Single chain self-assembly: Preparation of α,ω-donor-acceptor chains via living radical polymerization and orthogonal conjugation

Article abstract of DOI:10.1039/c0cc00702a

α,ω-Hydrogen donor/acceptor functional polymer strands are prepared via a combination of living radical polymerization and orthogonal conjugation and subsequently self-assembled as single chains to emulate - on a simple level - the self-folding behaviour of natural biomacromolecules.

Full text of DOI:10.1039/c0cc00702a

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Single chain self-assembly: preparation of a,x-donor–acceptor chains via
living radical polymerization and orthogonal conjugationw
Ozcan Altintas,a Peter Gerstel,a Nico Dingenoutsb and Christopher Barner-Kowollik*a
Received 31st March 2010, Accepted 2nd July 2010
DOI: 10.1039/c0cc00702a
a,x-Hydrogen donor/acceptor functional polymer strands are
prepared via a combination of living radical polymerization and
orthogonal conjugation and subsequently self-assembled as
single chains to emulate—on a simple level—the self-folding
behaviour of natural biomacromolecules.
(position of the hydrogen donors and acceptors along the
polymer backbone) as well as their secondary structure
(the spatial arrangement between recurring structural units).
In the present contribution we thus prepare—as the simplest
system—an ATRP initiator which can function as a hydrogen
donor and provides for the a-end of the macromolecules. The
halogen terminus of the polymer is transformed into an azide
moiety, which is subsequently ligated to an acetylene functional
hydrogen acceptor (a Hamilton wedge11) to provide the o-end.
The resulting a,o-donor/acceptor substituted polymer chain is
subsequently (under conditions of low chain concentrations)
subjected to a nuclear magnetic resonance (NMR) and dynamic
light scattering (DLS) study, investigating the self-assembly
behaviour of the chains in circular form.
Reversible activation/deactivation radical polymerization
processes such as atom transfer radical polymerization (ATRP)
allow for fine control over the molecular architecture, molecular
weight and polydispersity of synthetic polymers.1,2 Combined
with recent modular and orthogonal polymer ligation
protocols, a powerful toolset exists with which well-defined
polymer chains can be constructed.3–6 Concomitantly, complex
macromolecular designs can be achieved via the ligation of
polymeric entities by hydrogen donor/acceptor pairs. Indeed,
an elegant example of controlled folding of single polymer
chains into nano-particles via donor/acceptor groups on the
polymer backbone has recently been reported.7 In addition, the
self-assembly of block copolymers via such donor/acceptor
interactions has been described8 as well as donor/acceptor
functional poly(oxynorbornenes).9 Furthermore, ATRP techni-
ques have been employed to prepare end-functionalized
hydrogen-bonding polymers to establish their melt-phase blend
behaviour.10 Inspired by the synthetic possibilities of the
combination of controlled radical synthesis, orthogonal
modular conjugation and hydrogen bonding driven self-
assembly, we provide a single chain self-assembly system that
carries a,o-donor/acceptor chain termini, which are sub-
sequently employed to reversibly link a single chain at its ends.
The long term aim of our efforts is the generation of well-
defined macromolecules having non-identical hydrogen donor/
acceptor entities at well-defined points within their backbone,
allowing for a geometrically defined folding/unfolding action
into a defined geometry similar to a natural protein. Thus, the
key idea behind the current first step is to evaluate the
possibility of employing single polymer chains in self-assembly
procedures that are inspired by those of natural proteins.
Therefore, the synthetic a,o-donor/acceptor substituted
polymer chain seeks to mimic the primary protein structure
Scheme 1 depicts the applied synthetic procedure. The
detailed individual experimental procedures and characterization
data can be found in the ESI.w
Fig. 1A depicts the size exclusion chromatogram of the
bromide functional hydrogen donor chain 6, of its azide
variant 7 as well as of the a,o-functional hydrogen donor/
acceptor system 8. The size exclusion chromatography (SEC)
traces clearly indicate the low polydispersity of the polymer
and that the transition from 7 to 8 leads to a shift in the
molecular weight commensurate with the addition of 3. The
1
corresponding H-NMR spectra of the compounds 3, 4 and 5
can be found in the ESI.w
The successful transformation of 7 and 3 to 8 is further
supported by inspection of the ATR-IR spectra of the polymers.
Fig. 1B depicts the ATR-IR spectra of 6 and 7, where the
absorption associated with the azide-terminal polymer 7 at
2095 cmÀ1 is clearly visible. After the conjugation reaction, the
azide band has disappeared (compound 8). Table 1 summarises
the molecular weights of the polymers depicted in Scheme 1 as
1
determined via both SEC as well as H NMR spectroscopy.
Before undertaking a self-assembly reaction between the
a,o-donor/acceptor chain ends of 8, it seemed mandatory to
establish what a full associated system (in its non-circular
form) would behave like in the NMR analysis. The interaction
1
of 6 with compound 3 was investigated by H NMR spectro-
scopic titration carried out in CDCl3. For the 1H NMR
studies, the concentration of 6 was kept constant at 4 mM
and the change in the chemical shift was followed as a function
of increasing concentrations of 3. The NMR titration experi-
ments revealed a significant downfield shift of the signal
associated with the imide protons due to the complexation
of 3. As shown in Fig. 1C and 2, the peak at d = 7.98 ppm was
assigned to the N–H protons of the cyanuric acid recognition
unit at the a-end of the polymer 6. When polymer 6 (4 mM)
was mixed with 1 equiv. of compound 3 in CDCl3, the
chemical shift of the proton resonance of the imide protons
a Preparative Macromolecular Chemistry, Institut fur Technische
¨
Chemie und Polymerchemie, Karlsruhe Institute of Technology
(KIT), Engesserstr. 18, 76128 Karlsruhe, Germany.
E-mail: christopher.barner-kowollik@kit.edu
b Polymeric Materials, Institut fur Technische Chemie und
¨
Polymerchemie, Karlsruhe Institute of Technology (KIT),
Engesserstr. 18, 76128 Karlsruhe, Germany. Web: www.macroarc.de;
Fax: +49 721-6085740; Tel: +49 721-6085641
w Electronic supplementary information (ESI) available: The ESI
contains information regarding the employed materials, synthetic
procedures, instrumentation as well as detailed chracterization data
(NMR, FT-IR, ESI-MS, and DLS). See DOI: 10.1039/c0cc00702a
c
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Chem. Commun., 2010, 46, 6291–6293 6291

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Scheme 1 General strategy for preparing a,o hydrogen donor/acceptor
functional polymers and their subsequent single chain self-assembly.
Fig. 1 (a) Evolution of SEC chromatograms for 6, 7, and 8. (b) ATR-IR
spectra of 6, 7, and 8. (c) Expanded 1H NMR spectra of the 6Á3
self-assembly system in different concentration ratios in CDCl3 at
ambient temperature. The concentration of 6 was kept constant at 4 mM.
of polymer 6 changed from 7.98 to 10.83 ppm. When the
polymer 6 (4 mM) was mixed with 2, 3, 4, and 5 equiv. of the
compound 3 in CDCl3, the chemical shift for the proton
resonance of the imide protons of polymer 6 changed from
7.98 to 11.99, 12.79, 12.89, and 12.98 ppm, respectively,
indicating the increasing complexation. Moreover, the peaks
at d = 8.46 and 7.86 ppm were assigned to the N–H protons of
the Hamilton wedge in CDCl3 (see Fig. S2, ESIw). When
polymer 6 was mixed with compound 3, the N–H protons of
the Hamilton wedge appeared at 9.24 and 8.40 ppm due to the
self-assembly. With increasing concentration of the compound
3, the N–H protons of the Hamilton wedge shifted slightly
further up-field due to the formation of the strong assembly
between 6 and 3. These changes are characteristic for the
formation of a multiple-hydrogen bonding complex.12
Table 1 Number average molecular weights, Mn, of the precursor
and final polymers determined via SEC and NMR
SEC a
Mn
NMR b
Polymer
Mn
PDI
6c
7
5000
5000
6100
5500
5400
6000
1.04
1.04
1.03
8
a
All number average molecular weights are provided in g molÀ1
.
Mn,NMR = (I6.5–7.2/I7.98)(2/5)104.15 + 378.22. The quantitative
b
c
NMR analysis of 6 reveals that the polymer carries 96% Br end groups
relative to cyanuric acid termini.
d = 7.98 to a strong resonance at d = 11.49 ppm and a weaker
signal at d = 12.63 ppm, indicating the presence of species
with different stabilities. A significant downfield shift of
the imide protons of the cyanuric acid moieties is observed.
When a 2 mM solution of 8 is prepared, the resonances at
d = 11.49 ppm becomes weaker relative to the resonance at
d = 12.63 ppm. When the polymer 8 was prepared as a 1 mM
solution, the signal at d = 11.49 ppm shifted to d = 11.98 and
Evidence for the formation of the (single chain) hydrogen-
bonded self-assembly of 8 in CDCl3 came from 1H NMR and
dynamic light scattering (DLS) studies. For the 1H NMR
studies, a solution of the polymer 8 was prepared in CDCl3 of
4 mM and left for 12 h at ambient temperature to allow
self-assembly. The chemical shift for the proton resonance of
the imide protons of the cyanuric acid unit of 8 changed from
c
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Fig. 4 Hydrodynamic diameter of polymer 8 in different concentra-
tions (mM) in CHCl3.
Fig. 2 Chemical shifts of the imide protons of polymer 6 as a function
of equivalents of 3. The concentration of 6 was kept constant at 4 mM.
solutions were measured to be 4.1 nm, 4.1 nm, 4.3 nm, 4.6 nm,
5.0 nm, and 5.0 nm, respectively. Concomitantly, a PS
standard (9100 Da) was analysed via DLS at variable
concentrations (Fig. 4). The mean hydrodynamic diameter of
polymer 8 increases with increasing concentrations in contrast
to the PS standard (Dh(c) = const.), indicating the formation
of inter-chain assemblies of 8. As its concentration is reduced,
the diameter of 8 is observed to progressively lower, thus
supporting the formation of the more compact single-chain
self-assembled cyclic structures.
1
the peak at d = 12.63 ppm further increased. Thus, the H
NMR spectra show a downfield shift of the imide protons as
the concentration of polymer 8 is decreased. This shift—in
significant excess of the expected 10.83 ppm from the 1 : 1
association of 3 and 6 (see Fig. 1)—indicates the formation of
stabilized (circular) structures via an entropy driven
preferential assembly. These results indicate that in more
dilute solutions (o1 mM) stable self-assemblies are formed
with significantly reduced exchange processes (Fig. 3) congruent
with ring formation.
We demonstrate the single chain self-assembly of very
narrow polydispersity synthetic macromolecules through
a,o-hydrogen-bonding between
a cyanuric acid and a
Hamilton wedge. 1H NMR and DLS analyses support the
existence of strong entropically driven hydrogen-bonding
interactions between the a-donor and o-acceptor of the
polymer 8 leading to single chain circular self-assembly.
While the NMR experiments indicate that stabilized
structures due to (circular) entropy driven self-assembly occur,
only a measurement of the hydrodynamic diameter, Dh, can
provide evidence for the single chain circular self-assembly.
Thus, Dh of self-assemblies of 8 and polystyrene (PS) standards
were determined by DLS in CHCl3 at 20 1C. The Dh of the
polystyrene standards (Mn = 9100 Da and Mn = 3400 Da)
were measured as 4.6 nm and 2.4 nm, respectively, which is in
excellent agreement with the theoretical values (see Table S1,
ESIw). The polymer 8 (Mn,NMR = 6000 Da) was subjected to
DLS in six concentrations. The Dh of the polymers in these
Predominant single chain self-assembly of
8 occurs at
(or below) concentrations of approximately 0.5 mM.
C.B.-K. is grateful for continued support from the
Karlsruhe Institute of Technology (KIT) in the context of the
Excellence Initiative. O.A. thanks the Islamic Development
Bank (IDB) for a PhD scholarship. The authors thank
A. J. Inglis (KIT) for fruitful discussions.
Notes and References
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Fig. 3 Expanded 1H NMR of the polymer 8 in different concentrations
in CDCl3.
c
This journal is The Royal Society of Chemistry 2010
Chem. Commun., 2010, 46, 6291–6293 6293