Stable polymer micelles formed by metal coordination

Article abstract of DOI:10.1021/ma301323z

Metal-containing polymer micelles have attracted much attention due to their potential for medical and nanotechnological applications. In this paper, we present a method to prepare stable metal-containing polymer micelles. A diblock copolymer poly(4-vinylpyridine)-b-poly(ethylene oxide) (P4VP ₄₈-b-PEO₁₉₃) with terdendate ligand groups grafted to the PVP block is synthesized. Added metal ions cross-link the ligand-carrying blocks together, while the hydrophilic block stabilizes the formed coordination complex, leading to the formation of micelles. The structure and stability of the formed micelles are investigated by light scattering and cyro-TEM. The strong coordination bonds provide high stability of the micelles: adding salt or EDTA hardly affects the formed micelles.

Full text of DOI:10.1021/ma301323z

Article
pubs.acs.org/Macromolecules
Stable Polymer Micelles Formed by Metal Coordination
Junyou Wang,*,† Martien A. Cohen Stuart,† Antonius T. M. Marcelis,‡ Mathieu Colomb-Delsuc,§
Sijbren Otto,§ and Jasper van der Gucht†
†Laboratory of Physical Chemistry and Colloid Science, Wageningen University, Dreijenplein 6, 6703 HB Wageningen, The
Netherlands
‡Laboratory of Organic Chemistry, Wageningen University, Dreijenplein 8, 6703 HB Wageningen, The Netherlands
§Centre for Systems Chemistry, Stratingh Institute, University of Groningen, Nijenborgh 4, 9747 AG Groningen, The Netherlands
S
* Supporting Information
ABSTRACT: Metal-containing polymer micelles have at-
tracted much attention due to their potential for medical
and nanotechnological applications. In this paper, we present a
method to prepare stable metal-containing polymer micelles. A
diblock copolymer poly(4-vinylpyridine)-b-poly(ethylene
oxide) (P4VP48-b-PEO193) with terdendate ligand groups
grafted to the PVP block is synthesized. Added metal ions
cross-link the ligand-carrying blocks together, while the
hydrophilic block stabilizes the formed coordination complex,
leading to the formation of micelles. The structure and stability
of the formed micelles are investigated by light scattering and
cyro-TEM. The strong coordination bonds provide high stability of the micelles: adding salt or EDTA hardly affects the formed
micelles.
dissociate around 200 mM salt.17,18 In these examples,
micellization is driven by either hydrophobic or ionic
INTRODUCTION
■
Self-assembly based on coordination interaction is a very
interactions; the metal−ligand coordination is just an assistant
driving force. As an alternative strategy, the coordination
interaction can also act as the direct driving force for
micellization. To achieve this, a diblock copolymer consisting
of a neutral hydrophilic block and a block with ligand groups is
required. Added metal ions cross-link the ligand-carrying blocks
together, and the formed complex is stabilized by the
hydrophilic block, leading to the formation of micelles. Indeed,
diblock copolymers with carboxylic groups or pyridine groups
in one of the blocks were reported to form micelles with Ca2+
and Pt2+ metal ions.19−21 However, both carboxylic and
pyridine groups are monodendate ligands and only give weak
coordination bonds. Here, we develop a diblock copolymer
where one block carries terdendate ligand groups, which
provide strong coordination bonds for micellization. The metal
binding constants of the ligand groups used here are about a
factor of 105 larger than those of pyridine or carboxylic acid
groups.22−24 The formed micelles are therefore expected to be
much more stable than micelles based on either electrostatic
interaction or weak coordination.
promising strategy for the preparation of organic−inorganic
hybrid functional materials.1−3 Metal−ligand coordination
bonds have been used to build supramolecular polymers,
micelles, vesicles, dendrimers, and cross-linked hydrogels.4−6 In
particular, metal-containing polymer micelles have attracted
much attention because of their potential for medical or
nanotechnological applications. In recent years, ingenious
strategies have been developed to make such metal-containing
polymer micelles. In most cases, a hydrophobic polymer is
modified with a ligand group at one side of the chain. The
hydrophobic parts form the micellar core, while the hydrophilic
ligand groups and the coordinated metal ions are exposed to
the aqueous solution.7−9 These micelles are stabilized by the
net charge of the metal−ligand complexes, which makes them
rather sensitive to added salt. Schubert and co-workers have
used diblock copolymers in which a hydrophilic and a
hydrophobic polymer were connected by a metal coordination
complex to make micelles or vesicles.10−12 A similar strategy
was followed by other groups.13−15 More recently, Yan et al.
reported a novel type of self-assembled metal-containing
micelles,16 based on the electrostatic interaction between a
polycationic−neutral diblock copolymer and an anionic
reversible coordination polymer consisting of metal ions
coordinated by a ditopic ligand. Such metal-containing complex
coacervate micelles can accommodate a large number of metal
ions in the micellar core. However, the electrostatic driving
force limits their stability at high ionic strength: typically, they
Received: June 26, 2012
Revised: August 18, 2012
Published: August 28, 2012
© 2012 American Chemical Society
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KRC
Rθ
1
M
1
1
S(q)
EXPERIMENTAL SECTION
■
=
×
×
P(qR)
(2)
Materials. 4-Hydroxypyridine-2,6-dicarboxylic acid (chelidamic
acid) and 1,2-dibromoethane are obtained from Aldrich and used
without further purification. The diblock copolymer, poly(4-vinyl-
pyridine)-b-poly(ethylene oxide) (P4VP48-b-PEO193, Mw/Mn = 1.10,
Mn = 13.5K) is purchased from Polymer Source. All stock solutions are
prepared in MES (2-(N-morpholino)ethanesulfonic acid) buffer (20
mM, pH 6) with 0.1 M NaCl. The Zn-containing micelles are made by
direct mixing the aqueous solutions of modified polymer and
Zn(NO3)2·4H2O (analytical grade).
where Cparticle is the weight concentration of micelles, Mparticle is their
molar mass, and q is the scattering vector. P(q) and S(q) are the form
factor and the structure factor, respectively. K is the optical constant
defined as
2
4π2n2 dn
N λ0
⎛
⎞
⎟
⎜
K =
4
⎝
⎠
dc
(3)
Av
Synthesis of the Diblock Copolymer. Synthesis of the
chelidamic acid derivatives and modification of the diblock copolymer
P4MVP48-b-PEO193: (a) SOCl2, CH3CH2OH, 80 °C, reflux 20 h
(67%); (b) BrCH2CH2Br, CH3CN, 80 °C (76%).
where n is the refractive index of solvent, NAv is Avogadro’s number, λ0
is the wavelength of the incoming beam (532.0 nm), and dn/dc is the
refractive index increment of the Zn-L-P4VP48-b-PEO193 micelles. We
measured dn/dc of the micellar solutions using a differential refractive
index detector (Shodex RI-71).
In our experiments, the scattering vector q = (4πn/λ0) sin(θ/2) is
∼0.023 nm−1 (θ = 90°), so that qR is small for the micelles (which
have a radius on the order of 15 nm). We therefore assume that P(qR)
= 1. At low concentrations, the structure factor can be approximated as
1
S(q)
C
= 1 + 2B
2 M
(4)
Substitution into eq 2, we get
KRC
Rθ
1
M
C
=
+ 2B2
M2
(5)
By plotting KRC/Rθ versus C, we can obtain the molar mass of the
micelles from the intercept, from which we can obtain the aggregation
number of the micelles. The second virial coefficient B2 obtained from
the slope of the curve is used to calculate the effective excluded volume
1
4
3
(Veff) and radius (Reff): B2 = /2NAvVeff, Veff = /3πReff
.
The hydrodynamic radius of the micelles was measured with
dynamic light scattering. Intensity correlation functions were measured
using an ALV-7002 digital correlator and converted to the field
autocorrelation function g1(τ). For a system consisting of polydisperse
particles, this field correlation function can be written as an integral
sum of decay curves:
4-Hydroxypyridine-2,6-dicarboxylic acid (chelidamic acid, 1) is
esterified with ethanol to diethyl 4-hydroxypyridine-2,6-dicarboxylate
(2).25 Diethyl 4-(2-bromoethoxy)pyridine-2,6-dicarboxylate (3) is
then synthesized following a published procedure.26 The modification
of the diblock copolymer P4VP48-b-PEO193 is carried out as follows:
Diethyl 4-(2-bromoethoxy)pyridine-2,6-dicarboxylate (5.35 g, 15.5
mmol) and P4VP48-b-PEO193 polymer (1.0 g, 3.5 mmol pyridine
groups) were dissolved in 60 mL of methanol. The solution was
heated at 60 °C and refluxed for 3 days under a N2 atmosphere. The
methanol was evaporated afterward, and 5 g of K2CO3 and 90 mL of
H2O were then added to the residual powder, and the mixture was
stirred at 70 °C for 24 h. The resulting solution was transferred to a
dialysis tube and dialyzed against water for 1 week to remove all low
molecular mass molecules. After the dialysis, the solution was filtrated
(450 nm filter) and concentrated to a viscous phase, followed by
freeze-drying from water to provide a brown product 4 (1.0 g).
The structure of the modified polymer (L-P4VP48-b-PEO193) was
g (τ) = 0 G(Γ)e−Γτ dΓ
∫
1
(6)
∞
where G(Γ) is an intensity-weighted coefficient. First, we used the
cumulant expansion method27 to obtain the average decay rate ⟨Γ⟩,
from which we calculate the mean apparent hydrodynamic radius (Rh)
Rh = kTq2/6πη⟨Γ⟩
(7)
where k is the Boltzmann constant, T is the absolute temperature, and
η is the viscosity of the solvent. Second, regularized Laplace inversion
of eq 6 using the CONTIN method28,29 was used to find the intensity-
weighted distribution of decay rates, which we convert into an
intensity-weighted size distribution using eq 7.
Cryogenic Transmission Electronic Microscopy (Cryo-TEM). A few
microliters of sample were placed on a Quantifoil 3.5/1 holey carbon-
coated grid, and the excess of liquid was removed with filter paper,
followed by shooting the grid into liquid ethane cooled to −170 °C.
The sample vitrification procedure was carried out using Vitrobot
(FEI, Eindhoven, The Netherlands) equipped with humidity and
temperature chamber. Samples were studied in a Philips CM12 cryo-
electron microscope operating at 120 kV with a Gatan model 626
cryo-stage. Images were recorded under low-dose conditions with a
slow-scan CCD camera (Gatan, model 794). For each sample, images
were collected for a number of different regions in the sample.
1
confirmed by H and 13C NMR spectra and FT-IR. The degree of
quaternization of the pyridine groups on the side chain was about 34%
as determined from UV−vis titration (see Supporting Information).
Methods. Light Scattering. Light scattering at an angle of 90° was
performed with an ALV light scattering apparatus, equipped with a 400
mW argon ion laser operating at a wavelength of 532 nm. All the
measurements were performed at room temperature. The light
scattering intensity is expressed as the excess Rayleigh ratio Rθ divided
by the polymer concentration. Rθ is obtained as
ns2olvent
nt2oluene
Isample − Isolvent
Rθ =
× Rtoluene ×
Itoluene
(1)
where Isample is the scattering intensity of the micellar solution and
Isolvent is the intensity of the solvent. Itoluene is the scattering intensity of
toluene (the reference), and Rtoluene is the known Rayleigh ratio of
toluene (2.1 × 10−2 m−1).
The Rayleigh ratio can be linked to the concentration and mass of
the scattering objects:
RESULTS AND DISCUSSION
■
The terdendate ligand group chosen in this work is chelidamic
acid (also known as dipicolinic acid), a widely studied chelate
group for building coordination structures.30 NMR and FT-IR
spectra confirm that the ligand groups are attached on the PVP
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block successfully. The degree of quaternization of pyridine
groups is determined by a UV−vis titration with Fe3+ and was
found to be around 34% (see Supporting Information).
As shown in Scheme 1, the modified copolymer L-P4VP48-b-
PEO193 has both positive charge on the quaternized pyridinium
copolymer. The latter is soluble in water at low pH (<5) and
forms micelles above pH 5 (Supporting Information), based on
hydrophobic interaction between the PVP blocks.31 The light
scattering intensity in Figure 1a shows a maximum around pH
4, which is likely to be the isoelectric point of L-P4VP48-b-
PEO193. Below pH 4, also the second carboxylic group of the
ligand becomes protonated and the polymer acquires an overall
positive charge, leading to the redissolution of the polymer.
To study micelle formation with metal ions (Zn2+, added in
the form of a Zn(NO3)2 solution), we choose conditions (pH
6, 0.1 M NaCl) where the L-P4VP48-b-PEO193 polymer
dissolves completely, so that any aggregate formation can be
ascribed to the action of the metal ions. Indeed, the scattering
intensity of the L-P4VP48-b-PEO193 solution in the absence of
metal salt is very low, but it increases strongly when Zn2+ is
added to the solution. Figure 2a shows the light scattering
intensity and hydrodynamic radius of Zn-L-P4VP48-b-PEO193
micelles formed at different metal ion to ligand ratios M/L as a
function of time. While the size of the scattering objects
remains more or less constant in time, the intensity first
increases rapidly, followed by a more gradual increase over
several days. To explain this, we hypothesize that, upon adding
Zn2+ to the block copolymer solution, we do not only obtain
micellar aggregates but also smaller intramolecular complexes,
where one Zn2+ ion binds with two ligands from the same
polymer chain. The latter do not contribute much to the
scattering intensity compared to the micelles. Our observation
that the intensity keeps increasing slowly after the initial rapid
increase must then imply that some of the intramolecular
complexes convert into intermolecular complexes to form more
micelles. Apparently, there is an energy barrier associated with
this reorganization, which makes further aggregation a slow
process, leading to a slow increase of the intensity. This two-
step scenario must imply that intermolecular complexes are
more favorable than intramolecular complexes. Probably, the
polymer chain must bend or twist slightly in order to form an
intramolecular complex, leading to a strained or low-entropy
conformation. This strain is released when intermolecular
complexes are formed. To test this two-step hypothesis, we
measured the increase of light scattering intensity of Zn-L-
P4VP48-b-PEO193 micelles at different polymer concentrations
with M/L fixed at 0.5. Both the probabilities of inter- and
intramolecular complex formation and the rate of reorganiza-
tion should depend on the polymer concentration, so we expect
a faster micelle formation at higher polymer concentration. As
shown in Figure 2b, the intensity of micelles at higher polymer
concentration indeed shows a faster increase than that of
Scheme 1. Structure of L-P4VP48-b-PEO193 Polymers (top)
and Illustration of the Formation of Zn-L-P4VP48-b-PEO193
a
Micelles (bottom)
a
Small dots represent the Zn2+ ions.
group and negative charges on the carboxylic groups. Hence,
we first studied the self-assembly of this diblock copolymer as a
function of pH in the absence of metal ions. The L-P4VP48-b-
PEO193 becomes soluble in water above pH 6 (Figure 1a),
where most of the carboxylic groups dissociate and the net
charge of the polymer is negative. Decreasing the pH below 6
leads to the partial protonation of the carboxylic groups and a
decrease of the overall net charge of the polymer. We find that
the diblock copolymers start to aggregate below pH 6, initially
forming nanoparticles with a hydrodynamic radius around 90
nm. These particles are not stable and a precipitate is formed
after a few hours. However, the white precipitation can be
dissolved completely by adding salt (Figure 1b). This strongly
suggests that the aggregates are formed by electrostatic
interaction between the positive charges on the pyridinium
group and the negative charges of the carboxylic group. The
pH-dependent aggregation behavior of L-P4VP48-b-PEO193 is
completely different from that of unmodified P4VP48-b-PEO193
Figure 1. (a) Light scattering intensity (expressed by the excess Rayleigh ratio R90 divided by the total polymer concentration) and hydrodynamic
radius of aggregates from L-P4VP48-b-PEO193 polymers in the absence of metal salt at different pH (0.64 g/L polymer). (b) The effect of salt on the
intensity and size of aggregates from P4VP48-b-PEO193 formed at pH 4.
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Figure 2. (a, b) Variations of light scattering intensity and hydrodynamic radius of Zn-L-P4VP48-b-PEO193 micelles formed at different M/L ratios
(a) and different polymer concentrations (b). (c) Light scattering intensity and hydrodynamic radius as a function of the M/L ratio. (d) CONTIN
analysis of particle size and intensity-weighted size distribution of Zn-L-P4VP48-b-PEO193 micelles formed at different M/L ratios (measured after 5
days). For (a, c, d), polymer concentration is fixed at 1.2 g/L.
micelles at lower polymer concentration, while the micelle size
at all polymer concentrations hardly changes over time.
Figure 2c shows the light scattering intensity and hydro-
dynamic radius of Zn-L-P4VP48-b-PEO193 micelles as a function
of the ratio between metal ion and ligand group concentration,
M/L. All data points in this figure correspond to the light
scattering intensity after an equilibration time of 5 days after
mixing the components directly at the desired ratio.
Figure 3. Cryo-TEM images of Zn-L-P4VP48-b-PEO193 micelles at
different M/L: (a) 0.25, (b) 0.5, and (c) 1 (polymer concentration is
fixed at 2.53 g/L, MES buffer, pH 6, 0.1 M NaCl, measured after 5
days).
Surprisingly, the intensity varies nonmonotonically with M/L
ratio. Around M/L equal to 0.3, the intensity goes through a
maximum and then decreases until it reaches a constant value
around M/L 0.5, where every Zn2+ ion can coordinate two
ligand groups. Adding more metal ions (up to a ratio M/L of
1.2) does not lead to a decrease in intensity, indicating that an
excess of Zn2+ ions does not disrupt the formed micelles. The
hydrodynamic radius decreases monotonically from 21 nm at
M/L 0.1 to 15 nm at M/L 0.5 and then becomes constant for
M/L > 0.5. However, additional experiments indicate that the
micellar objects are not equilibrium structures, even after
several days. Adding additional Zn2+ to a 1 day old micelle
solution prepared at M/L 0.25 did not lead to a decrease in
size. Likewise, adding additional polymer to a solution prepared
initially at M/L 0.5 did not give the same size as for a solution
which is prepared directly at M/L 0.25. This means that the
coordination interaction is quite strong in this system, and the
formed micelles are nonequilibrium structures. The CONTIN
results (Figure 2d) confirm the micellar size and indicate that
there is one dominant kind of particle in solution at all M/L
ratios. We also characterized the micelles with cryo-TEM. As
shown in Figure 3, at M/L = 0.25, we see objects with radii of
5−10 nm. We presume that these structures are the micellar
cores, where the metal ions reside. The corona of the PEO
blocks provides insufficient contrast to be visible. Comparing
the size of the core to the hydrodynamic radius (20 nm at this
ratio), we find that the corona has a thickness around 10 nm, in
agreement with values found for other micelles.16,32 At M/L
ratios of 0.5 and 1 the micellar core is smaller, around 3−6 nm.
Hence, the decrease in light scattering intensity and hydro-
dynamic radius seems to be caused by a decrease in size of the
core.
What causes this decrease in core size upon increasing the
metal concentration? One possible explanation is the repulsion
between the unoccupied ligands. When a Zn2+ ion binds to two
ligand groups, the overall charge of the L-Zn-L complex is −2,
which just compensates the two positive charges of the pyridine
groups to which the ligands are attached (see Scheme 1). This
means that at a M/L ratio of 0.5, where all the ligand groups are
involved in a L-M-L complex, the overall charge of the polymer
approaches zero. The attraction between the negative L-M-L
complexes and the positive pyridine groups may then lead to a
compaction of the micellar core. At M/L ratios below 0.5, there
are still unoccupied ligand groups on the polymer chain. The
repulsion between them then probably prevents compaction of
the core, resulting in the larger sizes seen with cryo-TEM and
light scattering. We tried to measure zeta potentials of the Zn-
L-P4VP48-b-PEO193 micelles in the solution, but unfortunately
we could not obtain reliable data due to the electrostatic
screening of the background electrolyte (0.1 M NaCl). Note
that the electrostatic screening length does not vary
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Figure 4. (a) Light scattering intensity and hydrodynamic radius versus total concentration of polymer and Zn2+. Inset shows a zoom-in for low
concentrations. (b) KRC/R90 is plotted as a function of C (C = Ct − CMC, Ct is the total concentration of polymer and Zn2+). Zn-L-P4VP48-b-
PEO193 micelles are prepared at M/L 0.25, 0.5, and 1 in 20 mM MES buffer, pH 6, 0.1 M NaCl; the 0.5-S sample is prepared at M/L 0.5, in 20 mM
MES buffer, pH 6, 0.8 M NaCl.
significantly in our experiments because the salt concentration
changes by at most a few percent upon adding metal due to the
relatively high concentration of background electrolyte.
ligand and metal ions. One of the advantages of using
coordination bonds as the direct driving force for micellization
is that coordination bonds are not very sensitive to added salt.
To test whether this reduced sensitivity indeed leads to more
stable micelles, we investigated the effect of the salt
concentration on the Zn-L-P4VP48-b-PEO193 micelles (M/L
0.5). Figure 5a shows that the light scattering intensity and
hydrodynamic radius of Zn-L-P4VP48-b-PEO193 micelles do not
change up to salt concentration as high as 0.4 M NaCl and then
even go up as the salt concentration increases further to 1 M.
The increase in intensity at high salt concentration can be
explained by the screening effect of the salt ions that weakens
the electrostatic interaction between the positively charged
pyridine groups and the negatively charged metal complexes,
leading to swelling of the core (without disrupting it). This also
leads to an increase of the aggregation number of the micelles,
and an increase of the excluded volume, as shown by the light
scattering results (Table 1). Our results contrast strongly with
previous observations for metal-containing complex coacervate
core micelles based on electrostatic coassembly, where the
scattering intensity decreased strongly upon adding salt,17,18
and confirm that the micelles do not dissociate at high ionic
strength. The high stability of the micelles is due to the strong
coordination bonds between the chelidamic acid ligand groups
and Zn2+ ions. To test how strong these bonds are, we added
EDTA to the micellar solution as a competing ligand. We did
not notice any change in the light scattering intensity and
hydrodynamic radius of the micellar solution after adding
EDTA over a period of 8 days, indicating that the coordination
bonds that keep the micelles together are indeed very strong.
Probably, the cross-linked micellar structure and the favorable
electrostatic interaction with the pyridinium groups make the
coordination bonds even stronger than for free chelidamic acid.
An alternative explanation for the decrease in size upon
increasing the M/L ratio is a decrease in aggregation number of
the micelles going from from low to high M/L. We carry out
light scattering experiments at different concentrations to test
this. Figure 4a shows the changes of light scattering intensity
and hydrodynamic radius of Zn-L-P4VP48-b-PEO193 micelles
upon diluting with buffer solution. By extrapolating the
intensity to the baseline, we found that the critical micelle
concentration (CMC) is about 0.02 g/L. The aggregation
number of micelles formed at different M/L ratios is obtained
by plotting KRC/R90 as a function of the concentration C
(Figure 4b) and using eq 5. The results are summarized in
Table 1. Indeed, the aggregation number of the micelles is
Table 1. Critical Micelle Concentration (CMC), Aggregation
Number (Nagg), Second Virial Coefficient B2, and Effective
Excluded Volume Veff and Corresponding Radius Reff of the
Micelles as a Function of the M/L Ratio and the Salt
a
Concentration
CMC
(g/L)
dn/dc
B2
Reff
(nm)
M/L
(m3/kg)
Nagg (m3/mol)
Veff (m3)
0.25
0.5
0.019
0.020
0.010
0.010
1.34 × 10−4
1.25 × 10−4
1.25 × 10−4
1.25 × 10−4
71
60
62
91
198
111
171
202
6.58 × 10−22
3.68 × 10−22
5.68 × 10−22
6.70 × 10−22
54
44
51
54
1
0.5-S
a
Values were obtained by analyzing the light scattering data shown in
Figure 4.
larger at M/L < 0.5 than at M/L ≥ 0.5, while the CMC does
not depend strongly on the M/L ratio. The second virial
coefficient B2 has a minimum at M/L 0.5, where the micelles
are most compact.
At first sight, it seems surprising that the aggregation number
is larger at low M/L ratios, where the electrostatic repulsion
between the unoccupied ligand groups is stronger. However, it
must be kept in mind that the micelles are not equilibrium
structures, so that the aggregation number is determined largely
by kinetic effects. Probably, at M/L < 0.5 the metal ions have
more opportunities to cross-link a larger number of polymer
chains, leading to larger aggregation numbers at smaller M/L
ratios.
CONCLUSION
■
We report a stable metal-containing polymer micelle system. A
diblock copolymer P4VP48-b-PEO193 is modified with a
terdendate ligand grafted to the PVP block. Upon mixing
with metal ions, micelles are formed, directly driven by the
metal−ligand coordination interaction. The formed Zn-L-
P4VP48-b-PEO193 micelles have a hydrodynamic radius of
about 15 nm, while the radius of the micellar core is around 5
nm. Adding salt and EDTA hardly affects the Zn-L-P4VP48-b-
PEO193 micelles, confirming the high stability of the structures.
Preliminary results show that micelles can also be made with
other metal ions than Zn2+ (Ni2+, Mn2+, Gd3+), demonstrating
As mentioned in the Introduction, Zn-L-P4VP48-b-PEO193
micelles are formed based on the strong coordination between
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ACKNOWLEDGMENTS
■
The authors thank Henk van As and Pieter de Waard
(Laboratory of Biophysics and Wageningen Nuclear Magnetic
Resonance Center, Wageningen University, Dreijenlaan 3, 6703
HA Wageningen, The Netherlands) for help with NMR
experiments and Remco Fokkink (Laboratory of Physical
Chemistry and Colloid Science, Wageningen University,
Dreijenplein 6, 6703 HB Wageningen, The Netherlands) for
the help of light scattering data analysis.
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ASSOCIATED CONTENT
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AUTHOR INFORMATION
Corresponding Author
*E-mail: junyou.wang@wur.nl.
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Notes
The authors declare no competing financial interest.
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