Supramolecular block copolymers with cucurbit[8]uril in water

Article abstract of DOI:10.1002/anie.200705591

(Figure Presented) Be my guest! A supramolecular amphiphilic diblock copolymer was prepared with a cucurbit[8]uril molecular "handcuff" (see picture). It subsequently undergoes a hierarchical self-assembly process, resulting in the formation of a tertiary, compartmentalized nanostructure.

Full text of DOI:10.1002/anie.200705591

Communications
DOI: 10.1002/anie.200705591
Polymer Architectures
Supramolecular Block Copolymers with Cucurbit[8]uril in Water**
Urs Rauwald and Oren A. Scherman*
Supramolecular
polymers
have
expanded the scope of polymer science,
allowing for the design and development
of stimuli-responsive and dynamic mate-
rials.[1–3] Most prominently, hydrogen-
bonding arrays[1,4] and metal–ligand
interactions[5–9] have been used for the
creation of supramolecular polymers.
Utilizing metal coordinate bonds, block
copolymers can be formed that are stable
even in aqueous media.[10–13] In these
instances, however, the metal–ligand
interactions employed forfeit much of
the dynamic nature of reversible binding,
and their incorporation may curtail cer-
tain biological applications. Multiple
hydrogen-bonding motifs in linear
arrays have been utilized to achieve
Figure 1. Formation of dynamic, noncovalent macromolecular architectures based on CB[8] CT
complexes.
high association constants in common organic solvents;[4,14–18]
however, they have not been replicated in aqueous environ-
ments, as the water molecules compete for the hydrogen-
bonding sites.[19,20]
Our initial results of utilizing CB[8] as a linking unit for
polymeric systems are described. In a first step, linear
polymers were prepared that contained terminal groups,
such as 2-naphthol and methylviologen derivatives, for
selective encapsulation by CB[8]. Poly(ethylene glycol)
(PEG) and cis-1,4-poly(isoprene) (PI) were chosen as the
polymers (Scheme 1). Their combination allows for the
formation of an amphiphilic block copolymer that is expected
to exhibit higher order nanostructures in solution.[36]
Herein we report a methodology for developing dynamic
materials in aqueous media by interconnecting polymer
chains through a ternary host–guest complex which can be
controlled reversibly by an external stimulus. The host we
have chosen to employ is the barrel-shaped container
molecule cucurbit[8]uril (CB[8]),[21–24] which acts as a “supra-
molecular handcuff” for the polymer chains (Figure 1).
Cucurbit[8]uril is a remarkable host molecule; it is able to
bind two organic guest molecules simultaneously with high
association constants (Ka ꢀ 1011mÀ2) in an aqueous environ-
ment.[25–27] Kim et al. have demonstrated that a stable charge-
transfer (CT) complex is formed inside the cavity of CB[8]
between viologen derivatives and hydroxynaphthalenes,[25]
leading to the self-assembly of small molecular systems and
architectures.[28–33] Kaifer et al. subsequently employed this
principle to connect asymmetric dendritic units.[34,35]
Treatment of a 5000 gmolÀ1 methylviologen-terminated
poly(ethylene glycol) monomethyl ether (1) with one equiv-
alent of CB[8] in D2O resulted in an upfield shift and
1
broadening of the signals in the H NMR spectrum arising
from the aromatic protons on the viologen moiety. This result
[*] U. Rauwald, Dr. O. A. Scherman
Melville Laboratory for Polymer Synthesis
Department of Chemistry, University of Cambridge
Cambridge, CB2 1EW (UK)
Fax: (+44)1223-334-866
E-mail: oas23@cam.ac.uk
[**] This work was supported by the Walters-Kundert Trust. The authors
would like to thank Prof. Ulrich Wiesner (Cornell University) for
supplying the poly(isoprene) starting material and Dr. StØphanie
Deroo and Prof. Carol Robinson for recording the ESI mass
spectrometry data.
Scheme 1. End-group functional polymers prepared based on mono-
functional poly(ethylene glycol) monomethyl ethers (1, 2) and cis-1,4-
poly(isoprene) (4). Octadecyl methyl viologen (3) was prepared as a
small-molecule hydrophobic guest.
Supporting information for this article is available on the WWW
under http://www.angewandte.org or from the author.
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Chemie
indicates the complexation of a methylviologen guest inside
the cavity of the CB[8] host.[25] The steric bulk of 1 was
therefore not prohibitive in host–guest molecular recognition.
As CB[8] is able to simultaneously bind two guests forming a
1:1:1 ternary complex, the 1ꢁCB[8] complex was exposed to
an aqueous solution of 2-naphthol. Formation of the ternary
complex was confirmed by both 1H NMR spectroscopy,
exhibiting a further upfield shift and broadening, and UV/
Vis spectroscopy, in which a strong charge-transfer (CT) band
(lmax = 395 nm, with a shoulder at 503 nm) was observed.
Similar results were also obtained for several other polymer–
small-molecule conjugates, such as a 5000 gmolÀ1 2-naph-
thoxy-terminated poly(ethylene glycol) monomethyl ether
(2), a methyl heptyl viologen (8), and CB[8] (see Figure S1 in
the Supporting Information). In addition, complex formation
was confirmed by ESI-mass spectrometry, by which the
doubly charged 2 + 8ꢁCB[8] could be observed directly (see
Figure S2 in the Supporting Information). All of these
observations are in keeping with their small molecular
analogues.[29]
Figure 3. 1H NMR spectra (500 MHz, D2O) of 3 and polymer 2
a) before and b) after addition of CB[8], demonstrating that the
solubility of a hydrophobic guest can be increased upon binding to the
polymer.
To investigate CB[8] binding of two polymeric guests, 2
was added to a solution of 1ꢁCB[8] in D2O. 1H NMR
spectroscopy again indicated complex formation. UV/Vis
spectra of 1, 2, and CB[8] (Figure 2) show that solutions of
both 1 and 2 alone have no appreciable absorption beyond
solution of 2 and 3 led to complex formation, as seen by the
upfield shift of aromatic proton signals. More impressively,
the solubility of 3 increases notably, as the hydrophobic
viologen is now noncovalently linked to 2 by CB[8].
Following the observation that the solubility of hydro-
phobic compounds in water can be enhanced by CB[8]
complexation with PEG guests, it was envisioned that an
amphiphilic diblock copolymer based on CB[8] could be
created. Thus, 10500 gmolÀ1 2-naphthoxy-terminated cis-1,4-
poly(isoprene) (4) was prepared and added to a solution of
1ꢁCB[8] in D2O followed by sonication and rigorous shaking
for several hours. 1H NMR spectra obtained from the filtered
D2O solutions indicated that a CT complex was indeed
formed (Figure 4). Although no proton signals for the poly-
(isoprene) backbone were observed in the 1H NMR spec-
trum, signals corresponding to the 2-naphthoxy end-group
were visible, and are shifted considerably upfield, which is
indicative of the 1:1:1 ternary CT complex with 1 and CB[8].
Upon successful complexation of the 1ꢁCB[8], an amphi-
philic diblock copolymer with the hydrophobic PI should be
formed. Subsequent self-assembly into a compartmentalized
solution architecture, such as a micelle or vesicle, with 4
Figure 2. UV/Vis spectra in water (1.75 mm) of 1, 2, a 1:1 mixture of 1
and 2, and the 1+2ꢁCB[8] complex mixture, illustrating the formation
of a CT complex in the presence of CB[8] by the appearance of new
charge-transfer bands.
400 nm. After both solutions were mixed together, a slight
increase in UV/Vis absorption resulted, signifying a weak CT
interaction of the respective polymer end groups. In the
presence of CB[8], this CT interaction is enhanced and the
emergence of a charge-transfer band beyond 500 nm provides
evidence for complexation. This result demonstrates that
polymer chains can be extended using CB[8] as a linking unit
as depicted in Figure 1b.
Viologen 3 was synthesized with an octadecyl chain. This
only sparingly water-soluble guest can be drawn into water by
2 in the presence of CB[8], as observed by 1H NMR
spectrscopy. As Figure 3 illustrates, addition of CB[8] to a
Figure 4. 1H NMR analysis (500 MHz, D2O) of the 1+4ꢁCB[8]
system, indicating the existence of a CT complex, as viologen and
naphthol end-group protons are shifted upfield.
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Communications
existing as a non-solvated core domain, would then explain
Cucurbit[8]uril is capable of recognizing specific polymer
chain ends in aqueous media. Its capability to selectively bind
two guest molecules by a dynamic interlink has been
exploited in the design of new polymeric block copolymers.
Polymer–small-molecule conjugates, elongated polymer
chains, and amphiphilic diblock copolymers were all synthe-
sized, showing the versatility of this approach. In comparison
to existing strategies for noncovalent polymer preparation,
CB[8] offers a strong yet dynamic binding profile in aqueous
environments which is controllable by external stimuli. This
approach will lead to potential applications in both the
materials as well as the biomedical realm. In particular, it
would allow for supramolecular polymers to interact with
biomolecules, biomaterials, or drug molecules, giving rise to a
potentially new class of stimuli-responsive drug-delivery
systems. It is therefore believed that utilization of CB[8] as
a supramolecular handcuff for interconnecting polymeric
systems will allow for the building up of dynamic functional
materials by a designed hierarchical self-assembly approach.
why the PI signals were absent in the NMR spectrum.[37]
Further evidence for the formation of a tertiary solution
structure was provided by dynamic light scattering (DLS)
measurements (Figure 5). In both volume and number
Experimental Section
1
Synthesis and characterization of compounds 1–4 and 6–9, H NMR
spectra of 2 and 8 with and without CB[8], and the ESI mass spectrum
of 2 + 8ꢁCB[8] complex can be found in the Supporting Information.
Supramolecular CB[8]-containing complexes were typically pre-
pared by dissolving cucurbit[8]uril in aqueous solutions (millipore
water, 18.2 MWcm, or deuterium oxide for NMR experiments) of the
guest molecule(s) by sonication and with mild heating overnight,
followed by filtration through 0.45 mm PVDF filters.
Received: December 6, 2007
Revised: January 26, 2008
Keywords: amphiphiles · block copolymers · cucurbituril ·
.
self-assembly · supramolecular chemistry
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