Click-Functionalization of a Poly(Tetrazine-co-Fluorene)-Conjugated Polymer with a Series of trans-Cyclooctene Derivatives

Article abstract of DOI:10.1002/anie.202010795

A soluble poly(tetrazine) polymer was prepared via Suzuki polycondensation of 3,6-bis(5-bromofuran-2-yl)-1,2,4,5-tetrazine and a fluorene diboronate derivative. It can undergo efficient and quantitative post-polymerization inverse-electron-demand Diels–Al

Full text of DOI:10.1002/anie.202010795

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Conjugated Polymers
Hot Paper
Click-Functionalization of a Poly(Tetrazine)-co-Fluorene-Conjugated
Polymer with a Series of trans-Cyclooctene Derivatives
Vladimir Kardelis, Maria M. Denk, and Alex Adronov*
Abstract: A soluble poly(tetrazine) polymer was prepared via
Suzuki polycondensation of 3,6-bis(5-bromofuran-2-yl)-
1,2,4,5-tetrazine and a fluorene diboronate derivative. It can
undergo efficient and quantitative post-polymerization in-
verse-electron-demand Diels–Alder click reactions with a vari-
ety of trans-cyclooctene (TCO) derivatives. The resulting
polymers were oxidized to convert dihydropyridazine rings
into pyridazines. The absorption spectra of the product
polymers, both before and after oxidation, showed hypsochro-
mic shifts that correlated with steric hindrance of the appended
side chains. They also exhibited a significantly enhanced
fluorescence intensity relative to the original poly(tetrazine).
While gel-permeation chromatography indicated that the
product polymers exhibited longer retention times, NMR
end-group analysis showed that the polymers retained rela-
tively constant degrees of polymerization. Graft copolymers
were easily prepared via reaction with TCO-functionalized
poly(ethylene glycol) chains and a cross-linked foam was
produced by reacting the poly(tetrazine) with a bis-TCO
crosslinker.
molecular weight and dispersity in conjugated polymers
remains a challenge in all but a few specialized polymeri-
zation methods.[15–21] These factors greatly impact the resul-
tant polymer morphologies and other physical properties,
such as solubility. Thus, post-polymerization functionalization
has been widely considered. Although modification of a pre-
formed conjugated polymer can be routinely achieved
through the chemistry of side-chains, quantitative changes
to the conjugated backbone are much more difficult. Only
a few examples of efficient modification of a conjugated
polymer backbone have been published, including Cu(OTf)2-
catalyzed benzannulation of phenylene ethynylenes,[22] and
nucleophilic aromatic substitution on aryl fluoride derivatives
of benzothiadiazole monomer units.[23]
In previous work, we have shown that post-polymeri-
zation functionalization of a dibenzocyclooctyne (DIBO)-
containing conjugated polymer is possible via strain-promot-
ed alkyne-azide cycloaddition (SPAAC).[24–26] Not only is
SPAAC functionalization rapid (2nd order rate constant of
0.031 MÀ1 sÀ1), but the reaction was shown to be efficient
enough to quantitatively functionalize the polymer backbone
with 24 kDa polystyrene azide, resulting in a graft copolymer
having a number average molecular weight (Mn) exceeding
800 kDa.[24] Though a versatile polymer, the DIBO-contain-
ing polyimine is plagued with poor hydrolytic stability,[27] and
the multi-step synthesis to the monomer is prohibitive to its
applications (six steps; overall yield of 7%). In addition,
classic metal-mediated cross-coupling conditions cannot be
used to polymerize the cyclooctyne monomer, as it rapidly
generates metallocycles with the strained triple bond. Fur-
thermore, upon SPAAC coupling with azide derivatives, we
found that the polymer backbone adopts a severely kinked
conformation, which detracts from any favourable optoelec-
tronic properties that the parent polymer exhibits.
Rather than working with strained cyclooctynes as the
reactive moiety, which precludes classic transition metal-
catalyzed cross coupling polymerizations, we decided to
introduce the s-tetrazine moiety into the polymer backbone.
1,2,4,5-Tetrazines undergo inverse-electron-demand Diels–
Alder (IEDDA) reactions with various cyclooctenes, cyclo-
octynes, and norbornenes with 2nd order rate constants
ranging from 1 to 106 MÀ1 sÀ1.[28] In addition to their fast
reaction rates and bioorthogonal reactivity, 1,2,4,5-tetrazines
are relatively simple to synthesize, often in 1–2 steps from
commercially available starting materials. Furthermore, they
tolerate Suzuki conditions, which facilitate the formation of
high molecular weight conjugated polymers. Herein, we
describe a convenient method for synthesizing a conjugated
s-tetrazine-containing polymer and its resultant series of
Introduction
Since their discovery, conjugated polymers have played an
increasingly important role in numerous disruptive technol-
ogies. The wide array of structures that constitute the polymer
backbone allows their optimization for applications that
include lighting and displays,[1] energy generation and stor-
age,[2,3] sensors,[4,5] field-effect transistors,[6,7] as well as
information storage and computing.[8] Avariety of conjugated
polymer properties can be modified by varying polymer
structure, including band gap, HOMO and LUMO levels,
extinction coefficient, quantum yield, conductivity, and sol-
ubility.[9–14] However, modification of polymer properties
typically requires the preparation of new polymer structures,
which are prepared via de novo synthesis incorporating new
monomers.[12] When developing polymers for new applica-
tions, it is often necessary to prepare libraries of homologous
polymers that exhibit only small changes from one to another.
Such small changes are difficult to achieve when carrying out
polymerizations with different monomers, as control over
[*] V. Kardelis, M. M. Denk, A. Adronov
Department of Chemistry and Chemical Biology and the Brockhouse
Institute for Materials Research, McMaster University
1280 Main Street West, Hamilton, Ontario, L8S 4M1 (Canada)
E-mail: adronov@mcmaster.ca
Supporting information and the ORCID identification number(s) for
the author(s) of this article can be found under:
https://doi.org/10.1002/anie.202010795.
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Scheme 1. Synthesis of the s-tetrazine-Br2 monomer (a), and synthesis of the s-tetrazine containing polymer P1 (b).
cycloadduct polymers via post-polymerization IEDDA
chemistry.
Preparation of TCO Derivatives
Having prepared the reactive polymer P1, we set out to
investigate its ability to undergo inverse electron demand
Diels–Alder (IEDDA) reactions with a small library of trans
cyclooctene (TCO) derivatives. This began with the prepara-
tion of rel-(1R, 4E, pR)-Cyclooct-4-enol (5) from the corre-
sponding (Z)-cyclooct-4-enol following the procedure of Fox
and co-workers.[31] The TCO derivatives were synthesized via
activation of 5 using nitrophenyl chloroformate to form
carbonate 6, followed by the substitution of the activated enol
with a series of amines to yield carbamates 7a–f (Scheme 2).
Aliphatic and benzylic amines were used due to their
relatively high nucleophilicity, allowing the reactions to be
performed at room temperature, thereby minimizing the risk
of thermal reisomerization to the (Z)-cyclooctenol. All
coupling reactions with the small molecule derivatives
proceeded to high conversion, allowing isolation of the
desired products (7a–e) in excellent yield ( ꢀ 90%) after
chromatographic purification. In addition, a 5 kDa a-me-
thoxy w-amino poly(ethylene glycol) (PEG-NH2) was ap-
pended in order to investigate the formation of a graft
copolymer via IEDDA. The resulting PEG-TCO derivative
(7 f) was isolated in 74% yield after precipitation.
Results and Discussion
Preparation of s-Tetrazine-Containing Polymer (P1)
The tetrazine monomer 2 was synthesized according to
a literature procedure,[29] wherein commercially available 2-
furonitrile undergoes a modified Pinner reaction with hydra-
zine hydrate followed by an oxidation with isoamyl nitrite to
generate the s-tetrazine 1 (Scheme 1a). This tetrazine was
then doubly brominated using N-bromosuccinimide to yield
the desired s-tetrazine-Br2 monomer 2 in a modest 31% yield
over the two steps. Monomer 2 was readily copolymerized
with a previously synthesized fluorene bis(pinacolato)boro-
nate ester comonomer 3[30] via Suzuki polycondensation
under mild conditions (508C for 15 minutes) to yield the
progenitor s-tetrazine-containing polymer P1 (Scheme 1b).
The Suzuki reaction produced a polymer with a number
average molecular weight of 38.8 kDa and a dispersity (ꢀ) of
1.6, as determined by gel permeation chromatography (GPC).
To provide a functional NMR handle that could be used to
corroborate the GPC data for P1 and all subsequent cyclo-
adduct polymers, growing polymer chains were end-capped
by adding p-anisole pinacolato boronate ester 4 and allowing
the mixture to stir for 30 min. Anisole was used because the
phenyl methoxy group provides a distinct 1H-NMR resonance
at ꢀ 3.85 ppm, which does not overlap with any other signals
corresponding to the polymer chain (See Supporting Infor-
mation, Figure S26). Based on the integration of this signal,
the degree of polymerization (DP) for P1 was found to be 44,
which corresponds to an Mn (NMR) of 36.3 kDa, in excellent
agreement with the GPC data. The reactive, conjugated
polymer P1 was further characterized via UV/Vis, and
infrared (IR) spectroscopy, as well as by thermogravimetric
analysis (TGA), with details provided in the Supporting
Information. The TGA thermogram of this polymer showed
two distinct decompositions, including a 7% mass loss at
ꢀ 2808C corresponding to the loss of N2, and a 78% mass loss
at ꢀ 4008C corresponding to the loss of the hexadecyl side-
chains of the fluorenyl monomer (Figure S62).
Scheme 2. Preparation of a library of trans-cyclooctene (TCO) deriva-
tives.
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Post-Polymerization IEDDA Onto P1
The IEDDA reactions between P1 and the TCO deriv-
atives 5 and 7a–e were carried out by combining a small
excess (1.5 equiv per polymer repeat unit) of each derivative
with P1 in tetrahydrofuran at room temperature (Scheme 3).
Upon mixing, effervescence was immediately observed as
a result of N2 evolution, providing visual confirmation that the
reaction was occurring. Stirring the reaction mixture at room
temperature for 30 minutes resulted in a visible increase in
solution viscosity, and quantitative conversion of the tetra-
zines to the cycloadducts. This could be easily confirmed by
the complete disappearance of signals at 7.05 and 7.90 ppm in
the NMR spectrum, which correspond to the furyl protons
that are adjacent to the tetrazine groups in P1 (Figure 1a). It
should be noted that, because the TCO derivatives are not
symmetrical about the C2 axis, each of the dihydropyridazine
subunits within the products (P2, P2a–f) is formed as
a mixture of two regioisomers (Scheme 3b), which consid-
erably complicates the 1H-NMR spectra associated with these
products. It should also be noted that IEDDA of trans-
cyclooctenes onto s-tetrazines yields 4,5-dihydropyridazines,
which readily tautomerize into 1,4-dihydropyridazines as
evident by the presence of an N-H resonance between 8
1
and 9 ppm in the H-NMR spectra (see spectrum for P2a in
Figure 1a, as well as additional 1H-NMR spectra in the
Supporting Information, Figures S27–S33). In addition to
NMR analysis, IR corroborated the introduction of the TCO
derivatives on the polymer backbone with the strong carbonyl
stretch of the primary carbamates observed at 1708–
1722 cmÀ1 for each of the products (see Supporting Informa-
tion, Figures S72–S78). The molecular weight of each of the
functionalized product polymers was measured by both GPC
and NMR, with observed values provided in Table 1. In most
cases, the apparent number average molecular weight (Mn)
observed by GPC was in good agreement with the corre-
sponding value from NMR, both of which indicated a small
Figure 1. a) NMR data illustrating the sequential transformation of P1
upon clicking and oxidation. b) UV/Vis absorption data for P1 (black),
P2-a (blue), and P3-a (green), illustrating the effect of breaking
conjugation (hypsochromic shift) upon click coupling, followed by
reformation of conjugated structures upon oxidation (bathochromic
shift).
Table 1: GPC and NMR molecular weights for polymers produced.
Polymer
NMR
GPC
Mn [kDa]
DP
Mn [kDa]
Mw [kDa]
ꢀ
P1
P2
36.3
36.0
53.3
45.9
45.0
46.5
47.2
36.8
51.0
47.5
41.8
45.9
56.6
44
39
45
44
45
44
44
40
43
45
42
44
44
38.8
12.2
46.8
40.9
39.3
38.4
33.5
12.9
24.6
14.1
16.4
25.5
17.8
63.7
15.0
67.8
71.8
82.5
79.6
53.4
22.6
45.4
24.2
28.8
45.4
33.1
1.64
1.23
1.45
1.76
2.10
2.07
1.60
1.76
1.84
1.72
1.76
2.08
1.86
P2a
P2b
P2c
P2d
P2e
P3
P3a
P3b
P3c
P3d
P3e
increase in molecular weight as a result of the side chains that
were appended via the IEDDA reactions. In the case of P2,
the significant decrease in apparent molecular weight from
the GPC measurement was likely caused by interactions
between the hydroxyl groups in this product with the sta-
tionary phase of the GPC columns, which delays its elution
and results in an observed Mn value that is lower than the
actual value. Additionally, reaction progress could be moni-
Scheme 3. Inverse Electron Demand Diels Alder (IEDDA) reaction to
functionalize polymer P1 with TCO derivatives (a). Illustration of the
two regioisomers that are possible at each clicked repeat unit (b).
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tored by UV/Vis spectroscopy, where the strong absorption of
sponding to the dihydropyridazine between 8 and 9 ppm
P1, centered around 460 nm, undergoes a significant hypso-
chromic shift to 400 nm in P2. The extent of this shift for each
of the polymers, including P2a–e, is given in Table 2, and
correlates well with steric hindrance from the appended side-
chain, which would result in a twisting of the polymer
backbone and decreased conjugation length. In addition,
while the unreacted poly(tetrazine) P1 exhibited only very
weak fluorescence, the cycloadduct dihydropyridazine poly-
mers (P2, P2a–e) exhibited much stronger fluorescence, with
a broad emission band centered around 510 nm (Supporting
Information, Figures S54–S59). In fact, the onset of fluores-
cence could be observed by carrying out the reaction while
irradiating the reaction vessel with UV light at 365 nm (video
1, Supporting Information).
(Figure 1a), indicating that the oxidation was effective. The
IR spectra of the product polymers did not change appreci-
ably upon oxidation (Figures S72–S79), but the absorption
spectrum of each polymer underwent a bathochromic shift,
ranging from 16 to 38 nm (Table 2 and Figures S47–S52). This
indicates that the formation of pyridazine rings results in
increased conjugation along the polymer backbone. In all
cases, fluorescence of the oxidized polymers slightly increased
in intensity, and spectra exhibited small changes to fine
structure (see Supporting Information, Figures S54–S59). The
changes in absorption and emission spectra for P3 relative to
the original polymer P1 are illustrated in Figure 2, which
Table 2: Absorption spectrum lmax values and resultant hypsochromic
and bathochromic shifts produced upon cycloaddition and oxidation of
the polymers, respectively.
Polymer lmax
Polymer lmax
Shift Polymer lmax
Shift
[nm]
[nm] [nm]
[nm] [nm]
P1
457
P2
400
388
402
412
404
405
À57
À69
À55
À45
À53
À52
P3
423
426
424
428
428
427
+23
+38
+22
+16
+24
+22
P2a
P2b
P2c
P2d
P2e
P3a
P3b
P3c
P3d
P3e
Figure 2. Overlay of absorption and emission spectra comparing P1
and P3.
Reaction Kinetics of P1 with TCO-OH (5)
To determine the rate of the reaction between the
poly(tetrazine) P1 and TCO-OH (5), a kinetics study was
performed. The reaction was carried out in a quartz cuvette
with equimolar concentrations of both P1 and 5 (0.242 mM),
and reaction progress was monitored by measuring the
absorption of the reaction mixture at 500 nm over the course
of 90 min. The starting polymer, P1, exhibits a strong
absorption at this wavelength, while the product, P2, exhibits
negligible absorption (Figure 1b). The kinetics study was
performed in triplicate, and resulted in an average second
order rate constant of 1.25 Æ 0.07 MÀ1 sÀ1 (see Supporting
Information). Although a modest rate constant for typical
tetrazine ligations with trans-cyclooctenes, the IEDDA on P1
is two orders of magnitude faster than strain-promoted
alkyne-azide cylooaddition (SPAAC) reactions that we have
previously carried out on polymeric substrates.[32]
shows the significant hypsochromic shift in the absorption
spectrum, and the increase in fluorescence intensity. Interest-
ingly, upon oxidation of the dihydropyridazine backbone to
yield the poly(pyridazines) P3, P3a–e, the observed GPC
molecular weights decrease, while the NMR molecular
weights remain relatively unchanged. The largest decrease
was for P3, which can again be explained by the presence of
hydroxyl groups along the polymer backbone that interact
with the stationary phase of the column. The lower than
expected GPC values for P3a–e indicate that these structures
must either adopt a more compact conformation in solution
than the P2 series, or that the formation of the pyridazine
rings also results in enhanced interaction with the stationary
phase, causing delayed elution. Chain scission as a result of
1
the oxidation process was ruled out by H-NMR end-group
analysis (see Figures S34–S39), which indicated that the
molecular weights were not significantly changed upon
oxidation (Table 1). TGA analysis of the product polymers
was also carried out under Ar atmosphere to determine their
Oxidation of Poly(1,4-Dihydropyridazines)
Considering the goal of producing a set of homologous
conjugated polymers, it was necessary to oxidize the dihy-
dropyridazine rings in P2, and P2a–e in order to aromatize
them into pyridazines. This was accomplished by treating each
of the polymers with 2,3-dichloro-5,6-dicyano-1,4-benzoqui-
none (DDQ) in THFat room temperature for 1 h, resulting in
1
polymers P3, P3a–e (Scheme 4). Upon oxidation, H-NMR
showed a clean disappearance of the N-H resonance corre-
Scheme 4. Oxidation of the clicked poly(1,4-dihydropyridazine) series.
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thermal decomposition patterns and temperatures (see Sup-
Post-Polymerization IEDDA of 5 kDa PEG Onto P1
porting Information, Figures S63–S68). In all cases, two
distinct decompositions were observed, which correspond to
the loss of the Diels–Alder adducts at 200–3008C (4–23%
mass loss, depending on the molecular weight of the TCO
derivative), followed by the loss of the hexadecyl side-chains
of the fluorenyl units at ꢀ 4008C (50–61% mass loss).
To further test the efficiency of the IEDDA cycloaddition
reaction in functionalizing the polymer backbone, a 5 kDa
poly(ethylene glycol)-TCO derivative 7 f was grafted onto P1.
Reaction with 7 f was found to be significantly slower than
with the small molecule derivatives, requiring slight heating
and a longer reaction time. Thus, a small excess (1.2 equiv.) of
7 f was stirred with P1 at 408C for 8 hours, which resulted in
quantitative functionalization of the backbone. Dialysis in
water over 72 h using a 50 kDa molecular weight cutoff
dialysis membrane allowed for the removal of the excess
PEG-TCO carbamate from the reaction mixture, leaving
behind the pure dihydropyridazine graft copolymer P2 f.
Analysis of Polymer Geometry—DFT Calculations
In order to probe the effect of backbone functionalization
via IEDDA on the overall structure of the polymer, we
carried out modeling studies using semi-empirical methods
(Parametric Method 3, PM3). This involved construction of
three separate oligomers (3 repeat units each) corresponding
to the structures prior to functionalization, post functional-
ization with 5, and after oxidation of the dihydropyridazines
with DDQ, followed by geometry optimization of each
structure. As shown in Figure 3, the geometry of starting
polymer P1 is planar, as would be expected from its
conjugated structure. Upon IEDDA with 5, the geometry
retains much of its planarity, with only slight perturbations
caused by the introduction of cyclooctyl rings and the
decreased conjugation that results from formation of the
dihydropyridazines. After oxidation, the calculations indicate
that the P3 polymer backbone adopts a slightly puckered
structure relative to the planarity of P1, but overall remains
relatively planar. This puckering in P2 and P3 is likely caused
by steric interactions between the cyclooctyl ring and the
neighbouring furans, which changes the angle between the
two ring structures away from planarity. To corroborate this,
we carried out additional DFT geometry optimizations on
truncated model compounds and found that the coplanar
rings on either side of the tetrazine unit adopt a ꢀ 308 angle in
the puckered dihydropyridazine structure, but only a 48 angle
upon oxidation to the more planar pyridazine (Figure S3).
These slight changes between P1, P2, and P3 might also
explain some of the differences in apparent hydrodynamic
diameter that contribute to the changes in molecular weight
values observed from GPC.
1
Figure 4 shows the H-NMR spectrum of P2 f overlaid with
the starting polymer P1. The aromatic region displays a similar
shifting of the furyl proton resonances as observed in the
small molecule cycloadditions. Additionally, a large reso-
nance corresponding to the methylene protons of the PEG
chains is observed at 3.7 ppm, indicating the presence of the
graft on the P1 backbone. Consistent with the small molecule
click reactions, an hypsochromic shift is observed in the
polymer UV/Vis spectrum, though the shift is much larger in
the case of P2 f, amounting to over 110 nm (Figure S53). This
large blue-shift is likely caused by a significant twisting of the
polymer backbone away from conjugation in order to
accommodate all of the appended PEG chains. The molecular
weight of PEG graft poly(1,4-dihydropyridazine) P2 f could
not be accurately measured by GPC due to interactions
between the PEG grafts and the column stationary phase,
leading to extensive retention on the column. Additionally,
the functional methoxy end-group handle could not be
accurately integrated via 1H-NMR due to overlap of the
signals with those of the PEG methylene units. As a result,
only a theoretical molecular weight is listed in the Supporting
Figure 4. (a) 1H-NMR spectra of P1 and P2 f, illustrating the shift of
furyl aromatic signals and the appearance of PEG signals upon click
coupling. b) Photograph of the biphasic mixtures of water and toluene
where P1 remains in the organic phase (i), while P2 f dissolves in the
aqueous phase (ii). c) Photograph of the same two mixtures under UV
light irradiation (365 nm), showing that P1 is not appreciably fluores-
cent, while P2 f exhibits strong emission.
Figure 3. Optimized geometry (PM3) of trimers P1 (a), P2 (b), and P3
(c). Note the minimal amount of puckering in the backbones of P2
and P3 upon undergoing IEDDA. Alkyl chains were replaced with
methyl groups to ease computational loads.
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Information. Thermogravimetric analysis of P2 f showed
an intractable red foam as the product. The foam was treated
a single, large mass loss at approximately 4008C, which
corresponds to the decomposition of the grafted PEG chains
that make up nearly 90% of the mass of P2 f.
The PEG-grafted P2 f was found to exhibit a significant
solubility change relative to the parent polymer, P1. While P1
is soluble in organic solvents, such as chloroform, dichloro-
with DDQ to oxidize any dihydropyridazines and isolate the
crosslinked P4 (Figure 5). The spongy red solid was found to
exhibit fluorescence when irradiated with a hand-held UV
lamp at 365 nm.
methane, tetrahydrofuran, and toluene, P2 f exhibits solubil- Conclusion
ity in more polar organics (tetrahydrofuran, alcohols) and was
even soluble in water. Figure 4b illustrates this difference,
showing that P1 remains in the organic phase of a biphasic
mixture of toluene and water, while P2 f prefers the aqueous
phase. When irradiated with a hand-held UV lamp at 365 nm,
only the graft copolymer exhibits fluorescence, with a lem at
ꢀ 475 nm (Figure 4c; see Supporting Information, Fig-
ure S60, for the complete emission spectrum).
We have demonstrated the synthesis of a high molecular
weight conjugated polymer containing reactive s-tetrazine
moieties within the backbone. Functionalization of the
progenitor poly(tetrazine) P1 was conducted via IEDDA
using a series of TCO derivatives to generate a small library of
dihydropyridazine polymers (P2, P2a–e) which were further
oxidized to produce the corresponding conjugated poly(pyr-
idazines) (P3, P3a–e). The product polymers, both before and
after oxidation, exhibited substantial hypsochromic shifts in
absorption, and increased emission intensity, relative to P1.
Molecular modeling studies showed that, upon undergoing
the “click” reaction, the pyridazine rings along the polymer
backbone do not exhibit a significant change in conformation,
remaining relatively planar. NMR analysis indicated that the
“click” reaction did not alter the average degree of polymer-
ization of the polymers. Additionally, IEDDA “click” reac-
tions on the backbone of P1 occur at rates comparable to
those of small molecule s-tetrazines with TCO. The high
efficiency of the IEDDA reaction was demonstrated by
grafting a 5 kDa poly(ethylene glycol)-TCO chain, a reaction
that resulted in quantitative functionalization over 8 hours at
408C. Finally, the P1 backbone can be rapidly crosslinked
with a difunctional TCO resulting in the generation of a foam-
like material.
Crosslinking of P1 with Bis-TCO Carbamate Derivative (8)
In addition to the grafting of poly(ethylene glycol) onto
the backbone of P1, it is also possible to carry out a cross-
linking reaction. Reaction of the nitrophenyl carbonate 6 with
1,4-diaminobutane resulted in the difunctional crosslinker 8
(Figure 5), which could be subsequently used to carry out
IEDDA chemistry to crosslink polymer P1. The crosslinking
chemistry occurs rapidly over the course of several minutes,
liberating a crosslinked network polymer (see Supporting
Information, Video 2, for a video of the process). The N2 gas
evolved from this reaction acts as a blowing agent, resulting in
Acknowledgements
Financial support for this work was provided by the Natural
Science and Engineering Research Council of Canada
(NSERC). V.K. is grateful for support through the NSERC-
PGS-D program. We further thank Dr. S. A. McNelles for
assistance with dialysis and acquisition of MALDI spectra.
Conflict of interest
The authors declare no conflict of interest.
Keywords: click coupling · conjugated polymers ·
functionalization · inverse-electron-demand Diels–
Alder reaction · tetrazine
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Figure 5. a) Use of the bis-TCO crosslinker 8 to crosslink P1 and
produce the network polymer P4. b) Photograph of the crosslinked
foam.
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Angewandte
Research Articles
Chemie
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Manuscript received: August 6, 2020
Revised manuscript received: October 17, 2020
Version of record online: && &&
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Angew. Chem. Int. Ed. 2020, 59, 2 – 9
These are not the final page numbers!

Angewandte
Research Articles
Chemie
Research Articles
Conjugated Polymers
A conjugated polymer containing tetra-
zine groups in the backbone was pre-
pared and found to undergo rapid
inverse-electron-demand Diels–Alder
(IEDDA) click chemistry, enabling facile
functionalization with a variety of trans-
cyclooctene derivatives. The product
polymers change color, become fluo-
rescent, and exhibit changes to their
physical properties, such as solubility,
depending on the functionality that is
appended.
V. Kardelis, M. M. Denk,
A. Adronov*
&&&& — &&&&
Click-Functionalization of
a Poly(Tetrazine)-co-Fluorene-Conjugated
Polymer with a Series of trans-
Cyclooctene Derivatives
Angew. Chem. Int. Ed. 2020, 59, 2 – 9
ꢀ 2020 Wiley-VCH GmbH
www.angewandte.org
&&&&
These are not the final page numbers!