Core-bound polymeric micellar system based on photocrosslinking of thymine

Article abstract of DOI:10.1039/b700686a

Bioinspired core-bound polymer micellar aggregates were synthesized by photocrosslinking thymine-functionalized cores using short UV irradiation; H-bonding between thymines in the core is also believed to increase micellar aggregate stability. The Royal S

Full text of DOI:10.1039/b700686a

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Core-bound polymeric micellar system based on photocrosslinking of
thymine{
Kei Saito,a Laura R. Ingalls,a Jun Leeb and John C. Warner*a
Received (in Austin, TX, USA) 17th January 2007, Accepted 22nd February 2007
First published as an Advance Article on the web 21st March 2007
DOI: 10.1039/b700686a
Bioinspired core-bound polymer micellar aggregates were
synthesized by photocrosslinking thymine-functionalized cores
using short UV irradiation; H-bonding between thymines in the
core is also believed to increase micellar aggregate stability.
In our efforts to develop environmentally benign materials using
the principles of green chemistry,1 we have explored a number of
bioinspired mechanisms.2 Nature provides abundant and elegant
examples of the synthesis of materials in terms of both atom
economy and energy utilization. By identifying naturally occurring
mechanisms that can be extrapolated to synthetic systems, we hope
to develop novel materials based on the principle of green
chemistry. One such natural mechanism involves the H-bonding
and photodimerization of thymine within DNA.3,4 Thymine, one
Scheme 1
of the nucleic bases in DNA, features the ability to form relatively
applications such as polymer electrolyte fuel cell membranes and
other high proton conductive materials.7 The block copolymer
hydrogen bonding of thymine is well known to stabilize the double
strong hydrogen bonds as well as the ability to photocrosslink. The
helix structure of DNA.3 The photodimerization of thymine, a UV
synthesis was carried out by a TEMPO-mediated living radical
polymerization system in
a water–ethylene glycol mixture
induced 2p + 2p photocyclization, results in the covalent
dimerization of adjacent thymines and disrupts the helical structure
of DNA. This process has been linked with the development of
certain forms of skin cancer.4 Deriving inspiration from this
biological mechanism, we have sought to create novel materials.5
Self-assembling amphiphilic block copolymer nanoparticles
obtained in aqueous media through a micellization process are
of interest because of their potential for applications in
nanofabricated materials.6 Unfortunately, these amphiphilic block
copolymer micelles often disassociate into unimers when diluted or
subjected to elevated temperatures. It is critical that the
amphiphilic block copolymer micelles be stable if they are to be
of utility in any practical application. We report here the
preparation and properties of a core-bound micellar system
obtained from poly(vinylbenzylthymine)-b-poly(styrene sulfonic
acid sodium salt) by leveraging H-bonding and photocrosslinking
properties of thymines (Scheme 1).
(Scheme 2).8 It is worth noting that this living radical polymeriza-
tion can be carried out in an aqueous mixture, a principle of green
chemistry. The use of water also allows the polymerization of VPS
without the protection and the subsequent deprotection of sulfonic
acid, another principle of green chemistry. Both low molecular
weight (MW) poly(vinylbenzylthymine)-b-poly(styrene sulfonic
acid sodium salt), poly(VBT-b-VPS)-L (Mn = 2.2 6 104,
Mw/Mn = 1.58), and high MW poly(VBT-b-VPS)-H (Mn = 8.1
6 104, Mw/Mn = 1.59) were synthesized. 3-Methyl-1-(4-vinylben-
zyl)thymine (VMT) was obtained by methylation of VBT and the
amphiphilic block copolymer of VMT and VPS, poly(VMT-
b-VPS) (Mn = 3.5 6 104, Mw/Mn = 1.72), was synthesized to
examine the effect of hydrogen bonding on the stability of micelles.
Dialysis was used to form micellar aggregate and the micellar
aggregate size was measured using dynamic light scattering (DLS).
Low MW poly(VBT-b-VPS)-L (Mn = 2.2 6 104) formed a small
average diameter micelle aggregate (87 nm) and the high MW
poly(VBT-b-VPS)-H (Mn = 3.5 6 104) formed a large micelle
aggregate (164 nm), suggesting a relationship between the polymer
MW and size of micellar aggregates and thus the size of micellar
The hydrophobic block was composed of thymine-functiona-
lized monomer vinylbenzylthymine (VBT), synthesized from para-
vinylbenzyl chloride and thymine in aqueous ethanol, and the
hydrophilic block was composed of vinylphenylsulfonate (VPS).
We chose VPS as the hydrophilic block monomer because
sulfonic acid functionalized polymers have found use in various
aCenter for Green Chemistry, University of Massachusetts Lowell, One
University Avenue, Lowell, MA 01854, USA.
E-mail: John_Warner@uml.edu; Fax: 978-934-2074; Tel: 978-934-4543
bCenter for High-rate Nanomanufacturing, University of Massachusetts
Lowell, One University Avenue, Lowell, MA 01854, USA
{ Electronic supplementary information (ESI) available: Experimental
details. See DOI: 10.1039/b700686a
Scheme 2
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In addition to covalent photocrosslinking, H-bonding in the
core might be expected to confer additional stability on the
micellar aggregates. For example, in spite of its higher molecular
weight, micelle aggregates of poly(VMT-b-VPS) (Mn = 3.5 6 104)
are smaller in size (48 nm) than the corresponding low MW
poly(VBT-b-VPS)-L (Mn = 2.2 6 104), suggesting that factors
other than polymer MW are involved. We believe that H-bonding
between thymine units in the micellar core could be playing an
important role, e.g., the smaller aggregate size in poly(VMT-
b-VPS) could be due to the 3-methyl substituent that would disrupt
H-bonding between thymine units in the micellar core.
Examination of the micellar aggregate solution by IR was carried
out in an attempt to demonstrate the H-bonding of thymine units
but this was inconclusive because of the multiple broad peaks
around 3000–3500 cm21. However, secondary evidence consistent
with H-bonding is provided by critical micelle concentration
(CMC) measurements on these systems.
Fig. 1 The UV absorption spectra of poly(VBT-b-VPS)-H micellar
aggregates solution upon irradiation with 254 nm UV light at 0, 0.3, 5,
10 J cm22
.
The CMC of a given system is a measurement of the ease of
formation of micelles and therefore an indirect measurement of the
stability of the micelle. A lower CMC value indicates higher
stability. The CMC value of the block copolymer system was
determined by fluorescence measurements in aqueous solution
using pyrene as a probe.10 Pyrene has a strong fluorescence in a
nonpolar environment, but in a polar environment such as water,
fluorescence quenching is greatly enhanced. Thus the CMC can be
determined by measuring the micelle concentration point at which
the fluorescence emission intensity of pyrene becomes constant.
The CMC of the poly(VMT-b-VPS) system was compared to
poly(VBT-b-VPS)-H to examine the role of H-bonding in the
stability of the micelle (Table 1). Our hypothesis is that the
poly(VMT-b-VPS) system is incapable of forming self-assembled
H-bond dimers in the core because of methylation, and
consequently, has a much higher CMC (140 ppm) than the
poly(VBT-b-VPS)-H system (31 ppm). It must be pointed out that
the higher CMC value of the poly(VMT-b-VPS) system could also
be due to other factors, such as its low molecular weight compared
to the poly(VMT-b-VPS) system or steric inhibition to micellar
packing due to the 3-methyl substitution, etc., although the
inability to H-bond in the micellar core could still be dominant. It
is unclear at the present time how quantitative the cumulative
effects of H-bonding and the size of the H-bonded core would be
in increasing micellar stability, and whether they would be enough
to tip the scale against classical aggregation forces such as
hydrophobic interaction. In any case, when comparing the two
forces, i.e., H-bonding and photocrosslinking, the latter is more
straightforward.
aggregates can be somewhat controlled. Photocrosslinked micellar
aggregates were prepared by pouring a micelle solution into a
quartz tube and irradiating at short wave UV at 0.3, 5, and
10 J cm22. It has been shown previously that thymine has an
absorption at 270 nm which decreases as a result of 2p + 2p
photodimerization.9 After each irradiation, the UV spectrum of
the micellar aggregate solution was measured. As the irradiation
dose increases, the intensity of the absorption at 270 nm decreases
(Fig. 1), consistent with photocrosslinking of the thymine units in
the micellar aggregates core. The decrease in intensity of the peak
at 270 nm corresponds to y15% crosslinking of thymine units
which is the maximum degree of crosslinking obtained using
254 nm wavelength UV light. It is to be noted that this only y15%
crosslinking of the thymine units leaves the remainder of the
thymine units to dissociate freely (discussed in the CMC section
below). As expected, DLS measurements showed no significant
change in average aggregate size upon irradiation.
TEM images of poly(VBT-b-VPS)-H micellar aggregates were
obtained from aqueous solution containing uranyl acetate as a
negative stain on carbon-coated copper grids. TEM images before
and after photocrosslinking show approximately spherical shaped
micellar aggregates having diameters in the 100–140 nm range. The
AFM image of dried poly(VBT-b-VPS)-H core-photocrosslinked
micellar aggregates on freshly cleaved mica was obtained in the
tapping mode (Fig. 2). The image shows an elliptical object of
larger weight and lower height than is consistent with the flattening
of the labile and fluid micellar aggregates upon drying on a flat
mica surface during the sample preparation.
For example, the CMC values of the poly(VBT-b-VPS)-H
system that had been irradiated at the different irradiation doses
(0, 0.3, 5 J cm22) were measured to determine the effect of
Table 1 Critical micelle concentration (CMC) values of block
copolymer systems
Irradiation/
J cm22
Entry
Polymer code
CMC ppm/mg mL21
1
2
3
4
poly(VMT-b-VPS)
poly(VBT-b-VPS)-H
poly(VBT-b-VPS)-H
poly(VBT-b-VPS)-H
0
0
0.3
5
140
31
27
Fig. 2 TEM and AFM of poly(VBT-b-VPS)-H photocrosslinked
micellar aggregates (5 J cm22 UV irradiation).
9.8
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photocrosslinking on the stability of the micellar system (Table 1).
The CMC of the poly(VBT-b-VPS)-H system decreases with
increased irradiation dosage, e.g., with 5 J cm22 UV irradiation,
the CMC becomes 3 times smaller (9.8 ppm) compared to the non-
irradiated control (31 ppm). Micelles having size .100 nm have
been observed previously.10,11 Our CMC studies are meant merely
to highlight the effect of photocrosslinking and potential
H-bonding in influencing the aggregation behavior of this class
of polymers.
Notes and references
1 P. T. Anastas and J. C. Warner, Green Chemistry: Theory and Practice,
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2 J. C. Warner, Pure Appl. Chem., 2006, 78, 2035–2041.
3 J. D. Watson and F. H. C. Crick, Nature, 1953, 171, 737–738;
A. K. Boal, F. Ilhan, J. E. DeRouchey, T. Thurn-Albrecht, T. P. Russell
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H. Ozhalici, C. L. Elkins, C. Heisey, T. C. Ward and T. E. Long,
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4 A. A. Lamola and J. P. Mittal, Science, 1966, 154, 1560–1561; W. Harm,
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5 C. M. Cheng, M. J. Egbe, M. J. Grasshoff, D. J. Guarrera, R. P. Pai,
L. D. Taylor and J. C. Warner, J. Polym. Sci., Part A: Polym. Chem.,
1995, 33, 2515–2519; C. Kiarie, J. Bianchini, S. Trakhtenberg and
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6 I. W. Hamley, Encyclopedia of Polymer Science and Technology, ed.
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It is interesting to note that our y15% crosslinked system is
different from conventional core-crosslinked micellar systems
which are much more crosslinked and cannot, therefore, dissociate
to unimers (below their uncrosslinked CMC). Our lightly cross-
linked system can reversibly dissociate into micellar aggregates and
unimers (albeit, y15% crosslinked), opening up new opportunities
to possibly tune the aggregate size, shape, etc, by UV irradiation.
For example, the control of the CMC of the block copolymer
micellar system by photocrosslinking should prove of use in the
controlled release of materials encapsulated in the micelles.
Furthermore, micellar aggregates from VBT and VPS block
copolymers have the potential to encapsulate guest materials by
H-bonding with the attached thymine in the core. It is known that
photocrosslinking of thymine can be reversed either by exposure to
lower wavelength UV irradiation or enzymatically.12 Either of
these mechanisms should allow one to reversibly control the
photocrosslinking of these thymine functionalized micellar aggre-
gates. Investigation of the controlled release of encapsulated
materials and the reversible core-photocrosslinked micelle is in
progress.
7 K. Matsumoto, T. Hirabayashi, T. Harada and H. Matsuoka,
Macromolecules, 2005, 38, 9957–9962; K. Saito, T. Masuyama and
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12 J. Whitfield, A. Morelli and J. C. Warner, J. Macromol. Sci., Pure Appl.
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The authors thank the Pfizer Corporation for financial support.
We also thank Dr Timothy Kotyla and Dr Robert J. Nicolosi for
useful discussions and providing the DLS instrument, Dr Jayant
Kumar for providing the fluorometer and Dr Roger Boggs and Dr
Sanjeev K. Manohar for fruitful discussions.
This journal is ß The Royal Society of Chemistry 2007
Chem. Commun., 2007, 2503–2505 | 2505