Urea-bearing copolymers for guest-dependent tunable self-assembly

Article abstract of DOI:10.1039/b613778d

RAFT polymerization was used to synthesize urea-bearing methyl methacrylate copolymers for binding carboxylate isosteres. The Royal Society of Chemistry.

Full text of DOI:10.1039/b613778d

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Urea-bearing copolymers for guest-dependent tunable self-assembly{
Amanda C. Kamps, Teddie Magbitang and Alshakim Nelson*
Received (in Austin, TX, USA) 23rd September 2006, Accepted 15th November 2006
First published as an Advance Article on the web 6th December 2006
DOI: 10.1039/b613778d
RAFT polymerization was used to synthesize urea-bearing
methyl methacrylate copolymers for binding carboxylate
isosteres.
Supramolecular polymers are emerging as a promising class of
materials for a broad range of applications, including thermo-
plastic materials1 and as frameworks toward device fabrication.2
The self-assembly of these materials is driven by noncovalent
forces3—including electrostatic, hydrogen bonding, metal coordi-
nation, and van der Waals interactions—to afford noncovalent
networks tunable in strength and reversibility.4 Polymers bearing
Fig. 1 A–A and A–B interactions with urea functionalities.
pendant molecular recognition elements are an important subset
of these materials.5–10 For example, Schubert and Hofmeier5
in concert with hydrogen bonding—and are effective in a range
synthesized methyl methacrylate copolymers bearing terpyridyl
functionalities to create reversible supramolecular networks in the
presence of Fe2+ or Zn2+ ions. Other researchers have utilized
noncovalent interactions to alter the miscibility of polymer blends
which are typically immiscible.6
of hydrogen bonding and non-hydrogen bonding solvents.
Herein, we present (Scheme 1) the controlled radical copoly-
merization of methyl methacrylate and a urea-bearing methacryl-
ate monomer —via RAFT polymerization—for binding a range of
carboxylate isosteres.
Two approaches are possible in the formation of molecular
recognition-bearing polymers: (1) post-modification of a polymer
backbone containing reactive side groups, and (2) the polymeriza-
tion of a molecular recognition-containing monomer. Rotello and
co-workers7 have derivatized polystyrene-based random and block
copolymers with hydrogen bonding units for the formation of
micelles and vesicles, using the post-modification approach.
Alternatively, there have been significant contributions by Weck
and co-workers8 who demonstrated the ring-opening metathesis
polymerization (ROMP) of monomers bearing hydrogen bonding
and metal coordination elements. While many of these polymers
have been synthesized using radical polymerization schemes,9 there
has been less attention to employing controlled metal-free radical
polymerization routes,10 such as reversible addition–fragmentation
chain transfer (RAFT) polymerization11 and nitroxide mediated
polymerization (NMP).12
The urea-containing monomers 1a and 1b are easily synthesized
from the commercially available isocyanatoethyl methacrylate in
the presence of aniline or 4-fluoroaniline, respectively. Both mono-
mers are purified by recrystallization, and, thus, do not require any
chromatography (ESI{). The fluorine in the para-position of 1b
was added both to increase the binding strength of the urea, and
also as an 19F NMR probe to observe the binding of guests.
Copolymerization of methyl methacrylate (MMA) with the
urea-containing monomer 1b was investigated using a 122 : 12 : 1
The choice of molecular recognition functionalities employed is
a key component of supramolecular polymers. Urea functionalities
are one example that have been utilized to form supramolecular
polymers and polymeric networks via self-recognition—i.e., urea
functionalities interacting with other urea functionalities (A–A
system)—particularly by Meijer and co-workers (Fig. 1).13 Ureas
are known,14 however, to bind carboxylate derivatives and their
isosteres (such as sulfonates, phosphonates, and phosphates), and
have been incorporated into host molecules for binding anion
guests.15 These noncovalent interactions employ ion–dipole forces
IBM Almaden Research Center, 650 Harry Road, San Jose, CA, 95120,
USA. E-mail: alshak@us.ibm.com; Fax: (+1) 408-927-3310;
Tel: (+1) 408-927-2449
{ Electronic supplementary information (ESI) available: Experimental
procedures and H NMR spectra. See DOI: 10.1039/b613778d
1
Scheme 1 Polymerization by RAFT.
954 | Chem. Commun., 2007, 954–956
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ratio (methyl methacrylate : 1b : cyanoisopropyl dithiobenzoate
chain transfer agent) in DMF-d7 at 65 uC. The relationship
between the molecular weight (Mn) and the percent conversion is
linear, which suggests that the polymerization is a controlled living
process (ESI{). Moreover, the linearity of the semilogarithmic
kinetic plot suggests a constant concentration of active radical
species during the polymerization. The polydispersity index (PDI)
was low, with the highest value being 1.14 at near full conversion.
Several polymers, varying in composition and molecular weight,
were synthesized (Table 1) by altering the monomer-to-initiator
ratio and/or the methyl methacrylate to urea-bearing methacrylate
ratio. The incorporation of the urea-bearing monomer 1a or 1b
into the polymer backbone was verified by 1H NMR spectroscopy.
The percent incorporation of 1a into 2a and 2b, and 1b into 2d,
was consistent with the initial composition of 1a/b and methyl
methacrylate in the reaction mixture. However, in cases where the
composition of 1a/b in the reaction was greater than 10%, the
polymerization rate was greatly diminished, resulting in a bimodal
distribution of polymers and a lower yield of polymer 2c (ESI{).
These data suggest that, while both 1a and 1b have similar
reactivities to methyl methacrylate, the intermolecular hydrogen
bonding interactions of the urea moieties can hinder the
polymerization.
Fig. 2 Sulfonate 3a, carboxylate 3b, and phosphonate 3c guests for
binding urea-bearing polymers.
Table 2 Association constants (Ka) for monomer 1a and polymers 2a
and 2d (10 mM solutions in DMSO-d6 with respect to urea
functionalities) for binding to guest molecules 3a–c
Ka for
1a/M21 a
Ka for
2a/M21 a
Ka for
2d/M21 a
Ka for
2d/M21 b
Guest
3a
3b
3c
a
.10
149
3010
.10
117
2970
.10
145
—
.10
146
—
c
c
The Ka values were determined by 1H NMR spectroscopy
(400 MHz, 298 K) titration experiments and the data were analyzed
b
using the NMR-Tit18 curve-fitting program. The Ka values were
determined by 19F NMR spectroscopy (376 MHz, 298 K) titration
experiments and the data were analyzed using the NMR-Tit18 curve-
fitting program. Decomposition of the urea functionalities was
The polymers were soluble in a range of polar and nonpolar
solvents. In non-hydrogen bonding solvents such as CDCl3, the
1
urea N–H resonances in the H NMR spectrum (10 mM of the
c
observed.
urea side chain, 298 K) were significantly broad and flattened,
suggesting their involvement in inter- and intramolecular hydrogen
bonding interactions with other urea functionalities or methyl ester
groups of the polymer backbone. While the polymer is initially
soluble in CDCl3, a precipitate—likely arising from the aggrega-
tion of polymer chains via intermolecular interactions—was
observed in the solution after a period of two days. The formation
of aggregates was reversible, and the solution became homo-
geneous with heating. However, in DMSO-d6, the polymers are
readily soluble and the N–H resonances were present as distinct
broad singlets due to the solvation of the urea functionalities by
solvent molecules.
The binding properties16 of the copolymers were determined in
DMSO-d6 by1H NMR spectroscopy (and 19F NMR spectroscopy
in the case of polymer 2d). This solvent was chosen for our
investigations for two reasons: (1) the urea–urea interactions are
negligible in this solvent,17 and (2) the guest molecules 3a–c (as
their tetrabutylammonium salts) are readily soluble in DMSO-d6
but not CDCl3. As representative examples for the binding studies,
polymers 2a and 2d (Mn = 22.1k and 17.0k, respectively) were
investigated. Titration of a solution of guest 3a, 3b, or 3c (Fig. 2)
into the host copolymer 2a resulted in a downfield shift of the
N–H resonances (6.01 and 8.56 ppm) of the urea functionalities.
The NMR-Tit curve-fitting program18 was used to determine the
association constants (Ka) for the 1 : 1 interactions between guests
and receptors (Table 2).19 The binding affinity was dependent
upon the guest molecule, with the order of Ka’s from weakest to
strongest being: sulfonate 3a , carboxylate 3b , phosphonate 3c.
Kelly and Kim,14 in the investigation of their urea-based anion
receptors, noted the same trend for the binding of carboxylate
isosteres, which correlates to the pKb of the guest ion—as the
basicity of the anion increases, the strength of the interaction
increases. Interestingly, the association constants observed for the
binding of each guest to the polymer-bound urea are of the same
order as the individual urea–guest interactions (Table 2). And thus,
the strength of the molecular recognition is only slightly mitigated
by having the urea component attached to the polymer backbone.
Copolymer 2d, which contains a fluorophenyl urea, was also
investigated for its binding to the guest molecules. The fluorine
atom was sensitive to the binding of the guest and could be
observed by 19F NMR spectroscopy. The shift of the fluorine
signal with the titration of guest, was used to determine the Ka’s
for the binding of guests 3a and 3b. The association constants
determined by 19F NMR spectroscopy for guests 3a and 3b were
Table 1 Characterization of polymers
1
consistent with the values obtained by H NMR spectroscopy.
MMA monomer :
urea-MMA
In the presence of guest 3c, the 19F NMR spectrum became
increasingly complex—with the appearance of several new
resonances—which is indicative of the decomposition of the urea
functionalities. This phenomenon has been observed previously—
Gale, and Amendola et al. have both noted previously20 that
electron withdrawing substituents increase the acidity of the urea
protons, thus making them more susceptible to deprotonation by
basic anions.
Mn 61023
/
Urea composition
in polymer (%)b
Polymer g mol21 a
PDIa monomer
2a
2b
2c
2d
a
22.1
10.3
4.6
1.09 20:1
1.10 10:1
8:1
1.06 20:1
4.5
10.1
23.5
4.7
1.16c
17.0
b
Determined by GPC in THF.
Determined by 1H NMR
c
spectroscopy. Bimodal distribution (see ESI).
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Fig. 3 Solution viscosity measurements at 26 uC of 2a and pMMA (Mn =
15.1k, PDI = 1.10) in DMSO (20 g L21) with increasing amounts of
divalent 4a or 4b. The relative viscosity was determined using polymer 2a
as the reference. Equivalents of guest is relative to urea units on the
polymer.
10 R. Shenhar, A. Sanyal, O. Uzun, H. Nakade and V. M. Rotello,
Macromolecules, 2004, 37, 4931; G. N. Tew, K. A. Aamer and
R. Shunmugam, Polymer, 2005, 46, 8440; for representative examples
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Solution viscosity measurements using disulfonate 4a and
dicarboxylate 4b were measured in order to investigate the
supramolecular crosslinking of the polymer chains. As shown in
Fig. 3, the viscosity of a solution of polymer 2a (20 g L21 in
DMSO) increases with the addition of divalent guest 4a or 4b. The
increase in viscosity observed with polymer 2a is consistent with an
increase in molecular weight due to supramolecular crosslinking of
the polymer chains. In comparison, when the divalent 4b is added
to a pMMA homopolymer a viscosity response is not observed.
Changes in the viscosity are also related to the strength of the
noncovalent interaction—smaller changes were observed with
disulfonate 4a than dicarboxylate 4b. This result parallels the
weaker urea–guest interactions observed with sulfonate 3a than
carboxylate 3b by NMR spectroscopy.21
In conclusion, we have investigated the synthesis of methacrylate
copolymers bearing pendant urea groups using RAFT polymeriza-
tion. Copolymers containing up to 10 mol% of the urea func-
tionality were synthesized in a controlled living process to afford
polymers with defined molecular weights and low PDI’s. The
molecular recognition elements employed in this paper can all be
synthesized relatively easily. The urea-containing methyl metha-
crylate monomers were synthesized and isolated with minimal
purification required. Since urea functionalities interact with
carboxylate anions and its isosteres with varying degrees of
strength, a route for tuning the strength of these interactions has
been developed.
16 K. A. Connors, Binding Constants, Wiley, New York, 1987; L. Fielding,
Tetrahedron, 2000, 56, 6151.
17 The chemical shifts of the urea N–H signals did not change with
concentration, which indicates that the self-associating interactions of
the ureas are weaker than the detectable limit of NMR spectroscopy.
18 NMR-Tit is available from Professor Chris Hunter’s website at:
www.chris-hunter.staff.shef.ac.uk. A. P. Bisson, C. A. Hunter,
J. C. Morales and K. Young, Chem.–Eur. J., 1998, 4, 845.
19 The downfield shift of the urea resonance at 8.56 ppm with the addition
of guest was used to determine the association constant.
20 P. A. Gale, Acc. Chem. Res., 2006, 39, 465; V. Amendola, D. Esteban-
Gomez, L. Fabbrizzi and M. Licchelli, Acc. Chem. Res., 2006, 39,
343.
21 These experiments demonstrate subtle changes to the viscosity with the
addition of 4a or 4b, even when in excess relative to the urea
functionalities. It is likely that the changes to viscosity are the result of a
combination of monovalent and divalent binding of 4a and 4b to the
polymer.
Notes and references
1 F. J. M. Hoeben, P. Jonkheijm, E. W. Meijer and A. P. H. J. Schenning,
Chem. Rev., 2001, 101, 4071; C. Hilger and R. Stadler, Polymer, 1991,
32, 3244.
956 | Chem. Commun., 2007, 954–956
This journal is ß The Royal Society of Chemistry 2007