Invertible amphiphilic homopolymers

Article abstract of DOI:10.1021/ja047816a

Stimuli-responsive polymers and assemblies are viable candidates for the so-called "smart" materials. In this communication, we report a new class of amphiphilic homopolymers that forms micelle-like structures in polar solvents and inverted micelle-like structures in apolar solvents. We demonstrate that these superstructures are the result of the changes in the molecular-level conformations in the monomer. Copyright

Full text of DOI:10.1021/ja047816a

Published on Web 07/24/2004
Invertible Amphiphilic Homopolymers
Subhadeep Basu, Dharma Rao Vutukuri, Subarana Shyamroy, Britto S. Sandanaraj, and
S. Thayumanavan*
Department of Chemistry, UniVersity of Massachusetts, Amherst, Massachusetts 01003
Received April 15, 2004; E-mail: thai@chem.umass.edu
Self-organization of amphiphilic polymers has resulted in as-
semblies such as micelles, vesicles, fibers, helical superstructures,
and macroscopic tubes.1 These nanoscale to macroscale morphol-
ogies are of interest in areas ranging from material science to
biology.2 Stimuli-responsive versions of these assemblies are likely
to further enhance their scope as “smart” materials. Thermo- or
pH-sensitive polymer micelles3a,b and vesicles3c have been reported
in which the nature of the functionality at the corona changes in
response to the stimulus. To date, little attention has been paid to
realize an environment-dependent switch from a micelle-type
assembly with a hydrophilic corona to an inverted micelle-type
assembly with a lipophilic corona.4 Here, we report on a new class
of polymer superstructures that exhibit such properties. We
demonstrate that the change in the surface of the assembly is an
amplified consequence of change in molecular-level conformation
within each monomer unit. Polymers with such properties could
find use in applications such as carriers for trafficking drugs through
the lipid bilayers and as components of smart adhesives.
Figure 1. Structures of monomers and polymers.
Scheme 1. Schematic Representation of Micelle-Type and
Inverse Micelle-Type Assemblies
All these solutions were optically clear. We hypothesized that the
observed solubility characteristics could be the result of formation
of a micelle-like structure in water, in which the hydrophilic
carboxylate groups are exposed to the bulk solvent and the
hydrophobic benzyl substituents are tucked in the interior of an
assembly (Scheme 1). Similarly, an inverted micelle-like structure
would be expected in apolar solvents, in which the functional group
placements are reversed.
Block copolymers are often the choice for a wide variety of
supramolecular assemblies, in which the fundamental driving force
involves the mutual immiscibility of the blocks and/or the im-
miscibility of one of the blocks in the bulk solvent. For example,
poly(styrene-co-acrylic acid) block copolymers exhibit several
interesting amphiphilic assemblies.5 These self-assembled structures
are the result of the incompatibility between the hydrophobic
polystyrene block and the hydrophilic poly(acrylic acid) block. The
consequences of incorporating carboxylic acid and benzyl moieties,
the key hydrophilic and hydrophobic functionalities in poly(acrylic
acid) and polystyrene respectively, within the same monomer of a
homopolymer should be interesting from an intramolecular phase
separation perspective.6 Accordingly, we conceived a styrene-based
monomer shown by the structure 1a (Figure 1). The hydrophilic
carboxylic acid functionality, the hydrophobic benzyl moiety, and
the polymerizable olefinic bond are all placed at meta-positions
with respect to each other on a benzene ring. The design strategy
is that the relative placement of these three functionalities should
facilitate the phase segregation of the amphiphilic moieties within
the polymer assembly. Monomers 1a and 1b, which have the
carboxylic acid functionality in its masked form for synthetic
reasons, were derived from 3,5-dihydroxybenzoic acid in six steps.7
Free radical polymerization of the monomer 1a using AIBN (1 mol
%) as the initiator afforded polymer 2a, with Mn ) 57 000, PDI )
2.3, and an average DP ) 167, as determined by size exclusion
chromatography (SEC) against polystyrene standards.7 Hydrolysis
of polymer 2 afforded the carboxylic acid-based polymer 3a.
Addition of 1 to 2 equiv of bases such as NaOH or KOH per
carboxylic acid functionality renders the polymer soluble in water.
Interestingly, polymer 3a was found not to be soluble in apolar
solvents such as dichloromethane and toluene. However, addition
of 1 equiv of base along with 2 to 3 equiv of water rendered the
resultant carboxylate polymer 3c soluble in these apolar solvents.
To investigate the structure of the assemblies, we utilized the
darker contrast provided by heavy atoms in TEM images as the
probe. To identify the placement of the hydrophilic carboxylic acid
moiety, we treated the polymer 3a (M ) H) with CsOH to convert
the acid to the corresponding carboxylate species (3e). The resulting
Cs+ counterion is a high atomic weight species that should provide
the necessary contrast to identify the placement of the hydrophilic
functionality within the polymer assemblies. In this case, the
aqueous solution of the polymer (micelle-like assembly) would
place the heavier Cs+ counterion at the corona to afford a dark
ring. The experimental observations correspond to this structure
as shown by comparing parts A and B of Figure 2, which are
obtained from aqueous solutions containing KOH and CsOH,
respectively. Note the presence of a dark ring around the particles
in the corona in Figure 2B relative to the core; no such contrast
could be seen in Figure 2A. Similarly, the inverse micelle-type
structure should place the carboxylate moiety and thus the Cs+
counterions at the core. This placement should afford a dark spotted
core in the TEM image. As expected, the toluene solution of
polymer 3e (Figure 2D) exhibits the image containing a darker core
spot compared to that derived from KOH (3c) (Figure 2C).
Our structural hypothesis also suggests that the hydrophilic
carboxylic acid unit and the hydrophobic benzyl moiety will be
placed on the opposite sides of the polymer backbone in solvents
of different polarity. While the above experiments show the position
of the hydrophilic carboxylic acid moieties, it does not provide
information on whether the benzyl moieties are placed on the
opposite face. For this purpose, we synthesized polymer 3b (Mn )
41 410, PDI ) 2.5, average DP ) 114), which is similar to the
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C O M M U N I C A T I O N S
of the normal micelle-like structure in Figure 2E using a density
profiling software ImageJ indicated that the dark spot within Figure
2E is not uniformly distributed.8 In fact, there is a darker ring
followed by a lighter gray core in these assemblies. Thus, the
distribution of the bromophenyl functionality within a micelle-like
assembly is consistent with the spatial distribution of the carboxylate
groups indicated in Figure 2B. However, similar density profiling
of the spots in Figure 2D indicated a uniform distribution of
darkness at the core. This is not surprising, since the contrast
providing Cs+ ions are not covalently attached to the polymer
backbone and the solvated ion is likely to be distributed throughout
the water-filled core. We also noted that the integrity of both
micelle-like and inverted micelle-like assemblies was intact even
at 10-9 M concentration of the polymers.7
In summary, a new class of amphiphilic homopolymers contain-
ing both hydrophilic and lipophilic functionalities in each repeat
unit has been synthesized. These polymers are soluble in both
aqueous and organic solvents, where they assemble into micelle-
like or inverse micelle-like structures. Amphiphilic functions
reported here are likely to form the basis for new nanoscale
assemblies in solution and in solid state, which could have
implications in a broad range of applications.
Figure 2. TEM images of the micelle-like and inverted micelle-like
structures formed by polymers 3c, 3d, and 3e. (A) Image of normal micelle-
like particle from aqueous solution of the polymer 3c. (B) Image from an
aqueous polymer 3e. (C) Image of an inverted micelle-like particle formed
by a toluene solution of the polymer 3c. (D) Image from a toluene solution
of polymer 3e. (E) Image from an aqueous solution of the polymer 3d. (F)
Image from a toluene solution of the polymer 3d.
Acknowledgment. Partial support for this work from NIH-
NIGMS (R01-GM-65266) is gratefully acknowledged. This work
also received support from the NSF-funded MRSEC at the
University of Massachusetts, and we thank Louis Raboin for help
with the TEM experiments.
polymer 3a (Figure 1), but with an additional bromine functionality
in the 4-position of the hydrophobic benzyl substituent. Assemblies
obtained from both aqueous and toluene solutions of 3c and 3d
were then compared using TEM. The locale where the bromine
atoms are concentrated should exhibit a higher contrast in TEM
images. If the hydrophobic benzyl moieties are directed toward the
interior in an aqueous solution, the image for polymer 3d should
have a darker spotted core relative to 3c (Scheme 1). This was
indeed the observed result, as could be seen by comparing the
images in Figure 2A and E obtained from aqueous solutions of
polymers 3c and 3d, respectively. Note that the images obtained
from polymer 3c exhibit uniform darkness, whereas the images from
polymer 3d show a darker core compared to the corona. Similarly,
if the hydrophobic benzyl moieties are directed toward the exterior
in the inverse micelles, the heavier bromine functionalities in 3d
are now placed at the corona. The resulting image for the polymer
3d should exhibit a dark ring in the corona relative to 3c (Scheme
1). The images in Figure 2C and F obtained from toluene solutions
of polymers 3c and 3d, respectively, are consistent with the expected
features.
Supporting Information Available: Synthetic, TEM, and other
experimental details are outlined. This material is available free of
charge via the Internet at http://pubs.acs.org.
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The spatial distribution of the dark corona, which is indicative
of the spatial distribution of the heavy atom species, is about 5 nm
for an average particle size of 55 nm. However, the darker core
from Figure 2D and E seems to be distributed throughout the
interior. Note that the hydrophobic and the hydrophilic function-
alities are stitched together within the same monomer in polymers
3c, 3d, and 3e. Therefore, it would be expected that the spatial
distribution of the interior groups of the assembly closely follow
the distribution of functionalities in the corona. Close examination
(7) See Supporting Information for details.
(8) ImageJ is free software that can be downloaded from the National Institute
of Health web site (http://www.nih.gov).
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