Preparation and Properties of a Hydrolytically Stable Cyclooctyne-Containing Polymer

Article abstract of DOI:10.1055/s-0037-1610636

A poly[(phenylene vinylene)-co-dibenzocyclooctyne] polymer prepared by Wittig polymerization chemistry between dibenzocyclooctyne bisaldehyde [DIBO-(CHO) ₂ ] and bis(triethyleneglycol)phenylbis(tributylphosphonium) dibromide is reported. The re

Full text of DOI:10.1055/s-0037-1610636

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Preparation and Properties of a Hydrolytically Stable Cyclooc-
tyne-Containing Polymer
Kelvin Li
Stuart A. McNelles
Alex Adronov*
Department of Chemistry, McMaster University,
1280 Main Street West, Hamilton, Ontario, L8S 4M1,
Canada
adronov@mcmaster.ca
Published as part of the Cluster Synthesis of Materials
Received: 10.07.2018
Accepted after revision: 13.08.2018
Published online: 03.09.2018
mer properties, this approach can be problematic if the
modified monomer differs in its reactivity toward polymer-
ization. In cases where length of the polymer is critical to
the application, de novo polymerization of structurally dif-
ferent monomers can cause difficulties in attaining con-
stant molecular weight. In these cases, post-polymerization
modification of the polymer is an ideal alternative.32 Such
modification allows for the systematic preparation of dis-
tinct polymer structures with a uniform degree of polymer-
ization (DP). However, efficient chemistry must be used if
quantitative conversion of each repeat unit is required. Al-
though this approach has been demonstrated for side-chain
modification of conjugated polymers,33 the ability to quan-
titatively modify the backbone is much less common.34
Recently, we reported the preparation of a dibenzocy-
clooctyne- (DIBO) containing conjugated Schiff-base poly-
mer [poly(DIBO), Scheme 1],35 which undergoes rapid and
efficient strain-promoted azide-alkyne cycloaddition
(SPAAC). We have shown that this polymer can be used to
easily prepare large graft copolymers, self-healing organo-
gels,36 and libraries of different polymer structures that are
useful for the investigation of polymer interactions with
single-walled carbon nanotubes (SWNTs).37 The strained
cyclooctyne repeat units along the polymer backbone were
found to quantitatively react with a variety of azides under
mild conditions, resulting in a series of structurally differ-
ent polymers, but all having identical DP. Unfortunately,
imine linkages are hydrolytically unstable, which limits the
potential applications for this polymer scaffold. To circum-
vent this limitation, we sought alternative linkage chemis-
try, which required modification of the polymerization
method. It should be noted that, although the cyclooctyne-
containing polymer exhibits alternating single and double
(or triple) bonds along its backbone, the strained alkynes
prevent optimal overlap of the p orbitals between the
DOI: 10.1055/s-0037-1610636; Art ID: st-2018-r0431-c
Abstract A poly[(phenylene vinylene)-co-dibenzocyclooctyne] poly-
mer prepared by Wittig polymerization chemistry between dibenzocy-
clooctyne bisaldehyde [DIBO-(CHO)2] and bis(triethyleneglycol)phenyl-
bis(tributylphosphonium) dibromide is reported. The resulting polymer
exhibits moderate molecular weight (Mn: 10.5 kDa, Mw: 21.3 kDa, Ð:
2.02) and is fluorescent. It could be readily functionalized by strain-pro-
moted alkyne-azide cycloadditon with different azides, and fluores-
cence of the polymer was preserved after functionalization. Grafting
azide-terminated 5 kDa poly(ethylene glycol) monomethyl ether chains
drastically affected the solubility of the polymer. Cross-linking the poly-
mer with poly(ethylene glycol) that was terminated at both ends with
azide groups gave access to a fluorescent organogel that could be dried
and reswollen with water to form a hydrogel.
Key words Wittig reaction, cycloaddition, cyclooctyne, conjugated
polymer, polymer functionalization, cross-linking
The structural diversity of conjugated polymers enables
the preparation of materials with interesting and useful op-
toelectronic properties. Since the conductivity of polyacet-
ylene was discovered,1,2 many different conjugated polymer
backbones have been prepared and investigated. These in-
clude polyarylenevinylene,3 polyfluorene,4,5 polythio-
phene,6,7 polycarbazole,8 and a number of others.9 It is well
documented that variation of the monomer structure al-
lows modification of the polymer properties, such as solu-
bility and processability,10,11 conductivity,12 HOMO–LUMO
levels,13 band gaps,13,14 quantum yields,15 as well as absorp-
tion and emission maxima.16,17 This has led to numerous
applications of conjugated polymers, which include light-
emitting diodes,18–22 field effect transistors,23,24 photovolta-
ics,25,26 printed electronics,27 batteries,28,29 supercapaci-
tors,30 and sensors.31 Although modification of monomers
prior to polymerization is an effective strategy to tune poly-
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cyclooctyne unit and the rest of the π system. Thus, these
polymers do not exhibit the extended π conjugation of
more traditional conjugated polymers.
formation of the enol triflate from 1, and subsequent elimi-
nation afforded 2. A modified Bouveault aldehyde synthesis
converted 2 into the dialdehyde monomer 3, which allows
access to any of the metal-free polymerization reactions
mentioned above. Since we chose to investigate Wittig
chemistry, we next prepared the phosphonium salt co-
monomer 5 by quaternization of tributylphosphine with
dibenzyl bromide 449 at 75 °C (Scheme 2, b).
Conjugated polymers are typically prepared by step-
growth polymerization utilizing transition-metal- (i.e. Pd,
Ni, Cu) catalyzed cross-coupling reactions.38–40 However,
transition-metal catalysts form metallocyclopropenes with
strained cyclooctynes,35 instead of catalyzing the desired
coupling reactions to form productive bonds. Alternative
metal-free polymerization methods include Wittig chemis-
try, Horner–Wadsworth–Emmons chemistry, and Knoeve-
nagel condensation.9,41–43 Recent developments in Wittig
chemistry allow for mild conditions to be used,44–46 making
it a powerful carbon–carbon bond forming reaction. In con-
trast to canonical reaction conditions involving triphenyl-
phosphoranylides, use of trialkylphosphoranylides has
been shown to result in higher yields, stereocontrol, and
ease of purification because of the solubility of short trial-
kylphosphine oxide by-products in polar solvents such as
water and alcohols.44–46 The efficacy afforded by trialkyl-
phosphoranylides has been utilized to prepare high molec-
ular weight conjugated polymers in the past.47,48 Here, we
show that these modern Wittig reaction conditions can be
used to produce high molecular weight conjugated poly-
mers that contain the DIBO repeat unit.
Monomers 3 and 5 were polymerized by first deproton-
ating 5 with LiOH·H2O to form the trialkylphosphoranylide,
followed by addition of dialdehyde 3 and heating at reflux
overnight to afford the product polymer P0 (Scheme 3).50
1
The polymer was initially characterized using H NMR and
FT-IR spectroscopy, as well as gel permeation chromatogra-
phy (GPC). The 1H NMR spectrum for this polymer exhibits
the expected aromatic signals from the backbone, aliphatic
signals from the oligo(ethylene glycol) side chains, and a set
of vinyl proton signals characteristic of the alkenyl linkages
between repeat units (Figure 1). On the basis of the NMR
and FT-IR data, it can be concluded that the stereochemis-
try of the double bonds is a combination of cis (proton sig-
nals appearing at 6.6–6.8 ppm) and trans (proton signals at
~7.2 ppm, overlapping with aromatic protons). Although
the trans linkages cannot be easily distinguished in the
NMR spectrum, the FT-IR spectrum clearly shows a signal at
955 cm–1, which is consistent with an out-of-plane bending
mode for the trans stereochemistry (Figure S2). In addition,
the protons corresponding to the ethylene bridge of the cy-
clooctyne repeat unit were observed at 2.42 and 3.3 ppm,
though the latter could not be resolved as it overlaps with
the protons of the oligo(ethylene glycol) side chains. End-
group analysis of the aldehyde (proton signal at 9.99 ppm),
and the methyl group of the tributylphopshonium (proton
signal at 0.94 ppm) affords a number-average polymer mo-
lecular weight of 22.8 kDa (end-group NMR signals are
magnified in the Supporting Information, Figure S13). How-
ever, GPC indicated a lower molecular weight (Mn: 10.5
kDa, Mw: 21.3 kDa, Ð: 2.02) for the conjugated polymer. The
Scheme 1 The chemical structure of polyimine poly(DIBO) and its tri-
azole derivative upon click coupling by strain-promoted azide-alkyne
cycloaddition (SPAAC)
Our synthetic approach toward a suitable DIBO mono-
mer substitute started with the diiodo intermediate 1
(Scheme 2, a), prepared according to literature procedures
from the commercially available dibenzosuberone.35 In situ
Scheme 2 Synthesis of the 2,7-dialdehydedibenzocyclooctyne [DIBO-(CHO)2] monomer 3 (a), and the bis(tributylphosphonium salt)benzene dibro-
mide co-monomer 5 (b)
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Scheme 3 Synthesis of the strained cyclooctyne-containing polymer P0 from 3 and 5, and its click functionalization to produce P1 and P2
disparity between the observed molecular weights may be
attributed to the mixture of cis and trans linkages within
the backbone, which results in a significantly kinked, com-
pact structure whose molecular weight is underestimated
by GPC. Further characterization was carried out by absorp-
tion and fluorescence spectroscopy. The absorption spec-
trum for P0 is shown in Figure 2, a and exhibits an absorp-
tion maximum at 392 nm (ε = 14,045 M–1 cm–1). Interest-
ingly, this polymer is fluorescent upon irradiation with a
handheld UV lamp, and its fluorescence spectrum is shown
in Figure 2, b (λex = 392 nm; λem = 447, 474 nm). Quantum
yield of fluorescence measurements were performed rela-
tive to a quinine sulfate standard, and furnished a value of
14%.
Having prepared P0, we set out to investigate its post-
polymerization functionalization chemistry. Two different
azides were investigated as reaction partners for P0, includ-
ing octyl azide and a 5 kDa poly(ethylene glycol) mono
methyl ether that had been end-functionalized with an
azide (N3-mPEG5k) by mesylation and subsequent substitu-
Figure 1 1H NMR in CD2Cl2 of P0 and P1. The complete disappearance of the chemical environments for the ethylene bridge protons of P0 indicates
quantitative functionalization of the strained alkyne. The inset highlights the ethylene bridge proton signals of interest.
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ganic solvents, such as methanol and ethanol, as well as in
aqueous solution. This contrasts with the solubility of P0
and P1, both of which dissolve in relatively nonpolar sol-
vents such as tetrahydrofuran, chloroform, toluene, and
N,N-dimethylformamide, and are insoluble in polar/aque-
ous solvents. Figure 3, a depicts two vials containing a bi-
phasic mixture of 1:1 hexanes/toluene, and water, along
with a small amount of either the P0 starting material (left),
or the P2 click product (right). It can clearly be seen that the
reaction with N3-mPEG5k resulted in a dramatic change in
the polymer’s solubility, from organic to aqueous solvents.
Fluorescence from the polymer before and after the click re-
action could be observed upon irradiation with a handheld
UV lamp at 365 nm, as depicted in Figure 3, b.
Figure 3 Photos of biphasic mixtures of 1:1 hexanes/toluene and wa-
ter containing P0 (left) and P2 (right) dissolved in the organic and aque-
ous layers, respectively. The vials were photographed under ambient
light (a) and upon irradiation with a handheld UV lamp at 365 nm to
show polymer fluorescence (b).
Figure 2 Absorption (a) and emission (b) spectra of P0 in THF.
The stability of the alkene bridging polymer was investi-
gated by adding a drop of 6 M HCl to a solution of P0 in THF.
No physical change in the polymer solution was observed
upon addition of acid. GPC showed no significant change in
the molecular weight of the polymer upon addition of the
acid, even after allowing the mixture to stand overnight
(Figure S3). In comparison, the corresponding polyimine
hydrolyzes within only a few minutes, as observed in our
previous studies.37 The optical properties of P0 after click
coupling in THF were also studied. Upon introduction of the
octyl chain in P1, the UV-vis absorption spectrum exhibits
no significant changes, indicating that the SPAAC coupling
did not lead to any electronic modification to the polymer
backbone (Figure S5). Likewise, the fluorescence spectrum
before and after click coupling does not exhibit any appre-
ciable changes (Figure S6), and the quantum yield of fluo-
rescence for P1 in THF was measured to be 13%, which is al-
most identical to what was measured for P0. However, dis-
solving P2 (Figure 3, b) in water results in a bathochromic
shift, with the emission spectrum exhibiting a maximum at
486 nm (Figure S7).
tion with sodium azide.51 To carry out the SPAAC function-
alization with the octyl chain, the polymer was added to a
50 mM solution of octyl azide in THF (1.5 equiv per alkyne)
and the mixture was stirred for 30 minutes at room tem-
perature (Scheme 3). The solvent was then evaporated, and
the residue was triturated in ether to purify P1,52 which
was isolated as a yellow-brown solid. To confirm that quan-
titative SPAAC functionalization occurs at each cyclooctyne
of the polymer, we followed the distinct 1H NMR signals of
the ethylene bridging protons, which undergo a shift from
2.46 ppm to 2.92 and 3.13 ppm (Figure 1, inset). Similarly,
P0 was allowed to react overnight at room temperature
with N3-mPEG5k. The longer reaction time was required to
quantitatively functionalize P0 with the macromolecular
1
side chain. Again, H NMR spectroscopy provided evidence
of complete conversion in the form of a clean shift of the
ethylene bridge protons (Figure S15). As expected, the graft
copolymer product, P2,53 exhibits significantly increased
hydrophilicity, becoming highly soluble in both polar or-
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Scheme 4 Preparation of a covalently cross-linked organogel from P0 and PEG10k-(N3)2
As a final set of experiments, we chose to crosslink P0
by the SPAAC reaction with a bifunctional PEG-based cross-
linker. The crosslinked gels of P0 are also of interest, as gels
composed of fluorescent π-conjugated building blocks have
attracted recent attention.54,55 Previously, we prepared an
organogel from the corresponding polyimine [poly(DIBO),
Scheme 1], but the addition of a poly(ethylene glycol) cross-
linker, and the accompanying water retained by this hydro-
philic cross-linker resulted in the gradual loss of rigidity of
the gel over the course of several hours due to hydrolysis.36
Here, we cross-linked P0 with a 10 kDa poly(ethylene gly-
brating the gel in water, the cross-linked network under-
went significant swelling, and increased in volume relative
to the organogel. The resulting hydrogel retained its fluo-
rescence upon excitation with 365 nm light, showing prom-
ise as a scaffold to prepare a variety of fluorescent gels in
either organic or aqueous solvent, under mild conditions.
In conclusion, by switching from the hydrolytically un-
stable imine bonds to more robust vinylene linkages, we
prepared a polymer with strained cyclooctyne moieties
whose backbone is stable under acidic and aqueous condi-
tions. Using 1H NMR spectroscopy, we demonstrate that
each cyclooctyne repeat unit undergoes functionalization
in the presence of an organic azide. Utilizing this reactivity,
we functionalized P0 to yield a water-soluble graft copoly-
mer, and a fluorescent gel that can be interchanged with ei-
ther organic or aqueous solvent. In addition, we character-
ized the optical properties of both the alkyne polymer and
the functionalized triazole polymer. The parent polymer
and all subsequent functionalized polymers and gels are
fluorescent, showing promise as a scaffold to prepare a
range of fluorescent materials.
col) terminated at both ends with azide groups [PEG10k
-
(N3)2], allowing it to gel in an organic solvent. Cross-linking
was performed by mixing P0 and PEG10k-(N3)2 in a 1:1 mo-
lar ratio of the alkyne repeat unit relative to the azide end
group of PEG10k-(N3)2 in THF at a concentration of 0.05 M
with respect to the functional groups (Scheme 4). Gelation
was observed upon standing for 15 minutes in a mold (see
Supporting Information). The resulting yellow-brown gel
held its shape upon removal from the mold, and exhibits
fluorescence upon excitation with 365 nm light (Figure 4).
By removing the organic solvent under vacuum, and equili-
Figure 4 Successive photographs of the gel prepared from P0 and PEG10k-(N3)2: (a) As-prepared organogel in THF; (b) excitation of the organogel with
365 nm light; (c) vacuum-dried cross-linked polymer; (d) cross-linked polymer swelled in water to form a hydrogel; (e) excitation of the hydrogel with
365 nm light
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Funding Information
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Financial support for this work was provided by the Natural Science
and Engineering Research Council of Canada (NSERC). S.M. is grateful
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We thank Darryl Fong for kindly supplying the N3-mPEG5k
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Supporting Information
Supporting information for this article is available online at
https://doi.org/10.1055/s-0037-1610636.
S
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(50) Synthesis of P0
A 3 mL microwave vial equipped with a stir bar was charged
with 5 (0.500 g, 0.503 mmol), lithium hydroxide monohydrate
(0.093 g, 2.213 mmol, 4.4 equiv), and dry THF (1.2 mL). The
reaction mixture was stirred at r.t. for 15 min, followed by the
addition of 3 (0.131 g, 0.503 mmol, 1 equiv). The reaction vessel
was crimped with a cap and stirred overnight at 67 °C. Cau-
tion!! Pressure can build up in the microwave vial when heated
above the boiling point of the solvent. The molecular weight of
the polymer was monitored by GPC. Once the desired molecular
weight was achieved, the reaction mixture was acidified with 1
M HCl and dissolved with DCM. Once dissolved, the reaction
mixture was precipitated into cold 1:9 DCM/EtOH, and filtered.
(Note: Prevention of solvent evaporation is crucial to reproduc-
ible formation of product. Significant solvent evaporation typi-
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cally leads to formation of insoluble product. Other experimen-
tal conditions were explored, including the addition of 10 equiv
of base, and the solvent and base combination of DMF and
Cs2CO3, both of which resulted in similar polymer formation, as
long the solvent did not evaporate.) Yield: 75% (0.248 g, 0.378
mmol of the repeat unit) of a yellow-brown solid. 1H NMR (600
MHz, CD2Cl2): δ = 7.55–7.11 (m, 9 H), 6.80–6.59 (m, 1 H), 4.24–
4.13 (m, 3 H), 3.92–3.20 (m, 27 H), 2.39 (m, 2 H) ppm. GPC: Mn:
10.5 kDa, Mw: 21.3 kDa, Ð: 2.02.
dried under vacuum. Yield: 99% (10.4 mg, 0.012 mmol) of a
yellow-brown solid. 1H NMR spectrum in the Supporting Infor-
mation. Mn: 10.0 kDa, Mw: 17.8 kDa, Ð: 1.79 (GPC).
(53) Synthesis of P2
A 20 mL glass vial equipped with a stir bar was charged with
N3-mPEG5k (23.9 mg, 0.0048 mmol, 1.5 equiv) and THF (0.950
mL), and heated briefly until the azide dissolved. P0 (2.1 mg,
0.0032 mmol, 1 equiv) was added, and the mixture was soni-
cated briefly until the polymer dissolved. After dissolving the
polymer, the mixture was stirred at r.t. over night. The THF was
removed under reduced pressure, and the polymer was tritu-
rated with Et2O (3 × 3 mL, to remove excess azide) and then
dried under vacuum. Yield: 99% (18.0 mg, 0.0032 mmol) of a
(51) Harris, J. M.; Struck, E. C.; Case, M. G.; Paley, M. S.; Yalpani, M.;
Van Alstine, J. M.; Brooks, D. E. J. Polym. Sci., Polym. Chem. Ed.
1984, 22, 341.
(52) Synthesis of P1
1
A 20 mL glass vial equipped with a stir bar was charged with
the octyl azide (2.9 mg, 0.019 mmol, 1.5 equiv), THF (0.380 mL),
and P0 (8.3 mg, 0.013 mmol, 1 equiv), and the mixture was son-
icated briefly until the polymer dissolved. After dissolving the
polymer, the mixture was stirred at r.t. for 30 min. THF was
evaporated under reduced pressure, and the polymer was tritu-
rated with Et2O (3 × 1 mL, to remove excess azide) and then
yellow solid. H NMR spectrum in the Supporting Information.
Mn: 71.4 kDa, Mw: 107.7 kDa, Ð: 1.51 (GPC).
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2005, 127, 366.
(55) Ji, X.; Yao, Y.; Li, J.; Yan, X.; Huang, F. J. Am. Chem. Soc. 2013, 135,
74.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2018, 29, A–G