"Clicking" polymer brushes with thiol-yne chemistry: Indoors and out

Article abstract of DOI:10.1021/ja9071157

(Chemical Equation Presented) Thiol-yne click chemistry is demonstrated as a modular platform for rapid and practical fabrication of highly functional, multicomponent surfaces under ambient conditions. The principle is illustrated using a postmodification strategy in which poly(propargyl methacrylate) brushes were generated via surface-initiated photopolymerization and sequentially functionalized using the radical-mediated thiol-yne reaction. Brush surfaces expressing a three-dimensional configuration of "yne" functionalities were modified with high efficiency and short reaction times using a library of commercially available thiols, including functional thiols that demonstrate applicability for pH responsive surfaces and for bioconjugation. Sequential thiol-yne reactions in conjunction with simple UV photolithography were also applied to afford micropatterned, multicomponent surfaces. The practicality of the platform was further demonstrated by carrying out thiol-yne surface reactions in sunlight, suggesting the possibility of large scale modifications using renewable energy resources. Considering the mild reaction conditions, rapid throughput, and compatibility with orthogonal chemistries, we expect this platform to find widespread use among the materials science community.

Full text of DOI:10.1021/ja9071157

Published on Web 09/24/2009
“Clicking” Polymer Brushes with Thiol-yne Chemistry: Indoors and Out
Ryan M. Hensarling, Vanessa A. Doughty, Justin W. Chan, and Derek L. Patton*
School of Polymers and High Performance Materials, UniVersity of Southern Mississippi,
118 College DriVe #10076, Hattiesburg, Mississippi 39406
Received August 22, 2009; E-mail: derek.patton@usm.edu
Engineering the chemistry and topography of surfaces affords
technological advancements for a variety of applications ranging
from biosensors to microelectronics. This broad range of applica-
tions necessitates the development of a modular approach to surface
engineering, ideally one that (1) enables the rapid generation of a
diverse library of functional surfaces from a single substrate
precursor, (2) utilizes a structurally diverse range of commercially
available or easily attainable reagents, (3) proceeds rapidly to
quantitative conversions under mild conditions, and (4) opens the
door to orthogonal and site-selective functionalization. These criteria
are, of course, similar to those that define a class of reactions
commonly known as “click” chemistry.1 Click chemistry, particu-
larly Cu-catalyzed azide-alkyne cycloaddition (CuAAC), has
proven a powerful approach toward meeting the aforementioned
criteria for surface engineering.2-4 However, the biotoxicity of Cu
and the limited availability of cycloalkynes used in Cu-free AAC5
reactions may limit utility in certain arenas. Modular surface
reactions that circumvent these issues while retaining click-like
characteristics are highly desirable. In this communication, we
Figure 1. (a) Schematic procedure of surface-initiated photopolymerization
present thiol-yne chemistry as a modular approach toward surface
of TMS-protected propargyl methacrylate, deprotection, and subsequent
thiol-yne functionalization. (b) Schematic procedure for photopatterning
“yne”-containing polymer brush surfaces with sequential thiol-yne reactions.
engineering. Using this approach, we demonstrate the rapid
generation of a library of highly functional, patterned, and multi-
component polymer brush surfaces under ambient conditions from
a single substrate precursor. We also demonstrate the practicality
of this approach by performing thiol-yne surface modifications using
outdoor, ambient-air reactions with sunlight as the radiation source.
The recently highlighted utility and click-like characteristics of
the radical-mediated thiol-yne reaction,6-9 and the more thoroughly
investigated thiol-ene reaction,10,11 have been amply demonstrated
in areas of macromolecular design,12,13 postpolymerization
modification14-19 and even bioconjugation.20 Thiol-ene reactions
have also been demonstrated as a viable approach to surface
modification by the Bowman21,22 and Waldmann23 groups; thiol-
yne reactions, however, have yet to be explored for this purpose
despite many common advantages. Notably, thiol-yne reactions
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, the thiol-yne reaction is orthogonal to a wide
range of chemistries including the phosphine-catalyzed nucleophilic
thiol-ene reaction.7 The hydrothiolation reaction can also be
photoinitiated in the UV-visible range (254-470 nm) affording
both temporal and spatial control of the reaction site. The vast
number of commercially available thiols is yet another advantage
of this chemistry as a broadly applicable platform. Considering these
attributes, we envisioned the fabrication of highly functional
surfaces using thiol-yne reactions to modify the three-dimensional
configuration of reactive “handles” expressed by densely tethered
“yne”-containing polymer brushes. Similar postmodification of
brush surfaces has been successfully demonstrated using pendant
active esters24 and azide modified nanoparticles.25
Figure 2. Commercially available thiols used for thiol-yne click reactions:
mercaptopropionic acid (1), 1-dodecanthiol (2), thioglycerol (3), N-acetyl-
L-cysteine (4), benzyl mercaptan (5), 1-adamantanethiol (6), thiochlolesterol
(7), and 3-mercaptopropyl polyhedral oligomeric silsequioxane (POSS, 8).
As shown in Figure 1a, silicon substrates were first functionalized
with a chlorosilane derivative of commercially available 2-hydroxy-
4′-(2-hydroxyethoxy)-2-methylpropiophenone (Irgacure 2959) pho-
toinitiator.26 These substrates were then inserted into a microchannel
reactor (see Supporting Information) containing trimethylsilane-
protected propargyl methacrylate (PgMA-SiMe3, 1:1 in toluene)
and surface-initiated by irradiating with UVλmax)365 nm light (20 mW
cm-1, 45 min, ∼25 nm). Notably, the fabrication of a 14 mm × 65
mm substrate using our microchannel reactor requires only 400 µL
of monomer solution (additional solution required depending on
volume of connecting tubing), significantly reducing the cost of
this approach. After Soxhlet extraction in toluene, the deprotection
of the p(PgMA-SiMe3) brush in KOH/MeOH was followed by
ATR-FTIR. Quantitative deprotection was confirmed by the disap-
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C O M M U N I C A T I O N S
Figure 4. Condensation images of sequential thiol-yne micropatterned
brushes showing water droplets selectively nucleating on the hydrophilic
MPA areas: (a) MPA/DDT (square/bars), 300 mesh; (b) MPA/DDT (squares/
bars), 2000 mesh; (c) inverse DDT/MPA (squares/bars), 300 mesh; (d)
Sunlight MPA/DDT (squares/bars); (e) static water contact angle measure-
ments showing pH responsive reversible wettability of MPA surfaces
prepared outdoors in sunlight. Note: Color variations result from thin film
interference under humid conditions.
Figure 3. ATR-FTIR spectra of brushes on SiOx substrates (key peaks
are identified): (a) poly(propargyl methacrylate) brush (3283 cm-1 CtCsH
(red), 2129 cm-1, CdC (green)) reacted with (b) 3-mercaptopropionic acid
reactions) as indicated by the disappearance of the peaks assigned
to the alkyne (CsH 3288 cm-1, CtC 2131 cm-1) for the entire
series of functional brushes (Figure 3). Further, the spectra clearly
show peaks that are indicative of the incorporated thiols (see Table
SI.1 for additional spectra/peak assignments). For small MW thiols,
(3320-3000 cm-1, COOsH) (c) 1-dodecanethiol (2955, 2922, 2852 cm-1
,
CsH), (d) 1-thioglycerol (3600-3000 cm-1), (e) N-acetyl-L-cysteine (3354
cm-1 COsNH), (f) benzyl mercaptan (3061, 3028, 3000 cm-1, dCsH;
1601 cm-1 CdC) (g) 1-adamantanethiol (2905, 2849 cm-1, CsH), (h)
thiocholesterol (2934, 2905, 2868, 2870 cm-1, CsH), (i) 3-mercaptopropyl
polyhedral oligomeric silsequioxane (1115 cm-1, SisO). The blue line
indicates the position of the vinyl sulfide species (1609 cm-1).
we see little evidence for the vinyl sulfide species (∼1609 cm-1
,
position shown by blue marker in Figure 3)6 that would result from
monosubstitution of the alkyne indicating full conversion to the
1,2-dithioether adduct. However, full conversion to the disubstituted
adduct may be more difficult to achieve as the MW (or steric bulk)
of the thiol increases. As shown in Figure 3g,h, there exists a very
weak band at ∼1609 cm-1 that could be assigned to the vinyl
sulfide, but quantitative analysis is potentially complicated by weak
absorbance and spectral overlap. Further to this point, we observe
an increase in brush thickness (Table SI.2), which is attributed to
the increase in molar mass of the monomer repeat unit and,
consequently, an increase in MW of the brush after functionaliza-
tion.24 We note that other factors may also contribute to the changes
in film thickness observed, including molecular stacking, hydro-
phobicity effects, etc. From cursory analysis of the film thickness
increase relative to the MW of the thiol derivatives (where the MW
of the thiol would dictate a one or two times increase in the molar
mass of the monomer repeat depending on whether mono- or
disubstitution occurs), it is apparent that larger MW thiols are not
fully substituted to the 1,2-dithioether adduct. For example, the
brush thickness increases by a factor of ∼4.5 after functionalization
with 1-dodecanethiol (DDT) and only by ∼2.7 for thiocholesterol,
despite DDT being half the molecular weight of the latter (202.4
and 402.72 g/mol, respectively). A similar dependence of substitu-
tion efficiency on the increasing MW of amines was observed with
N-hydroxysuccinimide brushes.24 In our case, the effect is exac-
erbated by the steric hindrance of adding a second bulky thiol per
alkyne within the densely grafted polymer brush. Model studies
using time-resolved reactions and application of the relationships
reported by Murata et al.24 to calculate the predicted film thickness
at full 1,2-adduct conversion are ongoing to better understand the
efficacy of the thiol-yne reaction within the confinements of the
brush surface. Ultimately, we believe this observation does little
to affect the potential of the thiol-yne reaction as a platform for
surface engineering.
pearance of the protected alkyne CtC stretch (∼2185 cm-1) and
the appearance of the characteristic peaks of the unprotected alkyne
(CsH 3288 cm-1, CtC 2131 cm-1) (Figure SI.1).27 The resulting
“yne” functionalized polymer brush served as a “universal” reactive
precursor for subsequent thiol-yne reactions eliminating the syn-
thetic effort associated with the use of multiple functional monomers.
The radical-mediated reaction of a thiol with an alkyne generates
a dithioether adduct as shown in Figure 1a. The reaction occurs in
a two-step process involving the addition of the thiyl radical to the
CtC bond yielding an intermediate vinyl sulfide species that
subsequently undergoes a second, formally thiol-ene reaction,
yielding the 1,2-dithioether adduct.6 To explore the efficacy of the
thiol-yne reaction at surfaces, we selected a library of commercially
available thiols (Figure 2), including 3-mercaptopropionic acid
(MPA, 1), of interest for pH responsive surfaces, N-acetyl-L-cysteine
(4) as a model for the attachment of peptide fragments to brush
surfaces, and thiocholesterol (7) as a ubiquitous component of
biomembrane structures.28 Thiol-yne reactions were carried out in
the presence of R,R-dimethoxy-R-phenylacetophenone (Irgacure
651, 2 wt % I:thiol) at 365 nm under ambient air, temperature, and
humidity conditions to afford the functional brushes. Reactions were
performed solvent-free when possible, but in some cases, solvent
was required to solubilize the thiol and/or solvate the brush. After
the thiol-yne reaction, substrates were washed extensively with
multiple solvents to remove any physisorbed species and then
characterized by water contact angle and ATR-FTIR. Static water
contact angles confirmed the expected changes in wettability
associated with each functional moiety conjugated to the surface
(Figure SI.2). ATR-FTIR was used to follow the thiol-yne func-
tionalization of the brushes. Under these conditions, quantitative
conversion of the tethered alkynes was observed within minutes
(compared with hours typically required for CuAAC surface
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C O M M U N I C A T I O N S
To illustrate both the modularity and the versatility of our
approach, we conducted sequential and area-selective thiol-yne/
thiol-yne brush modifications using a simple photopatterning
technique. The process is schematically shown in Figure 1b. Copper
grids (300 mesh, 58 µm holes/25 µm bars and 2000 mesh, 7.5 µm
holes/5 µm bars) were used as photomasks. The grids were placed
in direct contact with the brush surface, immersed in MPA
containing 2 wt % Irgacure 651, and irradiated with UVλmax)365 nm
light (8 min) yielding a patterned MPA/“yne” surface. After
removing the grid and washing with THF, the unexposed and
unreacted “yne” was then subjected to a second thiol-yne reaction
with DDT (8 min) affording the micropatterned, multicomponent
surface. Figure 4a-b show the optical condensation images for the
MPA/DDT patterned surface. As shown, the hydrophilic MPA
regions (deprotonated with 0.01 M KOH) preferentially nucleate
condensation of water permitting facile visualization of the chemi-
cally patterned surface.29 The inverse pattern DDT/MPA was also
demonstrated (Figure 4c). Well-defined edges and droplet confine-
ment indicate a sharp interface between the hydrophilic MPA and
hydrophobic DDT regions.
Since thiyl radicals can be generated close to visible wave-
lengths,16 we further demonstrate the practicality of the thiol-yne
approach for surface modification by performing homogeneous and
patterned thiol-yne surface reactions outdoors using sunlight as a
radiation source. Reactions were carried out in Petri dishes with
nonpurged thiol solutions. For consistency, we again used 2 wt %
Irgacure 651 although photoinitiators that absorb further into the
visible are readily available. Quantitative conversion of the tethered
alkynes was observed within 1 h of sunlight exposure (Figure SI.3).
Figure 4d shows the condensation image of the resulting sunlight
patterned MPA/DDT brush. The results are analogous to those
obtained in the lab suggesting the possibility of large scale surface
modifications using renewable energy resources. As a final point,
we show that homogeneous, pH responsive MPA functionalized
brushes can easily be synthesized in sunlight. These surfaces exhibit
reversible wettability upon protonation and deprotonation of the
carboxylic acid functionalities as shown in Figure 4e.
Urban research group for help with ATR-FTIR and the Rawlins
research group for help with optical microscopy. This paper is
dedicated to the late Prof. Charles E. Hoyle for his pioneering work
in the field of photopolymerization and photochemistry.
Supporting Information Available: Details of synthesis procedures,
water contact angle measurements, and additional FTIR characterization
and assignments. This material is available free of charge via the Internet
at http://pubs.acs.org.
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Acknowledgment. The financial support for this research was
provided by the University of Southern Mississippi startup funds.
We thank Ms. Megan Aumsuwan and Dr. Cathrin Corten of the
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