Temperature-sensitive dendritic micelles

Article abstract of DOI:10.1021/ja054542y

Syntheses up to three generations have been achieved of biaryl-based amphiphilic dendrons with a charge-neutral pentaethylene glycol as the hydrophilic part and a decyl chain as the hydrophobic part. Studies on the temperature-dependent characteristics re

Full text of DOI:10.1021/ja054542y

Published on Web 09/30/2005
Temperature-Sensitive Dendritic Micelles
Sivakumar V. Aathimanikandan, Elamprakash N. Savariar, and S. Thayumanavan*
Contribution from the Department of Chemistry, UniVersity of Massachusetts,
Amherst, Massachusetts 01003
Received July 8, 2005; E-mail: thai@chem.umass.edu
Abstract: Syntheses up to three generations have been achieved of biaryl-based amphiphilic dendrons
with a charge-neutral pentaethylene glycol as the hydrophilic part and a decyl chain as the hydrophobic
part. Studies on the temperature-dependent characteristics revealed that these dendrons exhibit a
generation-dependent lower critical solution temperature (LCST). This behavior is attributed to the
combination of the amphipathic nature of the hydrophilic pentaethylene glycol side chain and dendritic
effect. Interestingly, this biaryl-based scaffold also maintains the ability to form a micelle-like assembly in
polar solvents and an inverted micelle-like assembly in apolar solvents. Polarity of the dendritic interior
was investigated using dye-based microenvironment studies. The aggregation behavior of these micelles
was analyzed by fluorescence spectroscopy and dynamic light scattering. Critical micelle concentrations
(CMC) of these assemblies were investigated using fluorescence excitation spectra of the sequestered
guest molecule, pyrene.
Introduction
variety of physical properties in dendritic structures through
functional group modifications at the core, branches, and the
The globular shape, excellent control over polydispersity, and
the ability to display a high density of functionalities on its
surface are among the factors that have made dendrimers
attractive scaffolds for a variety of applications.1 Examples of
where dendrimers have been explored for applications include
drug delivery,2 gene therapy,3 magnetic resonance imaging,4
catalysis,5 and light-harvesting antennae.6 The diversity of these
applications arises from the fact that one was able to instill a
periphery of these highly branched macromolecules. Incorpora-
tion of stimuli-sensitive character into dendrimers7 could
significantly expand the scope of these molecules in applications
such as the ones mentioned above. A feature that is significantly
under-explored with dendrimers involves temperature-sensitive
behavior.8 Macromolecules with temperature-sensitive properties
have advantages in applications such as controlled drug release,9
molecular separations,10 and tissue culture substrates.11 We have
been interested in eliciting thermally responsive properties into
our amphiphilic dendrimers,12 since such a system combines
the complementary advantages of temperature sensitivity and
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10.1021/ja054542y CCC: $30.25 © 2005 American Chemical Society

Temperature-Sensitive Dendritic Micelles
A R T I C L E S
Chart 1. Structures of Dendrons 1-4
Scheme 1. Synthesis of Repeating Monomer Unit
micellar properties for applications such as controlled release
and catalysis.
We have recently introduced a new class of biaryl-based
facially amphiphilic dendrimers that exhibit a unique functional-
ity switch, depending on the solvent environment.12 In our
preliminary communication, we have reported on dendrimers
with carboxylate as hydrophilic functionalities that exhibited a
micelle-like assembly in water and an inverted micelle-like
assembly in apolar solvents such as toluene.12a Our interest in
utilizing a charge-neutral oligoethylene glycol as the hydrophilic
side chain in this work stems from the possibility of incorporat-
ing temperature sensitivity into these dendritic structures. We
have previously attempted triethylene glycol monomethyl ether
as the hydrophilic moiety and the butyl group as the hydrophobic
functionality in these dendrimers.12b Those dendrimers did not
exhibit the appropriate solubility characteristics to investigate
a solvent-sensitive or a temperature-sensitive behavior. In this
contribution, we describe the syntheses and study of the biaryl-
based dendrimers with pentaethylene glycol monomethyl ether
as the hydrophilic unit and a decyl group as the hydrophobic
functionality. The resultant dendrimers exhibit generation-
dependent temperature sensitivity in the form of the lower
critical solution temperature (LCST), while maintaining the
ability to form micelles or inverted micelles, depending on the
solvent environment. Syntheses and details of the physical
organic characterization of these assemblies are reported here.
of the monomer 5 was achieved in seven steps, with Suzuki
coupling as the key biaryl coupling reaction, from the aryl
boronic acid 612b and the bromo aryl ester 7 (Scheme 1).
Compounds 6 and 7 were reacted with Pd(PPh3)4 in DME in
the presence of potassium phosphate to afford the corresponding
tert-butyldimethylsilyl protected biaryl compound. Since the
separation of the coupling product from the bromoaryl ester 7
proved to be difficult, the mixture was taken to the next step
without further purification. The tert-butyldimethylsilyl groups
were deprotected using TBAF to afford the corresponding
diphenolic compound in 47% yield. Note that the hydrophilic
part was not installed in 7 prior to the coupling reaction, because
installation of the long-chain oligoethylene glycol moiety
Results and Discussion
Synthesis. Structures of the targeted generation-zero to
generation-three (G0-G3) dendrons 1-4 are shown in Chart
1. The dendrons were assembled from a basic biaryl building
block unit, represented by structure 5 in Scheme 1. Synthesis
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A R T I C L E S
Aathimanikandan et al.
Scheme 2. Synthesis of Peripheral Monomer Unit
Scheme 3. Synthesis of Dendrons
hampered the Suzuki coupling, resulting in products with less
than 5% yield. Since the hydrophilic chain was to be installed
in the place of the MOM group, the two free phenolic
functionalities were reprotected with the allyl group to obtain
compound 8. Then, deprotection of the MOM group by using
a Dowex-acidic resin yielded the compound 9. The hydrophilic
moiety was now introduced onto compound 9 by using the
tosylate of pentaethylene glycol monomethyl ether13 under the
alkylation conditions to obtain compound 10. Deprotection of
the TBS group and protection with the allyl group had to be
carried out, since the TBS group proved to be unstable to the
alkylation conditions and the allyl group is unstable to the
Suzuki coupling conditions.14 Deprotection of the allyl groups
by using Pd(PPh3)4/NaBH4 followed by a reduction reaction
with LiAlH4 afforded the required building block monomer 5.
The periphery of the dendrons was synthesized from com-
pound 1112a by alkylating with tosylate of pentaethylene glycol
monomethyl ether in the presence of potassium carbonate and
18-crown-6 (Scheme 2). The resultant hydroxymethyl derivative
12 was converted to the corresponding bromomethyl derivative
13 using NBS and PPh3. Compound 13 with hydrophobic
n-decyl group and a hydrophilic pentaethylene glycol mono-
methyl ether group was used as the peripheral monomer.
The first-generation dendron G1 (2) was synthesized by
reacting 5 and 13 in the presence of potassium carbonate and
18-crown-6 with 89% isolated yield. Conversion of this hy-
droxymethyl compound to the corresponding bromomethyl
compound using a PPh3/NBS reagent system followed by an
alkylation reaction with the repeat unit 5 afforded the second-
generation dendron 3 in 84% yield. Another iteration of these
two steps using compounds 3 and 5 afforded the third-generation
dendron 4 in 85% yield (Scheme 3). All dendrons were
In the amphiphilic assemblies based on our biaryl dendrimers,
the hydrophilic functionalities are presented on the convex
exterior in water, while the hydrophobic functionalities are pre-
sented in the concave interior.12 In the assemblies formed from
dendrons 1-4, the hydrophilic functionalities presented on the
exterior involve the pentaethylene glycol units. We envisaged
the possibility that, upon increasing the temperature of the
solution, the solvation of the pentaethylene glycol units by water
would decrease, resulting in an LCST behavior. This was indeed
observed, as evident from the formation of a precipitate from
an aqueous solution upon heating, as shown in Figure 1 with
the G3-dendron 4. This process is thermally reversible.
Figure 1. Photographs show an aqueous solution of G3 (4), (a) before
heating, (b) after heating.
1
characterized by H NMR, 13C NMR, and MALDI-ToF mass
spectrometry. GPC was used as an additional check of purity.
Temperature Sensitivity of Dendrons. The primary purpose
of incorporating oligoethylene glycol units within these am-
phiphilic dendrimers is to bring about a temperature-sensitive
behavior to these macromolecules. It has been reported that
polymers containing oligo- or polyethylene glycol functionalities
exhibit LCST behavior, which has been attributed to a temper-
ature-sensitive hydrogen bonding ability of these moieties with
the solvent, water.15 It is suggested that the degree of hydration
of the ethylene oxide chains decreases with increasing temper-
ature. Such a reduced hydration of the oligoethylene glycol unit
increases its interfacial energy with water, which results in
precipitation of the molecule.
To identify the point at which the LCST transformation occurs
in these dendrimers, we carried out turbidity measurements at
various temperatures. This was achieved by monitoring the high
tension (HT) voltage in the CD spectrophotometer. In conven-
tional CD, the voltage at the photomultiplier tube increases with
absorbance and can be used for monitoring turbidity.16 HT
voltage of the solution was monitored at 600 nm while the
temperature was slowly varied (2 °C/min). The LCST of G2
and G3 dendrons (3 and 4) were found to be around 32 and 31
°C, respectively, whereas that of G1 (2) is around 42 °C (Figure
2a). Interestingly, the compound 1 (G0) did not exhibit any sharp
transition point that resembles an LCST behavior (Figure 2b).
These results suggest that the temperature-sensitive character
of the dendrons is dependent on the generation.
(13) Pentaethylene glycol derivative was synthesized according to the reported
procedure: Lauter, U.; Meyer, W. H.; Wegner, G. Macromolecules 1997,
30, 2092.
(14) Vutukuri, D. R.; Bharathi, P.; Yu, Z.; Rajasekaran, K.; Tran, M.-H.;
Thayumanavan, S. J. Org. Chem. 2003, 68, 1146.
This observation is intriguing because all these dendrons could
form multimolecular assemblies through aggregation. Our
expectation that these dendrons are likely to form amphiphilic
(15) Saeki, S.; Kuwahara, N.; Nakata, M.; Kaneko, M. Polymer 1976, 17, 685.
(b) Aoshima, S.; Oda, H.; Kobayashi, E. J. Polym. Sci., Part A: Polym.
Chem. 1992, 30, 2407.
(16) Arvinte, T.; Bui, T. T. T.; Dahab, A. A.; Demeule, B.; Drake, A. F.; Elhag,
D.; King, P. Anal. Biochem. 2004, 332, 46.
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Temperature-Sensitive Dendritic Micelles
A R T I C L E S
Figure 2. Dependence of changes in HT voltage with temperature for (a) G1, G2, and G3; (b) G0; and (c) the polymer 15.
Scheme 4. Synthesis of Styrene-Based Amphiphilic Polymer 15
assemblies through aggregation is based on the fact that the
analogous carboxylate dendrons do form aggregates in water.12a
To examine whether a similar aggregation behavior is observed
with the dendrons 1-4, we probed the aqueous solutions of
these molecules using dynamic light scattering (DLS). The
hydrodynamic radius (RH) for G1 was found to be about 75
nm, while those of G2 and G3 were around 125 nm. The size
of the aggregate formed from G0 is also around 125 nm. Since
all these assemblies are rather large and are formed from very
similar building blocks, it is reasonable to expect that the
generation of the dendron should have very little effect on the
LCST behavior. However, we notice a significant generation
dependence. Since the sizes of the assemblies are different, one
could attribute the difference in LCST as a simple manifestation
of the aggregate size. However, the reason seems to be more
complicated. The size of the assembly formed from compounds
1 and 4 (G0 and G3) are very similar, whereas the LCST be-
haviors of the assemblies from these molecules are very dif-
ferent. Presentation of the pentaethylene glycol units in a den-
dritic architecture at a critical generation seems to be important
for the observed temperature-sensitive behavior, the so-called
dendritic effect.
We were also interested in identifying further whether this
property is unique to dendritic architectures. For this purpose,
we synthesized a styrene-derivative containing a pentaethylene
glycol moiety as the hydrophilic functionality and a decyl group
as the hydrophobic functionality. Compound 12 from the
peripheral monomer synthesis was oxidized using PCC, and the
resultant aldehyde derivative under Wittig reaction conditions
afforded compound 14. Polymerization of the styrene-derivative
14 under a controlled radical polymerization condition, revers-
ible addition-fragmentation chain transfer (RAFT) polymeri-
zation, afforded the polymer 15 with an Mn of 11 kDa (molecular
weight of G3 is 8225 Da) and a PDI of 1.1 (Scheme 4).
Examination of the change in HT voltage of an aqueous solution
of this molecule at different temperatures showed that the
polymer 15 does not exhibit any LCST characteristics (Figure
2c). This result in combination with the generation-dependent
behavior above suggests that dendritic structures do provide
certain architectural advantages in the observed LCST behavior.
Thus, the obtained trend in LCST behavior is attributed to the
dendritic effect.
assemblies. To investigate this aspect, we used the encapsulation
of pyrene as the hydrophobic probe in aqueous solutions. The
combination of absorption, emission, and excitation spectra
provides valuable information about the micellar assemblies
obtained from these dendrons.
The absorption spectra of pyrene in water in the presence of
dendrons 2-4 are shown in Figure 3. In the absence of any
dendron, no pyrene could be detected in water as evident from
the fact that the absorption spectrum of this solution is prac-
tically indistinguishable from the solvent baseline. These results
are taken to indicate that the dendrons are capable of providing
an apolar microenvironment that sequesters the hydrophobic
pyrene molecule within its interior. As noted above, DLS studies
Micelle and Aggregation Behavior of Dendrons. As
mentioned above, we were also interested in studying whether
these biaryl dendrons still preserve the ability to form micellar
Figure 3. Absorption spectra of pyrene in aqueous solutions of dendrons
(10-5 M).
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A R T I C L E S
Aathimanikandan et al.
Figure 4. Emission spectra of pyrene in water at different concentrations
of G3 (4).
Figure 5. Plot of I1/I3 in the emission spectra vs concentrations of dendrons.
show that the assembly in water involves the formation of a
75-125-nm particle. The generation dependence of the seques-
tering ability is clearly evident from the absorption spectra. On
the basis of the absorption spectra, one could also quantitatively
estimate the number of pyrene molecules sequestered per
dendron. The G-1 dendron 2 is able to take up 1.6 molecules
per dendron, while the G-2 and G-3 dendrons 3 and 4 were
able to bind to 3.3 and 7 pyrene molecules per dendron,
respectively.
Since the fluorescence spectrum of pyrene is sensitive to
changes in its microenvironment, this technique is useful in
probing the polarity of the dendritic interior that binds the
hydrophobic guest molecule. The relative intensity of the first
and the third emission peaks (I1/I3) in the emission spectrum of
pyrene is known to be sensitive to the polarity of its microen-
vironment.17 The fluorescence behavior is exemplified using the
spectra of pyrene at different concentrations of the G-3 dendron
4 in Figure 4. The I1/I3 value obtained for all the compounds
1-4 is about 1.2, which is similar to that observed in PS-PEO
block copolymer micelles where PS forms the core of the
micelle.18 Interestingly, the I1/I3 ratio was found to vary with
the concentration of the dendrons in water.19 The trend observed
in Figure 5, upon plotting this ratio against the log [dendron],
allows us to note the presence of a critical micelle concentration
(CMC) for these dendrons. It is not surprising that a finite CMC
would be observed for these molecules, unlike those reported
with the classical amphiphilic dendrimers,20 since the current
dendrons are known to afford large aggregates (see the DLS
studies above).
Figure 6. Excitation spectra of pyrene in water at different concentrations
of G3 (4).
333 to 338 nm in the excitation spectra, in combination with
decrease in I1/I3 in emission spectra at a higher concentration
of dendrons, indicates the partitioning of pyrene from an aqueous
environment to a hydrophobic environment. At lower concentra-
tions, the I338/I333 takes the value of pyrene in water as shown
in Figure 7. The plot of I338/I333 as a function of log c is steady
at low concentration and becomes sigmoidal in the crossover
region. The CMC value can be taken from the intersection of
the tangent to the curve at the inflection point with the horizontal
tangent through the points at low dendron concentrations. The
A more common way of measuring CMC involves a plot of
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Vergelati, C.; Yu, D. Chem. Mater. 1999, 11, 1267.
I
338/I333 ratio as a function of log [dendron] from the excitation
spectra of the pyrene at different concentrations of dendrons,
as shown in Figure 6. The red-shift of the low-energy band from
(17) Kalyanasundaram, K.; Thomas, J. K. J. Am. Chem. Soc. 1977, 99, 2039.
(18) Wilhelm, M.; Zhao, C.-L.; Wang, Y.; Xu, R.; Winnik, M. A.; Mura, J.-L.;
Riess, G.; Croucher, M. D. Macromolecules 1991, 24, 1033.
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I. C.; Kim, Y.-H.; Jeong, S. Y. Macromolecules 1999, 32, 1847. (b)
Lysenko, E. A.; Bronich, T. K.; Slonkina, E. V.; Eisenberg, A.; Kabanov,
V. A.; Kabanov, A. V. Macromolecules 2002, 35, 6351. (c) Gitsov, I.;
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Temperature-Sensitive Dendritic Micelles
A R T I C L E S
Figure 8. Absorption spectra of R6G in G0 (1), G1 (2), G2 (3), and G3
(4).
We were also interested in identifying whether these dendrons
could exhibit reverse-micelle characteristics in an apolar solvent.
This could be interesting for certain applications. For example,
it is imaginable that dendrimers containing neutral functionalities
showing reverse micelle characteristics will have significant
implications on stabilizing a protein in nonaqueous solvent and
monitoring the enzyme kinetics in organic solvent. We chose
toluene as the apolar solvent for this purpose. Since, both the
decyl chain and the pentaethylene glycol unit are soluble in
toluene, it is difficult to imagine the formation of a reverse mi-
celle. However, when one introduces a small amount of water
that is a selective solvent for the pentaethylene glycol unit, this
functionality could phase-separate from the decyl moiety.
Accordingly, we added 20 equiv of water with respect to each
of pentaethylene glycol unit in toluene. The water-soluble dye
rhodamine 6G (R6G) was taken as a fluorescent probe to exam-
ine the formation of reverse-micelle dendrimer. The solutions
of dendrons with R6G were analyzed by absorption and fluor-
escence spectroscopy. When we used only 3 equiv of water or
no water, the extent of the dye sequestration was very small.
The dye was well taken up by these dendrons and could be
seen from the absorption spectra as shown in Figure 8. The
absorbances of all the dendrons were normalized to 0.2, and
fluorescence spectra were taken in comparison with absorbance-
matched aqueous solution of R6G. The absorbance matching
of both solutions states that we have an equal amount of R6G
in both solutions, but the fluorescence emissions from the
solutions containing the dendrons were significantly less than
that from the aqueous control solution, as indicated in Figure
9. The quenching was high in G3, followed by G2, G1, and
G0, which can be directly interpreted from the absorbance
spectra where G3 has taken up more number of dye molecules
followed by G2, G1, and G0. It is known that R6G exhibits
self-quenching with an increase in concentration, due to the
increased proximity between two R6G molecules.21 The ob-
served reduction of fluorescence emission in this case suggests
that the R6G is trapped in a confined space, which in turn
suggests the formation of reverse-micelle-like assembly.
To further characterize the morphology of these micelles, we
utilized TEM, and the particle size was also analyzed using
Figure 7. Plot of I338/I333 in the excitation spectra vs concentration of
dendrons.
Table 1. CMC Value of Dendrons 1-4
CMC (M)
CMC (mg/L)
G0 (1)
G1 (2)
G2(3)
G3(4)
7 × 10-6
4 × 10-6
8 × 10-7
3 × 10-7
8
8
3
3
obtained CMC values are shown in Table 1. When one looks
at the CMC value in terms of molarity, the G2 and G3 dendrons
(3 and 4) exhibit a CMC of an order of magnitude compared to
that of G0 and G1 dendrons. However, since the number of
amphiphilic repeat units in these dendrons are different, the more
appropriate value would involve mg/L of these molecules. The
CMC, in terms of wt % is about 3 mg/L for G2 and G3, whereas
it is about 8 mg/L for G1 and G0 (Table 1). Thus, the gain in
CMC upon increasing to higher generations is only about 2.7.
At first glance, it could be surprising that the generation of
the dendrons only has a minor effect on the CMC. However,
this observation could be based on the size of the micellar
assemblies. All these dendrons form fairly large micellar
structures (75-125 nm). For example, both G0 and G3 dendrons
(1 and 4) afford the same size micellar particle of about 125
nm. However, the number of G0 molecules that need to come
together to make the assembly would be much greater than that
of G3, since G0 as a molecule is much smaller than G3 as a
molecule. Therefore, it is likely that G0 would pay a greater
entropic penalty for the formation of the 125-nm assembly. On
the other hand, the flexible linkages between the repeat units
allow for several conformations within the 15-mer G3 dendron.
To form the micellar assembly from these possible conforma-
tions, the G3 dendron has to pay significant entropic penalty to
intramolecularly organize and present the oligoethylene glycols
on the solvent-exposed exterior surface, while tucking the
hydrophobic decyl groups in the interior. In the case of G0, the
intramolecular requirement does not exist but is compensated
by the need for organizing a greater number of molecules
intermolecularly. We speculate that these opposing effects of
generation dependence vs entropy are the reasons for the small
differences in CMC values for the dendrons.
(21) Jung, H. M.; Price, K. E.; McQuade, D. T. J. Am. Chem. Soc. 2003, 125,
5351.
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A R T I C L E S
Aathimanikandan et al.
It was observed that these assemblies were spherical reverse
micelles as shown in Figure 10e, f, g, and h for G0, G1, G2,
and G3, respectively. The particle size (RTEM) was around 60
nm for G3; for G2 and G1, it was around 40 nm, and G0 had
a size around 30 nm. We attempted to analyze the size of the
inverse-micelle-type assemblies in toluene solutions with the
use of DLS. We were able to obtain a size (RH) of 55 nm for
G3 dendron 4, whereas reliable data could not be obtained for
other dendrons with DLS. Also, as mentioned above, when the
pentaethylene glycol side chains are not fully hydrated due to
the deficient amount of water in the toluene solution, the ability
of these dendrimers to sequester R6G was significantly reduced.
To investigate the type of morphology that is formed under these
conditions, we obtained TEM pictures of the dendrons in toluene
with only 3 equiv of water per pentaethylene glycol unit. As
can be seen from Figure 10i, wormlike assemblies are obtained
when a deficient amount of water is used in toluene solution.
Figure 9. Relative emissions of R6G in the toluene solution of dendrons.
The control spectrum is from an aqueous solution of R6G, which is
absorbance matched with the toluene solutions of dendrons.
Summary
We have synthesized biaryl-based neutral amphiphilic den-
drons up to three generations with pentaethylene glycol as the
hydrophilic functionality and decyl chain as the hydrophobic
functionality. The synthesized dendrons are capable of forming
micelles and reverse micelles in polar and apolar solvents,
respectively. The CMC and the polarity of the microenvironment
of these dendrimer micelles were analyzed by using pyrene as
fluorescent probe. The dendritic architecture was found to be
responsible for the obtained LCST behavior of these dendrons
and changes significantly as we go from G1 to G2 and stays
almost constant at G3. The LCST and micellar behavior of these
molecules open up the possibility of utilizing these dendrons
for applications such as drug delivery,22 catalysis,23 cloud point
extraction,24 and microbial biotransformation.25
Experimental Section
1H NMR spectra were recorded on a 400 MHz NMR spectrometer
using the residual proton resonance of the solvent as the internal
standard. Chemical shifts are reported in parts per million (ppm). When
peak multiplicities are given, the following abbreviations are used: s,
singlet; d, doublet; t, triplet; q, quartet; quin, quintet; m, multiplet; b,
broad. 13C NMR spectra were proton decoupled and recorded on a 100
MHz NMR spectrometer using the carbon signal of the deuterated
solvent as the internal standard. EI mass spectra were obtained at the
Molecular Weight Characterization Facility at University of Mas-
sachusetts. Flash chromatography was performed with 37-75 µm silica
gel. Analytical thin-layer chromatography was performed on silica plates
with F-254 indicator and the visualization was accomplished by UV
(22) (a) Hoffman, A. S. J. Controlled Release 1987, 6, 297. (b) Chung, J. E.;
Yokoyama, M.; Yamato, M.; Aoyagi, T.; Sakurai, Y.; Okano, T. J.
Controlled Release 1999, 62, 115. (c) Chung, J. E.; Yokoyama, M.; Okano,
T. J. Controlled Release 2000, 65, 93. (d) Kim, I. S.; Jeong, Y. I.; Cho, C.
S.; Kim, S. H. Int. J. Pharm. 2000, 205, 165. (e) Liu, S. Q.; Tong, Y. W.;
Yang, Y.-Y. Biomaterials 2005, 26, 5064.
(23) (a) Mariagnanam, V. M.; Zhang, L.; Bergbreiter, D. E. AdV. Mater. 1995,
7, 69. (b) Komori, K.; Matsui, H.; Tatsuma, T. Bioelectrochemistry 2005,
65, 129.
(24) The hydrophobic substance can be removed from water through cloud point
extraction. As a proof-of-principle, the pyrene was encapsulated G3 aqueous
solution and measured the absorbance; it was 0.3 (10-6 M of G3). The
same solution was heated in a glass syringe to precipitate the dendrimer
and then filtered through the 0.22 µm filter and then the absorbance was
measured. The absorbance was decreased from 0.3 to 0.07. The complete
removal of pyrene could not be obtained, which is likely due to the inability
to maintain a warmer temperature during filtration. For examples of cloud
point extraction, see: (a) Lee, C.-K.; Su, W.-D. Sep. Sci. Technol. 1999,
34, 3267. (b) Li, J.-L.; Bai, R.; Chen, B.-H. Langmuir 2004, 20, 6068.
(25) Wang, Z.; Zhao, F.; Chen, D.; Li, D. Enzyme Microb. Technol. 2005, 36,
589.
Figure 10. Micelles formed in water from (a) G0 (1), (b) G1 (2), (c) G2
(3), (d) G3 (4). Reverse micelle formed in toluene solution with 20 equiv
of water per pentaethylene glycol unit (e) G0 (1), (f) G1 (2), (g) G2 (3),
(h) G3 (4). (i) Wormlike assemblies from toluene solution of G2 with 3
equiv of water per pentaethylene glycol unit.
TEM. These particles seem to be spherical micelles, and G0,
G2, and G3 were similar in size as shown in Figure 10a, c, and
d respectively, while the size of G1 (Figure 10b) was slightly
smaller, consistent with the DLS results above.
To investigate the morphology of the reverse micelles, we
analyzed the TEM of the dendrons from the toluene solutions.
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Temperature-Sensitive Dendritic Micelles
A R T I C L E S
lamp or using an iodine chamber. THF and toluene were distilled over
Na/Ph2CO. All other chemicals were obtained from commercial sources
and used as received, unless otherwise mentioned. Synthetic procedures
and the characterization data for all the compounds are given in
Supporting Information.
Sample Preparation for Micelle Study. The solution for the micelle
study was prepared initially by dissolving the dendrons in acetone (1
mL) and water (10 mL) was added dropwise (50 µL/min) to that
solution. Then acetone was evaporated on a rotary evaporator, and the
resultant solution was dialyzed against water using 1000-Da cut off
dialysis membrane. Excess of pyrene was added to the aqueous solution
of these dendrons, and stirred at room temperature for 5h. Then the
solution was filtered through a 0.22 µm filter. The absorption spectra
of these solutions were recorded using quartz cells.
Emission and Excitation Spectra. The pyrene stock solution (5 ×
10-7 M) was made in acetone. Required amount of this solution was
transferred into a vial, and the acetone was evaporated. Then necessary
amount of the dendrimer solution was added to make the pyrene
concentration 5 × 10-7 M. Emission spectra were obtained by exciting
the pyrene solution at 339 nm. For excitation spectra λem was fixed at
374 nm. The scanning speed was set at 50 nm/min.
Sample Preparation for Reverse Micelle. A solution of dendrons
(10-4 M) was prepared in toluene, twenty equivalents of water was
added to this solution to induce the phase segregation and sonicated
for 2 h at 40 °C. Then excess of rhodamine 6G was added and sonicated
for further 1 h and the solutions were filtered through a 0.2 µm filter.
Absorption spectra of these solutions were recorded on a UV-Vis
spectrophotometer using quartz cells.
was a solid-state laser system, operating at 514 nm. The temperature
was kept constant at 25 °C throughout the experiments. Dust was
eliminated by filtering the solution through a 0.22 µm filter. All
measurements were done at a correlation time of 2 min. The particle
size was analyzed using both nonnegative nonlinear least-squares
(NNLS) and constrained regularized continuous inversion (CONTIN)
algorithm program.
Turbidity Measurements. Turbidity measurements were carried out
for all dendrons (G0-G3) and the polymer using a CD spectropho-
tometer. The same dialyzed aqueous solutions prepared for micelle study
were taken in quartz cell and the HT voltage was monitored at different
temperature.
TEM Measurements. TEM measurements were performed using a
JEOL 100CX 100KV TEM. Samples were prepared by dipping copper
EM grids (precoated with the thin film of Formvar and then coated
with carbon) in aqueous or toluene solutions of the dendrons and dried
at room temperature and visualized under TEM.
Acknowledgment. Partial support for this work was obtained
from the NIGMS of the National Institutes of Health (R01
GM65255-01). We are also grateful to the NSF for the
equipment facilities through the MRSEC and for a Career award
to S.T.
Supporting Information Available: Synthesis and charac-
terization of compounds; fluorescence spectra of pyrene in G0
(1), G1 (2), and G2 (3). This material is available free of charge
via the Internet at http://pubs.acs.org.
Dynamic Light-Scattering (DLS) Experiments. DLS experiments
were performed in a digital correlator and goniometer. The light source
JA054542Y
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