Application of new photolabile protecting groups as photocleavable joints of block copolymers

Article abstract of DOI:10.1039/c3cc44799e

New photoresponsive block copolymers (BCPs) have been developed by incorporating photocleavable units. These photocleavable units are derived from robust photolabile protecting groups (PPGs); UV irradiation cleaves the BCPs and releases a well-defined chemically active functional group at the cleaved end of a PS polymer. The Royal Society of Chemistry 2013.

Full text of DOI:10.1039/c3cc44799e

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Application of new photolabile protecting groups as
photocleavable joints of block copolymers†
Wenya Lu,a Chong Tian,a Punith Thogaripally,a Jun Hub and Pengfei Wang*a
Cite this: Chem. Commun., 2013,
49, 9636
Received 26th June 2013,
Accepted 21st August 2013
DOI: 10.1039/c3cc44799e
www.rsc.org/chemcomm
New photoresponsive block copolymers (BCPs) have been devel-
oped by incorporating photocleavable units. These photocleavable
units are derived from robust photolabile protecting groups (PPGs);
UV irradiation cleaves the BCPs and releases a well-defined chemi-
cally active functional group at the cleaved end of a PS polymer.
Block copolymers (BCPs) have widespread applications. For
example, self-assembly of BCPs has been developed as one of
the best strategies for the preparation of porous polymers. In
making nanoporous thin films, the underlying strategy consists
of the self-assembly of the BCPs into the desired structures on a
surface followed by removing the sacrificial polymer segment.1–14
There are two strategies to remove the sacrificial polymer: either
degrading it to small fragments or disconnecting it from the
BCPs at the junction between the microphase-separated blocks.
The latter is deemed more general and flexible because it relies
Scheme 1 PPGs featuring benzylic C–O bond cleavage.
We have recently developed a series of novel PPGs for
on the chemical nature of the linker rather than the sacrificial protection of carbonyl and hydroxyl groups (Scheme 1).22–31
polymer. The interest in using PPG-based cleavable joints in BCPs For example, a carbonyl compound (1) can be protected by our
in this regard has grown rapidly.7,8,15–21 In addition to the general new PPG reagent 2 and be converted to an acetal/ketal (3), and
advantages of photo stimulus (such as mild reaction conditions, an alcohol (4) can be protected as an ether by the new PPG
remote control over reaction time and location, and the absence reagent 5. Upon UV irradiation, the acetal/ketal 3 and the ether
of a need for additional chemical reagents), there are more 6 release the carbonyl compound and the alcohol, respectively.
advantages of using PPG-based linkers. For example, PPGs will These new PPGs are structurally simple, easy to prepare and
release various well-defined and chemically active functional use, and can be removed at high efficiency from a variety of
group pendants from the polymer framework, offering more solvents including water without excluding air. They are stable
options for polymer manipulation/functionalization. Recent under indoor lighting and withstand treatments of various
efforts to study PPG-mediated light-responsiveness of polymers chemical reagents. For carbonyl protection, selective removal
have been mainly focused on using the o-nitrobenzyl series of of different new carbonyl PPGs has been achieved by changing
PPGs. To further advance applications of new PPGs and to irradiation wavelength.26,29 Removal of some carbonyl and
explore new opportunities in PPG-based photoresponsive BCP hydroxyl PPGs can be successfully carried out with irradiation
development, herein we report the use of new PPGs recently of sunlight, which is a particularly useful feature for large scale
developed in our laboratory as photocleavable BCP joints.
and low cost applications.
Herein we report design and synthesis of new amphiphilic
polystyrene-block-poly(ethylene glycol) (i.e., PS-l-PEG) BCPs
bearing our novel PPG-based photocleavable joints. By remov-
ing the sacrificial PEG domain of the new PS-l-PEG BCPs under
mild irradiation conditions, the carbonyl-functionalized PS
domain is obtained. Amphiphilic BCPs, in particular, PS-b-
PEG based systems are important in making defect-free porous
a Department of Chemistry, University of Alabama at Birmingham, Birmingham,
AL 35294, USA. E-mail: wangp@uab.edu; Tel: +1 2059965625
b Department of Chemistry and Biochemistry, University of South Carolina,
Columbia, SC 29208, USA
† Electronic supplementary information (ESI) available: Experimental details,
spectroscopic data, and NMR spectra of new compounds. See DOI: 10.1039/
c3cc44799e
c
9636 Chem. Commun., 2013, 49, 9636--9638
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thin films.1,5 It has been recently demonstrated that by remov-
ing the sacrificial PEG domain, functional groups, i.e., thiol,6
carboxyl,7,8,16 amino,32 and hydroxyl amino groups,33 can be
left on the PS domain. The resulting thin film can be further
functionalized through these exposed functional groups. We
envision that the carbonyl-functionalized porous thin films can
be more biochemically/biomedically relevant and useful in that
the carbonyl group can effectively interact with amino groups of
various biological molecules via imine formation.
Our synthesis started from 5-aminosalicylic acid 7 (Scheme 2).
A three-step sequence of esterification, acetylation, and Grignard
reaction provided the salicyl alcohol 8.24 Its reaction with the
aldehyde 9 under the neutral reaction conditions and the subse-
quent reduction of the amide moiety led to the known acetal 10
in 84% yield (two steps). Treatment of 10 with propargyl
Scheme 3 Photocleavage of BCP 12a and the GPC profile.
bromide followed by 2-bromo-2-methylpropanoyl bromide intensity. GPC analysis also confirmed photocleavage of the BCP.
resulted in the photolinker 11a in 89% yield (two steps). After irradiation, the peak of the BCP 12a at 23.8 min was not
A one-pot copper(I)-catalyzed simultaneous atom transfer radi- observed, and two new peaks appeared. The major new peak at
cal polymerization (ATRP) reaction34–36 and azide–alkyne click 24.7 min corresponds to the PS domain 13a (Mn = 26 kg molÀ1
,
reaction (CuAAC)37–39 produced the BCP 12a (PS-l1-PEG) Mw = 28 kg molÀ1, PDI = 1.07) and the minor peak at 26.2 min is
(Mn = 32 kg molÀ1, Mw = 37 kg molÀ1, PDI = 1.15).8,40 characteristic of the PEG domain (Scheme 3).8 IR spectroscopy
A BCP 12a solution (1 mM in THF–H2O 95 : 5 (v/v)) was first indicated drastic reduction in intensity of the typical C–O–C
irradiated with a Pyrex-filtered 450 W medium pressure mercury stretch of the PEG backbone at 1105 cmÀ1 after rinsing the
lamp (Scheme 3). The reaction progress was monitored using irradiation products with MeCN–H2O.
1H NMR spectroscopy. Disappearance of the acetal proton at
We then examined photocleavage using different UV
4.85 ppm after 5 min of irradiation indicated completion of the sources. A Rayonet photoreactor equipped with 350 nm lamps
photocleavage. To further confirm cleavage of the BCP and to took 3 h to achieve 94% cleavage, and sunlight exposure (a local
have a quantitative measure of the reaction efficiency, the UV index o5 during the reaction time) took 6 h to reach 91%
cleaved PEG fragment was removed by rinsing the reaction cleavage. Similar results were also obtained from irradiation of
mixture with MeCN–H2O (9: 1). The percentile of cleavage was 12a in DMF–H2O (95 : 5 v/v). It appeared that the size of BCP did
calculated from the NMR integrals of the PS domain and the not affect the efficiency of photocleavage; the BCP 12a and
residual PEG domain of the unreacted 12a.16 Thus, after 5 min other two PS-l1-PEG BCPs of different molecular weights
of irradiation, the photoreaction achieved 97% cleavage. (i.e., 10k-l1-5k and 40k-l1-5k) cleaved with about the same
Production of the product 13a is evidenced by the appearance efficiency as those achieved in releasing small molecule
of the CHO signal at 9.5 ppm (see ESI†). Prolonged irradiation carbonyl compounds from protection of the parent PPG.26,29
did not improve cleavage further, instead diminished the CHO
Photocleavage was also performed in the solid state. A
polymer film of PS-l1-PEG was prepared by evaporating a
toluene solution of the BCP (4 mg mLÀ1) on top of water. This
film (1 mg BCP/200 cm2) was irradiated with a Pyrex-filtered
450 W medium pressure mercury lamp for 5 min to give 82%
cleavage. Exposure of the polymer film to sunlight (a local UV
index 9 during the reaction time) for 1 hour cleaved 51% and
for 2 hour cleaved 87% of the BCP.
By substituting styrene with t-butyl acrylate in the one-pot
procedure illustrated in Scheme 2, the same linker 11a was also
incorporated into a PtBA-l1-PEG BCP (10k-l1-5k) (see ESI†).
Irradiation of this BCP in solution (1 mM in THF–H2O 95: 5 (v/v))
for 5 min with a Pyrex-filtered 450 W medium pressure mercury
lamp led to 98% cleavage. The aldehyde moiety in the resulting
PtBA domain is evidenced by the CHO peak at 9.8 ppm.
Similar to preparing 11a, we prepared two different photo-
linkers 11b and 11c (Scheme 4). Linker 11b is derived from another
carbonyl PPG,22,26,29 and linker 11c is derived from a hydroxyl
PPG.27 By using the same one-pot copper(I)-catalyzed simultaneous
ATRP and CuAAC, BCPs 12b (PS-l2-PEG) (Mn = 29 kg molÀ1, Mw =
32 kg molÀ1, PDI = 1.10) and 12c (PS-l3-PEG) (Mn = 36 kg molÀ1
Mw = 40 kg molÀ1, PDI = 1.13) were produced.
,
Scheme 2 Synthesis of PS-l1-PEG 12a bearing a PPG-based photocleavable
linker.
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Irradiation of 12b in solution (1 mM in THF–H2O 95 : 5 (v/v))
with a Pyrex-filtered mercury lamp led to nearly complete
cleavage of the BCP as evidenced by 1H NMR and GPC analysis.
In contrast to 12a, the BCP 12b is stable under 350 nm irradia-
tion, which is consistent with the UV absorption of the
chromophore and the photochemical properties of the corre-
sponding parent PPG.26,29 Sunlight cleaved only 25% of the
BCP 12b after 6 h exposure. Irradiation of the BCP 12c in
solution (1 mM in THF–H2O 95 : 5 (v/v)) with the Pyrex-filtered
mercury lamp resulted in 94% cleavage in 30 min. No cleavage
was observed under 350 nm irradiation. Under sunlight for 6 h,
the BCP cleaved 81%.
In conclusion, we have synthesized new photoresponsive
block copolymers containing photocleavable linkers derived
from the novel carbonyl and hydroxyl PPGs recently developed
in our laboratory. Under mild irradiation conditions, the joints
can be cleaved efficiently and can produce the carbonyl- or
hydroxyl-functionalized PS domain. These photoresponsive
BCPs should be potentially useful in applications such as
making nanoporous thin films from self-assembly of BCPs,
owing to their mild and reagent-free cleavage conditions. More-
over, selective cleavage of different BCPs by changing the
irradiation wavelength can be valuable in making multiple
nanoscale templates with different porosity.10,11
We thank ACS PRF (PRF# 51827-ND7) for the support. We
also thank Prof. Biran C. Benicewicz, Michael Bell and Tony
Neely for assistance with GPC.
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9638 Chem. Commun., 2013, 49, 9636--9638