Clickable amphiphilic triblock copolymers

Article abstract of DOI:10.1002/pola.25989

Amphiphilic polymers have recently garnered much attention due to their potential use in drug delivery and other biomedical applications. A modular synthesis of these polymers is extremely desirable, because it offers precise individual block characteriza

Full text of DOI:10.1002/pola.25989

JOURNAL OF
POLYMER SCIENCE
ARTICLE
WWW.POLYMERCHEMISTRY.ORG
Clickable Amphiphilic Triblock Copolymers
Michael J. Isaacman,1,2 Kathryn A. Barron,2 Luke S. Theogarajan2,3
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DOI: 10.1002/pola.25989
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INTRODUCTION Self-assembly on the nanoscale is a key
property that nature relies on to generate biological mem-
branes. These membranes provide a structural framework
via a microenvironment and a functional framework by
incorporation of channels, receptors, and pumps. By exploit-
ing hydrophobic–hydrophilic interactions, these membranes
assemble into bilayers and other structures. If we hope to
mimic the principles of natural nanoarchitectures, the self-
assembling membrane is a critical component. Recently, a
plethora of polymeric systems has successfully exploited
self-assembly for the purposes of drug delivery,1 biomedical
coatings,2 virus-assisted gene delivery,3 and nanoreactors.4
These are amphiphilic diblock or triblock copolymers that
self-assemble into micelles, worm-like micelles, tubular
structures, membranes, or vesicles in a suitable solvent.5
of control allows for sophisticated scientific exploration and
will enable the understanding of the underlying structure–
function relationships that influence the physics of self-
assembly in these macromolecules.
Although there are myriad block copolymer architectures,
the ABA triblock copolymer is particularly attractive from a
self-assembly standpoint due to its inherent ability to form
vesicular structures, albeit with high hydrophobic to hydro-
philic ratios.7 From a biomedical perspective, the pseudo-
polypeptide architecture offered by poly(oxazoline) is partic-
ularly attractive and was chosen as the hydrophilic A-block.8
Poly(siloxane)s, especially those that contain at least one
methyl group, exhibit very low-glass transition temperatures
and are mostly liquids at room temperatures, due to the par-
tial ionic character of the SiACH3 bond.9 Furthermore, poly
(siloxane)s have very low-surface energy and are extremely
hydrophobic; thus, they were chosen as the B-block. This
ABA block copolymer system has been studied by our group
and others using a macroinitiation-based synthesis scheme
and has been shown to possess interesting biomedical and
self-assembling properties.10–14 However, macroinitiation-
based schemes suffer from low yields and poor repeatability.
To increase yield and enable accurate molecular weight con-
trol of the hydrophilic blocks, we envisioned that a modular
click-based approach would be superior. In this work, we
report for the first time a facile and versatile click-based
Recently, click chemistry has found considerable use in poly-
mer–polymer conjugation via the copper-catalyzed azide–
alkyne cycloaddtion (CuAAC) reaction.6 Click-based conjuga-
tion allows for the modular synthesis of block copolymer
architectures with well-defined block lengths and end-
groups. This allows for systematic investigation of the effect
of a single parameter variation on the self-assembling prop-
erties of the macromolecular system. For example, by using
individually well-characterized hydrophobic and hydrophilic
blocks, the effect of the hydrophilic block length on the self-
assembling properties could be studied. This exquisite level
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methodology for the synthesis of poly(oxazoline)–poly(silox-
ane)–poly(oxazoline)-based block copolymers (Scheme 1).
methylhydrosiloxane [P(DMS-co-MHS)], with free SiAH
groups available for further derivatization. Synthesis of the
poly(methyloxazoline) (PMOXA) A-block with alkyne func-
tionality was accomplished in high yield using a propargyl
tosylate initiator. We envisioned the alkyne end-group would
allow for facile and modular attachment of a PMOXA block
to each end of the bis-azide poly(siloxane)s block via CuAAC.
The bis-azide PDMS was used as a model for CuAAC reac-
tions with PMOXA, with that methodology later applied to
the more functionally complex P(DMS-co-MHS) copolymer.
The polymer–polymer conjugation of these blocks was thor-
oughly investigated using an array of CuAAC click conditions.
RESULTS AND DISCUSSION
Although our main objective was to demonstrate the synthe-
sis of amphiphilic ABA triblock copolymers that contain a
poly(siloxane) B-block and poly(oxazoline) A-blocks (Scheme
2), we used a cohesive approach that optimized every step.
We began with the synthesis of two telechelic bis-azide poly
(siloxane) B-blocks; one consists of poly(dimethylsiloxane)
(PDMS), the other is a copolymer of dimethylsiloxane and
SCHEME 2
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additional steps reduced the acidic cleavage of disiloxane,
providing the bis-tosylate end-blocker in an improved yield
of 70%. Bis-iodide end-blocker (3) was synthesized in 70%
yield, by conversion of the hydroxyl groups of 1 using a
known iodination procedure.16
The synthesis of bifunctional poly(siloxane)s was achieved
via cationic ring-opening polymerization (CROP) of cyclic
siloxane monomers, terminated by a short-chain disiloxane
(Scheme 3). This short-chain disiloxane is commonly referred
to as the end-blocker, because it serves as the end-groups of
poly(siloxane) and also terminates the polymerization. The
reactivity of short-chain disiloxanes is higher than the corre-
sponding cyclic in a CROP, allowing the disiloxane to serve
as an initiator.15 Acid-labile SiAO bonds are constantly bro-
ken and reformed during the cationic polymerization; thus,
the acid-stable SiAC bonds of the end-blocker terminate the
growing chain and serve as end-groups.15 Bis-tosylate end-
blocker (2) was synthesized from commercially available
1,3-bis(4-hydroxybutyl)tetramethyldisiloxane (1). Previously,
we reported the synthesis of tosylate end-blockers that suf-
fered from poor yields.14 This was primarily due to acidic
cleavage of the highly acid-labile disiloxane bond, probably
due to the hydrochloric acid by-product produced during the
course of the reaction and/or acidic cleavage by silica chro-
matography used for purification. The addition of 10 equiv
of triethylamine (rather than the 4 equiv of triethylamine
used previously) ensured neutralization of the hydrochloric
acid by-product during the course of the reaction. Siloxane
cleavage during purification was circumvented by passing
the crude product through a silica gel plug that had been
deactivated by spinning in a triethylamine solution. These
Synthesis of Bifunctional Poly(siloxane)s
Bifunctional poly(siloxane)s were synthesized rapidly and in
excellent yields via CROP of cyclic siloxane monomers
(Scheme 3). Molecular weight control was achieved using the
end-blocker method. When octamethylcyclotetrasiloxane (D4)
was used as the siloxane monomer and bis-tosylate disilox-
ane (2) as the end-blocker, TsO-PDMS-OTs (4) was synthe-
sized in high yield. Using bis-iodide disiloxane end-blocker
(3) with a combination of D4 and 1,3,5,7-tetramethylcyclote-
trasiloxane (D4H) afforded the copolymer of dimethylsiloxane
and methylhydrosiloxane, I-P(DMS-co-MHS)-I (5). Bis-iodide
disiloxane (3) was used as the end-blocker for the siloxane
copolymer synthesis as opposed to bis-tosylate disiloxane
(2), which allows for room-temperature conversion of the
poly(siloxane) end-groups to azides. This prevents undesired
heat-activated reaction pathways that give rise to side prod-
ucts as discussed in the next section. Our group previously
reported the synthesis of a TsO-P(DMS-co-MHS)-OTs polymer
that used a bis-tosylate end-blocker and used p-toluenesul-
fonic acid as the catalyst.14 However, this method suffered
from moderate yields and long reaction times, with
W
W
W
.
M
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2
0
1
2
,
0
0
0
,
0
0
0
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0
0
3

JOURNAL OF
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(Fig. 1). Poly(methylhydrosiloxane) is a known reducing
agent18 and thus interacted with radicals produced during the
reaction. We therefore hypothesized an antioxidant radical
scavenger such as ethylenediaminetetraacetic acid (EDTA)
would preserve the SiAH groups. Indeed, when the reaction
was repeated with the addition of EDTA, 1H NMR revealed
that the SiAH peaks were unaffected while the desired substi-
tution at the end-groups occurred quantitatively to give N3-
P(DMS-co-MHS)-N3 (7). In addition, we attempted an azide
substitution reaction on a TsO-P(DMS-co-MHS)-OTs polymer
using the conditions used to synthesize 7, but found that con-
version to the azide was incomplete at room temperature.
Upon heating to 60ꢀC conversion to the azide proceeded to
completion, however, the SiAH peaks were perturbed in a
similar manner to Figure 1. Hence, as mentioned earlier, we
chose to use iodo-functionalized end-blockers when reactive
SiAH groups were present. Azide conversion of 6 and 7 was
further supported by FTIR spectroscopy with the appearance
of an azide peak at 2096 cmꢂ1 (see Supporting Information).
Synthesis of Alkyne-Functionalized
Poly(methyloxazoline)
The hydrophilic poly(methyloxazoline) (PMOXA) A-block was
synthesized via CROP using a propargyl tosylate initiator,
which ensured terminal alkyne functionality on one end of
the polymer (Scheme 4). Tosylation of propargyl alcohol pro-
1
FIGURE 1
H
N
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t
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b
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ꢀ
ceeded rapidly and in good yield at 0 C when a biphasic sol-
subsequent experiments revealing incomplete monomer con-
sumption and precipitation of the acid catalyst, indicating
the need for a different acid catalyst. When bulk polymeriza-
tions of siloxanes were conꢀducted using sulfuric acid as the
ring-opening catalyst at 80 C, the reactions proceeded over-
night in excellent yields with high-monomer consumption,
probably due to the better solubility of the acid catalyst. 1H
NMR was used to monitor reaction progress. After the re-
moval of unreacted cyclics in vacuo, followed by aqueous
workup, the poly(siloxane)s were provided. TsO-PDMS-OTs
(4) was synthesized in 94% yield with Mn ꢁ 5300, while
I-P(DMS-co-MHS)-I (5) was synthesized in 96% yield with
Mn ꢁ 5300. Molecular weights of the poly(siloxane)s were
vent system of NaOH (aq) and THF was used. Tosylation of
alcohols is generally carried out with an excess of tosyl chlo-
ride; however, chromatography is usually required to remove
unreacted tosyl chloride. Using a slight excess of propargyl
alcohol ensured complete tosyl chloride consumption while
allowing for easy removal of excess propargyl alcohol by
aqueous workup to provide propargyl tosylate (8) in 85%
yield.
Preparation of PMOXA with an acetylene end-group using a
microwave irradiation approach has been previously pub-
lished.19 In contrast, our synthesis used conventional meth-
ods and is described next. Propargyl tosylate (8) was kept
under reduced pressure overnight to remove trace water,
freshly distilled 2-methyl-2-oxazoline was then added to a
solution of the tosylate initiator in acetonitrile, and heated to
80 ꢀC. After 16 h, 1H NMR revealed quantitative initiation
1
determined by H NMR using end-group analysis.
Synthesis of Bis-azide Poly(siloxane)s
Poly(siloxane)s were converted into clickable partners for the
alkyne-functionalized poly(oxazoline) A-blocks by conversion
of the iodide or tosylate end-groups into azides, using sodium
azide (Scheme 3). Although we experienced no safety issues
when handling azides, we chose to convert the poly(siloxane)s
end-groups to azides postpolymerization, because azides can
be explosive—especially under acidic conditions.17 The tosyl-
ate end-groups of TsO-PDMS-OTs (4) were easily converted to
azides via nucleophilic substitution using sodium azide at 60
ꢀC to give N3-PDMS-N3 (6) in high yield. DMF is the classic
solvent used for this reaction,17 although the insolubility of
siloxanes in DMF required
a binary solvent system of
THF:DMF v/v 2:1 to ensure complete solubility of the silox-
anes. However, when azide substitution was conducted on I-
P(DMS-co-MHS)-I (5) using the same procedure, 1H NMR
revealed that the SiAH peak at 4.7 ppm was perturbed
SCHEME 4
( 9
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0
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0

JOURNAL OF
POLYMER SCIENCE
ARTICLE
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1
0
1
1
TABLE 1
R
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3
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along with complete monomer consumption. Choosing the
correct termination procedure is of the utmost importance
as side reactions with the acetylene end-group occur with
certain popular oxazoline-terminating methods. For example,
termination with methanolic potassium hydroxide20 resulted
in a side reaction at the acetylene group—as evidenced by
room temperature; however, full conjugation did not occur at
room temperature-even after days. Thus, heat was
2
required to drive the reaction to completion. Quantitative
conversion occurred after 1 h using 1 equiv of N3-PDMS-N3
(6) and 2 equiv of PMOXA (9), circumventing the need for
an excess of either block. These results were confirmed by
1H NMR with the disappearance of the PDMS-CH2-azide peak
at 3.3 ppm and PMOXA-CH2-alkyne peak at ꢁ4.0–4.3 ppm,
coupled with the appearance of triazole peaks at ꢁ4.2–4.6
and 7.6 ppm (Fig. 2). Further evidence was provided by
FTIR spectroscopy with the disappearance of the azide peak
at 2096 cmꢂ1 (see Supporting Information). Although
1
the absence of acetylene peaks in H NMR. Termination with
water is another popular method19; however, this does not
lead to well-defined end-groups.21 Secondary amines are an
ideal choice for termination due to their good nucleophilic-
ity; thus, the living chain ends of PMOXA were terminated
with piperidine. The resulting piperidine salt can be deproto-
nated with potassium carbonate,22 but doing so in situ
resulted in a side reaction at the acetylene group. Therefore,
excess piperidine must be removed before adding potassium
carbonate to ensure no side reactions occur. 1H NMR was
used to follow the termination progress as a shift in peaks
was seen with each termination step (see Supporting Infor-
mation). After workup, PMOXA (9) was obtained in quantita-
tive yield. End-group analysis using 1H NMR revealed Mn
1350, close to the expected Mn of 1500, and GPC indicated a
ꢁ
PDI of 1.17 using a poly(styrene) standard.
Synthesis of PMOXA–PDMS–PMOXA Triblock Copolymer
Via CuBr/PMDETA Method
Polymer–polymer conjugation of amphiphilic blocks is espe-
cially challenging due to the inherent incompatibility of the
blocks. We explored several popular CuAAC methods includ-
ing Copper(I) salt with an amine ligand, Copper(II) salt in
conjunction with a reducing agent, and a heterogeneous cou-
pling catalyst, namely copper nanoparticles. 1H NMR was
used to monitor reaction progress for all click reactions
using the appearance of the triazole-CH2-PMOXA peak at
4.58 ppm as a standard for percent conversion to triazole
from azide. The results of all methods studied are shown in
Table 1.
Click reactions with polymer applications frequently use
CuBr/PMDETA as the catalyst23; thus, we attempted to con-
jugate homopolymers PMOXA (9) and N3-PDMS-N3 (6) using
this catalytic method. Although tetrahydrofuran and dime-
thylformamide are frequently used solvents, we found that
the toulene:dimethylformamide v/v 1:1 solvent system was
most effective, because toluene is a theta solvent for silox-
anes.24 Many CuAAC reactions are known to proceed at
1
FIGURE 2
H
N
M
R
s
p
e
c
t
r
a
o
f
N
-
P
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-
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(
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,
9
3
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–
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5

JOURNAL OF
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SCHEME 5
S
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conversion was quantitative and rapid, the reaction yielded a
dark-green product due to the presence of copper, which
was rather difficult to purify.
filtration, albeit the triblock polymer was yellow/green—
indicating the presence of trace amounts of copper. When
CuSO4 was used as the catalyst, in the absence of sodium L-
ascorbate reducing agent, the reaction proceeded to 50%
completion after 2 h and quantitative completion in 15 h at
60 ꢀC. This reaction was also successful when acetone, 2-
propanol, or chloroform was used as the solvent system.
Removal of copper contaminate from PMOXA–PDMS–PMOXA
(10) was challenging for two reasons. First, the polyamide
functionality of PMOXA can chelate copper, making its disas-
sociation from the polyamide difficult. Second, any attempt
to remove copper in a solvent that does not solubilize both
blocks can cause polymer aggregation, allowing the copper
to be ‘‘hidden’’ in the polymer aggregate. Efficient copper re-
moval from CuBr/PMDETA click reactions proved unsuccess-
ful-even after purification steps such as EDTA (aq) wash, sol-
vent precipitation, soxhlet extraction, silica chromatography,
alumina chromatography, or the use of Dowex M4195-chelat-
ing resin.25 Sodium sulfide has been used for the removal of
copper from amine groups,26 owing to the insoluble copper
sulfide salt that is formed. When 1 equiv (to copper) of 1 M
Na2S (aq) was added to a solution of copper-contaminated
triblock in dichloromethane, a brown solution immediately
formed along with the insoluble copper sulfide, which was
removed by filtration. Although copper was successfully
removed using this method, the product was pale orange,
indicating the presence of trace amounts of sulfur.
The heterogeneous nature of Cu/Asc in ethanol led us to
attempt our conjugation reactions using copper nanopar-
ticles (CuNPs), owing to their use in the synthesis of block
copolymers.28 When the CuAAC reaction was conducted
using CuNPs in ethanol with 1 equiv of N3-PDMS-N3 (6) and
2 equiv of PMOXA (9) at 60 ꢀC, 1H NMR revealed quantita-
tive conjugation after 2 h (Scheme 5). Furthermore, after the
removal of the CuNPs via filtration, triblock copolymer 10
was obtained as a beige solid, unlike the yellow, green, or
blue products of previous methods, indicating negligible
copper contamination.
Synthesis of PMOXA-P(DMS-co-PHS)-PMOXA Triblock
Copolymer
The click methodology used for the synthesis of triblock 10
containing a PDMS B-block was used for the conjugation of
N3-P(DMS-co-MHS)-N3 (7) and PMOXA (9). Silanes are often
Synthesis of PMOXA–PDMS–PMOXA Triblock Copolymer
Via CuSO4/Sodium L-Ascorbate Method
used as reducing agents in organometallic chemistry18
;
Both PDMS27 and PMOXA19 have been used successfully in
CuAAC reactions using the CuSO4/sodium L-ascorbate (Cu/
Asc) method, leading us to consider it for PMOXA–PDMS–
PMOXA triblock synthesis. Most conditions involve a binary
solvent system that includes water, which serves to solubi-
lize Cu/Asc. All attempts to synthesize triblock 10 using an
aqueous-based binary solvent system were met with moder-
ate conversion <60%. We reasoned that the extreme hydro-
phobicity of poly(siloxane) causes self-aggregation in the
presence of water, thus hiding the azide end-groups and pre-
venting the reaction from proceeding to completion. We
therefore attempted the CuAAC reaction in ethanol, which
has the ability to solubilize both blocks, minimizing self-
aggregation. Despite the heterogeneous nature of Cu/Asc in
ethanol, the CuAAC reaction occurred quantitatively in 2 h at
60 ꢀC. Furthermore, the product can be isolated by simple
therefore, complications during the CuAAC reactions due to
the presence of copper were anticipated. Furthermore, Cop-
per(I) can also act as a hydrosilylation catalyst.29 Indeed,
when the aqueous Cu/Asc procedure was applied to the syn-
thesis of PMOXA-P(DMS-co-MHS)-PMOXA (11), an insoluble
product was produced indicating significant cross-linking of
the SiAH groups of the poly(siloxane) block. When the click
reaction was conducted using CuNPs in ethanol at 60 ꢀC,
conjugation was quantitative after 2 h (Scheme 5). However,
1H NMR showed the SiAH peak was perturbed in a similar
manner that occurred during azide substitution seen previ-
ously (Fig. 1). As with the synthesis of N3-P(DMS-co-MHS)-
N3 (7), the addition of EDTA to the CuAAC reaction using
CuNPs preserved the integrity of the SiAH groups due to
EDTA’s radical scavenging ability. Using CuNPs as the catalyst
with EDTA in ethanol at 60 ꢀC, PMOXA-P(DMS-co-MHS)-
6
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tion in the column. The ease of characterization, due to the
excellent PDI of the poly(oxazoline) obtained due to the
modular synthesis, makes the click-based approach very
attractive for synthesizing this family of triblock polymers.
Self-Assembly of Triblock Copolymer
The ability of amphiphilic ABA triblock copolymers to self-
assemble into higher architectures is well known5; thus,
vesicles of PMOXA–PDMS–PMOXA (10) were prepared by an
ethanol injection method.7 Briefly, an ethanolic solution of
the triblock was dropped into water under vigorous stirring
and then filtered through a 200 nm filter. Vesicle size in so-
lution was determined using dynamic light scattering (DLS),
which revealed the hydrodynamic diameter of these vesicles
to be 80 nm (see Supporting Information). Vesicles were
also imaged using transmission electron microscopy (TEM)
and shown to posses an average diameter of 150 nm (Fig.
4). The flattening of the vesicles under drying accounts for
the larger vesicle size observed with TEM.
1
EXPERIMENTAL
FIGURE 3
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Materials
Propargyl alcohol (Aldrich, 99%), p-toluenesulfonyl chloride
(TsCl) (Alfa Aesar, 98%), 4-(dimethylamino)pyridine (DMAP)
(Fluka, 99%), benzyltrimethylammonium chloride (Alfa Aesar,
97%), sodium hydroxide (NaOH) (Fisher Chemical), sodium
sulfate anhydrous (Na2SO4) (Fisher Chemical, 99%), potas-
sium carbonate anhydrous (K2CO3) (Fisher Chemical), 1,3-
bis(4-hydroxybutyl)tetramethyldisiloxane (Gelest, 95%), so-
dium azide (NaN3) (Sigma-Aldrich, 99.8%), sulfuric acid
(H2SO4) (Fisher Chemical, 98%), Ethanol (EtOH) (Gold Shield,
200 proof), copper(II) sulfate (CuSO4) (Sigma-Aldrich, 99%),
(þ)-sodium L-ascorbate (Aldrich, 99%), N,N,N0,N00,N00-pentame-
thyldiethylenetriamine (PMDETA) (Aldrich, 99%), triethyl-
amine (TEA) (Fisher Chemical), sodium sulfide nonahydrate
(Na2Sꢃ9H2O) (Sigma-Aldrich, 98%), iodine (I2) (Sigma-Aldrich,
99%), triphenylphosphine (PPh3) (Sigma-Aldrich, 99%),
PMOXA (11) was obtained after 2 h as a beige solid in quan-
titative yield, as confirmed by H NMR (Fig. 3).
1
In all of our triblock preparations, the proof of triblock
rather than diblock formation was gleaned by carefully com-
paring the integration of the SiACH3 protons of the poly
(siloxane)s block to the NACH2ACH2 and O¼¼CACH3 protons
of the poly(oxazoline) block using 1H NMR. The integration
of the SiACH3 protons in the triblock was set to the value
obtained for the poly(siloxane) homopolymer, and the result-
ing value of the poly(oxazoline) protons in the triblock inte-
grated to twice the value (within experimental error) of that
obtained from the poly(oxazoline) homopolymer. The proce-
dure for the NMR-based triblock validation is as follows: the
integration of the proton peak closest to the azide end-group
(SiACH2ACH2ACH2ACH2AN3) was set to 4; because there
are two end-groups, this resulted in an integration of 438
for the SiACH3 protons of N3-P(DMS-co-HMS)-N3 (7). Simi-
larly, using the proton peak next to the alkyne initiator (OTs-
CH2-alkyne), the integration of the NACH2ACH2 protons of
poly(oxazoline) (9) was determined to be 64. When the inte-
gration of the SiACH3 protons in the triblock was set to 438,
the integration of the NACH2ACH2 protons of the triblock
resulted in a value of 128, double the integration for the pol-
y(oxazoline) homopolymer, thereby confirming triblock for-
mation. The proton integration values yield a Mn of ꢁ8000
g/mol for the triblock.
This clearly indicates triblock formation and further lends
credence to power of the modular approach. Such characteri-
zation is not trivial, because in a macrointiation method, it
could always be argued that the hydrophilic block is just lon-
ger than anticipated. Furthermore, the amphiphilic nature of
these polymers does not allow for corroboration using classi-
cal characterization techniques such as GPC due to aggrega-
FIGURE 4
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imidazole (Sigma-Aldrich, 99%), EDTA (Sigma-Aldrich, 99–
100%), Copper nanopowder (CuNPs) (Aldrich, <50 nm parti-
cle size (TEM), 99.5%) were used as received. Copper(I) bro-
mide (CuBr) (Sigma-Aldrich, 98%) was purified by stirring in
glacial acetic acid overnight and washing with ethanol then
diethyl ether. Silica gel (Silicycle, 230–400 mesh) was deacti-
vated by spinning in an appropriate amount of TEA:hexanes
v/v 5:95 solution for 10 minutes followed by filtration and
several washes with hexanes. 2-Methyl-2-oxazoline (Aldrich,
98%) was purified by stirring in calcium hydride (CaH2) over-
night then fractionally distilling through a 10 cm vigreux col-
umn under argon. Piperidine (Sigma-Aldrich, 99%) was dis-
tilled under argon from CaH2. Octamethylcyclotetrasiloxane
(D4) (Gelest, 95%) and 1,3,5,7-tetramethylcyclotetrasiloxane
(D4H) (Gelest) were distilled from CaH2 under reduced pres-
sure. Tetrahydrofuran (THF), dichloromethane (DCM), toluene
(PhMe), acetonitrile (MeCN) and N-N-dimethylformamide
(DMF) were obtained from a PureSolv solvent purification
system.
ACH2ACH2ACH2AOTs), 21.8 (ASi(CH3)2ACH2ACH2ACH2
ACH2AOTs), 19.4 (ASi(CH3)2ACH2ACH2ACH2ACH2AOTs),
17.8 (ASi(CH3)2ACH2ACH2ACH2ACH2AOTs), 0.41 (ASi
(CH3)2ACH2ACH2ACH2ACH2AOTs). HRMS (m/z): calcd for
C
26H42O7S2Si2, 586.19; found, 609.18 [M þ Na]þ.
Synthesis of Bis-Iodide Disiloxane End-Blocker (3)
PPh3 (31.5 g, 120 mmol, 4 equiv) and imidazole (10.8 g, 159
mmol, 5.3 equiv) were dissolved in Et2O:MeCN v/v 3:1 (151
mL). The solution was cooled to 0 ꢀC, iodine (30.5 g, 120
mmol, 4 equiv) was added, and the solution was allowed to
stir for 20 min. 1,3-Bis(4-hydroxybutyl)tetramethyldisiloxane
ꢀ
(1) (8.37 g, 30 mmol, 1 equiv) was added dropwise at 0 C,
after which the solution was allowed to warm to room tem-
perature. After 1 h, TLC showed complete consumption of
the starting material. The precipitate was filtered off and the
filtrate concentrated. The resulting solid was washed with
hexanes, then filtered, and the solvent was concentrated to
give a clear oil. This oil was dissolved in hexanes and
washed with Na2S2O3 (aq), H2O, brine, dried over Na2SO4,
and concentrated to yield a clear oil. Yield: 10.4 g (70%).
Instrumentation
1H NMR spectra were recorded on
a Bruker Avance
1H NMR (500 MHz, CDCl3): d ¼ 3.21 (t, 4H; ASi(CH3)2ACH2
ACH2ACH2ACH2AI), 1.84 (m, 4H; ASi(CH3)2ACH2ACH2A
CH2ACH2AI), 1.44 (m, 4H; ASi(CH3)2ACH2ACH2ACH2A
CH2AI), 0.52 (t, 4H; ASi(CH3)2ACH2ACH2ACH2ACH2AI),
and 0.07 (s, 12H; ASi(CH3)2ACH2ACH2ACH2ACH2AI). 13C
NMR (600 MHz, CDCl3): d ¼ 36.9 (ASi(CH3)2ACH2ACH2
ACH2ACH2AI), 24.4 (ASi(CH3)2ACH2ACH2ACH2ACH2AI),
17.3 (ASi(CH3)2ACH2ACH2ACH2ACH2AI), 7.17 (ASi(CH3)2
ACH2ACH2ACH2ACH2AI), and 0.53 (ASi(CH3)2ACH2ACH2
ACH2ACH2AI). HRMS (m/z): calcd for C12H28I2OSi2, 497.98;
found, 482.96 [M-CH3]þ.
DMX500MHz SB NMR Spectrometer or Varian VNMRS
600MHz SB NMR Spectrometer using solutions of samples in
deuterated chloroform. Fourier transform infrared spectra
(FTIR) were recorded using a Nicolet Magna 850 FTIR Spec-
trometer. Gel permeation chromatography (GPC) studies
were performed using a Waters 2695 Separation Module
equipped with a 2414 Refractive Index Detector and 2996
Photodiode Array Detector. DLS experiments were obtained
on a DynaPro NanoStar from Wyatt Technology. HRMS data
were obtained using A Waters GCT Premier high-resolution
time-of-flight mass spectrometer. TEM images were obtained
using a FEI Tecnai G2 Sphera Microscope.
Synthesis of TsO–PDMS–OTs (4)
Bis-tosylate end-blocker (2) (1.96 g, 3.34 mmol, 1 equiv)
was added to an oven-dried round-bottomed flask with a
stir bar and stirred at 60 C under reduced pressure for 2.5
Synthesis of Bis-tosylate Disiloxane End-blocker (2)
1,3-Bis(4-hydroxybutyl)tetramethyldisiloxane (1) (8.36 g, 30
mmoꢀl, 1 equiv) was dissolved in DCM (150 mL) and cooled
to 0 C. TsCl (14.30 g, 75 mmol, 2.5 equiv) and DMAP (0.73
g, 6.0 mmol, 0.2 equiv) were added, followed by TEA (42
mL, 300 mmol, 10 equiv) dropwise, at which time a pale yel-
low precipitate developed. The reaction was kept at 0 ꢀC,
and, after 2 h, thin layer chromatography (TLC) showed com-
plete disappearance of the starting material in addition to
the appearance of bis-tosylate. The slurry was filtered, and
the DCM layer washed with H2O, brine, dried over Na2SO4,
and concentrated to yield a crude yellow oil. This oil was
purified by passing through a short plug of deactivated silica
gel to give a pale yellow oil. Yield: 11.77 g (70%).
ꢀ
h to remove trace water. The flask was cooled to room tem-
perature, freshly distilled D4 (19.65 mL, 63.3 mmol, 19
equiv) was added, and the mixture was stirred at room tem-
perature for 15 min. H2SO4 (0.15 mL, 2.8 mmol, 0.84 equiv)
was then added dropwise, at which time the solution became
viscous. The reaction was subsequently heated to 80 ꢀC. Af-
ter 17 h, an aliquot was taken for 1H NMR, which indicated
complete monomer consumption. Unreacted D4 was removed
in vacuo, and the polymer was isolated by dissolving in hex-
anes and washing with H2O, MeOH, brine, dried over Na2SO4,
and concentrated to give a clear viscous oil. Yield: 18.86 g
(94%), Mn,1HNMR ꢁ 5300.
1H NMR (500 MHz, CDCl3): d ¼ 7.78 (d, 4H; arom. H), 7.33
(d, 4H; arom. H), 4.03 (t, 4H; ASi(CH3)2ACH2ACH2
ACH2ACH2AOTs), 2.45 (s, 6H; APhACH3), 1.65 (m, 4H;
ASi(CH3)2ACH2ACH2ACH2ACH2AOTs), 1.31 (m, 4H; ASi
(CH3)2ACH2ACH2ACH2ACH2AOTs), 0.42 (t, 4H; ASi(CH3)2
ACH2ACH2ACH2ACH2AOTs), ꢂ0.01 (s, 12H; ASi(CH3)2
ACH2ACH2ACH2ACH2AOTs). 13C NMR (600 MHz, CDCl3): d
¼ 144.8 (arom. C), 133.5 (arom. C), 130.0 (arom. C), 128.0
(arom. C), 70.5 (APhACH3), 32.4 (ASi(CH3)2ACH2
1H NMR (500 MHz, CDCl3): d ¼ 7.78 (d, 4H; arom. H), 7.33
(d, 4H; arom. H), 4.03 (t, 4H; ASi(CH3)2ACH2ACH2
ACH2ACH2AOTs), 2.45 (s, 6H, APhACH3), 1.66 (m, 4H; ASi
(CH3)2ACH2ACH2ACH2ACH2AOTs), 1.34 (m, 4H; ASi(CH3)2
ACH2ACH2ACH2ACH2AOTs), 0.46 (t, 4H; ASi(CH3)2ACH2
ACH2ACH2ACH2AOTs), 0.071 (br. s, 432H; ASi(CH3)2AOA);
FTIR (KBr, cmꢂ1): 2963 (aliphatic CAH), 1446 (aromatic
C¼¼C), 1413 (CH2), 1372 (sulfonyl), 1261 (Si(CH3)2AO),
1098 (Si(CH3)2AO in poly(siloxane)s, and 809 (Si(CH3)2).
8
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Synthesis of I-P(DMS-co-MHS)-I (5)
The hexane layer was washed with H2O ꢄ 3, brine, dried
over Na2SO4, and concentrated to give a clear oil. Yield: 4.50
g (90%).
Bis-iodide end-blocker (3) (2.49 g, 5.00 mmol, 1 equiv) was
added to an oven-dried round-bottomed flask with a stir bar
and stirred at 60 ꢀC under reduced pressure for 2.5 h to
remove trace water. The flask was cooled to room tempera-
ture, freshly distilled D4 (20.17 mL, 65.0 mmol, 13 equiv)
was added, followed by freshly distilled D4H (9.76 mL, 40.0
mmol, 8 equiv), and the mixture was stirred at room tem-
perature for 15 min. H2SO4 (0.15 mL, 2.8 mmol, 0.84 equiv)
was added dropwise at which time the solution became vis-
cous. The reaction was heated to 80 ꢀC, and, after 16 h, an
1H NMR (500 MHz, CDCl3): d ¼ 4.70 (t, 24H, SiAH), 3.26 (t,
4H; ASi(CH3)2ACH2ACH2ACH2ACH2AN3), 1.63 (m, 4H; ASi
(CH3)2ACH2ACH2ACH2ACH2AN3), 1.42 (m, 4H; ASi(CH3)2
ACH2ACH2ACH2ACH2AN3), 0.56 (t, 4H; ASi(CH3)2ACH2
ACH2ACH2ACH2AN3), 0.070 (m, 392H ASi(CH3)2AOA);
FTIR (KBr, cmꢂ1): 2964 (aliphatic CAH), 2160 (silane), 2097
(azide N3), 1412 (CH2), 1261 (Si(CH3)2AO), 1094
(Si(CH3)2AO in poly(siloxane)s, and 800 (Si(CH3)2).
1
aliquot was taken for H NMR that indicated complete mono-
mer consumption. Unreacted D4 and D4H were removed in
vacuo, and the polymer was isolated by dissolving in hexanes
and washing with H2O, MeOH, brine, dried over Na2SO4, and
concentrated to give a clear viscous oil. Yield: 28.84 g
(96%), Mn,1HNMR ꢁ 5300.
Synthesis of Propargyl Tosylate (8)
To a 2.5 M NaOH (aq) solution (50 mL) cooled to 0 C, THF
(50 mL) was added, followed by propargyl alcohol (5.19 mL,
89.2 mmol, 1.1 equiv) and benzyltrimethylammonium chlo-
ride (1.66 g, 8.92 mmol, 0.11 equiv). A solution of TsCl
(15.30 g, 80.3 mmol, 1 equiv) in THF (50 mL) was added
ꢀ
1H NMR (600 MHz, CDCl3): d ¼ 4.70 (t, 24H; ASiAH), 3.19
(t, 4H; ASi(CH3)2ACH2ACH2ACH2ACH2AI), 1.84 (m, 4H;
ASi(CH3)2ACH2ACH2ACH2ACH2AI), 1.45 (m, 4H; ASi(CH3)2
ACH2ACH2ACH2ACH2AI), 0.55 (t, 4H; ASi(CH3)2ACH2A
CH2ACH2ACH2AI), 0.076 (m, 392H; ASi(CH3)2AOA); FTIR
(KBr, cmꢂ1): 2964 (aliphatic CAH), 2160 (silane), 1348
(CH2), 1261 (Si(CH3)2AO), 1096 (Si(CH3)2AO in poly(silox-
ane), and 800 (Si(CH3)2).
ꢀ
dropwise over 30 min, and the reaction was kept at 0 C. Af-
ter 30 min, TLC showed complete consumption of TsCl. The
reaction was then placed in a separatory funnel, and the
NaOH (aq) layer was removed. The organic layer was diluted
with EtOAc and washed with H2O ꢄ 3, brine, dried over
Na2SO4, and concentrated to give a clear oil. Yield: 15.95 g
(85%).
1H NMR (500 MHz, CDCl3): d ¼ 7.81 (d, 2H; arom. H), 7.35
(d, 2H; arom. H), 4.70 (d, 2H; alkyne-CH2-OTs), 2.47 (t, 1H,
alkyne-H), 2.46 (s, 3H; APhACH3). 13C NMR (600 MHz,
CDCl3): d ¼ 145.4 (arom. C), 133.1 (arom. C), 130.0 (arom.
C), 128.3 (arom. C), 77.5 (CH3), 75.5 (C), 57.5 (CH), and 21.8
(CH2).
Synthesis of N3-PDMS-N3 (6)
TsO-PDMS-OTs (4) was dissolved in THF (20 mL), and then
DMF (10 mL) was added, followed by NaN3 (0.18 g, 2.83
mmol, 3 equiv) at room temperature. The mixture was
heated to 60 ꢀC and after 22 h, 1H NMR showed complete
conversion to the bis-azide. The white precipitate that devel-
oped during the reaction was filtered off, and THF was
removed under reduced pressure. The mixture was diluted
with hexanes, then placed in a separatory funnel, and the
DMF was removed. The hexanes layer was washed with H2O
ꢄ 3, brine, dried over Na2SO4, and concentrated to give a
clear oil. Yield: 4.56 g (91%).
Synthesis of PMOXA (9)
Propargyl tosylate (8) (1.65 g, 7.83 mmol, 1 equiv) was
added to an oven-dried round-bottomed flask with a stir bar
and stirred at room temperature under reduced pressure
overnight to remove trace water. MeCN (10 mL) was added
followed by freshly distilled 2-methyl-2-oxazoline (10 mL,
1H NMR (500 MHz, CDCl3): d ¼ 3.26 (t, 4H; ASi(CH3)2
ACH2ACH2ACH2ACH2AN3), 1.63 (m, 4H; ASi(CH3)2ACH2A
CH2ACH2ACH2AN3), 1.42 (m, 4H; ASi(CH3)2ACH2ACH2A
CH2ACH2AN3), 0.56 (t, 4H; ASi(CH3)2ACH2ACH2ACH2
ACH2AN3), 0.071 (br. s, 432H ASi(CH3)2AOA); FTIR (KBr,
cmꢂ1): 2963 (aliphatic CAH), 2097 (azide N3), 1413 (CH2),
1261 (Si(CH3)2AO), 1019 (Si(CH3)2AO in poly(siloxane)s,
and 800 (Si(CH3)2).
ꢀ
118 mmol, 15 equiv), and the solution was heated to 80 C.
After 17 h, 1H NMR showed complete monomer consump-
tion. After cooling to room temperature, freshly distilled pi-
peridine (2.32 mL, 23.5 mmol, 3 equiv) was added dropwise,
and the solution was allowed to stir for 3 h. The solution
was then concentrated, and the solid was washed with Et2O
to remove excess piperidine. The solid was dissolved in
MeCN, K2CO3 (10.8 g, 78.3 mmol, 10 equiv) was added, and
the mixture was stirred at room temperature overnight. The
solution was then concentrated, dissolved in DCM, filtered,
and the filtrate was concentrated to yield PMOXA as a white
solid in quantitative yield. Mn,1HNMR ꢁ 1350, PDI 1.17 (PS
standards, Eluent: CHCl3 þ 0.25% triethylamine).
Synthesis of N3-P(DMS-co-MHS)-N3 (7)
I-P(DMS-co-MHS)-I (5) was dissolved in THF (20 mL), then
DMF (10 mL) was added, followed by EDTA (83 mg, 0.28
mmol, 0.3 equiv). The mixture was degassed by bubbling ar-
gon through it for 15 min. NaN3 (0.18 g, 2.83 mmol, 3 equiv)
was added, and the mixture was spun at room temperature.
1H NMR (500 MHz, CDCl3): d ¼ 4.27–4.08 (br. m, 2H;
alkyneACH2AN(¼¼O)), 3.47 (br. m, 64H; AN(¼¼O)ACH2
ACH2AN(¼¼O)), 2.79 (br. m, 2H; AN(¼¼O)ACH2ACH2Apip),
2.41 (br. m, 4H; pipACH2ACH2ACH2A), 2.15 (br. m, 48H;
N(CH3¼¼O), 1.56 (br. m, 4H; pipACH2ACH2ACH2A), 13.43
(br. m, 2H; pipACH2ACH2ACH2A); FTIR (KBr, cmꢂ1): 2963
1
After 14 h, H NMR showed complete conversion to the bis-
azide. The white precipitate that developed during the reac-
tion was filtered off, and THF was removed under reduced
pressure. The mixture was diluted with hexanes and then
placed in a separatory funnel, and the DMF was removed.
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(aliphatic CAH), 2117 (alkyne), 1635 (amide C¼¼O), and
1421 (CH3AN).
ACH2ACH2ACH2ACH2Atriazole),
1.56
(br.
m,
8H;
pipACH2ACH2ACH2A), 1.43 (br. m, 4H; pipACH2ACH2
ACH2A), 1.38 (br. m, 4H; ASi(CH3)2ACH2ACH2ACH2ACH2
Atriazole), 0.59 (br. m, 4H; ASi(CH3)2ACH2ACH2ACH2ACH2
Atriazole), 0.071 (br. s, 432H ASi(CH3)2AOA); FTIR (KBr,
cmꢂ1): 2962 (aliphatic CAH), 1636 (amide C¼¼O), 1420
(CH3AN), 1261 (Si(CH3)2AO), 1019 (Si(CH3)2AO in poly(silox-
ane)s, and 801 (Si(CH3)2).
General CuBr/PMDETA Click Procedure
N3-PDMS-N3 (6) (1.0 g, 0.19 mmol, 1 equiv) and PMOXA (9)
(0.51 g, 0.38 mmol, 2 equiv) were added to an oven-dried
round-bottomed flask with a stir bar, and then DMF (5.0 mL)
was added followed by PhMe (5.0 mL). PMDETA (40 lL,
0.19 mmol, 1 equiv) was added dropwise, and the solution
was degassed by bubbling argon through it for 15 min. CuBr
(28 mg, 0.19 mmol, 1 equiv) was added, and the flask was
flushed with argon and allowed to stir at 60 ꢀC for 1 h, at
which time 1H NMR showed complete conversion of the az-
ide and alkyne to triazole. The solvent was removed in vacuo
to give a green solid. This solid was dissolved in a minimal
amount of DCM and to this solution was added 1 M Na2S
(aq) (0.19 mL, 0.19 mmol, 1 equiv). Upon 1 M Na2S (aq)
addition, the solution turned brown, was filtered, and then
concentrated to yield a brown solid. The solid was dissolved
in i-PrOH, 3 g of MgSO4 was added, and the mixture was
stirred overnight at room temperature, filtered, and the fil-
trate concentrated to yield a pale orange solid in quantitative
yield.
General Copper Nanoparticles Click Procedure
N3-P(DMS-co-MHS)-N3 (7) (2.50 g, 0.47 mmol, 1 equiv) and
PMOXA (9) (1.27 g, 0.12 mmol, 2 equiv) were added to an
oven-dried round-bottomed flask with a stir bar and dis-
solved in EtOH (25 mL). EDTA (0.10 g, 0.34 mmol, 0.7 equiv)
was added, and the mixture was degassed by bubbling argon
through it for 15 min. CuNPs (50 mg) were added, and the
flask was flushed with argon and then allowed to stir at 60
ꢀC for 2 h at which time 1H NMR showed complete conver-
sion of the azide and alkyne to triazole. The mixture was
cooled, filtered through celite, and concentrated to yield a
beige solid. Yield: (3.13 g, 83 %).
1H NMR (600 MHz, CDCl3): d ¼ 7.56 (br. m, 2H; triazole-H),
4.70 (t, 24H, SiAH), 4.58 (br. m, 4H; triazoleACH2AN(¼¼O)),
4.38–4.29 (br. m, 4H; ASi(CH3)2ACH2ACH2ACH2ACH2A
triazole), 3.48 (br. m, 128H; AN(¼¼O)ACH2ACH2AN(¼¼O)),
2.79 (br. m, 4H; AN(¼¼O) ACH2ACH2Apip), 2.41 (br. m, 8H;
pipACH2ACH2ACH2A), 2.15 (br. m, 96H; N(CH3¼¼O), 1.94
(br. m, 4H; ASi(CH3)2ACH2ACH2ACH2ACH2Atriazole), 1.56
(br. m, 8H; pipACH2ACH2ACH2A), 1.43 (br. m, 4H;
pipACH2ACH2ACH2A), 1.38 (br. m, 4H; ASi(CH3)2ACH2A
CH2ACH2ACH2Atriazole), 0.59 (br. m, 4H; ASi(CH3)2A
CH2ACH2ACH2ACH2Atriazole), 0.071 (br. s, 392H;
ASi(CH3)2AOA); FTIR (KBr, cmꢂ1): 2962 (aliphatic CAH),
2160 (silane), 1636 (amide C¼¼O), 1420 (CH3AN), 1261
(Si(CH3)2AO), 1019 (Si(CH3)2AO in poly(siloxane)s, and 801
(Si(CH3)2).
1H NMR (600 MHz, CDCl3): d ¼ 7.56 (br. m, 2H; triazole-H),
4.58 (br. m, 4H; triazoleACH2AN(¼¼O)), 4.38–4.29 (br. m,
4H; ASi(CH3)2ACH2ACH2ACH2ACH2Atriazole), 3.48 (br. m,
128H; AN(¼¼O)ACH2ACH2AN(¼¼O)), 2.79 (br. m, 4H;
AN(¼¼O) ACH2ACH2Apip), 2.41 (br. m, 8H; pip
ACH2ACH2ACH2A), 2.15 (br. m, 96H; N(CH3¼¼O), 1.94 (br.
m, 4H; ASi(CH3)2ACH2ACH2ACH2ACH2Atriazole), 1.56 (br.
m, 8H; pipACH2ACH2ACH2A), 1.43 (br. m, 4H; pipACH2
ACH2ACH2A), 1.38 (br. m, 4H; ASi(CH3)2 ACH2ACH2
ACH2ACH2Atriazole), 0.59 (br. m, 4H; ASi(CH3)2 ACH2
ACH2ACH2ACH2Atriazole), 0.071 (br. s, 432H ASi(CH3)2
AOA); FTIR (KBr, cmꢂ1): 2962 (aliphatic CAH), 1636 (amide
C¼¼O), 1420 (CH3AN), 1261 (Si(CH3)2AO), 1019
(Si(CH3)2AO in poly(siloxane)s, and 801 (Si(CH3)2).
Vesicle Preparation Procedure
General CuSO4/Sodium Ascorbate Click Procedure
PMOXA–PDMS–PMOXA (10) triblock copolymer (10 mg) was
dissolved in ethanol (1 mL, 10 wt % polymer). The polymer
solution was then added dropwise to water (1 mL, 5 wt %
polymer) under vigorous stirring to yield an opaque solu-
tion, which cleared after ꢁ1 h of stirring. The vesicles were
then filtered twice through 0.2 lL filters (PTFE).
N3-PDMS-N3 (6) (0.33 g, 0.062 mmol, 1 equiv) and PMOXA
(9) (0.17 g, 0.12 mmol, 2 equiv) were added to an oven-
dried round-bottomed flask with a stir bar and dissolved in
EtOH (3.3 mL). Sodium L-ascorbate (5 mg, 0.025 mmol, 0.4
equiv) was added, and the mixture was degassed by bub-
bling argon through it for 15 min. CuSO4 (1 mg, 0.0062
mmol, 0.1 equiv) was added, the flask was flushed with ar-
CONCLUSIONS
ꢀ
gon, and then allowed to stir at 60 C for 2 h, at which time
We have successfully demonstrated a versatile yet facile
method for synthesizing amphiphilic triblock copolymers
using click chemistry. We have presented a matrix of condi-
tions under which such polymers can be synthesized, the
optimal method being that which uses copper nanoparticles.
We believe that the modular synthesis of these polymers
will allow for systematic investigation of their structure–
function relationships. The poly(oxazoline)–poly(siloxane)–
poly(oxazoline) ABA blocks can self-assemble into vesicles
under appropriate conditions. These polymers are ideal sys-
tems for biomedical applications such as drug delivery and
synthetic lipid bilayers for ion-channel studies. Furthermore,
1H NMR showed complete conversion of the azide and
alkyne to triazole. The mixture was cooled, concentrated, dis-
solved in DCM, and filtered to remove sodium L-ascorbate
and CuSO4, and then the filtrate was concentrated to yield a
yellow/green solid. Yield: (0.47 g, 94 %).
1H NMR (600 MHz, CDCl3): d ¼ 7.56 (br. m, 2H; triazole-H),
4.58 (br. m, 4H; triazoleACH2AN(¼¼O)), 4.38–4.29 (br. m, 4H;
ASi(CH3)2ACH2ACH2ACH2ACH2Atriazole), 3.48 (br. m, 128H;
AN(¼¼O)ACH2ACH2AN(¼¼O)), 2.79 (br. m, 4H; AN(¼¼O)
ACH2ACH2Apip), 2.41 (br. m, 8H; pipACH2ACH2ACH2A),
2.15 (br. m, 96H; N(CH3¼¼O), 1.94 (br. m, 4H; ASi(CH3)2
10
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we have shown that polymers with the SiAH functionality in
the middle block allows for further functionality via a hydro-
silylation reaction. We are currently exploring the functional-
ization of these polymers and their use in bioengineering
and medicine.
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The authors thank Damien Montarnal for useful discussions
regarding copper nanoparticles, Sukru Yemenicioglu for help
with the TEM images, and Peter Allen for the illustrations. The
authors gratefully acknowledge support from the National
Institutes of Health, through the NIH Director’s New Innovator
Award Program (1-DP2-OD007472-01), the National Science
Foundation under Award No. DMR-1121053, the Apprentice
Researchers Program, the California NanoSystems Institute, the
Center for Science and Engineering Partnerships as well as the
National Science Foundation LEAPS project under Award No.
DGE 0440576.
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2008, 57
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