, 123.5,
123.9, 130.0, 130.2, 134.4, and 141.1. HRMS (ESI): Theoretical
Mwþ = 385.23 g/mol. Found Mwþ = 385.32 g/mol.
1
to yield a light-brown gel (1.437 g, 92%). H NMR (400 MHz,
CDCl3): δ (ppm) 1.13 (s, 23H, -Si(C3H7)3), 2.63 (t, 1H, -CH2-
OH), 3.37 (s, 3H, -PEG-OCHH3), 3.49-3.65 (br, PEG), 3.91 (t,
2H, -PEG-CH2-CH2-TriAz-), 4.60 (t, 2H, -PEG-CH2-
CH2-TriAz-), 4.71 (d, 2H, -ArCH2OH), 7.43 (s, 1H, ArH), 7.80
(s, 1H, ArH), 7.93 (s, 1H, ArH), 8.12 (s, 1H, TriAz-H). 13C{1H}
NMR (125 MHz, CDCl3): δ (ppm) 11.3, 18.7, 30.3, 50.4, 59.0, 64.4,
69.4, 70.5, 71.9, 90.8, 106.6, 121.6, 124.0, 124.2, 128.0, 129.8,
131.1, 142.0, and 146.8. GPC: Mn=3485 g/mol. Mw/Mn=1.031.
A similar procedure was followed for the “click” reaction
using azide-terminated poly(ethylene glycol) monomethyl ether
with Mn ≈ 775.
Azide-terminated poly(ethylene glycol) monomethyl ethers,
Mn ≈ 775 (5a) and Mn ≈ 2000 (5b), were synthesized from their
commercially available monohydroxy forms by adopting a
literature procedure.15
Synthesis of Azide-Terminated Polystyrene, Mw ≈ 4-5000
(6b). To a solution of commercially available monohydroxy-
terminated polystyrene (20 g, 4.65 mmol) in dichloromethane
(DCM, 100 mL) cooled to 0 °C in an ice bath, methanesulfonyl
chloride (1.07 g, 9.30 mmol) and triethylamine (0.94 g, 9.30
mmol) were added in a dropwise fashion. The ice bath was
subsequently removed, and the reaction mixture was warmed to
room temperature over a period of 24 h while being continu-
ously stirred. The reaction mixture was then washed thoroughly
with water and dried over MgSO4. Upon removal of the solvent
in vacuo, a clear oil was obtained (19 g, 95%). The mesylate-
terminated polystyrene (19 g, 4.42 mmol) was dissolved in DMF
(100 mL) and heated to 50 °C, and sodium azide (1.44 g, 22.1
mmol) was added. The reaction mixture was stirred for 24 h.
Removal of Triisopropylsilyl (TIPS) Protecting Group (9). A
flask containing a solution of 8 (1.35 g, 0.546 mmol) in THF
(25 mL) was placed in a dry ice/acetone bath. After waiting
15 min for the solution to cool to approximately -78 °C, a
solution of Bu4NF (1.0 M solution in THF, 1.162 mL, 1.162
mmol) was added in a dropwise fashion. The bath was then
removed, and the reaction mixture was allowed to warm to
room temperature while stirring overnight. After removing the
solvent under vacuum, the solution was extracted into DCM.
After drying the extract over MgSO4 and removing the sol-
vent in vacuo, the residue was thoroughly washed with hexanes
(300 mL) to yield a brown gel (1.012 g, 80%). 1H NMR

Article
Macromolecules, Vol. 43, No. 13, 2010 5697
1
(400 MHz, CDCl3): δ (ppm) 3.12 (s, 1H, -ArCCH), 3.37 (s, 3H,
-PEG-OCHH3), 3.54-3.65 (br, PEG), 3.90 (t, 1H, -PEG-
CH2-CH2-TriAz-), 4.60 (t, 2H, -PEG-CH2-CH2-TriAz-),
4.71 (s, 2H, -ArCH2OH), 7.44 (s, 1H, ArH), 7.88 (s, 1H, ArH),
7.92 (s, 1H, ArH), 8.13 (s, 1H, TriAz-H). 13C{1H} NMR (125
MHz, CDCl3): δ (ppm) 30.9, 50.4, 59.0, 64.4, 69.4, 70.5, 71.9, 77.5,
83.3, 121.5, 122.8, 124.4, 128.2, 129.7, 131.3, 142.3, and 146.7.
GPC: Mn = 3151 g/mol. Mw/Mn = 1.041.
Miktoarm Star (14). H NMR (400 MHz, CDCl3): δ (ppm)
1.38 (m, PCL), 1.64 (m, PCL), 1.3-2 (br, PS), 2.303 (t, PCL),
3.373 (s, 3H, -PEG-OCHH3), 3.54-3.64 (br, PEG), 4.057 (t,
PCL), 6.3-7.2 (br, PS). 13C{1H} NMR (75 MHz, CDCl3): δ
(ppm) 24.7, 25.8, 28.7, 34.3, 40.3, 64.4, 70.7, 125.9, 127 (br), and
174.0. GPC: Mn = 15 000 g/mol. Mw/Mn = 1.59.
1
Miktoarm Star (15). H NMR (400 MHz, CDCl3): δ (ppm)
1.43 (m, PCL), 1.67 (m, PCL), 1.3-2 (br, PS), 2.309 (t, PCL),
3.377 (s, 3H, -PEG-OCHH3), 3.54-3.64 (br, PEG), 4.06 (t,
PCL), 6.3-7.2 (br, PS). 13C{1H} NMR (75 MHz, CDCl3): δ
(ppm) 24.5, 25.4, 29.0, 34.2, 40.6, 64.4, 70.6, 125.8, 127 (br), and
174.2. GPC: Mn = 6500 g/mol. Mw/Mn = 1.28.
Typical Procedure for “Click” Reaction of PS-N3 with the
Deprotected Alkyne for Addition of the Second Arm (10). CuBr
(0.068 g, 0.475 mmol) was added to a DMF solution (10 mL) of 2
(0.880 g, 0.380 mmol) in a Schlenk flask. After subsequent
addition of the azide-terminated polystyrene (1.634 g, 0.380
mmol, Mn ≈ 4300), the solution was degassed by three evacua-
tion/refill cycles and stirred to complete dissolution under
nitrogen. Then, nitrogen-purged PMDETA (0.082 g, 0.475
mmol) was added whereupon the reaction mixture developed
a dark green color. The solution was stirred at room tempera-
ture for 24 h while aliquots were periodically removed for
analysis by GPC. The solution was then exposed to air and
DMF was removed in vacuo. Upon dilution with DCM, the
solution was passed through a silica gel column to remove
both the copper catalyst and the unreacted starting materials
using a methanol/DCM (1:20) mixture as eluent. The solvent
was then removed, and the solution was dried under vacuum to
yield a brown oil (1.91 g, 83%). 1H NMR (500 MHz, CDCl3): δ
(ppm) 1.4-2.1 (br, PS), 3.38 (s, 3H, -PEG-OCHH3), 3.54-
3.64 (br, PEG), 3.90 (t, 2H, -PEG-CH2-CH2-TriAz-), 4.60
(t, 2H, -PEG-CH2-CH2-TriAz-), 4.8 (s, 1H, -ArCH2OH),
6.3-7.2 (br, PS). 13C{1H} NMR (125 MHz, CDCl3): δ (ppm)
13.7, 14.1, 19.8, 21.2, 22.6, 24.1, 29.4, 30.3, 31.6, 34.2, 40.3,
42-46, 50.4, 59.0, 69.4, 70.6, 71.9, 105.0, 123.5, 125-126,
126-128, 135.7, 145.3, and 151.5. GPC: Mn = 7261 g/mol.
Mw/Mn=1.055.
1
Miktoarm Star (16). H NMR (400 MHz, CDCl3): δ (ppm)
1.38 (m, PCL), 1.63 (m, PCL), 1.3-2 (br, PS), 2.304 (t, PCL),
3.38 (s, 3H, -PEG-OCHH3), 3.54-3.64 (br, PEG), 4.05 (t,
PCL), 6.3-7.2 (br, PS). 13C{1H} NMR (75 MHz, CDCl3): δ
(ppm) 24.8, 25.7, 28.6, 34.3, 40.6, 64.4, 70.7, 125.9, 127 (br), and
173.8. GPC: Mn = 10 900 g/mol. Mw/Mn = 1.55.
Preparation of Aqueous Micelles. Micelles of miktoarm poly-
mers were prepared by a dialysis method using a known lite-
rature procedure.21 In a typical procedure, 10 mg of the miktoarm
polymer was dissolved in 1 mL of DMF and stirred for ∼30 min.
Using a syringe pump, 10 mL of Milli-Q water was added dropwise
to the DMF solution under vigorous stirring at the rate of one drop
every 12 s. Afterward, the DMF was removed by dialysis against
2 L of Milli-Q water over a period of 24-48 h. The water was
periodically replaced at least five times throughout the dialysis in
order to ensure removal of DMF from solution.
Preparation of Dye-Encapsulated Aqueous Micelle Solutions.
Two different methods were followed for the preparation of dye-
encapsulated aqueous micelles of miktoarm polymers.
Extraction. The aqueous micelles already prepared from
dialysis were used for the encapsulation of Disperse Red 1. To
the solution, as described above, ca. 4 mL of a concentrated
solution of DR1 in tert-butyl methyl ether (1 mg/mL) was added
and stirred vigorously overnight. This concentration was chosen
to ensure an abundance of DR1 throughout the extraction.
Afterward, the solution was allowed to fully separate into two
phases, and the aqueous layer was withdrawn from the solution.
Dialysis. In this method, the preparation of micelles encap-
sulated with Disperse Red 1 was similar to that described for the
preparation of aqueous micelles. The only difference was that
ca. 5 mg of DR1 was added in addition to the polymer, prior to
dissolution in DMF. This amount was chosen to ensure an
abundance of DR1 so that the self-assembled polymers can
encapsulate as much DR1 as possible.
The same procedure was used for a “click” reaction with
azide-terminated polystyrene with Mn ≈ 2700.
Typical Procedure for the Ring-Opening Polymerization
(ROP) of ε-Caprolactone To Form the Miktoarm Star (11). A
solution of 3 (0.23 g, 0.036 mmol) in distilled toluene (10 mL)
was added to a warm three-neck flask equipped with a con-
denser. After the solution was degassed by three evacuation/
refill cycles, distilled ε-caprolactone (0.166 g, 1.456 mmol,
[CL]0/[I]0 = 40) was added via syringe through a rubber septa,
and the solution was warmed to 100 °C. A nitrogen-purged
solution of Sn(II) 2-ethylhexanoate (3 mg, 7.28 μmol) in toluene
(1 mL) was then added via syringe through a rubber septa, and
the reaction mixture was warmed to 130 °C, stirring for ∼20 h.
Aliquots were periodically removed for analysis by GPC. The
reaction mixture was then cooled to room temperature, dis-
solved in DCM, and precipitated in cold methanol under
vigorous stirring. After vacuum filtration, the precipitate was
dried under vacuum to constant weight to yield an off-white
powder (0.350 g, 70%). 1H NMR (400 MHz, CDCl3): δ (ppm)
1.38 (m, PCL), 1.63 (m, PCL), 1.3-2 (br, PS), 2.304 (t, PCL),
3.38 (s, 3H, -PEG-OCHH3), 3.54-3.64 (br, PEG), 4.05 (t,
PCL), 6.3-7.2 (br, PS). 13C{1H} NMR (75 MHz, CDCl3): δ
(ppm) 24.8, 25.7, 28.6, 34.3, 40.6, 64.4, 70.7, 125.9, 127 (br), and
173.8. GPC: Mn = 11 500 g/mol. Mw/Mn = 1.26.
Acknowledgment. We thank NSERC of Canada and Center
for Self-Assembled Chemical Structures (FQRNT, Quebec
Canada) for financial assistance.
Supporting Information Available: GPC data profiles for
the miktoarm polymers. This material is available free of charge
via the Internet at http://pubs.acs.org.
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Miktoarm Star (12). H NMR (400 MHz, CDCl3): δ (ppm)
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Miktoarm Star (13). H NMR (400 MHz, CDCl3): δ (ppm)
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