Synthesis of multifunctional polymer brush surfaces via sequential and orthogonal thiol-click reactions

Article abstract of DOI:10.1039/c1jm14762e

Fabrication of multifunctional surfaces with complexity approaching that found in nature requires the application of a modular approach to surface engineering. We describe a versatile post-polymerization modification strategy to synthesize multifunctional polymer brush surfaces via combination of surface-initiated photopolymerization (SIP) and orthogonal thiol-click reactions. Specifically, we demonstrate two routes to multifunctional brush surfaces: in the first approach, alkyne-functionalized homopolymer brushes are modified with multiple thiols via a statistical, radical-mediated thiol-yne co-click reaction; and in the second approach, statistical copolymer brushes carrying two distinctly-addressable reactive moieties are sequentially modified via orthogonal base-catalyzed thiol-X (where X represents an isocyanate, epoxy, or α-bromoester) and radical-mediated thiol-yne reactions. In both cases, we show that surface properties, in the form of wettability, can be easily tuned over a wide range by judicious choice of brush composition and thiol functionality. The Royal Society of Chemistry 2011.

Full text of DOI:10.1039/c1jm14762e

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PAPER
Synthesis of multifunctional polymer brush surfaces via sequential and
orthogonal thiol-click reactions†
a
a
a
b
Santosh B. Rahane, Ryan M. Hensarling, Bradley J. Sparks, Christopher M. Stafford and Derek L. Patton
a
*
Received 23rd September 2011, Accepted 27th October 2011
DOI: 10.1039/c1jm14762e
Fabrication of multifunctional surfaces with complexity approaching that found in nature requires the
application of a modular approach to surface engineering. We describe a versatile post-polymerization
modification strategy to synthesize multifunctional polymer brush surfaces via combination of surface-
initiated photopolymerization (SIP) and orthogonal thiol-click reactions. Specifically, we demonstrate
two routes to multifunctional brush surfaces: in the first approach, alkyne-functionalized
homopolymer brushes are modified with multiple thiols via a statistical, radical-mediated thiol-yne co-
click reaction; and in the second approach, statistical copolymer brushes carrying two distinctly-
addressable reactive moieties are sequentially modified via orthogonal base-catalyzed thiol-X (where X
represents an isocyanate, epoxy, or a-bromoester) and radical-mediated thiol-yne reactions. In both
cases, we show that surface properties, in the form of wettability, can be easily tuned over a wide range
by judicious choice of brush composition and thiol functionality.
alkyne Huisgen 1,3-dipolar cycloaddition (CuAAC) has been
demonstrated by several groups. For example, Murphy et al.16
simultaneously immobilized amine and acetylene-terminated
peptides onto a mixed self-assembled monolayer containing
complementary carboxylate and azide groups via orthogonal
carbodiimide condensation and CuAAC chemistry to create
multifunctional surfaces that present distinct peptides to stem
cells on a bioinert background. These surfaces enabled a better
understanding of multiple, distinct extracellular factors that
work in concert to regulate stem cell adhesion at interfaces. Im
et al.17 used orthogonal acetylene and amine functionalized thin
films obtained by plasma enhanced chemical vapor deposition
for synthesis of multifunctional nanopatterned surfaces via an
elegant one-pot transformation using CuAAC and carbodimide/
activated ester chemistries. Concern over the presence of residual
metal impurities following copper-catalyzed click reactions has
motivated the development of alternate, metal-free surface
modification strategies. Consequently, a wide variety of metal-
free click reactions - such as strain promoted azide-alkyne
cycloadditions,18–21 and Diels–Alder cycloadditions4–6 - are
increasingly becoming methods of choice to synthesize multi-
functional surfaces via orthogonal transformations. For
example, Orski and coworkers22 used cyclopropenone-masked
dibenzocyclooctynes tethered on a brush surface for light-acti-
vated and orthogonal immobilization of two azides via sequential
copper-free [3 + 2] cycloaddition click reactions. Similarly,
a route to bio-orthogonal multifunctional surface modification
using copper-free azide-alkyne click with electron-deficient
alkynes was recently demonstrated by Deng et al.23
Introduction
Multicomponent surfaces - where all components synergistically
control the surface properties - are ubiquitous in natural bio-
logical systems. For example, the unique superhydrophobic
properties of lotus leaves, butterfly wings, and rose petals result
from not only multi-scale surface topographies, but also coop-
erative interactions of these features with multicomponent
chemical compositions.1 The allure of mimicking nature’s
approach to surface engineering - particularly the ability to
install multiple chemical functionalities on surfaces in
a controlled fashion - has recently attracted significant attention
in terms of strategies leading to multifunctional surfaces and
advanced applications in biosensors, self-cleaning surfaces, etc.
Among several immobilization strategies reported for surface
modification, those that exploit ‘‘click’’ reactions, such as the
azide-alkyne Huisgen 1,3-dipolar cycloaddition,2,3 Diels–
Alder,4–6 and thiol-click,7–10 as well as other high efficiency
transformations like activated ester-amine reactions,11–13 are
particularly attractive for the fabrication of multifunctional
surfaces. These reactions - due to the possibility of orthogonal
reaction conditions - permit sequential and/or simultaneous
modifications resulting in the ability to control the number and
spatial location of multiple functional groups on the surface.3,14,15
Orthogonal modification of surfaces using Cu(I)-catalyzed azide-
aSchool of Polymers and High Performance Materials, University of
Southern Mississippi, Hattiesburg, Mississippi, 39406, USA
bPolymers Division, National Institute of Standards and Technology,
Gaithersburg, Maryland, 20899, USA
Alternatively, we andothers have shown thiol-based click reactions
- such as thiol-ene,24–28 thiol-yne27,29–33 and thiol-isocyanate34,35 - to be
† Electronic supplementary information (ESI) available. See DOI:
10.1039/c1jm14762e
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a powerful approach for engineering multifunctional materials and
surfaces in a modular fashion. Thiol-click reactions are advantageous
for this purpose in that they proceed at room temperature with high
efficiency and rapid kinetics, in the presence of oxygen/water, without
expensive and potentially toxic catalysts, and are highly tolerant of
a wide range of functional groups. Additionally, thiol-click reactions
are orthogonal to a wide range of chemistries.36 Notably, one only has
to look within the thiol-click class of reactions to realize a powerful set
of orthogonal transformations that enable the installation of multiple
chemical functionalities on a surface with high efficiency and
modularity. Herein, we describe a versatile post-polymerization
modification strategy to synthesize multifunctional polymer brush
surfaces via combination of surface-initiated photopolymerization
(SIP) and orthogonal thiol-click reactions. One of the principal
advantages of the post-modifiable brush platform is that it provides
a much larger number of modifiable sites per unit area of substrate as
compared to conventional self-assembled monolayers (SAMs), while
decoupling the polymer synthesis step from the immobilization of
sensitive functional groups on the surface thereby avoiding expensive
monomer synthesis and reducing potential side reactions.37 Specifi-
cally, we demonstrate two routes to multifunctional brush surfaces:
In the first approach, alkyne-functionalized homopolymer brushes
are simultaneously modified with multiple thiols via a statistical,
radical-mediated thiol-yne co-click reaction; and in the second
approach, copolymer brushes carrying two distinctly-addressable
reactive moieties are sequentially modified via orthogonal base-
catalyzed thiol-X (where X represents an isocyanate, epoxy,38 or a-
bromoester39–41) and radical-mediated thiol-yne reactions. In both
cases, we show that surface properties, in the form of wettability as
a model example, can be easily tuned over a wide range by judicious
choice of brush composition and thiol functionality.
further purification. Reagents, 1,8-diazabicyclo[5.4.0]undec-7-
ene (DBU) and 2,2-dimethoxy-2-phenyl acetophenone (DMPA),
for thiol-click reactions were also obtained from Aldrich and
used as received.
Synthesis of protected alkyne containing monomer, (3-trime-
thylsilylpropargyl) methacrylate (PgMA-TMS). PgMA-TMS was
synthesized according to a previously reported protocol.29
Briefly, PgMA-TMS was synthesized by reacting 1 equivalent of
PgOH-TMS with 1.2 equivalents of methacryloyl chloride in
presence of 1.2 molar equivalents of triethylamine in CH2Cl2.
First, methacryloyl chloride was added dropwise to the mixture
of PgOH-TMS and triethyl amine cooled in an ice bath. The
ꢀ
reaction mixture was stirred for 1 h at 0 C and then at room
temperature overnight. The salt byproducts were filtered and the
filtrate was washed with deionized water, saturated sodium
carbonate and brine, and the organic layer was dried over
MgSO4. The product was finally concentrated using rotavap
distillation and purified by column chromatography (silica gel
column with 40 : 1 hexane:acetone as eluent) to obtain pure
1
PgMA-TMS (73 % yield). H-NMR (CDCl3; d (ppm)): 0.19 (s,
9H, Si(C8H3)3), 1.97 (s, 3H, C3H3), 4.76 (s, 2H, C5H2), 5.62 (s,
1H, C1HH), 6.18 (s, 1H, C1HH); 13C-NMR (CDCl3; d (ppm)):
1.76, 20.41, 55.1, 94.2, 101.3, 128.7, 137.9, 168.9. Anal. Calcu-
lated for C10H16O2Si: C, 61.18; H, 8.21; O, 16.30; Si, 14.31;
Found: C 60.96; H 8.19. (+ESI-MS) m/z (%): 219 [M + Na] (100),
197 [MH+] (40). IR (neat): n ꢁ ¼ 2960, 1723, 1638, 1452, 1366,
1314, 1292, 1251, 1147, 1035, 971, 942, 842, 813, 761 cmꢂ1
.
Synthesis of a-bromoester containing monomer, 2-(2-bromo-
propanoyloxy) ethyl methacrylate (BrMA). BrMA was synthe-
sized by reacting 1 equivalent of HEMA with 1.1 equivalents of
2-bromopropionyl bromide in presence of 1 molar equivalents of
triethylamine in anhydrous CH2Cl2. First, 2-bromopropionyl
bromide was added dropwise to the mixture of HEMA and
triethyl amine cooled in an ice bath. The reaction mixture was
stirred for 1 h at 0 ꢀC and then at room temperature for 4 h. The
salt byproducts were filtered and the filtrate was washed with
deionized water and saturated sodium carbonate, and the
organic layer was dried over MgSO4. The product was finally
concentrated using rotavap distillation and purified by column
chromatography (silica gel column with 3 : 1 v/v hexane: ethyl
Experimental section
Materials and methods
Certain commercial materials and equipment are identified in the
paper in order to adequately specify the experimental details. In
no case does such identification imply recommendation by the
National Institute of Standards and Technology nor does it
imply that the material or equipment identified is necessarily the
best available for the purpose. All the solvents and reagents were
obtained at the highest purity available from Aldrich Chemical
Company or Fisher Scientific and were used as received unless
otherwise specified. Silicon wafers polished only on one side were
purchased from University Wafers. Commercially available
1
acetate as eluent) to obtain pure BrMA in 70 % yield. H-NMR
(CDCl3; d (ppm)): 1.79 (d, 3H); 1.92 (s, 3H); 4.37 (m, 5H); 5.57 (s,
1H); 6.11 (s, 1H). 13C-NMR (CDCl3; d (ppm)): 18.4, 21.8, 39.9,
62.3, 63.8, 126.5, 136.1, 167.3, 170.3. Anal. Calculated for
C9H13BrO4: C, 40.78; H, 4.94; Found: C 40.62; H, 5.09. IR
photoinitiator,
2-hydroxy-40-(2-hydroxyethoxy)-2-methyl-
propiophenone (Irgacure 2959), was obtained from Ciba
Specialty Chemicals and modified with trichlorosilane according
to a previously reported protocol.29,42
(neat): n ꢁ ¼ 2929, 1147, 1718, 1388, 940, 645 cmꢂ1
.
Immobilization of 2-hydroxy-40-(2-hydroxyethoxy)-2-methyl-
propiophenone trichlorosilane (HPP-SiCl3) on SiO2 surfaces.
Silicon wafers were cut into appropriate sized pieces and ultra-
sonically cleaned in acetone, ethanol, and toluene for 15 min in
each solvent. The substrates were dried under a stream of N2 and
treated with UV-ozone for 45 min. HPP-SiCl3 (4 mM) in toluene
was immobilized on the SiO2 surface at room temperature using
excess triethylamine as an acid scavenger for ꢁ 1 h. The samples
were then cleaned by extensively rinsing with toluene and
methanol and dried under a stream of N2. The acetate protecting
Monomers, glycidyl methacrylate (GMA; Acros Organics,
97%), hydroxyethylmethacrylate (HEMA, 98% Aldrich), and 2-
isocyanatoethyl methacrylate (NCOMA; TCI America, 98%),
were passed through basic and vacuum-dried neutral alumina
columns, respectively, to remove the inhibitor. Protected prop-
argyl alcohol, 3-trimethylsilylpropargyl alcohol (PgOH-TMS;
98%), was purchased from GFS Chemicals and was used as
received. All thiols were obtained at the highest available purity
from Aldrich Chemical Company and were used without any
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group was removed by immersing the wafers prepared above in
a suspension of 240 mg K2CO3 in 12 mL methanol containing
150 mL H2O for 1 h. The substrate was subsequently washed with
water, methanol, and toluene followed by drying with a stream of
N2. The functionalized silicon wafers were stored in toluene at
ꢂ20 ꢀC until use. Ellipsometric thickness of the immobilized
photoinitiator was 1.1 nm ꢃ 0.3 nm.
the normal. Refractive index values of 3.86, 1.45, 1.43 and 1.5 for
silicon, oxide layer, photoinitiator monolayer and all polymer
layers, respectively, were used to build the layer model and
calculate layer thicknesses.42,44 Wettability of the polymer brush
surfaces modified with various functionalities was tracked by
ꢀ
measuring static water contact angles using a rame-hart 200-00
Std.-Tilting B with 10 mL water droplets. The static contact angle
goniometer was operated in combination with accompanying
DROPimage Standard software. The chemical nature of the
polymer brush surfaces was characterized by Fourier transform
infrared spectroscopy (FTIR) in grazing-angle attenuated total
reflectance mode (gATR-FTIR) using a ThermoScientific FTIR
instrument (Nicolet 8700) equipped with a VariGATRꢀ acces-
sory (grazing angle 65ꢀ, germanium crystal; Harrick Scientific).
Spectra were collected with a resolution of 4 cmꢂ1 by accumu-
lating a minimum of 128 scans per sample. All spectra were
collected while purging the VariGATRꢀ attachment and FTIR
instrument with N2 gas along the infrared beam path to minimize
the peaks corresponding to atmospheric moisture and CO2.
Spectra were analyzed and processed using Omnic software. XPS
measurements were performed using a Kratos AXIS Ultra DLD
Spectrometer (Kratos Analytical, Manchester, UK) with
a monochromatic Al K X-ray source (1486.6 eV) operating at
150 W under 1.0 ꢄ 10ꢂ9 Torr. Measurements were performed in
hybrid mode using electrostatic and magnetic lenses, and the pass
energy of the analyzer was set at 20 eV for high-resolution
spectra and 160 eV for survey scans, with energy resolutions of
0.1 eV and 0.5 eV, respectively. Generally, total acquisition times
of 180 s and 440 s were used to obtain high resolution and survey
spectra, respectively. All XPS spectra were recorded using the
Kratos Vision II software; data files were translated to VAMAS
format and processed using the CasaXPS software package (v.
2.3.12). Binding energies were calibrated with respect to C 1s at
285 eV.
Synthesis of (co)polymer brushes by surface-initiated photo-
polymerization. All (co)polymer brushes were synthesized by
surface-initiated photopolymerization from a solution of the
monomer or a mixture of monomers in an appropriate solvent in
a custom-built and inert (nitrogen) atmosphere using a micro-
channel reaction device (fabricated from Norland 81 optical
adhesive). This microchannel device uses only 400 mL of mono-
mer solution for a 10 mm ꢄ 60 mm substrate and is especially
useful for expensive and custom-made monomers. For the sake
of brevity, the details of this microchannel-SIP procedure are
described elsewhere.29,43 SIP was carried out using a UV light
source (lmax ¼ 365 nm, Omnicure Series 1000 with a 5 mm
collimating adaptor) at a light intensity of 150 mW cmꢂ2 for
a specified time. The synthesized (co)polymer brushes were
typically sonicated in a good solvent to remove any physisorbed
(co)polymer chains, dried with a stream of nitrogen and stored
until further use. A brush thickness of 25 nm was targeted to
allow facile characterization by grazing-angle attenuated total
reflection FTIR. For trimethylsilyl-protected poly(propargyl
methacrylate) (p(PgMA-TMS)) brushes, the TMS group was
removed by immersing the wafer in KOH (0.6 g) in methanol (12
mL) at ambient temperature for 1 h to afford the alkyne func-
tionalized polymer brush. The substrate was subsequently
washed with water, methanol, toluene, and dried under a stream
of N2. Similarly, silver triflate (AgOTf) in THF/water (1 : 1 v/v)
was used to remove the TMS group from brush substrates with
base labile linkages (i.e. thiourethanes).
Thiol-click reactions on (co)polymer brushes. All thiol-click
reactions were conducted under ambient air, temperature and
humidity conditions as described in our previous publica-
tions.29,34 DBU (500 : 1 thiol:DBU mol/mol) was used as a cata-
lyst for all base-catalyzed thiol-click reactions and DMPA (2%
by mass with respect to the thiol) was used as a source of radicals
for all the light-induced thiol-yne reactions. Unless otherwise
specified, nucleophile-mediated thiol-click reactions were con-
ducted overnight, only to ensure complete reaction. All thiol-yne
reactions were conducted using a UV light source (lmax ¼ 365
nm, Omnicure Series 1000 with a 5 mm collimating adaptor) at
a light intensity of 40 mW cmꢂ2 for a specified time. The (co)
polymer brushes were sonicated in THF after thiol-click reac-
tions to remove unreacted thiols.
Results and discussion
One-pot thiol-yne reactions for dual-/multifunctional surfaces
Scheme 1 shows the general schematic for the synthesis of dual-
functional polymer brush surfaces using a one-pot thiol-alkyne
functionalization of a poly(propargyl methacrylate) (p(PgMA))
brush in the presence of a mixture of thiols. This facile synthesis
of dual-functional polymer surfaces is accessible due to the
similar reactivity of various thiols with the pendant alkyne
groups of the p(PgMA) brush. Fairbanks et al.45 recently showed
no statistical difference between the reaction rates of aliphatic
thiols and mercaptopropionates with various alkynes under
photopolymerization conditions; thus, a one-pot approach
would enable a simple route to obtain dual-functional polymer
brush surfaces where the final composition of the brush surface
depends on the composition of the initial functional thiol mixture
used in the thiol-yne reaction. This approach, using a single thiol,
was demonstrated previously by our group where it was observed
that model thiols reacted quantitatively with alkyne groups
within 8 min under the investigated conditions. Similar reaction
conditions were adopted here in the case of multiple thiol
compositions.
Characterization
Chemical structures of synthesized monomers were confirmed
using a Varian Mercury Plus 200MHz NMR spectrometer
operating at a frequency of 200.13 MHz. VNMR 6.1C software
was used for proton and carbon analysis. Ellipsometric
measurements were carried out using a Gaertner Scientific
Corporation LSE ellipsometer with a 632.8 nm laser at 70ꢀ from
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Scheme 1 General schematic for dual-functional polymer brushes by one-pot thiol-yne co-click reactions from PgMA brushes (DMPA ¼ 2,2-
Dimethoxy-2-phenylacetophenone). Based on similar thiol reactivities, the thiol-yne co-click reaction yields a distribution of 1,2-homo and 1,2-hetero
dithioether adducts within the brush surface.
p(PgMA-TMS) brushes were synthesized by surface-initiated
photopolymerization as previously described using the trime-
thylsilyl-protected alkyne monomer and subsequently depro-
tected using KOH/methanol to give the terminal alkyne.29 Fig. 1
(a) and 1(b) show the gATR-FTIR spectra for p(PgMA) brush
with pendant alkyne groups in protected and deprotected forms,
respectively. The peak at 2189 cmꢂ1 for the protected alkyne
group in Fig. 1a, and the peaks at 2125 and 3280 cmꢂ1 for the
deprotected alkyne in Fig. 1b are consistent with our previous
work and confirm the successful synthesis of the p(PgMA) brush.
The deprotected p(PgMA) brush was further functionalized via
radical-mediated thiol-yne click by exposing the surface to UV
light in the presence of a photoinitiator and a mixture of desired
thiols (thiol:THF, 50/50 v/v). All thiol-yne reactions were
conducted for 4 h at 40 mW cmꢂ2. The reaction time of 4 h was
selected to ensure complete conversion of alkyne groups of
p(PgMA) regardless of the fact that the actual time required for
complete conversion may be significantly shorter than 4 h.
Indeed, quantitative conversion of the alkyne groups was
observed following thiol-yne click reactions with equimolar
mixtures of various thiols as indicated by the disappearance of
the peaks corresponding to deprotected alkyne at 2125 cmꢂ1 and
3280 cmꢂ1 (gATR-FTIR spectra in Fig. 1c–e). The p(PgMA)
brushes showed an expected increase in thickness after thiol-yne
reactions with all of the thiol mixtures due to increase in
molecular mass of repeat units and was consistent with previous
results.29 Fig. 1c shows the gATR-FTIR spectrum for a p(PgMA)
brush after thiol-yne click from an equimolar mixture of
dodecanethiol and thioglycerol. As shown in Fig. 1(c), the broad
peak between 3600 and 3100 cmꢂ1 corresponding to the hydroxyl
groups of thioglycerol, and peaks at 2955, 2922 and 2853 cmꢂ1
corresponding to the aliphatic chain of dodecanethiol appear
indicating that both thiols simultaneously undergo thiol-yne
click reaction with p(PgMA) brush. The concentration of the
hydrophilic hydroxyl and hydrophobic aliphatic groups in
the clicked brush can be easily controlled by simply varying the
concentration of respective thiols to control the wettability of the
surface. As a second example, we selected a binary mixture of N-
acetyl cysteine, a biologically relevant thiol, and dodecanethiol to
perform the one-pot thiol-yne click reaction with a p(PgMA)
brush. Fig. 1(d) shows the gATR-FTIR spectrum of a p(PgMA)
brush clicked with the equimolar mixture of N-acetyl-cysteine
and dodecanethiol. Peaks at 1643 cmꢂ1 and 1605 cmꢂ1 for the
secondary amine groups of N-acetyl cysteine, and peaks at 2955
cmꢂ1, 2922 cmꢂ1 and 2853 cmꢂ1 corresponding to the aliphatic
chains of dodecanethiol appear suggesting successful simulta-
neous thiol-yne click reaction of both the thiols. The one-pot
thiol-yne click approach can be further extended to more
complex model systems via use of ternary thiol mixtures. Fig. 1(e)
Fig. 1 Poly(propargyl methacrylate) brush a) protected, 23.7 nm ꢃ 1.1
nm; b) deprotected, 11.4 nm ꢃ 1.1 nm; c) clicked with an equimolar
mixture of thioglycerol and dodecanethiol, 26.1 nm ꢃ 3.0 nm; d) clicked
with an equimolar mixture of dodecanethiol and N-acetyl cysteine, 26.9
nm ꢃ 2.3 nm; and e) clicked with an equimolar mixture of dodecanethiol,
mercaptopropionic acid and N-acetyl cysteine, 26.8 nm ꢃ 2.8 nm.
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shows the gATR-FTIR spectrum of p(PgMA) functionalized
with an equimolar ternary mixture of thiols containing dodeca-
nethiol to impart hydrophobic character, 3-mercaptopropionic
acid (MPA) to impart hydrophilic character and N-acetyl
cysteine as a model biological thiol. As can be observed in Fig. 1
(e), each of the thiols was successfully coupled with the p(PgMA)
brush in one-pot fashion: peaks at 2955 cmꢂ1, 2922 cmꢂ1 and
2853 cmꢂ1 confirm the functionalization with dodecanethiol; the
broad peak at 3250 cmꢂ1 confirms the functionalization with 3-
mercaptopropionic acid; and peaks at 1643 cmꢂ1 and 1605 cmꢂ1
confirm the successful coupling of N-acetyl cysteine. In principle,
this ternary brush surface constitutes a model for a biological
molecule embedded in a microenvironment with tunable wetta-
bility by virtue of the facile control over the proportion of MPA
and dodecanethiol in the ternary thiol mixture.
cmꢂ1) of dodecanethiol clearly show the differences in the surface
composition obtained at various thiol ratios. Quantitatively, the
peak area ratio of peaks corresponding to hydroxyl groups
(COOH) of MPA to the peaks corresponding to aliphatic groups
of dodecanethiol (APeak,MPA/APeak,DDT) was observed to be 3.13,
0.71 and 0.14 for p(PgMA) functionalized with a mixture of MPA
and dodecanethiol in the molar proportions of 3 : 1, 1 : 1, and
1 : 3. While APeak,MPA/APeak,DDT values do not reflect the accurate
concentrations of pendant COOH and aliphatic groups due to the
contribution of aliphatic groups of p(PgMA) main chain and
different extinction coefficients of the COOH and aliphatic
groups, the relative comparison of APeak,MPA/APeak,DDT values
qualitatively suggest that it is straightforward to control the
concentration of the functional groups, and in turn, the surface
properties (wettability in our case) of p(PgMA) brush after thiol-
yne reaction by simply varying the concentration of component
thiols in the initial mixture.
To demonstrate control over brush composition and ultimately
wettability, we modified the p(PgMA) brush via thiol-yne reac-
tions with mixtures containing different molar ratios of 3-mer-
captopropionic acid and dodecanethiol. Fig. 2 (a–c) shows the
gATR-FTIR spectra for polymer brushes clicked with different
concentrations of dodecanethiol and 3-mercaptopropionic acid;
(a) 3 : 1 MPA/dodecanethiol, (b) 1 : 1 MPA/dodecanethiol and
(c) 1 : 3 MPA/dodecanethiol. The characteristic bands for
hydroxyl groups (COOH) of clicked MPA (peak between 3650
and3050 cmꢂ1) andaliphatic groups (peaksat 2955, 2922and 2853
Fig. 3 shows the wettability of the clicked polymer brush as
a function of the initial MPA/dodecanethiol molar concentra-
tions evaluated by water contact angle measurements after a final
THF rinse. As expected, water contact angles of the dually-
clicked MPA/dodecanethiol polymer brush lie between the water
contact angles of polymer brushes clicked individually with MPA
(52ꢀ) and dodecanethiol (101ꢀ), and decrease as the concentra-
tion of MPA in the MPA/dodecanethiol reaction mixture
increases.
Additionally, methanol as a final rinse induces rearrangement
of the top surface of the dual-functional brush, which exposes
COOH groups at the surface. Thus, the water contact angles
after the methanol rinse are lower than the water contact angles
after THF rinsing treatment across the compositional series, but
in general, both follow similar trends. Though the one-pot
approach is an extremely simple method to synthesize dual or
multi-functional brushes with tunable surface properties, it
Fig. 3 Water contact angle of p(PgMA) brushes functionalized with 3-
mercaptopropionic acid and dodecanethiol via one-pot thiol-yne reac-
tions as a function of molar fraction of 3-mercaptopropionic acid in the
thiol mixture. Error bars represent one standard deviation of the data,
which is taken as the experimental uncertainty of the measurement. Some
error bars are smaller than the symbols.
Fig. 2 p(PgMA) brush clicked with a mixture of mercaptopropionic
acid (MPA) and dodecanethiol (DDT) in the ratio of a) 3 : 1, 32.1
nm ꢃ 7.3 nm; b) 1 : 1, 38.3 nm ꢃ 4.3 nm; and c) 1 : 3, 53.0 nm
ꢃ1.7 nm.
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suffers from a limitation that one-pot thiol-yne reactions are
random and non-specific, i. e. both functional groups are
arranged randomly within the polymer brush and as a mixture of
1,2-homo and 1,2-hetero dithioether adducts. Additionally, the
only control over surface composition of the clicked functional
groups in this approach is the molar ratio of the thiols in the
initial reaction mixture. In many cases, particularly where site-
specific modifications are of interest and warranted, i.e. block
copolymers, gradients, and patterned brush surfaces, it would be
advantageous to explore sequential and/or orthogonal surface
modification schemes.
necessary only to eliminate radical-mediated side reactions
during the synthesis of copolymer brushes by SIP.
Orthogonal thiol-isocyanate and thiol-yne functionalization to
form dual-functional polymer brush. SIP of NCOMA and PgMA-
TMS was performed for 45 min at 150 mW cmꢂ2 to synthesize
p(NCOMA-stat-PgMA). Fig. 4(a) shows the gATR-FTIR
spectrum for unmodified p(NCOMA-stat-PgMA). Peaks at 2180
cmꢂ1 and 2275 cmꢂ1 are attributed to the protected alkyne and
isocyanate groups, respectively, confirming the presence of both
alkyne and isocyanate groups in the statistical copolymer brush.
While the ratio of isocyanate and alkyne groups in the copolymer
brush could be varied simply by changing the ratio of NCOMA
and PgMA-TMS in the monomer mixture, quantifying the ratios
in the copolymer brush is beyond the scope of this study and will
not be discussed in detail here. Due to the reactivity of isocyanate
groups towards moisture, the p(NCOMA-stat-PgMA) surfaces
were stored under nitrogen at room temperature until ready for
further modification. Additionally, all thiol-isocyanate click
reactions were performed using dry solvents. Tertiary amine
catalysts facilitate rapid reactions via generation of 1) a more
electron deficient carbonyl carbon within the isocyanate moiety
and 2) a strongly nucleophilic thiolate ion.52,53 In the first click
reaction, benzyl mercaptan was reacted with isocyanate groups
in the copolymer brush for 1 h. Fig. 4(b) shows the FTIR spec-
trum of p(NCOMA-stat-PgMA) brush after the thiol-isocyanate
click reaction. The disappearance of the peak associated with the
isocyanate group (2275 cmꢂ1) and appearance of peaks indicative
of the thiourethane linkage (3326 cmꢂ1 NH-CO) and incorpo-
rated benzyl mercaptan (3018 and 3030 cmꢂ1 (]C–H); 1517,
1493 and 1451 cmꢂ1 (C]C)) confirm the successful thiol-isocy-
anate reaction. Notably, the peak at 2180 cmꢂ1 corresponding to
the protected alkyne group was found to be intact following the
thiol-isocyanate click reaction suggesting that thiol-isocyanate
transformations do not affect the protected alkyne groups and
can be utilized for further transformations to form a dual-func-
tional polymer brush.
Sequential/orthogonal click reactions for synthesis of multi-
functional polymer brushes. Due to different mechanisms for
reactions within the thiol-click toolbox, it is expected that
nucleophile-mediated and radical-mediated reactions of thiols
with various functional groups can be conducted in an orthog-
onal fashion. Indeed, the orthogonal nature of thiol-click reac-
tions, in combination with other chemistries, has been previously
harnessed by several authors to fabricate functional poly-
mers,46,47 surfaces,48 dendrimers49,50 and several other polymer
architectures.36,51 In this work, we specifically used the orthog-
onal nature of thiol-click reactions to fabricate dual-functional
polymer brushes. Close examination of the thiol-click toolbox
suggests that several pairs of thiol-clickable monomers can be
used to synthesize dual-functional polymer brushes. Synthesis of
these dual-functional brushes, as shown in Scheme 2, was per-
formed by first synthesizing copolymer brushes via copolymeri-
zation of monomers containing two different thiol-clickable
functional groups, followed by sequential and orthogonal thiol-
click reactions. Taking advantage of the orthogonal nature of the
radical-mediated thiol-yne reaction and nucleophilic reaction of
thiols with isocyanates, alkylhalides, and epoxides, we synthe-
sized copolymer brushes via SIP from mixtures of PgMA-TMS
with NCOMA, BrMA and GMA to form p(NCOMA-stat-
PgMA), p(BrMA-stat-PgMA) and p(GMA-stat-PgMA),
respectively. In all cases, the nucleophilic thiol-isocyanate, thiol-
halogen and thiol-epoxy reactions were performed first followed
by deprotection of alkyne group and thiol-yne click reaction. It
should be noted that protection of the alkyne group was
To perform the sequential thiol-yne reaction, alkyne groups
must be deprotected to remove the trimethylsilyl functionality.
Deprotection of the alkyne moieties under caustic conditions
Scheme 2 Schematic for synthesis of dual-functional polymer brushes by sequential and orthogonal and thiol-based click reactions.
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Scheme 3 General mechanism for Ag-mediated deprotection of trime-
thylsilyl-protected alkynes.54 Diffusion of triflic acid out of the brush
surface would result in incomplete deprotection and the presence of
brush-bound silver acetylide.
brush surface into solution resulting in incomplete deprotection
leaving alkyne groups in a silver acetylide form. High resolution
XPS indeed shows the presence of silver with an Ag3d binding
energy of 368.25 eV (see Supporting Information Figure S1†).
We posit that regardless of the exact nature of the alkyne group
after AgOTf-mediated deprotection, it should still be reactive in
the subsequent thiol-yne reactions. To prove this, we performed
the sequential radical-mediated thiol-yne reaction using dodec-
anethiol and DMPA on the AgOTf treated brushes. Fig. 4(d)
shows the gATR-FTIR spectrum after thiol-yne reaction with
dodecanethiol. As shown in Fig. 4(d), the appearance of peaks
corresponding to aliphatic groups of dodecanethiol at 2955 cmꢂ1
,
2922 cmꢂ1 and 2853 cmꢂ1 confirms the successful thiol-yne
reaction (regardless of the speculated silver acetylide complex)
and the successful sequential thiol-isocyanate/thiol-yne trans-
formations of the p(NCOMA-stat-PgMA) brush. Although not
ideal due to the fact that residual silver remains in the film even
after thiol-yne modification (see Supporting Information
Figure S1†), these results suggest that AgOTf-mediated depro-
tection of surface-tethered functional groups can be used as an
alternative in cases where highly caustic conditions might pose
a problem.
Fig.
4 a) gATR-FTIR spectra for p(NCOMA-stat-PgMA-TMS)
synthesized by SIP of 1 : 6 v/v PgMA:NCOMA, 76.4 nm ꢃ 2.8 nm; b)
after thiol-isocyanate click with benzyl mercaptan, 125.9 nm ꢃ 1.2 nm; c)
after deprotection using AgOTf, 101.7 nm ꢃ 1.8 nm; and d) after thiol-
yne click with dodecanethiol, 127.1 nm ꢃ 0.3 nm.
using KOH in methanol was first attempted. However, it was
found that the thiourethane bonds resulting from the initial thiol-
isocyanate click reaction are labile under these caustic conditions
leading to loss of tethered functionality. To eliminate thiour-
ethane cleavage, we adapted an alternate mild strategy to
deprotect the alkyne group. In this method, p(NCOMA-stat-
PgMA) brushes clicked with benzyl mercaptan were treated with
silver triflate (AgOTf) overnight using THF/water (1 : 1 v/v) as
solvent.54 Fig. 4(c) shows the p(NCOMA-stat-PgMA) after the
AgOTf-mediated deprotection step. The peak corresponding to
the protected alkyne at 2180 cmꢂ1 disappears after the treatment
with AgOTf; however, the peak expected for deprotected alkyne
at 2210 cmꢂ1 was not observed. While the disappearance of the
peak corresponding to the protected alkyne can be attributed to
the formation of silver acetylide complex, it is crucial to under-
stand the mechanism of AgOTf-mediated deprotection to
understand the absence of deprotected alkyne peaks. Typically,
in an AgOTf-mediated silyl deprotection shown in Scheme 3, the
silver acetylide complex and triflic acid are formed upon silver
activation of the alkyne and hydrolysis of the resulting
Me3SiOTf. This triflic acid then hydrolyzes the silver acetylide
complex to give a deprotected alkyne and regenerates AgOTf.54
However, in the case of deprotection of surface-tethered pro-
tected alkyne groups, we speculate triflic acid generated during
the deprotection step quickly diffuses away from the polymer
Orthogonal thiol-bromo and thiol-yne functionalization to form
multifunctional polymer brushes. A methodology similar to that
described previously for sequential thiol-isocyanate/thiol-yne
surface reactions was adapted for the synthesis of statistical
copolymer brushes comprised of BrMA and PgMA-TMS
allowing for sequential thiol-bromo and thiol-yne trans-
formations. In the case of thiol-bromo/thiol-yne surface reac-
tions, the weak FTIR signature of the secondary bromine in
pBrMA prevents the confirmation of the incorporated bromo
functionality using gATR-FTIR spectroscopy. Rather, XPS was
performed to follow the sequence of reactions for this system.
Fig. 5(a) shows the survey and corresponding high resolution
C1s, S2p, and Br3d spectra for a p(BrMA-stat-PgMA) brush
prepared via SIP from a 1 : 1 mixture of BrMA and PgMA in
THF. The C1s (285 eV), O1s (531 eV) and particularly the
presence of bromine (Br3d, 70 eV; Br3p, 182 eV; Br3s, 257 eV)
confirms the successful surface-initiated copolymerization. Due
to the thickness (10.9 nm for the unmodified brush) of the
polymer brush samples, signals from the silicon substrate (Si2p,
100 eV; Si2s, 149 eV) are also present. Evidence for the presence
of the TMS-protected alkyne was confirmed by gATR-FTIR as
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Fig. 5 Survey and N1s, S2p, and Br3d high-resolution XPS spectra for (a) unmodified statistical copolymer brush p(BrMA-stat-PgMa), 10.9 nm ꢃ 1.2
nm; (b) p(BrMA-stat-PgMa) with a-bromoesters clicked with dodecanethiol (DDT), 25.5 nm ꢃ 5.6 nm; and (c) p(BrMA-stat-PgMa) with a-bromoesters
clicked with dodecanethiol and alkynes sequentially clicked with N-acetyl cysteine, 28.2 nm ꢃ 4.8 nm.
previously described. Next, the a-bromo functional groups of
p(BrMA-stat-PgMA) brush surface were modified with dodeca-
nethiol under base-catalyzed (DBU) conditions. The disappear-
ance of the peaks associated with bromine (Br3d, 70 eV; Br3p,
182 eV; Br3s, 257 eV) and the appearance of peaks attributed to
sulfur (S2p, 163.4 eV; S2s, 229 eV) provide evidence for
a successful replacement of bromine with the thioether (Fig. 5
(b)). An expected increase in the C/O ratio was also observed as
a result of the incorporation of aliphatic dodecanethiol mole-
cules. Again, the presence of the protected alkyne was confirmed
by FTIR. After deprotection of the alkyne under KOH/methanol
conditions, the alkyne pendants were modified by radical-medi-
ated thiol-yne with N-acetyl cysteine as indicated by the
appearance of the nitrogen N1s peak (400 eV) in Fig. 5(c). It is
noteworthy that the preliminary investigations of thiol-bromo
surface reactions were much slower when conducted under
similar conditions of the thiol-isocyanate click reaction which
reflects the difference in reactivity between the a-bromoester and
isocyanate. Nonetheless, both systems reach quantitative
conversion (within the sensitivity of our surface measurements)
given sufficient reaction time.
synthesized by SIP from a mixture of GMA and PgMA-TMS.
Varying the thickness and composition of the brushes (vide-
infra) was easily achieved by changing the time of SIP and
composition of monomer mixture, respectively. Fig. 6(a) shows
the gATR-FTIR spectrum of p(GMA-stat-PgMA) synthesized
by SIP from a equimolar mixture of GMA and PgMA in THF.
The spectrum shows the characteristic peaks corresponding to
epoxy ring at 906 cmꢂ1 and protected alkyne at 2180 cmꢂ1 con-
firming the presence of both epoxy and alkyne clickable moieties
in the copolymer brush. Similar to the case of p(BrMA-stat-
PgMA) and p(NCOMA-stat-PgMA), the tertiary amine-cata-
lyzed thiol-epoxy transformation was performed first using thi-
oglycerol and DBU. Fig. 6(b) shows the gATR-FTIR spectrum
for thioglycerol-modified p(GMA-stat-PgMA) brush in which
the thiolysis of the epoxy was confirmed by disappearance of an
epoxy ring stretch at 906 cmꢂ1, and appearance of a strong, broad
peak at 3400 cmꢂ1 attributable to the hydroxyl groups of thio-
glycerol. Again, the peaks corresponding to the protected alkyne
at 2180 cmꢂ1 remain intact after the thiol-epoxy reaction. The
thioglycerol-modified p(GMA-stat-PgMA) brush was then
exposed to KOH/methanol to deprotect the TMS-alkyne group.
Fig. 6(c) shows the p(GMA-stat-PgMA) after deprotection step
indicating the disappearance of the protected alkyne group at
2180 cmꢂ1 and appearance of peaks corresponding to the
deprotected alkyne at 2230 cmꢂ1 confirming successful depro-
tection under caustic conditions. Additionally, peaks corre-
sponding to thioglycerol hydroxyl groups remain intact after
deprotection step indicating that the thioether bond resulting
from the thiol-epoxy reaction is stable under the caustic
Orthogonal thiol-epoxy and thiol-yne functionalization to form
multifunctional polymer brushes. The thiol-epoxy reaction has
recently been demonstrated as an efficient route to polymer
modification.38 Here, sequential thiol-epoxy and thiol-yne reac-
tions on p(GMA-stat-PgMA) brushes were carried out under
identical conditions as described above for the sequential thiol-
bromo/thiol-yne system. p(GMA-stat-PgMA) brushes were
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Tuning surface properties via orthogonal click transformations.
We have already demonstrated facile tunability of the composi-
tion and wetting properties of polymer brush surfaces using a one-
pot thiol-yne approach with binary and ternary thiol mixtures.
Similarly, it should be possible to impart tunability by controlling
the functional monomer feed ratios used in the statistical copo-
lymerization from the surface, which in turn dictates the final
composition and properties of the surface upon sequential click
reactions at full functional group conversion. To explore this
concept, statistical copolymer brushes containing varying
concentrations of epoxy and alkyne functionality were synthe-
sized by SIP from different monomer feed ratios of GMA and
PgMA. Fig. 7 (a–c) shows the FTIR spectra for copolymer
brushes synthesized by SIP from different GMA/PgMA feed
ratios containing 25% v/v, 50% v/v and 75% v/v GMA, respec-
tively. As the concentration of GMA in monomer feed increases,
the concentration of epoxy functionality relative to the alkyne
functionality in the copolymer brush increases as indicated by an
increase in the height of the peak at 906 cmꢂ1 corresponding to the
epoxy group and decrease in the height of the peak at 2180 cmꢂ1
corresponding to the protected alkyne group. The trend in the
concentration of epoxy and alkyne functionality in the copolymer
brush was confirmed by calculating peak area ratios for epoxy and
alkyne peaks (APeak,GMA/APeak,PgMA) in each of the FTIR spectra.
As the fraction of GMA in monomer feed increases, APeak,GMA
/
APeak,PgMA was calculated to be 1.70, 10.2, and 41.3 for copolymer
brushes synthesized from 25% v/v, 50% v/v and 75% v/v GMA
Fig. 6 gATR-FTIR spectrum for p(GMA-stat-PgMA) a) synthesized by
SIP of 1 : 3 v/v GMA:PgMA, 73.5 nm ꢃ 4.5 nm; b) after thiol-epoxy click
with thioglycerol, 122.7 nm ꢃ1.1 nm; c) after deprotection using KOH in
methanol, 92.9 nm ꢃ 5.8 nm; and d) after thiol-yne click with dodeca-
nethiol, 126.2 nm ꢃ 4.4 nm.
conditions, unlike the thiourethane bond discussed previously.
Subsequently, the deprotected pendent alkyne groups were
transformed by thiol-yne reaction using dodecanethiol as
a model thiol. Fig. 6(d) shows the spectrum for the p(GMA-stat-
PgMA) after final thiol-yne modification. The gATR-FTIR
spectrum clearly confirms the thiol-yne click showing the sharp
peaks at 2955, 2922 and 2853 cmꢂ1 corresponding to aliphatic
groups of dodecanethiol along with loss of peaks at 2125 and
3280 cmꢂ1 corresponding to deprotected alkyne groups. Thus,
a dual-functional brush containing hydroxyl and aliphatic
groups was synthesized by sequential thiol-based reactions
starting with a p(GMA-stat-PgMA) copolymer brush.
Taken together, these studies of functionalizing the copolymer
brushes containing two thiol-clickable groups prove, in concept,
that orthogonal thiol-click reactions can be conducted in
a sequential manner to yield dual-functional polymer brushes.
Though, for all three systems, only one type of thiol was used for
each of the click reactions, it has been shown previously by
numerous researchers that these thiol-click reactions can be con-
ducted with a multitude of thiols imparting the desired properties
to the polymer brush. Additionally, with the choice of two thiols,
the properties of the surface can be tuned by varying the compo-
sition of copolymer brush (concentration of one thiol-clickable
group relative to another thiol-clickable group). To demonstrate
tunability of the copolymer brushes, we synthesized dual-func-
tional polymer brushes of varying wettability by sequential and
orthogonal click reactions from p(GMA-stat-PgMA).
Fig. 7 gATR-FTIR spectra for p(GMA-stat-PgMA-TMS) synthesized
by SIP of a) 1 : 3 v/v GMA:PgMA-TMS, 73.5 nm ꢃ 4.5 nm; b) 1 : 1 v/v
GMA:PgMA-TMS, 40.9 nm ꢃ 2.1 nm; and c) 3 : 1 v/v GMA:PgMA-
TMS, 68.2 nm ꢃ 3.8 nm.
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fractions, respectively. The variation in epoxy/alkyne composi-
tion in the copolymer brush was also characterized by water
contact angle analysis. As shown in Fig. 8, the water contact angle
of copolymer brush decreases from the observed value for pure
pPgMA (96ꢀ) down to the observed for pure pGMA (56ꢀ) as the
fraction of GMA in the monomer feed increases. This trend in the
water contact angle is expected due to higher hydrophilicity of
pGMA as compared to pPgMA. These p(GMA-stat-PgMA)
surfaces were then employed as platforms for sequential thiol-
epoxy and thiol-yne modifications in the same manner previously
described. Due to the orthogonal nature of radical-mediated
thiol-yne and base-catalyzed thiol-epoxy transformations, the p
(GMA-stat-PgMA) copolymer brush can be modified with inde-
pendent thiol-click reactions. To demonstrate control of surface
properties, pendent epoxy groups were modified with hydrophilic
thioglycerol, and pendent alkynes were modified with
hydrophobic dodecanethiol. Fig. 9 shows the gATR-FTIR
spectra of p(GMA-stat-PgMA) brushes clicked with thioglycerol
and dodecanethiol via orthogonal thiol-epoxy and thiol-yne
transformations, respectively. As the GMA fraction in the parent
p(GMA-stat-PgMA) brush increases, the intensity of peaks cor-
responding to the hydroxyl groups at 3400 cmꢂ1 increase as
a result of the thiolysis of pendent epoxy moieties with thio-
glycerol. In contrast, after sequential thiol-yne click with dodec-
anethiol, the intensity of peaks corresponding to aliphatic groups
at 2955, 2922 and 2853 cmꢂ1 of dodecanethiol decreases as the
fraction of GMA in the brush increases. Accordingly, as shown in
Fig. 10, the water contact angle of the sequentially clicked
copolymer brush surfaces decreases as the GMA fraction in the
parent p(GMA-stat-PgMA) brush increases indicating the
amount of hydrophilic thioglycerol and hydrophobic dodeca-
nethiol incorporated in the brush is dictated simply from the
composition of the parent polymer brush (assuming complete
conversion of the epoxy and alkyne groups). Also shown in
Fig. 10, the modified brush surfaces undergo rearrangement as
a result of various solvent treatments. THF likely exposes
Fig. 9 gATR-FTIR spectra of p(GMA-stat-PgMA) after sequential
thiol-epoxy and thiol-yne with thioglycerol and dodecanethiol, respec-
tively. p(GMA-stat-PgMA) brushes are synthesized by SIP of a) 1 : 3 v/v
GMA:PgMA, 54.2 nm ꢃ 2.7 nm b) 1 : 1 v/v GMA:PgMA, 43.6 nm ꢃ
1.2 nm; and c) 3 : 1 v/v GMA:PgMA, 48.4 nm ꢃ 3.1 nm.
a greater fraction of dodecanethiol at the surface, and vice versa,
methanol likely exposes a greater fraction of thioglycerol.
Although some degree of rearrangement is expected, we are
particularly interested to probe the distribution of these func-
tional groups in the depth direction of the polymer brush to learn
more about the possibilities of creating unique polymer brush
architectures with compositional gradients by exploiting
Fig. 10 Water contact angle of p(GMA-stat-PgMA) brushes clicked
sequentially with thioglycerol and dodecanethiol via thiol-epoxy and
thiol-yne reactions as a function of volume fraction of GMA in the
GMA/PgMA monomer feed used for SIP. Error bars represent one
standard deviation of the data, which is taken as the experimental
uncertainty of the measurement.
Fig. 8 Water contact angle of p(GMA-stat-PgMA) brushes as a func-
tion of GMA in the GMA/PgMA comonomer feed used for SIP. Error
bars represent one standard deviation of the data, which is taken as the
experimental uncertainty of the measurement. Some error bars are
smaller than the symbols.
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5 X.-L. Sun, C. L. Stabler, C. S. Cazalis and E. L. Chaikof,
Bioconjugate Chem., 2005, 17, 52–57.
6 S. Arumugam and V. V. Popik, J. Am. Chem. Soc., 2011, 133, 15730–
15736.
size-dependent exclusion inherent to polymer brush systems. This
work is currently underway.
7 C. Hoyle, T. Lee and T. Roper, J. Polym. Sci., Part A: Polym. Chem.,
2004, 42, 5301–5338.
Conclusions
8 C. E. Hoyle, A. B. Lowe and C. N. Bowman, Chem. Soc. Rev., 2010,
39, 1355–1387.
9 C. E. Hoyle and C. N. Bowman, Angew. Chem., Int. Ed., 2010, 49,
1540–1573.
10 A. B. Lowe, C. E. Hoyle and C. N. Bowman, J. Mater. Chem., 2010,
20, 4745–4750.
11 D. Kessler, K. Nilles and P. Theato, J. Mater. Chem., 2009, 19, 8184–
8189.
In summary, we successfully demonstrated a versatile post-poly-
merization modification strategy to synthesize multifunctional
polymer brush surfaces via combination of surface-initiated pho-
topolymerization and orthogonal thiol-click reactions, namely the
base-catalyzed thiol-isocyanate, thiol-epoxy, or thiol-bromo
reactions in sequential combination with the radical-mediated
thiol-yne reaction. Initially, the applicability of the radical-medi-
ated thiol-yne reaction was extended to include one-pot statistical
co-click reactions of brush pendant alkyne groups with multiple
thiols. This simple one-pot approach was successfully applied to
various mixtures of thiols including a combination of thioglycerol
and dodecanethiol, which bestow hydrophilic hydroxyl and
hydrophobic aliphatic groups to the polymer brush, respectively,
and a combination of N-acetyl-cysteine and dodecanethiol to form
a modelpolymercoatingwitha biologicallyrelevantmolecule. The
one-pot approach was also shown to be easily extendable to
a mixture of three thiols. The ability to control the surface
properties (hydrophilicity in this work) by facile control over
relative concentration of thiols in a thiol mixture also exhibits the
robustness and versatility of the one-pot approach. Additionally,
sequential and orthogonal thiol-click reactions were successfully
applied to synthesize dual-functional polymer brushes by post-
polymerization modification of p(NCOMA-stat-PgMA),
p(GMA-stat-PgMA) and p(BrMA-stat-PgMA) via nucleophile-
mediated thiol-isocyanate, thiol-epoxy or thiol-bromo, respec-
tively, in combination with radical-mediated thiol-yne reactions.
Generally, the base-catalyzed reactions were conducted first, and
were observed to have no effect on the alkyne groups, which
enabled the sequential thiol-yne reaction. In this case, surface
properties were tailored by controlling the relative concentrations
of monomers in the monomer feed during the SIP, which in turn
dictates the composition of the thiol-clicked surface. While we
demonstrated our strategy with model and commercially available
thiols, we fully expect that this approach will be extended to
fabrication of multiplexed biomolecules, i.e. proteins, DNA
strands, antibodies, as well as the fabrication of complex polymer
brush architectures, i.e. mixed and block copolymer brushes.
€
12 H. Murata, O. Prucker and J. Ruhe, Macromolecules, 2007, 40, 5497–5503.
13 S. V. Orski, K. H. Fries, G. R. Sheppard and J. Locklin, Langmuir,
2010, 26, 2136–2143.
€
14 R. K. Iha, K. L. Wooley, A. M. Nystrom, D. J. Burke, M. J. Kade and
C. J. Hawker, Chem. Rev., 2009, 109, 5620–5686.
15 K. L. Christman, E. Schopf, R. M. Broyer, R. C. Li, Y. Chen and
H. D. Maynard, J. Am. Chem. Soc., 2008, 131, 521–527.
16 G. A. Hudalla and W. L. Murphy, Langmuir, 2010, 26, 6449–6456.
17 S. Im, K. Bong, B.-S. Kim, S. Baxamusa, P. Hammond, P. Doyle and
K. Gleason, J. Am. Chem. Soc., 2008, 130, 14424–14425.
18 J. M. Baskin, J. A. Prescher, S. T. Laughlin, N. J. Agard, P. V. Chang,
I. A. Miller, A. Lo, J. A. Codelli and C. R. Bertozzi, Proc. Natl. Acad.
Sci. U. S. A., 2007, 104, 16793–16797.
19 J. C. Jewett, E. M. Sletten and C. R. Bertozzi, J. Am. Chem. Soc.,
2010, 132, 3688–3690.
20 R. Manova, T. A. van Beek and H. Zuilhof, Angew. Chem., Int. Ed.,
2011, 50, 5428–5430.
21 A. Kuzmin, A. Poloukhtine, M. A. Wolfert and V. V. Popik,
Bioconjugate Chem., 2010, 21, 2076–2085.
22 S. V. Orski, A. A. Poloukhtine, S. Arumugam, L. Mao, V. V. Popik
and J. Locklin, J. Am. Chem. Soc., 2010, 132, 11024–11026.
23 X. Deng, C. Friedmann and J. Lahann, Angew. Chem., Int. Ed., 2011,
50, 6522–6526.
24 B. J. Sparks, J. G. Ray, D. A. Savin, C. M. Stafford and D. L. Patton,
Chem. Commun., 2011, 47, 6245–6247.
25 T. Cai, R. Wang, K. G. Neoh and E. T. Kang, Polym. Chem., 2011, 2,
1849–1858.
26 P. Jonkheijm, D. Weinrich, M. Koehn, H. Engelkamp,
P. Christianen, J. Kuhlmann, J. Maan, D. Nuesse, H. Schroeder,
R. Wacker, R. Breinbauer, C. Niemeyer and H. Waldmann, Angew.
Chem., Int. Ed., 2008, 47, 4421.
27 C. Wendeln, S. Rinnen, C. Schulz, H. F. Arlinghaus and B. J. Ravoo,
Langmuir, 2010, 26, 15966–15971.
28 M. Li, P. De, H. Li and B. S. Sumerlin, Polym. Chem., 2010, 1, 854–
859.
29 R. M. Hensarling, V. A. Doughty, J. W. Chan and D. L. Patton, J.
Am. Chem. Soc., 2009, 131, 14673–14675.
30 C. Wang, P. F. Ren, X. J. Huang, J. Wu and Z. K. Xu, Chem.
Commun., 2011, 47, 3930–3932.
31 Y. Huang, Y. Zeng, J. Yang, Z. Zeng, F. Zhu and X. Chen, Chem.
Commun., 2011, 47, 7509–7511.
32 D. Konkolewicz, S. Gaillard, A. G. West, Y. Y. Cheng, A. Gray-
Weale, T. W. Schmidt, S. P. Nolan and S. Perrier, Organometallics,
2011, 30, 1315–1318.
33 S. S. Naik, J. W. Chan, C. Comer, C. E. Hoyle and D. A. Savin,
Polym. Chem., 2011, 2, 303–305.
34 R. M. Hensarling, S. B. Rahane, A. P. LeBlanc, B. J. Sparks,
E. M. White, J. Locklin and D. L. Patton, Polym. Chem., 2011, 2,
88–90.
35 H. Li, B. Yu, H. Matsushima, C. E. Hoyle and A. B. Lowe,
Macromolecules, 2009, 42, 6537–6542.
Acknowledgements
This work was supported in part by NSF CAREER (DMR-
1056817) and the Office of Naval Research (Award N00014-07-
1-1057). RMH acknowledges fellowship support from the U.S.
Department of Education GAANN program (Award
#P200A090066).
36 J. W. Chan, C. E. Hoyle and A. B. Lowe, J. Am. Chem. Soc., 2009,
131, 5751–5753.
References
€
37 R. Barbey, L. Lavanant, D. Paripovic, N. Schuwer, C. Sugnaux,
1 C. Sanchez, H. Arribart and M. M. Giraud Guille, Nat. Mater., 2005,
4, 277–288.
2 C. Hartmuth, M. Finn and B. Sharpless, Angew. Chem., Int. Ed.,
2001, 40, 2004–2021.
S. Tugulu and H. A. Klok, Chem. Rev., 2009, 109, 5437–5527.
38 M. A. Harvison, T. P. Davis and A. B. Lowe, Polym. Chem., 2011, 2,
1347–1354.
39 B. M. Rosen, G. Lligadas, C. Hahn and V. Percec, J. Polym. Sci., Part
A: Polym. Chem., 2009, 47, 3931–3939.
3 L. Nebhani and C. Barner-Kowollik, Adv. Mater., 2009, 21, 3442–
3468.
40 B. M. Rosen, G. Lligadas, C. Hahn and V. Percec, J. Polym. Sci., Part
A: Polym. Chem., 2009, 47, 3940–3948.
4 P. T. Dirlam, G. A. Strange, J. A. Orlicki, E. D. Wetzel and
P. J. Costanzo, Langmuir, 2009, 26, 3942–3948.
942 | J. Mater. Chem., 2012, 22, 932–943
This journal is ª The Royal Society of Chemistry 2012

View Online
41 J. Xu, L. Tao, C. Boyer, A. B. Lowe and T. P. Davis, Macromolecules,
2010, 43, 20–24.
48 A. S. Goldmann, A. Walther, L. Nebhani, R. Joso, D. Ernst, K. Loos,
€
C. Barner-Kowollik, L. Barner and A. H. E. Muller, Macromolecules,
€
42 C. Schuh, S. Santer, O. Prucker and J. Ruhe, Adv. Mater., 2009, 21,
4706–4710.
2009, 42, 3707–3714.
49 P. Antoni, M. J. Robb, L. Campos, M. Montanez, A. Hult,
€
E. Malmstrom, M. Malkoch and C. J. Hawker, Macromolecules,
2010, 43, 6625–6631.
43 C. Xu, T. Wu, C. M. Drain, J. D. Batteas and K. L. Beers,
Macromolecules, 2004, 38, 6–8.
44 M. Beinhoff, J. Frommer and K. R. Carter, Chem. Mater., 2006, 18,
3425–3431.
50 K. L. Killops, L. M. Campos and C. J. Hawker, J. Am. Chem. Soc.,
2008, 130, 5062–5064.
45 B. D. Fairbanks, E. A. Sims, K. S. Anseth and C. N. Bowman,
Macromolecules, 2010, 43, 4113–4119.
51 J. Han, B. Zhao, Y. Gao, A. Tang and C. Gao, Polym. Chem., 2011, 2,
2175–2178.
46 L. M. Campos, K. L. Killops, R. Sakai, J. M. J. Paulusse,
D. Damiron, E. Drockenmuller, B. W. Messmore and
52 C. E. Hoyle, A. B. Lowe and C. N. Bowman, Chem. Soc. Rev., 2010,
39, 1355–1387.
C.
7070.
J.
Hawker,
Macromolecules,
2008,
41,
7063–
53 J. Shin, H. Matsushima, C. M. Comer, C. N. Bowman and
C. E. Hoyle, Chem. Mater., 2010, 22, 2616–2625.
ꢀ
47 K. Kempe, R. Hoogenboom, M. Jaeger and U. S. Schubert,
Macromolecules, 2011, 44, 6424–6432.
54 A. Orsini, A. Viterisi, A. Bodlenner, J.-M. Weibel and P. Pale,
Tetrahedron Lett., 2005, 46, 2259–2262.
This journal is ª The Royal Society of Chemistry 2012
J. Mater. Chem., 2012, 22, 932–943 | 943