Toward controlling folding in synthetic polymers: Fabricating and characterizing supramolecular single-chain nanoparticles

Article abstract of DOI:10.1021/ma902393h

We discuss in detail our facile method for producing supramolecular polymeric nanoparticles from the collapse of single polymer chains. A new family of poly(methyl methacrylate)-based nanoparticles confirm that our method is general and can be easily tuned toward a variety of applications. Thorough AFM characterization elucidates the conditions required to visualize single particles as well as complex assemblies of particles mediated by the evaporation of solvent. AFM studies also indicate that the intramolecular collapse resembles the cooperative folding process witnessed in biomacromolecules and that the particles possess a complex morphology that implies the internal organization of the UPy dimers used to induce the intramolecular collapse. Thermal studies support these observations in addition to confirming the applicability of this system in the fabrication of processable high-performance supramolecular materials.

Full text of DOI:10.1021/ma902393h

1430 Macromolecules 2010, 43, 1430–1437
DOI: 10.1021/ma902393h
Toward Controlling Folding in Synthetic Polymers: Fabricating and
Characterizing Supramolecular Single-Chain Nanoparticles
Erik B. Berda, E. Johan Foster, and E. W. Meijer*
Institute for Complex Molecular Systems and Laboratory of Macromolecular and Organic Chemistry,
Eindhoven University of Technology, P.O. Box 513, 5600 MB Eindhoven, The Netherlands
Received October 28, 2009; Revised Manuscript Received December 28, 2009
ABSTRACT: We discuss in detail our facile method for producing supramolecular polymeric nanoparticles
from the collapse of single polymer chains. A new family of poly(methyl methacrylate)-based nanoparticles
confirm that our method is general and can be easily tuned toward a variety of applications. Thorough AFM
characterization elucidates the conditions required to visualize single particles as well as complex assemblies
of particles mediated by the evaporation of solvent. AFM studies also indicate that the intramolecular
collapse resembles the cooperative folding process witnessed in biomacromolecules and that the particles
possess a complex morphology that implies the internal organization of the UPy dimers used to induce the
intramolecular collapse. Thermal studies support these observations in addition to confirming the applica-
bility of this system in the fabrication of processable high-performance supramolecular materials.
Introduction
polymer and solvent systems, further expanding its utility.
The methods used to fabricate and characterize this complex
Vigorous research efforts persist in the area of polymeric
nanoparticles. This is not surprising considering their applicabi-
lity across the sciences from materials to medicine.1-14 Recently,
a new method of producing polymer nanoparticles has become
popular: the intramolecular cross-linking and collapse of single
polymer chains.2,4,6-8,11,15-18 This method allows the facile
preparation of nanoparticles from 5 to 20 nm in diameter with
a wide variety of chemical compositions. The sizes of the particles
made in this fashion are tunable simply by controlling the
molecular weight of the parent polymer chain and the amount
of cross-linking used to effect the collapse. In a sense, this work
builds on previous work in foldamers19 by using a top-down
approach to study folding in synthetic polymers, rather than the
piecewise bottom-up approach used in foldamer synthesis.
In an attempt to advance the field of polymer nanoparticle
synthesis toward the efficiency witnessed in nature, we have
developed a method for producing well-defined polymeric nano-
particles using nature’s design: single chains suspended in a
metastable collapsed state by intramolecular, supramolecular
cross-links.16 While our collapsed single-chain nanoparticles
(SCNP) are by no means as structurally magnificent as folded
biomacromolecules, they represent an advancement toward un-
derstanding the process of controlled polymer folding. The choice
of polymer backbone composition for nature’s SCNP construc-
tion is generally limited: phosphate ester linked ribose rings in
nucleic acids or poly(amides) in proteins. In attempting to mimic
this complex behavior synthetically, the choice of backbone
architecture is daunting considering the virtually limitless possi-
bilities. Given the ease in which exotic polymer structures can be
made using ROMP,20-24 poly(norbornenes) (PNB) were a logi-
cal first choice for the backbone material of our SCNPs.16 We
discuss here a new family of particles based on poly(methyl
methacrylate) (PMMA) synthesized using a combination of
living radical polymerization and “click” chemistry, providing a
system that can be readily tuned. In doing so, we demonstrate
that our method is general and can be applied to a wide array of
molecular system are discussed in greater depth, and we provide
new insights as to their structure and behavior in the bulk when
deposited on a surface. Our goal through continued development
of this work is to create self-folding synthetic polymers which
closely mimic, in both structure and function, nature’s sophisti-
cated nanomachinery.
Results and Discussion
Polymer Design. Our method, illustrated in Figure 1,
involves the synthesis of a linear polymer chain functiona-
lized with an o-nitrobenzyl-protected 2-ureidopyrimidinone
(UPy) pendant moiety, linked to the polymer through a
urethane or urea group. By diluting the polymer below the
threshold concentration (c*) and irradiating with UV light,
we induce the intramolecular collapse via supramolecular
interactions. We chose to work with PMMA in this report of
a number of reasons: living radical polymerization techni-
ques such as ATRP25-33 and SET-LRP34-41 provide control
over molecular weight and molecular weight distribution. As
with ROMP, there is an enormous volume of work on the
synthesis of functionalized PMMA-based materials, all of
which could be potential SCNP candidates. While this is the
case for many other monomers besides MMA, the propen-
sity of PMMA to photodegrade gives us the opportunity to
demonstrate the efficacy of the photodeprotection process.
Finally, exchanging the PNB backbone for PMMA proves
that increasing the polarity of the polymer backbone does
not hinder the supramolecular collapse, opening this method
to variety of possible functional polymer architectures.
Synthesis. Scheme 1 illustrates our initial synthesis of the
PMMA SCNPs. Because of failed attempts to copolymerize
the protected UPy-urethane comonomer 1 with MMA under
normal ATRP conditions, we adopted the relatively new
technique ARGET ATRP32 which is more active than tradi-
tional ATRP due to the constant regeneration of the active
Cu(I) species. This route successfully provided protected
UPy-urethane functionalized polymer 2 albeit with molecular
*Corresponding author. E-mail: e.w.meijer@tue.nl.
pubs.acs.org/Macromolecules
Published on Web 01/14/2010
r 2010 American Chemical Society

Article
Macromolecules, Vol. 43, No. 3, 2010 1431
Scheme 2. Synthesis of UPy-Urethane Functionalized PMMAs via
“Click” Chemistrya
Figure 1. UV irradiation induced collapse of a single polymer chain
into a nanoparticle via the supramolecular cross-linking of the UPy-
urethane side groups (nitrosoaldehyde side product omitted for clarity).
Scheme 1. ARGET ATRP Synthesis of UPy-Urethane
Functionalized PMMAa
a Reagents and conditions: (i) 12-azidododecan-1-ol, DBDTL, CH2-
CL2; (ii) o-nitrobenzyl chloride, K2CO3, DMF; (iii) Cu(0), PMDETA,
DMSO; (iv) TBAF, acetic acid, THF; (v) toluene, 95 °C (6a and 6b) or
THF, Cu(0), PMDETA, 35 °C (6c).
UPy content on several polymers having identical contour
length and size distribution, we sought a more efficient
synthetic strategy. Synthesizing an alkyne functionalized
PMMA and “clicking” the UPy-urethane moiety to the
polymer proved a more effective route (Scheme 2). In addi-
tion to these general synthetic benefits, this method provides
a reactive handle to further functionalize these particles for
broader applicability.
In this synthesis we employed SET-LRP,41 both for the
convenience of working with Cu(0) when targeting higher
molecular weights on a small scale and the reported accelera-
ted polymerization times. Reacting 4 with clickable PMMA
5 afforded the protected, UPy functionalized precursor
polymers 6 via thermal (6a and 6b) or Cu mediated (6c)
“click” reaction.42 In the case of the highest UPy-urethane
loading Cu was needed to ensure complete conversion within
a reasonable time frame (less than 72 h). These polymers are
soluble in a wide range of organic solvents including THF,
toluene, chloroform, and acetone. Hexanes and heptanes
proved suitable for precipitation. The functionalized poly-
mers have been characterized using all of the routine techni-
ques; all spectra are in accordance with the assigned struc-
tures. GPC data are shown in Table 1.
Nanoparticle Fabricationand GPC Characterization. Nano-
particles are fabricated by dissolving the protected polymer in
CHCl3 (1 mg/mL) and irradiating with 350 nm UV light for
2 h (this is sufficient for complete deprotection by NMR based
on our previous studies16). Consistent with previous cova-
lently cross-linked SCNP work,7,8,11 the polymers show dec-
reased hydrodynamic volume after deprotection, which rela-
tes to supramolecular cross-linker density (Table 1). This
change in volume is a result of UPy dimerization after the
a Reagents and conditions: (i) HEMA, DBDTL, CH2Cl2; (ii) o-nitro-
benzyl chloride, K2CO3, DMF; (iii) macroinitiator, PMDETA, CuBr,
tin(II) 2-ethylhexanoate, toluene, 90 °C.
weights lower than targeted. We attribute these difficulties to
interactions between the protected UPy comonomer and the
copper catalyst. Increasing the concentration of the ligand
(thereby decreasing the likelihood of copper-UPy inter-
actions) marginally improved these polymerizations.
Given the difficulties associated with the aforementioned
method, as well as our desire to probe the effect of varying

1432 Macromolecules, Vol. 43, No. 3, 2010
Berda et al.
Table 1. Molecular Weight for Protected Polymers and Intramolecular Collapse
before irradiation after irradiation for 1 h after irradiation for 2 h
Mwa (kg/mol)
Mw/Mn
polymer
Mwa (kg/mol)
Mw/Mn
% change
Mwa (kg/mol)
Mw/Mn
% change
2a f 3a
2b f 3b
6a f 7a
6b f 7b
6c f 7c
5
22.4
18.5
87.9
82.0
79.0
64.4
1.29
1.39
1.54
1.4
1.42
1.37
18.6
15.9
74.1
69.2
55.3
1.24
1.40
1.39
1.38
1.37
16
14
15
16
30
17.4
14.9
71.8
62.0
36.0
64.3
1.24
1.40
1.42
1.32
1.31
1.37
22
19
18
24
54
a Determined by GPC in THF versus PMMA standards.
and urethane groups still present several hydrogen-bonding
sites available for supramolecular cross-linking, albeit with a
significantly depressed association constant. Taking this into
consideration, it may be the case that these weaker nonco-
valent interactions in essence prime the polymer for collapse
and that the collapse itself resembles a cooperative process,
proceeding quickly once the deprotection begins. AFM
studies of the deprotection support this: after just 30 min
of irradiation time, much shorter than what is required for
complete deprotection by NMR, well-defined single particles
are already present, and the ill-defined globs seen in the
protected sample disappear. Visualization after 60 and
90 min of irradiation reveals that as deprotection time
increases, particle size decreases: from ∼100 nm in diameter
after 30 min to ∼75 nm in diameter after 60 min and ∼50 nm
in diameter after 90 min. This is consistent with the GPC
results as well as the aforementioned supramolecular cross-
linking density dependence of particle size (increased irradia-
tion time frees more UPy’s for dimerization, thus increasing
the density of supramolecular cross-links). Initial experi-
ments on polymer samples lacking the urethane linker do
not show the same behavior, again implying that the collapse
relies on this secondary interaction between UPy-urethane
dimers and in this way resembles the cooperative folding
process witnessed in biomacromolecules.
AFM Characterization of Single-Chain Particles and Their
Assemblies. Although fabrication of SCNPs is relatively
simple, visualization of individual particles by AFM requires
a bit of finesse to find the ideal conditions. Sample concen-
tration and choice of surface and solvent strongly affect the
data. Further, the polymer sample itself determines these
conditions, as we have seen slight differences between these
PMMA SCNPs and our previous PNB examples. If condi-
tions are not perfect, aggregates of single particles dominate
the images seen when conducting AFM characterization.
This begs the question: how can one differentiate between
these aggregates and individual nanoparticles? The following
section explicitly describes this process.
Nanoparticles are first fabricated at 1 mg/mL, followed by
serial dilutions for visualization (described in the experimen-
tal section). Trial and error is required to find an appropriate
surface and solvent; for the samples discussed here the best
results were obtained when solutions were drop-cast from
chloroform onto a freshly cleaved mica surface. After selec-
tion of solvent and surface, measurements are conducted
over a range of concentrations. While the actual concentra-
tions required for visualizing each of the morphologies
presented here depend on the polymer sample used, this
method has been successfully applied to all of our SCNP
examples.
Figure 2. Supramolecular cross-linking monitored by AFM. All
images were taken from samples of polymer 2b (intermittently during
conversion to 3b) drop-cast (2 μL of a 10-8 mg/mL solution) on freshly
cleaved mica. Panel A: protected polymer; panel B: following 30 min of
irradiation (scale bar common for height and phase insets); panel C:
following 60 min of irradiation; panel D: following 90 min of irradiation
(scale bars are common in (C) and (D) for both height and phase
panels).
release of the protecting group and subsequent collapse of the
chain. Photodegradation of the backbone over this period can
be ruled out as (1) the PDI does not increase after irradiation,
as it would if chain scission where occurring, and (2) the UPy-
free polymer 5 remains unchanged when exposed to deprotec-
tion conditions. Interestingly, when comparing the data for
the protected polymers 6a, 6b, and 6c, the polymers show a
decrease in molecular weight with increasing protected UPy-
urethane content. Despite the fact that the protected UPy
groups are prevented from quadruple hydrogen bonding,
drastically lowering the association constant, therestill remain
several available hydrogen-bonding sites. This results in the
decreased hydrodynamic volume witnessed by GPC as the
mole fraction of protected UPy-urethane in the polymer
increases.
Deprotection Monitored by AFM. Consistent with the
GPC results discussed above, the chain collapse process
can be followed by AFM. Figure 2 shows that drop-casting
protected polymer 2b results in ill-defined clumps of poly-
mer, occasionally with the presence of a few small spheres.
The presence of these small particles even in the protected
samples is not surprising considering that the protected UPy
Individual Single-Chain Particles. Drop-casting extremely
dilute (10-8-10-10 mg/mL) nanoparticle solutions from
CHCl3 on mica results in large arrays of well-defined sin-
gle-chain nanoparticles (Figure 3, panel A). We can be sure
that the objects observed are single particles as dilution beyond
this point results increasingly sparsely spaced particles of

Article
Macromolecules, Vol. 43, No. 3, 2010 1433
Figure 3. AFM images of single-chain particles drop cast (2 μL of a
10-8 mg/mL solution) onto a mica surface: (A) 10 Â 10 μm scanning
area displaying thousands of well-defined particles; (B) blown-up
section of panel A and corresponding phase image showing the
darkened core of individual particles; (C) 5 Â 5 μm scan shown in 3-D.
Figure 4. High-resolution AFM scan of individual SCNP: (A) group of
a few particles; (B) height, amplitude, and phase images clearly
indicating the complex geometry and raised core; (C) three-dimensional
height image with phase retrace overlay of this particle. Panel D shows a
cartoon depicting the possible particle morphology: UPy-urethane
rich core (blue) immersed in a network of PMMA.
constant size. The size of these particles on the surface (see
below) agrees well with our previous work.16 The estimated
spherical radii of the particles agree well with the estimated
Rg for PMMA of the same contour length. There is some size
distribution to these individual particles; this is attributed to
the molecular weight distribution of the polymer sample.
The difference between small aggregates and individual
SCNPs is evident when comparing height and phase
images (panel B); the single particles show a darkened core,
whereas aggregates of a few particles show no changes
in phase. We attribute this to phase separation of the
UPy-urethane dimers from the PMMA backbone in the
core of the particle.
Evidence for this internal organization of UPy-urethane
dimers is observed via AFM when concentration is decreased
to ∼10-12 mg/mL. While the particles appear to be flattened
spheres or ellipsoids in the larger scans, high-resolution
images of single particles reveal otherwise. Scanning an
individual SCNP at high resolution reveals a complex geo-
metry containing a raised center that is clearly visible in the
height, phase, and amplitude images (Figure 4). The height
of the central portion of the particle closely matches the size
of the UPy-urethane dimer. This is consistent with the phase
difference in the core of the particle as seen in the larger
scans. In the high-resolution images this core is distinct from
the rest of the particle in height and phase as well. This
certainly supports the existence of a separate internal phase
rich in UPy-urethane dimers. Whether or not the dimers are
organized into well-ordered stacks is impossible to say for
certain from this data; however, our efforts to better under-
stand this behavior are continuous.
Table 2. Summary of Single Particle Sizes (in nm) by AFM
estimated spherical
radiusb
particle heighta
diametera
estimated Rg
c
3a
3b
7a
7b
7c
2-3
2-3
3-5
2-4
2-3
∼35-50
∼35-50
10-12
10-12
12
11
∼100-200 30-35
∼100-150 20-25
22d
22d
22d
∼50-75
12-20
a From AFM images with out tip correction (see Supporting Infor-
mation for AFM height profiles). b Estimated by calculating the volume
of the half-ellipsoid shaped particle on the surface and solving for the
radius of a sphere (see Supporting Information). c Calculated using the
formula Rg = N0.6 where N is the estimated contour length of the
polymer. d Calculated using the contour length of the clickable precursor
polymer 5.
polymers containing similar UPy-urethane concentration,
although more detailed studies on the effect of molecular
weight on particle size are underway. When comparing the
sizes of the polymers to the estimated Rg, they may seem large
for single chains: a collapsed particle, more like a hard
sphere, would be smaller than the Rg in radius. There are,
however, a few points that must be taken into consideration
when discussing the estimates described here. First, the Rg
estimates are very rough calculations based on the contour
length of the clickable precursor and are only meant to
provide some idea of dimensions for individual chains.
Second, the diameters measured by AFM are artificially
large due to the effects of the size and shape of the AFM
tip. Third, the volume calculation assumes the particles on
the surface resemble half-ellipsoid-like flattened spheres.
This is an oversimplification, evident when viewing the single
particle shown in Figure 3. The volume of the complicated
“fried egg” geometry of the particles is likely overestimated
by this calculation, leading to an overestimated spherical
radius for the unflattened particle. Finally, the steric require-
ments for housing UPy-urethane dimers within a particle
Table 2 summarizes the heights and diameters for each set
of SCNPs in this study as measured by AFM. As expected,
the trends resemble that of analogous covalently cross-linked
single chain particles: smaller particle size results from higher
cross-link density, consistent with the GPC data. Compa-
ring particles from polymer 3b with 7a shows an appa-
rent (although not unexpected) molecular weight effect for

1434 Macromolecules, Vol. 43, No. 3, 2010
Berda et al.
Figure 5. Aggregation of SCNP characterized by AFM: (A) large
assembly of aggregates mediated by drying; (B) amplitude and phase
images showing that this large assembly is comprised of smaller
aggregates; (C) 3-D image of this large nanoparticle assembly.
are quite large, requiring a minimum interchain distance of
roughly 6 nm. This means that there is a lower limit to how
much collapse of the chain can actually occur, making a densely
packed hard sphere an unlikely morphology for this system.
When taking these points into consideration, the sizes witnessed
here are perfectly reasonable for single chains.
Aggregates of Single-Chain Particles. Higher concentra-
tions (10-6-10-7 mg/mL) results in larger disklike aggre-
gates (∼10 nm in height and a few hundred nanometers in
diameter) along with even larger globules (Figure 5). These
images again display nicely that this effect is a result of
drying; the area immediately surrounding the large particle is
void of smaller particles (panel A). In addition, the amplitude
and phase images (panel B) show that this large object is indeed
an assembly of smaller individual aggregates forced together
by disappearing solvent, reminiscent of the “coffee stain”
effect where the particles concentrate in the center of a drying
drop during the final stages of solvent evaporation.43-45 This
phenomenon is also known to create concentration gra-
dients of deposited material on the surface, behavior we
have also been able to visualize for our particles by AFM
(see Supporting Information).
Figure 6. AFM image of large spherical aggregates, fibers, and net-
works of SCNPs: (A, B) large spherical aggregates; (C, D) fibers which
appear nucleated from these larger assemblies; (E) 1 Â 1 μm scan of a
network-like assembly of particles.
the UPy-urethane, there is still a significant driving force to
create this type of assembly, possibly by some type of
cooperative process. At the highest concentrations studied
(typically from 1 to 0.001 mg/mL) network-like arrays of
particles appear (panel E). This is in excellent agreement with
comparative simulation and experimental studies conducted
on the drying mediated self-assembly of inorganic nanopar-
ticles.45
The propensity for aggregation displayed by these parti-
cles on surfaces is also witnessed in solution. We believe that
some of the structures described above, such as the fibers,
actually begin to form in solution: on standing a transient
network is formed that can be disturbed by sonication,
reverting the system to free, individual particles.
Thermal Behavior of Protected Precursor Polymers and
Bulk Nanoparticle Films. In our last report16 we discussed
one possible application of these SCNPs: a solution proces-
sable formulation that could be turned into a high-perfor-
mance supramolecular material. The initial solubility studies
on the films of PMMA SCNP family are consistent with
results obtained for the PNB systems; i.e., cast films remain
soluble until thermal treatment induces the formation of an
insoluble supramolecular network. Thermal investigations
on bulk SCNPs and precursor polymers by DSC confirm this
conjecture (Figure 7). Trends can be seen based on the
amount of UPy-urethane incorporation that are consistent
At concentrations in the range of 10-4-10-6 mg/mL large
spherical agglomerates of particles appear (Figure 6). By
filtering the sample through a 200 nm filter before drop-
casting, we are certain that these large structures, on the
order of several hundred nanometers up to a few micro-
meters in diameter and 20-50 nm high (panels A and B), are
indeed the result of a drying effect. At concentrations in this
range, another interesting phenomenon is witnessed: the
appearance of tendril-like fibers, which are nucleated from
the larger assemblies of particles seen in panel B (panels C
and D). The height of these fibers is in agreement with the
height of the SCNPs. In our last report we described this as
linear assemblies of particles in which long stacks of dimeri-
zed UPys can extend beyond the individual particles creat-
ing these long fibers. This was witnessed previously only for
the urea-containing polymers; the results here confirm
that even with the decreased hydrogen-bonding ability of

Article
Macromolecules, Vol. 43, No. 3, 2010 1435
Figure 7. DSC data for protected polymers and SCNP film (arbitrary vertical offsets for clarity): (A) heating traces of protected polymers after erasure
of thermal history; (B) cooling traces of protected polymers; (C) first heating traces for protected polymers after aging at room temperature for 48 h;
(D) first heating traces for protected polymers after aging at room temperature for 1 week; (E) first heating trace of SCNP film; (F) subsequent heating
and cooling traces of the SCNP film.
with trends witnessed in the AFM data discussed above.
Panel A shows the heating traces for the protected polymers
6a, 6b, and 6c as well as the “clickable” precursor 5; panel B
shows the corresponding cooling traces. Both cases reveal a
decrease in Tg occurs with increasing UPy-urethane con-
tent. Looking at the first heating traces for the protected poly-
mers after aging at room temperature displays the highly dyna-
mic nature of this system. After just 48 h of aging (panel C)
the heating traces show significant steepening of the Tg as
well as shouldering due to enthalpic recovery. This is most
pronounced with polymer 6c having the highest amount of
UPy-urethane incorporation and least so in 6a with the least
amount of UPy-urethane incorporation;not surprising as
the increased density of hydrogen bonding sites will allow
faster reorganization of the material. The effects are more
significant after 1 week of aging. Enthalpic events at Tg are
now increasingly conspicuous, especially in sample 6a. While
this may seem incongruous with the previous result, examin-
ing the trace for 6c reveals otherwise: a dynamic reorganiza-
tion of the material occurs upon heating evident in the
complex endothermic process that immediately follows Tg.
Sample 6b, with an intermediate amount of UPy-urethane
content, displays behavior somewhere in between with a
more detectable endothermic process than 6c but a less
decided exothermic process. The dynamic nature of the
protected system demonstrated in these thermal experiments
is in full agreement with the behavior witnessed during the
AFM deprotection studies: in analogy to the intramolecular

1436 Macromolecules, Vol. 43, No. 3, 2010
Berda et al.
hydrogen bonding that can prime the polymer in solution for
collapse into a nanoparticle, aging the material results in
enough hydrogen bonding to produce a morphology that is
primed to reorganize once sufficient mobility is available
after heating above Tg. This type of transient network
formation has recently been characterized for UPy con-
taining poly(butyl methacrylates);46 similar to our results
this behavior is strongly dependent on UPy content and
distribution.
due to the existence of an internal phase rich in UPy-urethane
dimers. AFM images taken at various stages of photodeprotec-
tion show that the polymers appear to be primed for rapid
supramolecular collapse, resembling the cooperative process by
which biomacromolecules fold. The applicability of this system to
materials science has been demonstrated by thermal investiga-
tions: soluble films of nanoparticles undergo a curing process
upon heating, reorganizing the material into an insoluble supra-
molecular network. While the behavior we described here is
sophomoric in comparison to the elegant natural structures from
which we draw inspiration, we consider this an important
advancement in controlling the way synthetic polymers can fold
and self-assemble. Our efforts in this area continue, most speci-
fically toward the development of catalytically active single-chain
nanoparticles derived from complex architectures and diverse
supramolecular cross-linking agents that can perform a more
controlled collapse in an efficient and orthogonal fashion. In this
way we hope to more closely mimic in synthetic systems the
complex form and function of biomacromolecules.
Thermal studies conducted on nanoparticle films confirm
the applicability of this system to solution processable
supramolecular materials. The first scan of the bulk SCNPs
displays behavior completely different from the protected
samples: unmistakable exothermic activity indicative of a
curing process47-49 in which the nanoparticles unfold to
form a network with intermolecular noncovalent cross-links.
Once again, a trend can be seen based on the amount of
UPy-urethane incorporation. In 6c a distinct bimodal
exotherm beginning just above Tg is seen. As UPy content
decreases, this behavior becomes less distinct, with 6a show-
ing only broad exothermic activity beginning 30 °C above Tg
and continuing over the entire temperature range, rather
than the clear exotherm displayed by 6c. This is not un-
expected; with lower UPy-urethane density greater mobility
(and therefore higher temperature) would be required to
allow curing of material to occur via the reshuffling of
UPy-urethane dimers (or monomers as would be the case
at higher temperature). Once again, 6b shows behavior in
between the two extremes: a clear exothermic peak more
similar to 6c, but beginning nearly 30 °C above Tg (more
similar to 6a). All subsequent scans on all three samples
reveal flat thermograms over the entire temperature range,
confirming network formation upon thermal treatment.
Decomposition of the UPy moieties can be ruled out as a
cause for this change in behavior; in this case the polymer
would still display a Tg for the unaffected PMMA portion.
This is not witnessed in any of the heating or cooling traces
for any of the cured nanoparticle samples, indicating that
long-range motion in these samples is severely restricted by
these supramolecular cross-links. Although the melting of
well-ordered fibers in the cured samples was not witnessed, it
does not rule out the likelihood of internal structure within
the SCNP, as the formation of fibers long enough to produce
a detectable thermal transition are unlikely within the nano-
particles and would be significantly hindered in the film by
both the low mobility of the supramolecular network and the
polarity of the PMMA matrix. Efforts are under way to scale
up nanoparticle fabrication in order to produce gram or even
kilogram quantities of these materials for exhaustive materi-
als testing.
Acknowledgment. The authors thank Dr. X. Lou, R. Bovee,
andJ. L. J. van Dongen for assistance withGPC characterization,
A. J. H. Spiering for synthesis of some starting materials, and
ꢀ
Dr. P. G. A. Janssen and Dr. P. E. L. G. Leclere for enlightening
discussions on AFM characterization. Additionally, the authors
thank Prof. C. J. Hawker for his stimulating discussions and
inspiration to enter the field of single-chain nanoparticles.
The authors thank the Council for Chemical Sciences of The
Netherlands Organization for Scientific Research (NWO-CW)
for financial support as well as NSF DMR-05-20415 for travel
support.
Supporting Information Available: Detailed experimental
procedures, AFM images with height profiles, and full descrip-
tion for estimation of particle spherical radius. This material is
available free of charge via the Internet at http://pubs.acs.org.
References and Notes
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Our recently developed method for fabricating nanoparticles
from single polymer chains has been expanded in both scope and
utility in this report. We have introduced a new synthetic method
for the facile production of protected UPy-decorated polymers
that can be conjugated with further functionality, simultaneously
demonstrating that this method is not only general but also
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