Reactive, multifunctional polymer films through thermal cross-linking of orthogonal click groups

Article abstract of DOI:10.1021/ja207635f

The ability to produce robust and functional cross-linked materials from soluble and processable organic polymers is dependent upon facile chemistries for both reinforcing the structure through cross-linking and for subsequent decoration with active functional groups. Generally, covalent cross-linking of polymeric assemblies is brought about by the application of heat or light to generate highly reactive groups from stable precursors placed along the chains that undergo coupling or grafting reactions. Typically, these strategies suffer from a general lack of control of the cross-linking chemistry as well as the fleeting nature of the reactive species that precludes secondary chemistry. We have addressed both of these issues using orthogonal chemistries to effect both cross-linking and subsequent functionalization of polymer films by mild heating, which results in exacting control of the cross-link density as well as the density of the residual stable functional groups available for subsequent, stepwise functionalization. This methodology is exploited to develop a strategy for the independent and orthogonal triple-functionalization of cross-linked polymer thin-films through microcontact printing.

Full text of DOI:10.1021/ja207635f

ARTICLE
pubs.acs.org/JACS
Reactive, Multifunctional Polymer Films through Thermal
Cross-linking of Orthogonal Click Groups
Jason M. Spruell,* Martin Wolffs, Frank A. Leibfarth, Brian C. Stahl, Jinhwa Heo, Luke A. Connal,
Jerry Hu, and Craig J. Hawker*
Materials Research Laboratory, California NanoSystems Institute, Department of Materials, and Department of Chemistry and
Biochemistry, University of California, Santa Barbara, California, United States
S Supporting Information
b
ABSTRACT: The ability to produce robust and functional
cross-linked materials from soluble and processable organic
polymers is dependent upon facile chemistries for both reinfor-
cing the structure through cross-linking and for subsequent
decoration with active functional groups. Generally, covalent
cross-linking of polymeric assemblies is brought about by the
application of heat or light to generate highly reactive groups
from stable precursors placed along the chains that undergo
coupling or grafting reactions. Typically, these strategies suffer
from a general lack of control of the cross-linking chemistry as well as the fleeting nature of the reactive species that precludes
secondary chemistry. We have addressed both of these issues using orthogonal chemistries to effect both cross-linking and
subsequent functionalization of polymer films by mild heating, which results in exacting control of the cross-link density as well as
the density of the residual stable functional groups available for subsequent, stepwise functionalization. This methodology is
exploited to develop a strategy for the independent and orthogonal triple-functionalization of cross-linked polymer thin-films
through microcontact printing.
’ INTRODUCTION
following cross-linking are active for subsequent functionaliza-
tion steps.
Cross-linking is of crucial importance to endow enhanced
thermal stability, mechanical properties, and solvent resistance
to commodity materials.1À9 Two general strategies include (1)
the preparation of cross-linked materials directly through the
polymerization of multifunctional monomer units and (2) the
induced covalent cross-linking of preformed polymer chains in a
secondary step.10 The latter method allows facile processing and
may be brought about through reaction along the polymer chain
with difunctional small molecule cross-linkers, a process which
generally proceeds through mild and well-defined chemistry but
results in material that must be further purified to remove either
catalyst or unreacted small molecules. Alternatively, cross-linking
may be externally triggered by the application of heat, light, or
pressure to generate highly reactive intermediates that undergo
nonselective bond formation in an uncontrolled and ill-defined
manner.11À14 While many commodity materials are processed
in this way, such as the vulcanization of rubber at high tempera-
tures15 or the cross-linking of polyethylene through strong ion-
izing γ-ray irradiation,16 these conditions are often too harsh to
combine cross-linking with secondary functionalization. There-
fore, an approach combining the best of each established strategy
is necessary, where well-defined chemistry induced under mild
conditions without any small molecule additives is employed to
produce cross-linked materials. An additional advantage of using
such an approach is that residual functional handles remaining
Examples of controlled, externally triggered cross-linking
strategies include the photolytic generation of reactive nitrenes,17
the thermal activation of benzocyclobutene3,18 and the thermo-
lytic generation of ketenes from Meldrum’s acid derivatives.19
While these approaches have been used advantageously to pre-
pare polymer coatings3 for surface energy neutralization, to trap
assembled polymer domains,20À27 or prepare monofunctiona-
lized surfaces,19 the harsh conditions used to generate the active
cross-linking species often limit the functional group tolerance of
these processes and therefore the end-use of the resulting mate-
rials. One such application is as a general platform for functional
surface coatings, especially those bearing diverse orthogonal re-
active chemical functionalities available for covalent patterning.
The ability to selectively pattern multiple ligands within the
bulk of a material or at the surface enables many applications such
as differential surface wetting,3 site-specific biomolecule or cell
affinity,28 and multicomponent catalytic systems.29 A number of
elegant techniques have been developed to achieve spatial surface
patterning of orthogonal functionalities, including electron-beam
lithography,30 inkjet printing of reactive ligands,28 reactive im-
printing,31 dip-pen32 and direct-write nanolithography,33 as well
as microcontact printing (μCP).19,34 Such patterning is usually
Received: August 12, 2011
Published: September 15, 2011
r
2011 American Chemical Society
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Figure 1. Schematic representation of the thermal azideÀalkyne cycloaddition chemistry used to prepare cross-linked material with the residual azide
and alkyne groups being stable after cross-linking and amenable to secondary functionalization. The temperature used for cross-linking provides accurate
control of the cross-link density as well as the density of remaining functional groups.
achieved through the serial application35À38 of the same ligation
chemistry to append different molecular species in nonoverlap-
ping areas with little control over the extent of functionalization.
While orthogonal chemistries have been explored recently for
the multifunctionalization of surfaces,39À42 appending different
molecular functions to the same regions of a surface remains a
significant challenge.
Herein, we report a system that employs mild, orthogonal
chemistries to both cross-link and functionalize polymer struc-
tures in a controlled manner (Figure 1). We first describe the ther-
mal azideÀalkyne cycloaddition (TAAC) chemistry43 (Figure 2a)
to cross-link polymer films at low temperatures with fine control
Figure 2. Representative examples of mild and orthogonal covalent
bond forming chemistries, (a) thermal azideÀalkyne cycloaddition
(TAAC) and (b) thermolytic retrocyclization generation of acyl ketenes
followed by nucleophilic trapping.
over the extent of cross-linking and residual functionality. The
classical TAAC reaction was employed for a number of reasons,
including the ability to conduct the reaction under normal atmos-
pheric conditions without the use of additional reagents, sol-
vents, or catalysts. Both van Hest and co-workers41 as well as
Gonzaga and co-workers44 utilized these features to covalently
cross-link side-chain functional azide polymers using small di-
functional alkyne molecules, where effective cross-linking was
achieved at temperatures above 125 °C when unactivated alkyne
groups were employed. By placing both reactive groups along the
same polymer backbone, the need to use small molecule cross-
linkers is removed and, more importantly, effective cross-linking
of unactivated azide and alkyne moieties can be achieved at lower
temperatures. The resulting, mild conditions for TAAC cross-
linking also enable the incorporation of diverse residual func-
tional groups, active for subsequent ligation. To demonstrate the
potential of this strategy, the spatial surface ligation of small
molecules to these residual surface functionalities on the cross-
linked polymer films was performed using TAAC chemistry as
well as an orthogonal acyl ketene functional handle45 (Figure 2b).
This enables the patterning of independent and overlapping
regions of three unique functionalities.
’ RESULTS AND DISCUSSION
Polymer Synthesis and Cross-linking. Polymers containing
both azides and alkynes randomly incorporated along the back-
bone were prepared utilizing free radical copolymerization of a
three component mixture of styrene, TMS-protected propargy-
loxy-styrene,46 and vinylbenzyl azide (Scheme 1). Both the azide
and protected alkyne monomers have been used previously47À49
to provide macromolecules with functional azide and alkyne moi-
eties enabling efficient chain functionalization using Cu-based
click chemistries. Less commonly applied is the incorporation of
both azide and alkyne functionalities along the same polymer
backbone; these approaches have enabled intramolecular cross-
linking to afford single chain polymer nanoparticles.50À52 We
prepared a single macromolecule bearing both the azide and
alkyne functionalities in order to prevent possible phase separa-
tion and thus ensure the availability of both reactive partners for
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Scheme 1. Synthesis of Di-functional Linear Polymer Build-
ing Block 1
cross-linking. The ratio of azide to alkyne and the total incor-
poration were easily controlled by the feed ratio of the three
monomers with the terminal alkyne being obtained after depro-
tection with tetrabutylammonium fluoride (TBAF).46 Through
radical polymerization, we prepared difunctional polymer 1 with
a number average molecular weight of 17 kg/mol and bearing
5 mol percent each of azide and terminal alkyne repeat units
along the backbone (Scheme 1).53
The TAAC cross-linking was initially evaluated with the di-
functional polymer. Polymer films of 1 were prepared with an
average thickness of 160 nm through spin-coating onto hydro-
phobic n-octane functionalized silicon substrates; matching the
polarity of the surface and polymer allowed greater reproduci-
bility in the preparation of uniform polymer films. The resulting
thin films of 1 were heated under air across a range of tempera-
tures and lengths of time to induce TAAC-mediated cross-
linking, followed by washing with tetrahydrofuran to remove
un-cross-linked polymer chains. The ratio of final to initial film
thickness provides a metric of cross-linking efficiency. Examina-
tion of the film thickness ratio versus cross-linking temperature
(Figure 3a), reveals that critical cross-linking can be achieved at
temperatures below 100 °C and that a plateau in cross-linking
occurs after progressively longer times as the cross-linking tem-
perature is lowered. Appreciable cross-linking was achieved fol-
lowing heating at 60 °C for 20 h or 110 °C for 30 min, which
demonstrates the mild nature of the process (Figure 3b). In
control experiments, no cross-linking was observed for films of
monofunctional azide or alkyne polymers (see Supporting Infor-
mation, Figure S2) at even the highest temperatures effective for
cross-linking the difunctional polymer. This confirms that the
presence of both species is necessary and is indicative of the
TAAC reaction.
Spectroscopic techniques provided valuable insights into the
chemical and physical nature of the cross-linking process. Fourier
transform infrared (FT-IR) spectroscopy of bulk samples of
polymer heated at 90 °C for various times (see Supporting Infor-
mation, Figure S3) reveal a progressive and coupled attenuation
of absorbances attributed to both the azide (NdNdN) and
alkyne (tCÀH) functional groups with heating, suggesting
coreaction to form the desired triazole. However, to provide a
more detailed and quantitative picture of the chemistry occurring
during the cross-linking process, we employed solid-state nuclear
magnetic resonance (NMR) spectroscopy. The cross-polariza-
tion magic angle spinning 13C NMR spectrum of polymer 1 was
unsurprisingly dominated by resonances due to the polystyrene
backbone, providing little information even after prolonged ac-
quisition times. To achieve adequate signal-to-noise for the speci-
fic resonances arising from the alkyne moieties, a difunctional
polymer bearing 13C-labeled alkyne carbons was prepared from
Figure 3. Relationship between cross-linking (a) temperature and (b)
time and the extent of cross-linking for difunctional linear polymer 1.
13C3-propargyl alcohol (see Supporting Information). An added
advantage of using this labeled polymer was that high signal-to-
noise spectra could be recorded in less than 15 min, a feature
which allowed real-time in situ analysis of the cross-linking
reaction occurring in the solid state.
Bulk samples of the 13C-labeled polymer were loaded into 4
mm bore sample rotors and heated within the NMR spectro-
meter while recording 13C NMR spectra every 20 min. Initially,
as displayed in Figure 4b, two dominant resonances appear attri-
buted to the overlapping signals of both alkyne carbons, occur-
ring around 77 ppm, as well as the propargyl methylene carbon at
ca. 55 ppm. Additional signals also appear due to the natural
abundance 13C resonances for both the backbone aromatic and
aliphatic positions. After heating for extended periods, dramatic
changes are evident in the NMR spectra with a significant attenu-
ation occurring in the resonance intensity of the alkyne carbons
and a correlated growth in aromatic signals. The appearance of
the three aromatic signals correlate with the formation of both
1,4- and 1,5-triazole rings, as expected.54 A shift in the propargyl
methylene also correlates with its transformation into a methy-
lene neighboring the newly formed triazole ring. By performing
the cross-linking reaction within the rotor itself, while recording
spectra every 20 min, a wealth of kinetic data was obtained.
Quantitative data was extracted by calculating the percentage
change of any one resonance across time. The comparison of
the normalized changes in intensities of both the alkyne carbons
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Figure 4. Solid-state 13C NMR spectroscopy of (a) isotopically labeled cross-linkable polymer 1 provides (b) good signal-to-noise spectra detailing the
initial (top) and final (bottom) state of the material where the alkyne peak is attenuated and triazole signals arise after heating. (c) Alkyne consumption
and triazole production are observed in real time and are perfectly correlated, data shown collected at 110 °C; (d) the alkyne signal attenuation is used to
calculate the reaction conversion as a function of time. (e) Initial rate kinetics follow Arrhenius behavior (an enlargement of the Arrhenius plot insert is
displayed in the Supporting Information, Figure S8). (f) Two-stage heating experiment displays two distinct plateau regions.
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Figure 5. Proposed mechanism to polymer cross-linking in which (a) two basic steps are the important parameters, chain movement and cycloaddition
chemistry. Initially, the barrier to TAAC is the largest such that the reaction may be described as an activated process. (b) Over time chain mobility
becomes the most important term such that the extent of cross-linking may be tuned actively with temperature (and mobility of the chains). (c) Barrier to
chain movement increases until the available thermal energy disallows any further cross-linking.
signals and the sum of triazole carbon signals with time
(Figure 4c) reveals a clean transformation of the alkyne species
into triazole products—clearly demonstrating that the TAAC
reaction is the sole process occurring upon heating.
that the Tg of a bulk polymer sample steadily increased with pro-
gressive heating at 80, 90, 100, and 110 °C (see Supporting Infor-
mation, Figure S4) such that the cross-linking reaction is always
performed at a temperature below the Tg of the resulting cross-
linked network. Eventually, the chain mobility barrier becomes
dominant and the reaction stops. By heating the sample to higher
temperatures, the necessary thermal energy is introduced to allow
more chain mobility and hence further cross-linking to occur
(Figure 5c). The implications of this self-limiting mechanism are
that the cross-link density and concentration of remaining func-
tional groups may be accurately tuned by selection of the curing
temperature (Figure 2). We further speculate that conditions in
which the lowering of Tg at interfaces and/or in nanocon-
finement58 may be devised to affect the degree of cross-linking
and residual functionality in those regions; perhaps such effects
could allow cross-linking at even lower temperatures or could
be exploited to produce materials with a gradient of cross-linking
density/secondary reactive groups.
Interestingly, the trimethylsilyl (TMS)-protected alkyne di-
functional polymer (polymer S1, see Supporting Information)
demonstrates efficient thermal cross-linking. However, the effi-
ciency is greatly reduced at lower temperatures (around 60 °C),
but approaches comparable values at temperatures above 80 °C
(see Supporting Information, Figure S5). Solid-state 13C NMR
analysis of the 13C-labeled polymer S1 clearly demonstrates that
the TMS protecting group, rather than first being thermally
hydrolyzed to then allow the TAAC of the resulting terminal
alkyne and the azide moieties, remains in place throughout
the course of the TAAC reaction (see Supporting Information,
Figure S5). These data lend further support to our cross-linking
mechanism—the TAAC barrier is dominant at lower tempera-
tures such that drastic rate differences exist between the TMS-
protected and terminal alkyne difunctional polymers. At higher
temperatures, however, chain mobility becomes the rate-limiting
factor and the two different polymers cross-link at comparable
rates.59
Accurate control over the cross-linking process was also ap-
parent by observing the differences in reaction conversion as a
function of time for samples heated at different temperatures
(Figure 4d). In each case, the reaction conversion plateaued and a
distinct trend was observed linking the plateau conversion with
cross-linking. Closer examination of these data show that the
initial rates of the reactions (Figure 4e) are constant at each tem-
perature; an Arrhenius plot of the natural logarithm of the slope
of the initial rates versus the inverse of the temperature provided
a straight line, with no discontinuities, as might be expected,
around the glass transition temperature of polystyrene (around
100 °C).55 From these data it is apparent that the cross-linking
reaction proceeds as a thermally activated process; over time,
however, the reaction progress halts at a unique conversion, the
position of which is dictated by the cross-linking temperature. To
better understand the nature of these plateau regions, specifically
to determine if a trajectory effect determines the plateau position,
we performed a two part heating experiment, where a sample
heated to well within its plateau region at 80 °C was then subse-
quently heated higher to 110 °C. Interestingly, it was found that
upon higher heating, the reaction resumed at a rapid rate, plate-
auing at ca. 80% conversion (identical to the single heat treat-
ment experiment) free of any trajectory effects (Figure 4f).
The kinetic data together describe an interesting cross-linking
mechanism (Figure 5) where the cycloaddition proceeds as a
thermally activated process to a critical reaction conversion when
chain mobility begins to hinder reaction progress. Such behavior
has been studied in the thermosetting of bulk epoxy resins56,57
where the interplay of Tg and degree of cross-linking are aligned.
In the case of the TAAC cross-linking that occurs efficiently at
low temperatures (significantly below the Tg of polystyrene), the
mobility of reaction partners becomes an extremely important
parameter. This is best described using a reaction coordinate dia-
gram where we reduce the complexity to two simple barriers, the
first being a chain movement step and the second the actual bond
formation (Figure 5b). As bond formation progresses, the form-
ing cross-linked network increasingly hinders the movement of
chains. Hence, the barrier of movement necessary for reactive
alkyne and azide partners to find one another becomes larger
over time. This self-limiting mechanism is supported by the fact
Cross-linkedPolymerFilmFunctionalization.Theavailability
and controllable density of the reactive azide and alkyne function-
alities within cross-linked polymer films presents many attractive
possibilities for preparing multifunctional materials, especially
whenconsideringthepowerful clickchemistryparadigms thathave
developed recently.48,49 These groups, when presented within
cross-linked films at temperatures below those used for initial
cross-linking, are isolated from one another such that they are only
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Figure 6. Confocal fluorescence images of different polymer films each patterned with either (left) azide-, (center) alkyne-, or (right) amine-bearing
fluorescent dyes using thermal microcontact printing mediated covalent bond formation. The two left images utilized the difunctional polymer 1, while
the right image was recorded from a trifunctional polymer 2 substrate.
accessible for reaction with mobile complementary reactive part-
ners, typically small molecules. Taking advantage of these unique
features, we chose to decorate both the alkyne and azide moieties
at the surface of the cross-linked films by independent, covalent
patterning of the corresponding azide- and alkyne-bearing fluor-
escent probes through TAAC chemistry directed by microcontact
printing.
reproduction of the pattern in each case indicates that the ther-
mal printing process occurs efficiently and without significant
lateral diffusion of the probe molecules throughout the film.
The mild nature of the TAAC cross-linking and functionaliza-
tion enables other orthogonal, reactive groups to be easily intro-
duced into these cross-linked systems. To demonstrate this in-
herent versatility, trifunctional polymer, 2, incorporating 5 mol
percent each of azide, alkyne, and acyl ketene precursor, was
prepared through copolymerization of an acyl ketene styrenic
precursor with styrene, vinylbenzyl azide, and TMS-protected
propargyloxy-styrene (Scheme 2). The resulting polymer 2
provided easy access to a triply functional material, where the
orthogonal chemistries of the azide, alkyne, and acyl ketene
handles could be used to tailor the properties of any cross-linked
polymer material with three distinct and individually addressable
reactive handles. We have discovered significant opportunities19,26
for the ketene functional group in polymer chemistry, including
polymer cross-linking and functionalization. Acyl ketenes, as op-
posed to the alkyl derivatives previously studied, are generated at
significantly lower temperatures, do not participate in [2 + 2]
dimerizations, and are potent electrophiles. These features make
the acyl ketene an ideal orthogonal and complementary ther-
mally activated reactive group to the azide/alkyne chemistry used
for both cross-linking and functionalization.
Patterned elastomeric stamps of poly(dimethylsiloxane) (PDMS),
inked with solutions of either an azido-coumarin dye60 or an
alkynyl-perylene derivative61 were pressed onto films of polymer
1 that had previously been cross-linked at 90 °C for 12 h. This
prior cross-linking at 90 °C consumes roughly 35% of the total
azide and alkyne groups, leaving the remaining 65% isolated
from one another and available for functionalization. The “inks”
were transferred to the cross-linked polymer surface through di-
rect contact with the stamp which was pressed onto the subst-
rates during heat treatment at 90 °C for 30 min to induce co-
valent ligation. To remove any absorbed dye, the surfaces were
then washed extensively with dichloromethane, toluene, and
ethanol. The resulting 2-dimensional covalent patterns on the
cross-linked polymer surface were imaged using confocal fluor-
escence microscopy (Figure 6). The blue fluorescence pattern
observed for printed azido-coumarin features indicates the for-
mation of the triazole linkage with the residual alkyne units with-
in the cross-linked polymer network, as the coumarin azide dye
precursor was developed as a turn-on dye, only becoming fluo-
rescent upon reaction.60 The bright green features observed
for printed alkyne-functional perylene probe demonstrate that
the complementary azide units are also accessible.62 The faithful
Spin-coated films of the trifunctional polymer 2 were therefore
cross-linked by heating at 90 °C for 12 h in an analogous manner
to polymer 1. The acyl ketene precursor was shown to be stable
at temperatures below 150 °C and is thus fully compatible with
and orthogonal to the azideÀalkyne thermal cross-linking and
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Scheme 2. Synthesis of Tri-functional Linear Polymer Building Block 2
Figure 7. Single trifunctional polymer 2 film having been functionalized in a three-step process with blue, green, and red features orthogonally through
thermal microcontact printing mediated covalent bond formation. Imaging in separate color channels reveals the trifunctional pattern that is based upon
orthogonal chemistry and regions of double and triple functionality coexist with singly functionalized domains are easily identified by merging the three
channels.
functionalization strategy presented. Its thermolysis at higher
temperature activates it to the corresponding ketene, an excellent
electrophile for the attachment of a wide variety of nucleophiles
in a secondary step. In the case of a homopolymer of the acyl
ketene precursor monomer (see Supporting Information, Figure
S6), a mass loss of 20% corresponding to the liberation of ace-
tone (and generation of the acyl ketene species) was observed
by thermal gravimetric analysis (TGA) beginning around 170 °C
for the polymer in the solid-state. An analogous small molecule
study was conducted (see Supporting Information), in which
heating an acyl ketene precursor in the presence of benzyl amine
at 150 °C for 45 min resulted in the clean and near quantitative
conversion to the amide product. It is known63,64 that the envi-
ronment affects the kinetics of retrocyclic formation of acyl
ketenes and that the presence of an electron donating species
during the heating process could account for the lower tempera-
ture of ketene formation in the small molecule case.
To probe the presence of the acyl ketene functionality at the
surface of the cross-linked networks of trifunctional polymer 2,
we chose to thermally microcontact print a commercially avail-
able red fluorescent amine-containing dye, TAMRA-cadaverine,
as the “ink” onto the cross-linked film. Heating a substrate in con-
tact with the amino-functional red dye patterned stamp at 150 °C
for 30 min resulted in the thermolytic generation of the acyl
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ketene as well as its rapid nucleophilic trapping by the amino-
functional dye, as evidenced by the faithful fluorescence pattern
replication (Figure 6, right). No dye transfer or covalent attach-
ment was observed when temperatures less than 130 °C were
employed for thermal microcontact printing, indicating that acyl
ketene generation occurs only at higher temperatures and is an
ideal orthogonal handle to complement the azideÀalkyne chem-
istry occurring at lower temperatures. Similarly, no dye transfer
was observed when 1 was employed in the 150 °C thermal print-
ing because this polymer lacks the orthogonal acyl ketene pre-
cursor unit. Additionally, we confirmed that the benzyl azide
moieties were stable toward the 150 °C thermal treatment, only
thermolyzing at even higher temperatures17 to form highly re-
active nitrene functions, as evidenced by FT-IR measurements
(see Supporting Information, Figure S9).
While we were encouraged by the ability to separately address
each of the alkyne, azide, and acyl ketene functions within cross-
linked films of 2, the orthogonality of these chemistries is best
demonstrated through a multistep printing process onto a single
polymer film. Overlapping patterns were produced by successive
thermal printings onto the same substrate. Line features of both
blue and green dyes were printed in a perpendicular direction,
first printing the azido-coumarin dye in a horizontal line pattern
at 90 °C followed by printing of alkyne-perylene dye in the same
line pattern in the perpendicular direction with a second thermal
treatment. To this substrate was then printed the red amine dye
in a dot pattern by heating to 150 °C for 30 min. The resulting
film was rinsed with good solvents for the respective dye mole-
cules in between thermal treatments and again following the
final thermal patterning. Confocal fluorescence of the substrate
(Figure 7), simultaneously collecting data across all three chan-
nels for blue, green, and red, allowed the separate imaging of
features patterned in the same area on the substrate. The inter-
play of the three distinct probes, indicating three orthogonal
reactions, is revealed by merging the color channels. Significantly,
regions of colocalization of two and three dyes, as well as regions
where only one dye were observed, indicating the accessibility
and orthogonality of each functional unit. These features allow
multifunctional surfaces to be produced using two distinct chem-
istries, enabling first a controlled materials cross-linking and then
orthogonal materials functionalization utilizing three indepen-
dent and stable functional handles to provide overlapping and/or
separate chemical patterns.
’ ASSOCIATED CONTENT
S
Supporting Information. Complete experimental proce-
b
dures along with additional supporting data. This material is avai-
lable free of charge via the Internet at http://pubs.acs.org.
’ AUTHOR INFORMATION
Corresponding Author
jspruell@mrl.ucsb.edu; hawker@mrl.ucsb.edu
’ ACKNOWLEDGMENT
J.M.S. is grateful to the California NanoSystems Institute for
the Elings Prize Fellowship in Experimental Science. M.W. thanks
The Netherlands Organization of Scientific Research (NWO) for
funding through a Rubicon Fellowship. Financial support from
the National Science Foundation American Competitiveness in
Chemistry Fellowship (J.M.S.; CHE-1041958), NSF Chemistry
(CHE-0957492) and the MRSEC Program (DMR-1121053) is
gratefully acknowledged.
’ REFERENCES
(1) Malkoch, M.; Vestberg, R.; Gupta, N.; Mespouille, L.; Dubois, P.;
Mason, A. F.; Hedrick, J. L.; Liao, Q.; Frank, C. W.; Kingsbury, K.;
Hawker, C. J. Chem. Commun. 2006, 2774–2776.
(2) (a) Fairbanks, B. D.; Scott, T. F.; Kloxin, C. J.; Anseth, K. S.;
Bowman, C. N. Macromolecules 2009, 42, 211–217. (b) Granick, S.;
Kumar, S. K.; Amis, E. J.; Antonietti, M.; Balazs, A. C.; Chakraborty, A.
K.; Grest, G. S.; Hawker, C. J.; Janmey, P.; Kramer, E. J.; Nuzzo, R.;
Russell, T. P.; Safinya, C. R. J. Polym. Sci., Part A: Polym. Chem. 2003,
41, 2755–2793. (c) Min, E. H.; Ting, S. R.; Billon, L.; Stenzel, M. H.
J. Polym. Sci., Part A: Polym. Chem. 2010, 48, 3440–3455. (d) Matsushima,
H.; Shin, J.; Bowman, C. N.; Hoyle, C. E.J. Polym. Sci., Part A:Polym. Chem.
2010, 48, 3255–3264. (e) Durmaz, Y. Y.; Sangermano, M.; Yagci, Y.
J. Polym. Sci., Part A: Polym. Chem. 2010, 48, 2862–2868.
(3) Ryu, D. Y.; Shin, K.; Drockenmuller, E.; Hawker, C. J.; Russell,
T. P. Science 2005, 308, 236–239.
(4) Campos, L. M.; Meinel, I.; Guino, R. G.; Schierhorn, M.; Gupta,
N.; Stucky, G. D.; Hawker, C. J. Adv. Mater. 2008, 20, 3728–3733.
(5) Duering, E. R.; Kremer, K.; Grest, G. S. J. Chem. Phys. 1994,
101, 8169–8192.
(6) Suthar, B.; Xiao, H. X.; Klempner, D.; Frisch, K. C. Polym. Adv.
Technol. 1996, 7, 221–233.
(7) Achilleos, M.; Legge, T. M.; Perrier, S.; Patrickios, C. S. J. Polym.
Sci., Part A. 2008, 46, 7556–7565.
(8) Tsarevsky, N. V.; Matyjaszewski, K. Macromolecules 2005, 38,
’ CONCLUSION
3087–3092.
(9) (a) Nederberg, F.; Trang, V.; Pratt, R. C.; Kim, S.-H.; Colson, J.;
Nelson, A.; Frank, C. W.; Hedrick, J. L.; Dubois, P.; Mespouille, L. Soft
Matter 2010, 6, 2006–2012. (b) van Berkel, K. Y.; Hawker, C. J. J. Polym.
Sci., Part A: Polym. Chem. 2010, 48, 1594–1606.
(10) Tillet, G.; Boutevin, B.; Ameduri, B. Prog. Polym. Sci. 2011,
36, 191–217.
(11) Rouif, S. Radiat. Phys. Chem. 2004, 71, 527–530.
(12) Bhowmick, A. K.; Vijayabaskar, V. Rubber Chem. Technol. 2006,
79, 402–428.
(13) Tasdelen, M. A.; Kumbaraci, V.; Talinli, N.; Yagci, Y. Macro-
molecules 2007, 40, 4406–4408.
The thermal cycloadition of azides and terminal alkynes in
polymer films was exploited in the design of effective thermal
cross-linking strategies that are operationally simple and occur
under very mild reaction conditions. The thermal process occur-
ring within the polymer matrix allows control over cross-linking
density and the level of unreacted, stable azide and alkyne func-
tionality. By exploiting the site isolation and orthogonality of
these residual azide and alkyne functional groups, as well as addi-
tional reactive groups in the form of the acyl ketene, each indivi-
dual functional group can be addressed in select or overlapping
regions at the surface of the cross-linked polymer films. Such
triply functionalized surfaces represent a significant advance to
the current state of the art and enable applications in such areas as
catalysis, biofunctionalization, or sensors development. We are
currently pursuing these and other research goals utilizing the
materials and concepts reported here.
(14) Studer, K.; Nguyen, P. T.; Decker, C.; Beck, E.; Schwalm, R.
Prog. Org. Coat. 2005, 54, 230–239.
(15) Krejsa, M. R.; Koenig, J. L. Rubber Chem. Technol. 1993, 66,
376–410.
(16) Lewis, G. Biomaterials 2001, 22, 371–401.
(17) Bang, J.; Bae, J.; Lowenhielm, P.; Spiessberger, C.; Given-Beck,
S. A.; Russell, T. P.; Hawker, C. J. Adv. Mater. 2007, 19, 4552–4557.
16705
dx.doi.org/10.1021/ja207635f |J. Am. Chem. Soc. 2011, 133, 16698–16706

Journal of the American Chemical Society
ARTICLE
(18) Leiston-Belanger, J. M.; Russell, T. P.; Drockenmuller, E.;
Hawker, C. J. Macromolecules 2005, 38, 7676–7683.
(19) Leibfarth, F. A.; Kang, M.; Ham, M.; Kim, J.; Campos, L. M.;
Gupta, N.; Moon, B.; Hawker, C. J. Nat. Chem. 2010, 2, 207–212.
(20) Kakwere, H.; Perrier, S. J. Am. Chem. Soc. 2009, 131,
1889–1895.
(49) Golas, P. L.; Matyjaszewski, K. Chem. Soc. Rev. 2010, 39,
1338–1354.
(50) Schmidt, V. K. J.; Fechler, N.; Falkenhagen, J.; Lutz, J.-F. Nat.
Chem. 2011, 3, 234–238.
(51) Oria, L.; Aguado, R.; Pomposo, J. A.; Comenero, J. Adv. Mater.
2010, 22, 3038–3041.
(21) McCormick, C. L.; Sumerlin, B. S.; Lokitz, B. S.; Stempka, J. E.
Soft Matter 2008, 4, 1760–1773.
(22) Roy, D.; Cambre, J. N.; Sumerlin, B. S. Prog. Polym. Sci. 2010,
35, 278–301.
(52) de Luzuriaga, A. R.; Ormategui, N.; Grande, H. J.; Odriozola, I.;
Pomposo, J. A.; Loinaz, I. Macromol. Rapid Commun. 2008, 29,
1156–1160.
(53) Due to the differences in reactivity of trimethylsilylpropargylox-
ystyrene, styrene, and vinylbenzyl azide, a slight gradient incorporation
rather than true random incorporation might occur through the conven-
tional radical polymerization employed. Nevertheless, because of the very
low incorporation of functional monomers, any effect of such a slight
gradient on the bulk cross-linking studies should be very minimal.
(54) The presence of three new signals indicates the formation of
two separate triazole isomers (having up to four possible new signals)
where two of the individual resonances are overlapping yielding three
new signals. No direct measure of relative ratio of the two isomers was
obtained using the cross-polarization technique because signal intensity
is dependent upon spin polarization transfer, a feature that prevents
normal integral analysis; moreover, overlap of the growing triazole reso-
nances with the backbone aromatic resonances further complicates the
interpretation.
(55) A larger temperature range would allow a more comprehensive
assessment of the influence of Tg upon the initial rate kinetics of cross-
linking. The linear Arrhenius relationship could be explained because the
cross-linking reaction always seems to be occurring below the Tg of the
final cross-linked material(see Supporting Information, Figure S4).
(56) Enns, J. B.; Gillham, J. K. J. Appl. Polym. Sci. 1983, 28,
2567–2591.
(57) Wisanrakkit, G.; Gillham, J. K. J. Appl. Polym. Sci. 1990, 41,
2885–2929.
(58) Paeng, K.; Swallen, S. F.; Ediger, M. D. J. Am. Chem. Soc. 2011,
133, 8444–8447.
(59) The Tg of uncrosslinked polymer S1 is comparable (97 °C) to
that of uncrosslinked polymer 1 (104 °C); it is therefore most likely that
the differences in cross-linking efficiency arise from the reaction rate dif-
ferences of terminal versus protected alkynes rather than from mobility
differences within the polymer melt.
(23) Spruell, J. M.; Hawker, C. J. Chem. Sci. 2011, 2, 18–26.
(24) Du, J.; O’Reilly, R. K. Soft Matter 2009, 5, 3544–3561.
(25) Drockenmuller, E.; Li, L. Y. T.; Ryu, D. Y.; Harth, E.; Russell,
T. P.; Kim, H. C.; Hawker, C. J. J. Polym. Sci. A, Polym. Chem. 2005,
43, 1028–1037.
(26) Leibfarth, F. A.; Schneider, Y.; Lynd, N. A.; Schultz, A.; Moon,
B.; Kramer, E. J.; Bazan, G. C.; Hawker, C. J. J. Am. Chem. Soc. 2010,
132, 14706–14709.
(27) Joralemon, M. J.; O’Reilly, R. K.; Hawker, C. J.; Wooley, K. L.
J. Am. Chem. Soc. 2005, 127, 16892–16899.
(28) Gupta, N.; Lin, B. F.; Campos, L. M.; Dimitriou, M. D.; Hikita,
S. T.; Treat, N. D.; Tirrell, M. V.; Clegg, D. O.; Kramer, E. J.; Hawker,
C. J. Nat. Chem. 2010, 2, 138–145.
(29) Rodionov, V.; Gao, H.; Scroggins, S.; Unruh, D. A.; Avestro, A.;
Frꢀechꢀet, J. M. J. J. Am. Chem. Soc. 2010, 132, 2570–2572.
(30) Christman, K. L.; Schnopf, E.; Broyer, R. M.; Li, R. C.; Chen, Y.;
Maynard, H. D. J. Am. Chem. Soc. 2009, 131, 521–527.
(31) Subramani, C.; Cengiz, N.; Saha, K.; Gevrek, T. N.; Yu, X.;
Jeong, Y.; Bajaj, A.; Sanyal, A.; Rotello, V. M. Adv. Mater. 2011, 23,
3165–3169.
(32) Salaita, K.; Wang, Y. H.; Mirkin, C. A. Nat. Nanotechnol. 2007,
2, 145–155.
(33) Paxton, W. F.; Spruell, J. M.; Stoddart, J. F. J. Am. Chem. Soc.
2009, 131, 6692–6694.
(34) Spruell, J. M.; Sheriff, B. A.; Rozkiewicz, D. I.; Dichtel, W. R.;
Rohde, R. D.; Reinhoudt, D. N.; Stoddart, J. F.; Heath, J. R. Angew.
Chem., Int. Ed. 2008, 47, 9927–9932.
(35) Hensarling, R. M.; Doughty, V. A.; Chan, J. W.; Patton, D. L.
J. Am. Chem. Soc. 2009, 131, 14673–14675.
(36) Deng, X.; Friedmann, C.; Lahann, J. Angew. Chem., Int. Ed.
2011, 50, 6522–6526.
(37) Seo, H.; Choi, I.; Lee, J.; Kim, S.; Kim, D.-E.; Kim, S. K.; Yeo,
(60) Sivakumar, K.; Xie, F.; Cash, B. M.; Long, S.; Barnhill, H. N.;
Wang, Q. Org. Lett. 2004, 6, 4603–4606.
W.-S. Chem.—Eur. J. 2011, 17, 5804–5807.
(61) Langhals, H.; Obermeier, A. Eur. J. Org. Chem. 2008, 36,
6144–6151.
(62) Weaker fluorescence signal intensity was observed when the
thermal microcontact printing was performed at temperatures as low as
70 °C for 30 min, while no discernible signal was observed for printing
performed at lower temperatures.
(38) Orski, S. V.; Poloukhtine, A. A.; Arumugam, S.; Mao, L.; Popik,
V. V.; Locklin, J. J. Am. Chem. Soc. 2010, 132, 11024–11026.
(39) Im, S. G.; Bong, K. W.; Kim, B.; Baxamusa, S. H.; Hammond,
P. T.; Doyle, P. S.; Gleason, K. K. J. Am. Chem. Soc. 2008, 130,
14424–14425.
(40) Gonzalez-Campo, A.; Hsu, S.; Puig, L.; Huskens, J.; Reinhoudt,
D. N.; Velders, A. H. J. Am. Chem. Soc. 2010, 132, 11434–11436.
(41) Canalle, L.; Van Berkel, S.; De Haan, L.; van Hest, J. Adv. Func.
Mater. 2009, 19, 3464–3470.
(63) Fillion, E.; Fishlock, D. Tetrahedron 2009, 65, 6682–6695.
(64) Dumas, A. M.; Fillion, E. Acc. Chem. Res. 2009, 43, 440–454.
(42) Li, Y.; Niehaus, J. C.; Chen, Y.; Fuchs, H.; Studer, A.; Galla,
H.-J.; Chi, L. Soft Matter 2011, 7, 861–863.
(43) Huisgen, R. Angew. Chem., Int. Ed. Engl. 1963, 2, 633–645.
(44) Gonzaga, F. G.; Yu, G.; Brook, M. Macromolecules 2009,
42, 9220–9224.
(45) Clemens, R. J.; Witzeman, J. S. J. Am. Chem. Soc. 1989, 111,
2186–2193.
(46) Fleischmann, S.; Komber, H.; Voit, B. Macromolecules 2008,
41, 5255–5264.
(47) Mansfeld, U.; Pietsch, C.; Hoogenboom, R.; Becer, C. R.;
Schubert, U. S. Polym. Chem. 2010, 1, 1560–1598.
(48) (a) Hawker, C. J.; Wooley, K. L. Science 2005, 309, 1200–1205.
(b) Thibault, R. J.; Takizawa, K.; Lowenheilm, P.; Helms, B.; Mynar, J.
L.; Frechet, J. M. J.; Hawker, C. J. J. Am. Chem. Soc. 2006,
128, 12084–12085. (c) Kade, M. J.; Burke, D. J.; Hawker, C. J. J. Polym.
Sci., Part A: Polym. Chem. 2010, 48, 743–750.
16706
dx.doi.org/10.1021/ja207635f |J. Am. Chem. Soc. 2011, 133, 16698–16706