Homopolymer micelles in heterogeneous solvent mixtures

Article abstract of DOI:10.1021/ja056042a

Amphiphilic homopolymers containing a hydrophilic and a hydrophobic functionality in each monomer unit have been shown to form polar or apolar containers depending on the solvent environment. When presented with a mixture of solvents, these polymeric cont

Full text of DOI:10.1021/ja056042a

Published on Web 11/11/2005
Homopolymer Micelles in Heterogeneous Solvent Mixtures
Subhadeep Basu, Dharma Rao Vutukuri, and S. Thayumanavan*
Department of Chemistry, UniVersity of Massachusetts, Amherst, Massachusetts 01003
Received September 2, 2005; E-mail: thai@chem.umass.edu
Designing artificial scaffolds to bind guest molecules using
specific interactions is at the heart of supramolecular chemistry.1
Amphiphilic assemblies, such as micelles, use solvophobic interac-
tions as the primary driving force for binding.2 For example,
micelles are capable of sequestering lipophilic guest molecules in
water, which are otherwise insoluble.3 Similarly, inverse micelles
are capable of sequestering hydrophilic guest molecules in organic
solvents.4 We have recently reported a new class of amphiphilic
polymers that presents their functionalities in a solvent-dependent
fashion that are reminiscent of micelles in water and inverted
micelles in an apolar solvent.5 While one would expect these
polymers to behave like a micellar host or an inverse micellar host
in a polar or an apolar solvent respectively, what would be the
behavior of these assemblies in a heterogeneous mixture of both
solvents? This is especially interesting with these polymers because
these are known to form organized assemblies in both polar and
aopolar solvents. Would these assemblies disintegrate at the
interface and find a thermodynamically preferable solvent or would
these be stable in the solvents they are initially assembled in?
To address these questions, we synthesized polymers 1-5 shown
in Chart 1. These polymers differ from each other in the lipophilic
side chain, since we thought it is useful to study the effect of
hydrophilic-lipophilic balance on the container properties of the
amphiphilic assemblies formed from these homopolymers. All
polymers were synthesized from the corresponding styrene-based
monomer using the nitroxide-mediated polymerization method.6,7
On the basis of our prior report on the spatial disposition of the
amphiphilic functionalities in these assemblies,5 one would expect
these assemblies to bind to lipophilic guest molecules in water and
to hydrophilic guest molecules in an apolar solvent such as toluene.
However, it is useful to confirm that the polymers do exhibit these
properties before discussing their behavior in solvent mixtures.
Reichardt’s dye (RD, pyridinium-N-phenoxide betaine)8 is a
lipophilic dye molecule, the solvatochromic behavior of which spans
a wide wavelength range. This dye is insoluble in water as
evidenced by the lack of an absorption corresponding to the dye
molecule in Figure 1a. However, in the presence of the amphiphilic
polymers 1-5 (10-4 M at pH 10), the dye can be solubilized in
water as exemplified in Figure 1. This result indicates that the
micronevironment provided by the polymer assembly is hydropho-
bic in nature and is capable of sequestering lipophilic guest
molecules, such as RD (∼5.5 mol/per mol of 5). The absorption
maximum of RD in the presence of the polymer 5 is 502 nm. The
corresponding ET30 value of 56.9 indicates that the micellar
micronevironment is comparable to that of glycerol, which is typical
of surfactant-based assemblies.8 The λmax obtained for polymers
1-4 were similar. These micellar assemblies also exhibit the ability
to sequester other lipophilic guest molecules, such as orange-OT.
Similarly, to investigate the encapsulation properties of the
inverted micelle-type assembly from these polymers in apolar
solvents, we used rose bengal (RB) as the spectroscopic probe. RB
Figure 1. (a) Reichardt’s dye in water in the presence and absence of 5.
(b) Rose Bengal (RB) in toluene in the presence and absence of 5.
Figure 2. Extraction studies of dye molecules. (a) RD in aqueous solution
of 5. (b) The dye transferred into DCM (lower layer). (c) RB in toluene
solution of 5. (d) RB released into water (lower layer). (e) R6G in toluene
solution of 5. (f) R6G not released into water (lower layer). (g) and (i)
Mixture of RB and R6G in water and toluene solution of 5, respectively.
(h) R6G extracted into toluene solution of 5 (upper layer) from (g). (j) RB
released from the mixture of (i) into water (lower layer).
Chart 1. Structures of the Amphiphilic Homopolymers
is insoluble in toluene. However, in the presence of the amphiphilic
polymer, (10-4 M) a significant amount of RB is present in the
toluene solution, as is evident from the absorption spectra (Figure
1b).
As mentioned above, we have been interested in investigating
the behavior of these amphiphilic assemblies in a heterogeneous
mixture of solvents. To probe the micelle-type assembly, we added
dichloromethane to an aqueous solution containing the polymer 5
with RD sequestered in it. The resulting mixture was shaken for
about a minute and allowed to phase separate. It was noted that all
the sequestered RD had been released in to the dichloromethane
layer, as noted from Figure 2a and 2b. The change in color of the
solution from a to b in Figure 2 is due to the solvatochromic nature
of RD.8 Similarly, water was added to a toluene solution containing
the hydrophilic dye molecule, RB, sequestered in the inverse
micelle-type assembly of 5. Upon shaking the mixture, the dye
molecule was fully transferred from the toluene solution to the
aqueous layer as shown in c and d of Figure 2. The significant
change in the intensity of color between the solutions in c and d in
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C O M M U N I C A T I O N S
Considering this behavior of the polymers in an immiscible
mixture of solvents, the possibility of using these assemblies in
separations based on electrostatics-based host-guest interactions
exists. This is conceivable especially because we had observed that
the positively charged dye molecule, rhodamine-6G (R6G), does
not get released from the negatively charged inverse micelle (Figure
2 e and f). Accordingly, a toluene solution of polymer 5 was added
to an aqueous solution containing a mixture of R6G and RB. After
shaking the two solutions for a short time, both layers became
colored (g and h of Figure 2). Analyzing the toluene layer and
aqueous layer revealed that the polymer 5 was able to selectively
extract R6G out of the aqueous layer, while leaving behind RB in
water (Figure 3b). To a first approximation from the absorption
spectra, the separation seems to be quantitative. Similar separation
was also observed when both dye molecules were sequestered into
the inverse micelle in toluene and then washed with water (i and j
of Figure 2).
In summary, we have shown that: (i) the micelle and inverse
micelle-type assemblies exhibit nanocontainer properties. (ii) These
containers are stable in the solvent in which they are assembled in,
even in the presence of another immiscible, but favorable, solvent.
(iii) The mechanism of releasing the sequestered guest molecules
is due to the inherent partitioning of the guests between the micellar
interior and the bulk solvent. This property indicates that these
polymers have potential as controlled drug release vehicles. (iv)
The selective binding properties of these assemblies could be used
in separations. Further explorations of these polymers for applica-
tions in drug delivery and separations are underway in our
laboratories.
Figure 3. (a) Spectra of polymer 5 in aqueous and toluene layers of a
binary mixture after it is assembled in one of the solvents. Blue: assembled
in water; Red: assembled in toluene. (b) Normalized spectra of the selective
extraction studies of polymer 5 in toluene from a mixture of RB and R6G
in water.
Figure 2 could be due to the inherently different extinction
coefficients of RB in these two environments.
Three limiting mechanistic possibilities can be proposed for the
dye release from a micelle-type assembly: (i) the distribution
coefficient of the polymer dictates the partition in the aqueous phase
and the organic phase as micelle-type and inverted micelle-type
assemblies, respectively. The dye molecule gets released during
the process of this thermodynamically driven distribution of the
host. (ii) The polymer assembly disintegrates by disassembling at
the interface of the two solvents and therefore loses the container
property. (iii) The amphiphilic assemblies are stable in the solvent
they are assembled in. Thus, in water for example, the lipophilic
dye molecule is partitioned between the micellar interior and the
bulk water. The partition coefficient favors the micellar interior.
However, the small concentration of the dye in water is sufficient
to transfer the lipophilic dye from the micellar interior to water
and then to the apolar solvent.
To distinguish these possibilities, we carried out a simple set of
experiments. The micellar assembly of 5 was formed in water and
then mixed with toluene. The resultant heterogeneous mixture was
shaken for a while and then allowed to phase separate. The two
layers were analyzed for the presence of the polymer. The polymer
was completely retained in the water layer and no measurable
amount of polymer could be seen in the toluene layer (Figure 3a).
When a similar experiment was carried out with the inverted
micelle-type assembly in toluene, the polymer was fully retained
in the toluene layer, as shown in Figure 3a. Similar results were
obtained in the presence of the dye molecules as well. The observed
behavior is independent of the lipophilicity of the polymer 1-5.
In the mechanisms (i) and (ii), the polymer has the opportunity to
find a thermodynamic distribution between the two solvents, and
therefore the partition coefficient should be independent of the
starting point. Thus, the results above rule out the first two
mechanistic possibilities and are consistent with the third. These
assemblies exhibit very little change in size after being subjected
to the heterogeneous mixture (from DLS study).7
Acknowledgment. Partial support for this work from NIH-
NIGMS (GM-65255), Army Research Office, and the Office of
Naval Research are gratefully acknowledged.
Supporting Information Available: Synthetic, dye extraction
studies 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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