UV-responsive degradable polymers derived from 1-(4-aminophenyl) ethane-1,2-diol

Article abstract of DOI:10.1002/pola.27550

A UV-responsive polymer was prepared via condensation polymerization of 2-nitrobenzyl(4-(1,2-dihydroxyethyl)phenyl)carbamate and azalaic acid dichloride. When the polymer was irradiated with UV light, the nitrobenzyl urethane protecting group was removed and the deprotected aniline underwent spontaneous 1,6-elimination reactions, resulting in degradation of the polymer. Nanoparticles with encapsulated Nile Red were formulated with the degradable polymer and triggered burst release of Nile Red was observed when the nanoparticles were irradiated by UV light.

Full text of DOI:10.1002/pola.27550

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UV-Responsive Degradable Polymers Derived from 1-(4-Aminophenyl)
ethane-1,2-diol
Liang Ma,1 Ryan Baumgartner,2 Yanfeng Zhang,1 Ziyuan Song,1 Kaimin Cai,1 Jianjun Cheng1,2
1Department of Materials Science and Engineering, University of Illinois at Urbana–Champaign, Urbana, Illinois 61801
2Department of Chemistry, University of Illinois at Urbana–Champaign, Urbana, Illinois 61801
Correspondence to: J. Cheng (E-mail: jianjunc@illinois.edu)
Received 22 September 2014; accepted 13 January 2015; published online 00 Month 2015
DOI: 10.1002/pola.27550
ABSTRACT: A UV-responsive polymer was prepared via conden-
sation polymerization of 2-nitrobenzyl(4-(1,2-dihydroxyethyl)-
phenyl)carbamate and azalaic acid dichloride. When the
polymer was irradiated with UV light, the nitrobenzyl urethane
protecting group was removed and the deprotected aniline
underwent spontaneous 1,6-elimination reactions, resulting in
degradation of the polymer. Nanoparticles with encapsulated
Nile Red were formulated with the degradable polymer and
triggered burst release of Nile Red was observed when the
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nanoparticles were irradiated by UV light. 2015 Wiley Period-
icals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015, 00, 000–
000
KEYWORDS: degradable materials; depolymerization; nanopar-
ticles; photochemistry; polyester; self immolative; stimuli-sensi-
tive polymer; triggered release
self-elimination reactions of the BHA would result in polymer
backbone degradation. Thus, it is excessive to use the BHA for
the design of the trigger responsive domain (TRD) of CSPs, as
any benzyl alcohol can possibly be such a TRD as long as the
TRD has the (4-aminophenyl)methanol structure [Scheme
1(b)]. Herein, we report the use of 2-nitrobenzyl (4-(1,2-dihy-
droxyethyl)phenyl) carbamate (1) and azalaic acid dichloride
(2) for the design of the degradable poly(1/2) [Scheme 1(c)].
The resulting polymer undergoes a 1, 6-elimination reaction
upon removal of the nitrobenzyl protecting group with UV
irradiation. This polymer can be used for future applications
and materials in microcapsule shells for self-healing applica-
tions and in environmentally responsive coatings whose wett-
ability and adhesion change in response to a stimulus.
INTRODUCTION Polymers that can be degraded in response
to external triggers have been used in many applications,
such as controlled release, self-healing, tissue engineering,
sensors, and smart surface coatings.1–15 Substantial effort
has been devoted to developing degradable polymers with
stimuli-responsive groups incorporated into the polymer
backbones to control their degradation. Recently, there is
growing interest in designing polymers whose degradation is
controlled by the terminal or side-chain trigger-responsive
groups.16–24 Representative examples include the self-
immolative polymers developed by Shabat and coworkers
that can be degraded through removal of the terminal
trigger-responsive protecting group25,26 and the polymers
developed by the Almutairi24,27–30 and Gillies groups17,31,32
with trigger-responsive domains placed on the side groups
which control the polymer degradation. Inspired by these
works, we recently designed 2,6-bis(hydroxymethyl)aniline
(BHA), an analog of the key block of the self-immolative
polymers ((4-aminophenyl)methanol), and used it to develop
chain-shattering-polymers (CSPs)33 and chain-shattering
polymeric therapeutics.34 By removing the pendant urethane
EXPERIMENTAL
Materials
All chemicals were purchased from Sigma-Aldrich (St. Louis,
MO, USA) and used as received unless otherwise specified.
Anhydrous dichloromethane (DCM) and tetrahydrofuran
(THF) were dried by a column packed with alumina. Anhy-
drous dimethylformamide (DMF) was dried by passing the
solvent through a column packed with 4Å molecular sieves.
protecting groups, CSPs undergo
a spontaneous self-
elimination reaction which eventually breaks down the poly-
mer into smaller molecular weight species [Scheme 1(a)].
Instrumentation
NMR spectra were recorded on a Varian U500, a VXR500 or
on a UI500NB 500 MHz NMR spectrometer. High resolution
CSPs derived from BHA undergo a double 1,4-elimination
reactions [Scheme 1(a)] on each residue, leading to complete
backbone degradation; however, even one of the two
Additional Supporting Information may be found in the online version of this article.
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SCHEME 1 Illustration of the degradation of 2, 6-bis(hydroxymethyl) aniline (BHA) (a) and 1-(4-aminophenyl) ethane-1,2-diol based
polymers (b); (c) Synthesis of degradable poly(1/2) and chemical structure of control polyBoc.
electrospray ionization mass spectrometry (HR-ESI-MS)
experiments were conducted on a Waters Quattro II mass
spectrometer. Size-exclusion chromatography experiments
were performed on a system equipped with an isocratic
pump (Model 1100, Agilent Technology, Santa Clara, CA,
USA), a DAWN HELEOS multiangle laser light scattering
(MALLS) detector, and an Optilab rEX refractive index detector
(Wyatt Technology, Santa Barbara, CA). The detection wave-
length of HELEOS was set at 658 nm. Separations were per-
formed using serially connected size exclusion columns (50,
100, 500, and 103 Å Phenogel columns, 5 mm, 300 3 7.8 mm,
Phenomenex, Torrance, CA) at 60 ꢀC using DMF containing
0.1 M LiBr as the mobile phase. The MALLS detector is cali-
brated using pure toluene with no need for calibration using
polymer standards and can be used for the determination of
the absolute molecular weights (MWs). The molecular weight
of polymer was determined from the dn/dc value calculated
offline by means of the internal calibration system processed
by the ASTRA V software (Version 5.1.7.3, Wyatt Technology).
Scanning electron microscopy (SEM) images were collected
using a Hitachi S-4800 SEM at an operating voltage of 15 kV.
Particle size and dispersity were measured with a ZetaPlus
dynamic light scattering detector (15 mW laser, incident beam
at 676 nm, Brookhaven Instruments, Holtsville, NY). UV irradi-
ation was performed using a high pressure mercury vapor
short arc bulb from an Omnicure S1000 with the adjustable
collimating adaptor. The beam irradiating the sample was at a
power of 50 mW cm22. The probe sonication was performed
using a probe sonicator (700 W, 20 kHz, Fisher Scientific,
Pittsburg, PA, USA). HPLC was performed on a Shimadzu
HPLC system (LC-20AT) connected with PDA detector (SPD-
M20A) and fluorescence detector (RF-20A). Shimadzu C18
column (3 mm, 50 3 4.6 mm2 dimension) was used for analy-
sis. The mobile phase consisted of 0.1% TFA/Water and
acetonitrile with flow rate 1.5 mL/min. The UV wavelength
for detecting pyrene derivatives was set at 343 nm. UV–vis
absorption was recorded by Cary 5000 spectrophotometer
from Agilent Technologies.
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Polymer Synthesis
gation at 4000 r.p.m. and dried under vacuum. Poly (1/2)
was obtained as a light yellow solid (400 mg, yield 80%).
Mn 5 11,200 g mol21; Mw/Mn 5 1.24. 1H NMR (CDCl3, 500
MHz): d 8.09 (d, 1H, ArH), 7.67–7.21 (m, 7H, ArH), 5.95 (s,
1H, ArANHACOAOA), 5.58 (d, 2H, PhACH2AOACO), 4.28
(s, 2H, ACHACH2OACOA), 3.65 (s, 1H, PhACHACH2A),
2.35–2.23 (m, 4H, ACOACH2ACH2A), 1.59–1.19 (m, 10H,
AOCOACH2A (CH2)5ACH2A).
Synthesis of 2-Nitrobenzyl(4-vinylphenyl)carbamate
2-Nitrobenzyl alcohol (0.92 g, 6 mmol) in 5 mL anhydrous
THF was added to a stirred solution of phosgene (15 wt %
in toluene, 9 mL, 12.6 mmol) in 10 mL anhydrous THF
ꢀ
under nitrogen at 0 C. The reaction was stirred for 6 h and
then the solvent and excess phosgene was removed under
vacuum. The resulting oil was used directly without further
purification. 4-Vinylaniline (0.60 g, 5 mmol) was dissolved in
a 15 mL anhydrous THF and then added to 10 mL THF solu-
tion of above oil-like compound (1.29 g, 6 mmol). The result-
ing mixture was stirred at room temperature for 48 h. The
solvent was removed after filtration and the residue was
purified by silica gel column chromatography (hexane: ethyl
acetate 5 2:1, v/v) to afford the product as a white solid.
(1.0 g, yield 56%). 1H NMR (DMSO-d6, 500 MHz): d 9.97 (s,
1H, ArANHACOAOA), 8.13 (d, 1H, ArH), 7.87–7.71 (m, 2H,
ArH), 7.68–7.59 (m, 1H, ArH), 7.48–7.35 (m, 4H, ArH), 6.64
(d, 1H, APhACH@CH2), 5.70 (d, 1H, APhACH@CH2), 5.48 (s,
2H, PhACH2AOACO), 5.13 (d, 1H, APhACH@CH2).13C NMR
(DMSO-d6, 500 MHz): d 153.5, 148.0, 139.2, 136.8, 134.9,
132.9, 132.3, 129.9, 127.4, 125.6, 118.9, 113.2, 63.2. ESI-MS
(low resolution, positive mode): calculated for C16H15N2O4,
m/z, 299.1 [M 1 H]1; found 299.1 [M 1 H]1.
General Procedure for the Photolysis of Poly(1/2) or
PolyBoc and Analysis of the MWs by GPC
A DMF/H2O (95:5, v/v) solution (1 mL) of poly (1/2) or pol-
yBoc (10 mg/mL) in a quartz cuvette was placed under illu-
mination from the UV source (365 nm, 50 mW cm22) and
irradiated for 40 min or 2 h. The resulting solution was then
incubated under dark at 37 ꢀC for 96 h before it was dried
under vacuum. The residue was dissolved in DMF (1 mL)
and used for the MW analysis by GPC.
General Procedure for Analysis of Degradation Kinetics
1
of 3 by H NMR
The solution of 3 in DMSO-d6: D2O (5:1, v/v, 1.3 mM) in a
quartz cuvette was placed inside a photoreactor and irradi-
ated by UV light (365 nm, 50 mW cm22) for different time
(0, 40 min, 80 min) and then the resulted solution was incu-
ꢀ
bated at 37 C for different period of time. The solution was
Synthesis of 2-Nitrobenzyl(4-(1,2-
dihydroxyethyl)phenyl)carbamate (1)
1
used for the degradation analysis of 3 by H NMR.
2-Nitrobenzyl (4-vinylphenyl)carbamate (1.0 g, 3.3 mmol)
and K2OsO4 (62 mg, 0.165 mmol) were dissolved in ace-
tone/H2O (3:1, v/v, 100 mL), and then 4-methylmorpholine
N-oxide (NMO) (586 mg, 5 mmol) was added. The mixture
was stirred at room temperature overnight and saturated
aqueous solution of Na2S2O3 (10 mL) was then added to
quench the reaction. After 12 h, the resulting solution was
extracted by ethyl acetate (3 3 100 mL). The crude product
was obtained after removal of ethyl acetate. The product was
then purified by silica gel column chromatography using a
gradient elution (hexane: ethyl acetate 5 1:1 to 0:1, v/v) to
give compound 1 (0.87 g, yield 80%) as a white solid. 1H
NMR (DMSO-d6, 500 MHz): d 9.83 (s, 1H, ArANHACOAOA),
8.13 (d, 1H, ArH), 7.81 (d, 1H, ArH), 7.76–7.71 (m, 2H, ArH),
7.66–7.58 (m, 1H, ArH), 7.38 (d, 2H, ArH), 7.26–7.19 (m, 2H,
ArH), 5.47 (s, 2H, PhACH2AOACO), 5.12 (d, 1H, ACHAOH),
4.65 (t, 1H, ACH2ACHAOH), 4.49–4.42 (m, 1H, ACH2AOH),
3.40–3.34 (m, 2H, ACH2AOH).13C NMR (DMSO-d6, 500
MHz): d 153.6, 147.9, 138.4, 138.1, 134.8, 133.0, 129.9,
127.3, 125.5, 118.5, 74.1, 68.1, 63.0. ESI-MS (low resolution,
positive mode): calculated for C16H16N2O6Na 355.1, m/z,
[M 1 Na]1; found 355.1 [M 1 Na]1.
General Procedure for Analysis of Degradation Species
of 3 by HPLC
A CH3CN/H2O (9:1, v/v) solution of 3 (0.2 mg mL21) in a
quartz cuvette was placed under illumination from the UV
source (365 nm, 50 mW cm22) and irradiated for 1 h. The
resulting solution was incubated at 37 ꢀC under dark. At
different time point (0, 22, 44, 66, and 90 h), a small aliquot of
the solution (250 mL) was diluted with 500 mL CH3CN and
100 mL DMF before analysis by HPLC. F2 peak was confirmed
by ESI (high resolution mode; calculated for C48H40NO4
694.2964, m/z, [M 1 H]1; found 694.2957 [M 1 H]1.) and
F5 peak was confirmed by comparison with standard.
General Procedure for the Preparation of Nile Red
Encapsulated Polymer (1/2) Based Nanoparticles and
UV-Triggered Release of Nile Red from the Nanoparticles
Poly (1/2) (20 mg) and Nile Red (0.5 mg) were dissolved in
DCM (2 mL), and the solution was added to DI-water
(40 mL) containing 1% poly(vinylalcohol) (PVA). The mix-
ture was stirred at 1000 rpm for 10 min. The above mixture
was sonicated by probe sonication for 5 min (40 W, 1 s
pulse with 1 s delay) under ice bath. The suspension was
further stirred at 500 rpm using a magnetic stirrer to evapo-
rate DCM overnight. The nanoparticles were collected by
ultracentrifugation at 12 000 rpm for 20 min and washed
twice with water to remove PVA and dried by lyophilization.
An aqueous solution of Nile Red loaded nanoparticles of
poly (1/2) (50 mg mL21) in a quartz cuvette was irradiated
at 50 mW cm22 for a specific period of time. The resulting
solution was used for fluorescence analysis (kex 5 556 nm;
Synthesis of Poly (1/2)
To the solution of compound 1 (332 mg, 1 mmol) and aze-
laic acid dichloride (225 mg, 1 mmol) in DCM (3 mL), anhy-
drous pyridine (0.483 mL, 6 mmol) was added dropwise
over 10 min under nitrogen. The solution was stirred for
22 h at room temperature. The reaction mixture was concen-
trated to 0.5 mL under vacuum, and precipitated into cold
methanol (10 mL). The precipitate was collected by centrifu-
kem 5 634 nm). Known amount of dry Nile Red loaded
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FIGURE 1 (a) Proposed degradation mechanism for poly(1/2); (b) GPC curves of poly(1/2) treated under UV irradiation (365 nm, 50
mW cm22) for 0, 40, and 120 min in DMF/H2O (95: 5, v/v) and incubated for 96 h thereafter in the dark. [Color figure can be viewed
in the online issue, which is available at wileyonlinelibrary.com.]
nanoparticles was dissolved in DMSO and its UV-vis absorp-
tion was measured by spectrophotometer. Nile Red content
in nanoparticles was calculated based on its optical density
at 552 nm in DMSO (extinction coefficient 5 19,600 cm21
studies on self-immolative linkers based degradable poly-
mers.27,28 The solvent was then removed under vacuum fol-
lowed by dissolution of the residue in DMF. The changes in
polymer molecular weights (MWs) were then monitored
using GPC. As shown in Figure 1(b), the MWs of UV-
irradiated samples for 40 and 120 min were 9050 and 6
690 g mol21, corresponding to 19 and 40% reduction of
their original MWs, respectively. UV light induced degrada-
tion of poly(1/2) was also confirmed by 1H NMR spectrum
of poly(1/2) in DMSO-d6/D2O (10:1, v/v) (365 nm, 50 mW
cm22) after the UV treatment for 40 min and followed by
incubation at 37 ꢀC for 96 h (Supporting Information Fig.
S1). In a control experiment, we irradiated the polymer solu-
tion of polyBoc for 120 min with UV light and incubated the
resulting solution at 37 ꢀC for 96 h. As shown by the GPC
trace in Supporting Information Figure S2(a), no remarkable
change of molecular weight was observed. Moreover, after
incubation of the solution of poly(1/2) in the same condi-
tions in the dark for one week, the molecular weight of the
polymer remained unchanged [Supporting Information Fig.
S2(b)]. Taken together, these data indicate that polymer
backbone fragmentation is controlled exclusively by the
removal of the triggering groups through UV light and that
no side reactions such as hydrolysis occurred during the
long UV irradiation time or dark incubation time.
M21 35
)
by using following equation.
Nile Red Content in Nanoparticles ð%Þ
mass of Nile Red in nanoparticles
5
3100%
mass of nanoparticles
RESULTS AND DISCUSSION
We started with commercially available 2-nitrobenzyl alcohol
and treated it with phosgene to form 2-nitrobenzyl carbono-
chloridate which was then used to react with 4-vinyl aniline
to give 2-nitrobenzyl (4-vinylphenyl)carbamate [Scheme
1(c)]. The alkene of 2-nitrobenzyl (4-vinylphenyl)carbamate
was oxidized to form diol 1. Two-step yield for synthesizing
monomer 1 is about 45%. Protecting the aniline group
before generation of the hydroxyl groups avoided the protec-
tion/deprotection of hydroxyl groups, which occurred in the
preparation of precursors for self-immolative polymers and
BHA based CSPs.27,28,30,33,34 Compound 1 was then copoly-
merized with 2 in DCM in the presence of pyridine to afford
poly(1/2) with Mn of 11,200 g mol21 and PDI of 1.24 [Fig.
1(b)] by polycondensation.33 For a control study, we adopted
same method by using Boc protected monomer to prepare a
photostable polyBoc (Mn 5 8000 g mol21 and PDI 5 1.31).
(Supporting Information Scheme S1).
The degradation of poly(1/2) likely occurs by means of a
1,6-elimination at deprotected repeating unit [Fig. 1(a)].23,36
The degradation starts when the aniline moiety [A, Fig. 1(a)]
is unmasked by cleavage of the protecting group (P) to form
A1, which then undergoes spontaneous 1,6-elimination reac-
tion to cleave the ester at the benzylic position and form a
reactive azaquinone-methide intermediate (A2). Intermediate
A2 is then trapped by H2O to form A3. Ideally, when the
P group is removed from all the repeating units, the result-
ing P-depleted polymer (A1) becomes unstable and shatters
to A4.
We next evaluated the degradation of poly(1/2) in response
to UV irradiation by gel permeation chromatography (GPC).
Poly(1/2) in DMF/H2O (95: 5, v/v) was irradiated with UV
light (365 nm, 50 mW cm22) forꢀ0, 40, and 120 min, respec-
tively, and then incubated at 37 C for 96 h. Such long incu-
bation time used here is based on degradation kinetics
result of our model compound 3 (see below) and previous
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FIGURE 2 (a) Proposed degradation mechanism of 3 upon exposure to UV treatment; (b) LC-MS analysis of degradation fragments
of 3 after UV treatment (365 nm, 50 mW cm22, 2 h).
To confirm this degradation mechanism, we prepared 3 [Fig.
2(a)], a small-molecule analogue containing the triggering
structure of the poly(1/2) but with an easily detectable
was also detected because of trapping F2 by F1 before its 1,
6-elimination to form F4.
We then investigated the degradation kinetics of 3 by moni-
pyrene moiety via the reaction of TRD
1 and 1-
1
toring the released percentage of final fragments via H NMR
pyrenebutyric chloride [SI, Scheme S2]. Analysis of a solution
of 3 in DMSO-d6/D2O (5: 1, v/v) by LC-MS after UV irradia-
tion (365 nm, 50 mW cm22) for 2 h showed F4, F5, and F6
were the major degradation products, suggesting the desired
degradation occurred at the majority of repeating unit sites.
Interestingly both the nitrosobenzaldehyde (F1) was
observed, along with the detection of small amounts of the
unstable species F2. In our previous work with the BHA,33
we did not observe the aniline intermediate after UV irradia-
tion. The discrepancy suggests that 1,6-elimination reaction
mentioned herein to form F4 is not as fast as the 1, 4-
elimination reaction in CSPs prepared with BHA [Scheme
1(a)]. As such, it is not surprising that a small peak of F3
spectrum in DMSO-d6/D2O (5:1, v/v). A solution of 3 was
irradiated with UV light for 40 and 80 min, respectively, and
then incubated at 37 ꢀC at dark. 1H NMR analysis of the
resulting solution was recorded at appropriate time inter-
vals. Figure 3(b) reveals the spectrum of 3 after UV irradia-
tion for 80 min following incubation under dark for 80 h. To
identify the major peaks, we synthesized 2-hydroxy-2-
phenylethyl octanoate (4) for comparison (Supporting Infor-
mation Scheme S3 and Fig. S3) and its structure was con-
firmed by gHMBC and mass spectrometry. F5 is chosen as
the target molecule since it is the final degradation fragment
and its peak assignments can be exclusively identified by
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FIGURE 4 Degradation kinetics of 3, as measured by 1H NMR
spectroscopy in DMSO-d6: D2O (5: 1, v/v) after the UV irradia-
tion (365 nm, 50 mW cm22) for different time followed by incu-
bation at 37 ꢀC in the dark.
amount of F5 released was also found to 45% in the final
solution. The half-life of 1,6-elimination reaction in our study
is thus close to 40 h.
It should be mentioned that typical reaction-rate of 1, 6-
elimination using 4-aminobenzyl alcohol as a spacer is fast
and typically the substrate is able to be fully released within
1 - 2 h after de-masking the protecting group in aqueous
solution.37,38 The unexpected slow degradation kinetics of 3
likely arises from the effect of –CH2OCO- substitution at the
benzylic methylene position. It has been reported that elec-
tron donating substituents, such as a methyl group, increase
the elimination rate and it is expected that electron with-
drawing effects of the ester group in our work have the
opposite effect, leading to prolonged lifetime of the depro-
tected aniline moiety (F2).39,40 To confirm our hypothesis,
time course monitoring presence of the key intermediate
(F2) and final product (F5) was conducted by HPLC as
shown in Figure 5 and Supporting Information Figure S6. As
expected, F2 showed corresponding opposite change trend
as F5 indicating the substantial elongated lifetime of the
FIGURE 3 1H NMR spectra in DMSO-d6: D2O (5: 1, v/v) of (a) 3
before UV irradiation; (b) 3 after UV irradiation (365 nm, 50
mW cm22) for 80 min with incubation under dark at 37 ꢀC for
80 h; (c) authentic F5. Asterisks represent peaks due to sol-
vents. [Color figure can be viewed in the online issue, which is
available at wileyonlinelibrary.com.]
1
taking the H NMR spectrum of standard F5 [Fig 3(c)]. After
UV light irradiation (365 nm, 50 mW cm22) for 80 min, the
integration of peak l (5.41 ppm) decreased to 25%, which
means 75% of the nitrobenzyl group was removed after UV
light irradiation [Supporting Information Fig. S4]. At the
same time, a new peak e0 (3.31 ppm) assigned to F5
appeared whose integration increased with incubation time.
The percentage of released F5 was calculated by the integra-
tion of peak e0 versus the total integration of peak f0 and
peak f. (Supporting Information). As a comparison, without
any treatment, 3 showed no hydrolysis in one month as
demonstrated by unchanged 1H NMR spectra (Supporting
Information Fig. S5), revealing the release of F5 was due to
the cleavage of protecting group. Figure 4 shows the release
profile of F5 with incubation time after UV irradiation. After
about 90 h, target molecule F5 was released to reach its sat-
urated concentration. As we expected, 75% of F5 was
released from
3 when 75% of protecting group was
FIGURE 5 HPLC peak areas of F2 and F5 as a function of incu-
removed. In the case where UV irradiation was carried out
for 40 min, 45% of the nitrobenzyl group was cleaved and
after about 90 h postreaction incubation in the dark, the
bation time after 60 min UV irradiation (365 nm, 50 mW cm22
)
of 3 in CH3CN/H2O (9:1, v/v).
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trigger-induced removal of the aniline protecting groups
[Scheme 1(b)]. The degradation of these polymers contrasts
with that of self-immolative polymers, which depolymerize
sequentially from one chain end to the other. We used
poly(1/2) to prepare dye-containing NPs from which the
encapsulated molecules could be rapidly released upon
trigger-induced degradation. This study revealed the feasibil-
ity of making stimuli-responsive polymer by utilizing the
derivative of 1,4-aminobenzyl alcohol and its application as
delivery vehicles. Since the protecting group of 1,4-amino-
benzyl alcohol can be tuned easily and the degradation
kinetics of such derivatives might be controlled by choosing
different substituent groups on the benzylic methylene posi-
tion, this strategy may be a promising way to prepare
stimuli-responsive system owning both “on-demand” respon-
siveness and controlled degradation rate. Such program-
mable responsive system may have many potential
applications as microcapsule shell materials that release
healing reagents for self-repairing purpose12,41,42 and in
smart surface coatings that change wettability in response to
environment.43
FIGURE 6 (a) Size distribution of Nile Red loaded poly(1/2)
nanoparticles determined by DLS. (b) SEM image of Nile Red
loaded poly(1/2) nanoparticles. Scale bar: 1.0 mm. (c) Normal-
ized fluorescent intensity of Nile Red encapsulated poly(1/2)
nanoparticles upon UV irradiation (365 nm, 50 mW cm22).
(kEm 5 643 nm; kEx 5 556 nm). [Color figure can be viewed in
the online issue, which is available at wileyonlinelibrary.com.]
ACKNOWLEDGMENTS
This work was supported by the Dow Chemical Company via
the Dow-University of Illinois sponsored research program.
The authors thank Dr. Liang Hong and Dr. Keith Harris for
helpful discussions.
intermediates. This result may imply that different rates of
1, 6-elimination can be achieved by tuning the substituents
at the benzylic methylene position.
REFERENCES AND NOTES
We then explored the use of the trigger-responsive poly(1/
2) for controlled release applications. We first attempted to
control the release of the dye Nile Red from nanoparticles
(NPs) prepared from the poly(1/2). NPs encapsulating Nile
Red with 1.4% content were prepared from poly(1/2) by
means of conventional emulsion methods due to the negligi-
ble solubility of poly(1/2) in water. The average diameter of
the NPs was 351 nm 6 150, as determined by dynamic light
scattering (DLS) and confirmed by SEM [Fig. 6(a,b)]. The
release of the Nile Red payload from poly(1/2) NPs upon UV
treatment was detected by fluorescence spectroscopy. As
shown in Figure 6(c) and Supporting Information Figure S7,
the fluorescence intensity decreased by 74%, showing the
burst release of Nile Red from poly(1/2) based nanoparticles
after UV treatment for 30 seconds. In a control study, the
suspension of NPs without UV irradiation showed no dra-
matic change of fluorescence intensity over one week (Sup-
porting Information Fig. S8). The fluorescence intensity
dropped quickly, indicating the trigger-induced burst release
of Nile Red from the NPs into a more polar environment
(water) from hydrophobic NPs as reported in previous
literature.27,28
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