Self-assembly of dendron-helical polypeptide copolymers: Organogels and lyotropic liquid crystals

Article abstract of DOI:10.1039/b516625j

New macromolecular self-assembling building blocks, dendron-helical polypeptide copolymers, have been synthesized; these materials possess a well-defined 3-D shape and self-assemble in solution to form nanoribbon and lyotropic liquid crystalline phases. T

Full text of DOI:10.1039/b516625j

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Self-assembly of dendron-helical polypeptide copolymers: organogels
and lyotropic liquid crystals{
Kyoung Taek Kim,a Chiyoung Park,b Chulhee Kim,b Mitchell A. Winnik*a and Ian Manners*ac
Received (in Cambridge, UK) 23rd November 2005, Accepted 1st February 2006
First published as an Advance Article on the web 1st March 2006
DOI: 10.1039/b516625j
the gelation of PBLG diblock copolymers was suggested to be
different from that of the gelation of the PBLG homopolypeptide
because the random coil-PBLG diblock copolymers could not
form a liquid crystalline phase in dilute solution, which is essential
for homo PBLG gelation.12 Our proposed mechanism for the self-
assembly of the random coil-PBLG block copolymers implies that
a wide variety of PBLG block copolymers with novel architectures
other than random coil-helix could generate well-defined
supramolecular structures in solution. It appeared logical that
two well-defined macromolecular architectures, dendritic and
helical polymers, could be combined to generate polymeric
building blocks with a well-defined 3-D shape, which dictates the
self-assembly process and resulting supramolecular structures.
Here we report the synthesis of dendron-helical polypeptide (DHP)
copolymers and their self-assembly in solution.13 The DHP
copolymers form organogels as well as lyotropic liquid crystalline
phases via the architecture-directed self-assembly.
New macromolecular self-assembling building blocks, den-
dron-helical polypeptide copolymers, have been synthesized;
these materials possess a well-defined 3-D shape and self-
assemble in solution to form nanoribbon and lyotropic liquid
crystalline phases.
The secondary structure of peptide chains plays a crucial role in
the formation of the well-defined tertiary structure of proteins.
Biological functions such as enzymatic activity arise from these
specific tertiary structures. Unlike proteins, most synthetic
polymers lack the ability to retain specific 3-D structures in
solution or in the bulk phase due to their random coil
conformations. Such irregular conformations hamper the poten-
tial of synthetic polymers as useful building blocks for the
creation of self-assembled structures with well-defined size and
3-D shape. Therefore, rod–coil block copolymers which contain a
well-defined rigid segment as a rod block in their architecture
have received considerable attention due to their unique self-
assembly behavior which differs from that of conventional coil–
coil block copolymers.1 Also, dendrimers and dendrons2 have
been adopted for the generation of novel polymeric architectures
such as linear-dendritic block copolymers3 because of their
monodisperse and well-defined globular structures. Stupp and
coworkers have reported dendron-rod coil (DRC) molecules and
their self-assembly in solution.4 The DRC molecules form
nanoribbon structures similar to the self-assembly of organoge-
lator molecules5 in solution, in which directional non-covalent
interactions such as hydrogen bonding provide a main driving
force. These studies demonstrated the development of structu-
rally well-defined self-assembling building blocks for which the
self-assembly process could be highly directed and controlled.6
Poly(c-benzyl-L-glutamate) (PBLG) forms a stable a-helix under
various conditions.7 This rigid a-helical conformation is respon-
sible for the interesting phase behavior found for PBLG such as
lyotropic liquid crystalline ordering.8 Rod–coil block copolymers
based on a rigid PBLG helix have been studied extensively for
several decades.9 Recently, we found that random coil-PBLG
block copolymers with flexible polyferrocenylsilane blocks10 form
thermoreversible gels in toluene.11 The underlying mechanism of
The dendrons 1 and 2 were prepared from the alkoxy benzyl
ether dendrons by treatment with tri(ethylene glycol) and ethylene
diamine via 1,19-carbonyldiimidazole (CDI)-activated coupling
reactions.14,15 The DHP copolymers were synthesized by the
ring-opening polymerization (ROP) of c-benzyl-L-glutamate
N-carboxylanhydride (c-Bn-Glu a-NCA) with the dendrons as
macroinitiators. The polymerizations were performed in a THF/
DMF mixture at room temperature for 72 h. The precipitation of
the reaction solutions into diethyl ether gave the DHP copolymers
1
in good yields. The DHP copolymers were characterized by H
NMR and gel permeation chromatography (GPC). The average
number of amino acid units in the PBLG block was calculated by
1H NMR integration (Table 1). The GPC results of the DHP
copolymers gave exaggerated molecular weight values compared
to the absolute molecular weights obtained from 1H NMR
integration. The rigid conformation of the PBLG helix is
presumably responsible for the increased molecular weights
Table 1 Characterization and self-assembly characteristics of the
dendron-helical polypeptide copolymers
a
Mn
a
c
c
PDIb DPn,PBLG Cgel (wt%) Tgel (uC) Wrd (nm)
3
4
5
a
8,220 1.18 30
13,480 1.18 43
21,300 1.21 78
Molecular weight and degree of polymerization calculated by 1H
2.9
1.8
0.3
41
49
52
5.5
7.1
aDepartment of Chemistry, University of Toronto, 80 St. George Street,
Toronto, Ontario, M5S 3H6, Canada.
E-mail: mwinnik@chem.utoronto.ca
11.7e
b
NMR integration. Molecular weight polydispersity index (Mw/Mn)
bDepartment of Polymer Science and Engineering, Inha University,
Incheon, 402-751, Korea
c
measured by THF/[Bu4N]Br (0.003 M) GPC. Critical gelation
d
concentrations in wt% and gel–solution transition temperature. The
cThe School of Chemistry, University of Bristol, Bristol, UK BS8 1TS.
E-mail: Ian.Manners@Bristol.ac.uk
e
width of the ribbon formed in toluene measured by SAXS. The
width of the PBLG helix calculated by 1H NMR integration.
(Lhelix (nm) 5 NPBLG ? 0.15 nm where NPBLG is the average number
of residues in the PBLG helix determined by 1H NMR).
{ Electronic supplementary information (ESI) available: Synthetic details
and characterization of dendrons and polymers and AFM images of
toluene gels of 3 and 4. See DOI: 10.1039/b516625j
1372 | Chem. Commun., 2006, 1372–1374
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estimated by GPC. We confirmed the absence of aggregation of
the DHP block copolymers in the eluent for the GPC experiments
by dynamic light scattering.10,15
Fig. 1 a) TEM images of dried toluene gels of 3 (3.5 wt%). The scale bar
represents 1 mm. The scale bar in the inset indicates 200 nm. b) TEM
images of dried toluene gel of 4 (3 wt%). The scale bar indicates 500 nm. c)
SAXS profiles for dried gels of 3 (d 5 5.5 nm) and 4 (d 5 7.1 nm). d)
Schematic representation of the nanoribbon formed from the self-assembly
of DHP copolymers. The arrow indicates the distance between two peptide
helices in the nanoribbon structures.
We observed thermoreversible gelation of the DHP copolymers
in toluene. The DHP copolymer 4 having a PBLG helix with 43
amino acid residues formed a transparent gel at 1.8 wt% in
toluene. The length of the PBLG helix has an important effect on
the gelation of the DHP copolymers because the p–p interaction
between the PBLG helices11 is the main proposed driving force of
the self-assembly and accounts for the stability of the assembled
structures. We infer that hydrogen bonding between the DHP
copolymers is not involved in the gelation because the gel retains
the integrity and thermoreversibility in the presence of methanol,
which disrupts hydrogen bonding.
accommodate the bulky dendrons in the planar nanoribbon
structures without changing the morphology. This stacking of the
DHP copolymers in a 1-D ribbon gives a ca. 2 nm height profile in
AFM experiments. Due to the compact but bulky geometry in
which all the peripheral groups are emanating from the core of the
dendron, the dendritic block could prevent the DHP copolymers
from aligning into a nematic phase during self-assembly in dilute
solution, which was found in the homo PBLG gelation.
The self-assembled structures formed by 3 and 4 in toluene were
studied by transmission electron microscopy (TEM), atomic force
microscopy (AFM), and small-angle X-ray scattering (SAXS)
(Fig. 1). In both the AFM and TEM images, organogels of 3 and 4
showed bundles of fibers in which the unit fibers had a width of ca.
10 nm. In AFM height profiles,15 these unit fibers had a height of
ca. 2 nm, which indicates that the morphology of the fibrous
structure is a flat ribbon formed by stacking of the DHP
copolymers containing a PBLG helix (ca. 1.5 nm diameter) in a
1-D monolayer. From SAXS measurements on the dried toluene
gels, we inferred that the width of the ribbon is 5.5 nm for 3 and
7.1 nm for 4. This observation fits the molecular dimension of the
DHP copolymers (the calculated lengths of the PBLG blocks are
4.5 nm for 3 and 6.4 nm for 4). The SAXS of the gels also showed
a peak corresponding to a spacing of 1.5 nm, indicating the
distance between PBLG chains (Fig. 1d).
For PBLG itself, a smectic liquid crystalline phase in solution is
rarely observed, due to the polydisperse nature of PBLG made by
conventional ROP of a-NCA. Tirrell and coworkers showed that
The experimental results strongly suggest that the nanoribbon
mechanism for the self-assembly of random coil-helical polypep-
tide block copolymers11 also applies to the DHP copolymers. We
imagine that the DHP copolymers self-assemble in an anti-parallel
fashion in order to minimize the steric hindrance between dendritic
blocks and unfavorable orientation of the dipole moment of the
PBLG helix16 in the nanoribbon structures. The long axis of the
PBLG helix is parallel to the plane of the ribbon. The anti-parallel
stacking of the copolymers also could be inferred from the
observation that the organogel from the DHP copolymer 5 with a
bulkier dendritic block than other DHP copolymers also showed
the same structural features in both TEM and AFM (Fig. 2). In an
anti-parallel stacking mode, the distance between two neighboring
dendritic blocks facing the same side is ca. 3 nm, which could
Fig. 2 a) TEM image of dried toluene gel of 5 (1 wt%). The scale bar
represents 100 nm. b) AFM height images of dried toluene gel of 5 on a
mica substrate. c) Sectional analysis of the AFM height image. Red arrows
show 1.9 nm height for the individual ribbon. Green arrows show the
width of the ribbon (15 nm) at the half height. Black arrows indicate the
overlap of two ribbons and show a height of 3.9 nm.
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gelation of the DHP copolymers implies the generality of the
nanoribbon mechanism for the self-assembly of block copolymers
of the helical polypeptides.11 The architectural feature of the DHP
copolymers also enables the smectic ordering of the copolymers in
solution although the polydisperse nature of the DHP copolymers
closely resembles homo PBLG. Also, the synthetic methodology
used in this work could be readily applied to prepare various block
copolymers with structural diversity in both the dendritic and
polypeptide blocks.
We thank David A. Rider for AFM experiments. This work
was supported by the Emerging Materials Network of Materials
and Manufacturing Ontario. C. K. and C. P. thank HOMRC for
support. I. M. thanks the Canadian Government for a Research
Chair.
Fig. 3 a) Optical birefringent texture of THF solution (40 wt%) of 4 and
proposed layered structures of liquid crystalline state of 4 (inset). b) SAXS
profile of dried solid of THF solution (40 wt%) of 4.
monodisperse PBLG prepared by a genetic engineering method
undergoes smectic ordering in concentrated solution.17 Gallot and
coworkers demonstrated that PBLG block copolymers form
lamellar structures in concentrated solution, in spite of the PBLG
polydispersity, via hexagonal packing of the PBLG helices.18
Lecommandoux et al. have reported thermotropic liquid crystal-
line states, including a smectic phase for dendron-rod molecules,
which are based on the mesogenic rod molecules of the trimer and
tetramer of biphenylester moieties.19
Notes and references
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We anticipated that the DHP copolymers could form lyotropic
liquid crystalline phases in concentrated solution because of the
unique structural characteristics of the dendron block, which is
flexible enough to stabilize the liquid crystalline phase of
copolymer molecules and, at the same time, should not prevent
the alignment of the helices into the liquid crystalline phase due to
its compact chemical structure. Also, the DHP copolymers are
different from conventional PBLG block copolymers because of
the presence of the dendritic block which possesses a well-defined
structure with no polydispersity in molecular weight.
7 H. Block, Poly(c-benzyl-L-glutamate) and other glutamic acid containing
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11 K. T. Kim, C. Park, G. W. M. Vandermeulen, D. A. Rider, C. Kim,
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N. A. J. M. Sommerdijk and R. J. M. Nolte, Adv. Mater., 2002, 14,
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When we examined concentrated solutions (. 40 wt%) of the
DHP copolymers 3 and 4 in THF and CHCl3, we found these
solutions showed a similar birefringent texture under the polarized
optical microscope (Fig. 3). SAXS experiments on the dried solid
from the concentrated THF solution of 4 showed two diffraction
peaks at 7.2 nm and 3.3 nm, which suggests that 4 exhibits smectic-
like order in concentrated solution.20 We propose a layered
structure of 4 (Fig. 3a inset) in the liquid crystalline phase that
results from an anti-parallel stacking of 4 into a 2-D layer in a
manner similar to the nanoribbon formation. This result strongly
suggests that smectic ordering of the DHP copolymers in solution
is feasible with a dendritic molecule as a non-random coil block
even though the PBLG block is polydisperse in chain length.
The DHP copolymers reported here are distinguished from
previously reported dendron-rod–coil (DRC)4,6 and dendron-rod
molecules19 because of the macromolecular nature of the PBLG
block compared to the mesogenic rigid rod molecules in DRC and
dendron-rod molecules. The size of the PBLG helix, which could
be up to ca. 15 nm (100 amino acid units) in length and 1.5 nm in
diameter, is distinguished from the mesogenic oligo-biphenylester
groups in the dendron-rod molecules. The polymeric nature of the
PBLG helix and its defined conformation enable the block
copolymer to self-assemble into well-defined supramolecular
structures although the block copolymers only apparently use a
weak non-directional interaction, p–p interaction, as a driving
force of the self-assembly. It should be noted that thermoreversible
20 We assume the lyotropic liquid crystalline phase of 4 is not well-ordered
due to the polydispersity of PBLG blocks and the flexible nature of the
peripheral alkyl chains of the dendron block.
1374 | Chem. Commun., 2006, 1372–1374
This journal is ß The Royal Society of Chemistry 2006