A metathesis route for BODIPY labeled polyolefins

Article abstract of DOI:10.1021/ol401461h

It is demonstrated how acyclic diene metathesis polymerization (ADMET) provides an efficient strategy for the labeling of polyolefins. The versatility of phosphorus chemistry allows designing substituted BODIPY monomers or chain stoppers for the synthesis of precise labeled (degradable) polyphosphoesters.

Full text of DOI:10.1021/ol401461h

ORGANIC
LETTERS
2013
Vol. 15, No. 15
3844–3847
A Metathesis Route for BODIPY Labeled
Polyolefins
Filippo Marsico,§ Andrey Turshatov, Katja Weber, and Frederik R. Wurm*
Max Planck Institute for Polymer Research, Ackermannweg 10, 55128 Mainz, Germany
wurm@mpip-mainz.mpg.de
Received May 23, 2013
ABSTRACT
It is demonstrated how acyclic diene metathesis polymerization (ADMET) provides an efficient strategy for the labeling of polyolefins. The
versatility of phosphorus chemistry allows designing substituted BODIPY monomers or chain stoppers for the synthesis of precise labeled
(degradable) polyphosphoesters.
Chemical labeling exhibits great potential for obtaining
traceable steadily stained materials for versatile applica-
tions such as optical bioimaging and signal amplification
in biological diagnostics.1,2 In the family of organic dyes,
the set based on BODIPY (boron-dipyrromethene or 4,4-
difluoro-4-bora-3a,4a-diaza-s-indacene) has attracted in-
creasing attention over the past decade.3 BODIPY-based
functional materials continuously expand their range of
applications because of the unique photophysical proper-
ties, such as excellent thermal and photochemical stability,
good solubility, and intense absorption profile. BODIPY’s
chemical robustness allows the design of functional
systems for paint, ink compositions, and electrolumi-
nescent devices.4
One of the main features that makes this organic dye
extremely attractive is the possibility to modify its molec-
ular backbone in a straightforward manner. Great poten-
tial was recognized for biochemical purposes, resulting in
the raised awareness of this stable dye and its use among
biologists, for example for the labeling of biomacromole-
cules such as DNA.5
Because of their functionality and similarity to DNA, in
recent years synthetic polyphosphoesters have attracted
attention in biomaterial science.6 Typically, polyesters
dominate the field and are widely applied in pharmaceutics
and medical applications, because of their excellent bio-
compatibility and degradability.7
§ Graduate School Materials Science in Mainz, Staudinger Weg 9, 55128,
Germany.
(1) Beija, M.; Charreyre, M.-T.; Martinho, J. M. G. Prog. Polym. Sci.
The structural versatility of phosphorus, combined with
a straightforward synthetic approach, allows generating
novel functional polymerizable organophosphates.8 These
compounds can undergo acyclic diene metathesis (ADMET)
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r
10.1021/ol401461h
Published on Web 07/19/2013
2013 American Chemical Society

Scheme 1. Metathesis Polycondensation of Phenyl-di-(10-undecenyloxy)-phosphate 4 in Presence of BODIPY Dyes (2 and 3)
or ring-opening metathesis polymerization (ROMP) and
thus can be converted into synthetic polyphosphoesters.
To date different strategies for the synthesis of complex
BODIPYÀpolymer conjugates, mostly by anionic or rad-
ical polymerization, have been reported.9 In contrast,
little attention was given to the precise incorporation of
these dyes into degradable polymers, which has become of
particular scientific and application relevance.1 Different
synthetic strategies allow the synthesis of functional
BODIPY derivatives via cross-coupling of organometallic
compounds,10 click chemistry,11 or radical or photochemical
polymerizations.12 To the best of our knowledge, this is the
first report on a strategy (Scheme 1) based on ADMET for
the facile preparation of precise labeled polymers that
further expand the toolbox of biodegradable polyesters
based on phosphorus.
Figure 1. GPC elugram (in THF) for polymer 6 showing the
fluorescence (λ = 540 nm) and the refractive index detection.
A ROMP metathesis strategy for the synthesis of fluoro-
genic polymers was developed by using norbornene
derivatives and suitable fluorophores.13 However this
(8) (a) Marsico, F.; Wagner, M.; Landfester, K.; Wurm, F. Macro-
molecules 2012, 45, 8511. (b) Steinbach, T.; Alexandrino, E.; Wurm, F.
Polym. Chem. 2013, 4, 3800.
strategy is limited to only a few monomers that can be
polymerized by this technique. Our model system offers
€
€
€
(9) (a) Zettl, H.; Hafner, W.; Boker, A.; Schmalz, H.; Lanzendorfer,
€
many possibilities to design and label various types of
polyolefins, because a wide range of functional acyclic
diene monomers is available for ADMET14 in combina-
tion with a robust synthetic protocol based on phosphorus
oxychloride. Ruthenium-based complexes such as the
catalysts of Grubbs provide, furthermore, an efficient
and functional-group tolerant tool for olefin metathesis,
under mild conditions with quantitative conversion.15
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K.; Nagata, Y.; Chujo, Y. J. Am. Chem. Soc. 2008, 130, 15276.
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Graff, B.; Fouassier, J.-P. Macromolecules 2012, 45, 6864.
(13) (a) Mangold, S. L; Carpenter, R. T.; Kiessling, L. L. Org. Lett.
(14) Opper, K. L.; Wagener, K. B. J. Polym. Sci., Part A: Polym.
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(15) (a) Hilf, S.; Kilbinger, A. F. M. Nat. Chem. 2009, 1, 537. (b) Dias,
E. L.; Nguyen, S. T.; Grubbs, R. H. J. Am. Chem. Soc. 1997, 119, 3887.
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Org. Lett., Vol. 15, No. 15, 2013
3845

Scheme 2. Synthesis of Polymerizable BODIPY 2
Figure 2. UVÀvisible (solid lines) and fluorescent spectra
(dashed lines) for monomeric dyes and the respective polymers.
(a) BODIPY 2 in toluene (black), polymer 6 in toluene (red), and
thin solid film (blue); (b) BODIPY 3 in toluene (black), polymer
5 in toluene (red), and thin solid film (blue).
tailoring the monomer ratios as both carry electron-rich
olefins, leading to random incorporation into the poly-
mer backbone and high molecular weights via ADMET
(compare Table S30 in the Supporting Information); the
photophysical properties of the dye stay undisturbed after
polymerization when the polymer is dissolved in organic
solvent (Figure 2 and Table 1). Further, an incorporation
efficiency of 100% of 2 and 3 in the polymers was obtained
(Table S30). The precise percentage of labeling is crucial to
maintain the conformation of the polymer chain, minimiz-
ing self-quenching between dyes in close proximity. In a
second approach, we used metathesis to selectively label
the end groups with 3 that acts as a chain stopper in the
polycondensation reaction. In a one-step reaction, this
chain stopper was allowed to introduce precisely and
homogeneously the fluorescent moieties at the ends of the
polymer backbone in a quantitative manner; it can also be
used for labeling other compounds by cross metathesis,
making it a valuable compound for future work.
More importantly, this strategy allows tailoring the
desired molecular weight, as 3 is quantitatively incorporated.
Telechelic polymer 5 (Mw 30 000 g/mol, polystyrene stan-
dards in THF, PDI = 1.5) with high optical absorptivity per
weight of polymer was obtained (Scheme 3). These polymers
are promising candidates, for example, to generate fluores-
cent nanoparticles that could find applications as degradable
drug delivery vehicles and to monitor their cell uptake in vitro.
Phosphorus oxychloride is a key compound for the
synthesis of structural versatile organophosphates. This
intermediate can be reacted with a variety of alcohols
to obtain functional and polymerizable phosphoaldehyde
(1, Scheme 2) which is the perfect handle for building the
BODIPY moiety onto the olefinic monomer (details on
the synthesis of 2 and 3 can be found in the Supporting
Information).
As phenyl-di-(10-undecenyloxy)-phosphate 4 is a liquid,
it facilitates the bulk-metathesis copolymerization of the
olefinic BODIPYs allowing the generation of high molecular
weight polymers. In order to ensure covalent labeling of the
polymer, 2 or 3 was used as a comonomer or chain stopper,
respectively, during the polymerization. The relative amount
of 2 allows tailoring the percentage of dye in the polymer,
while BODIPY 3 acts as a terminating agent capping the
polymer chains to allow adjusting the molecular weight and
also the labeling position (at the chain ends in this case).
One important point that should be emphasized here is
the possible influence of the polymer chain on the spectro-
scopic properties of the dye and, conversely, the influence
of the dye on the polymer chain conformation. As proven
by GPC equipped with a fluorescence detector (Figures 1
and S34), homogeneous labeling of the polymers is
achieved. It is possible to tune the percent of labeling by
3846
Org. Lett., Vol. 15, No. 15, 2013

Table 1. Summary of Fluorescences of BODIPY Polymer
Conjugates in Solution and Film
Scheme 3. Structures of Labeled Polyphosphoesters Synthesized
via ADMETa
(λmax
)
lifetime (τ)
quantum yield
entry
nm
ns
(η)
6a
542
542
542
547
546
569
4.8
0.70
0.70
0.72
0.51
0.09
0.10
6aa
5a
4.7
4.6
6b
6ab
5b
2.4
0.95
0.97
a Solution of polymer in toluene. b Polymer film.
other olefinic compounds via olefin metathesis. The me-
tathesis approach offers the possibility of adjusting the
quantity and labeling position at tunable positions, i.e.
along the chain or at the chain end;or also via cross
metathesis to other compounds. As a model we prepared
unsaturated polyphosphoesters which were labeled along
the chain or at the chain ends by controlling the molecular
weights. This one-step olefin metathesis with mono- or
difunctional BODIPY-based dyes is a general protocol to
label polymers that can be prepared by ADMET, for
example, to follow their cell uptake behavior which is
currently under investigation in our group.
a The vial shows the fluorescence of polymer 6 in toluene.
An important property of the labeled polymer (5) is that
the fluorescence quantum yield is very similar to the
monomer (3) in solution but differs in the polymeric film.
The decrease of the quantum yield is likely to originate from
self-quenching because of the rather high dye content.
The direct copolymerization of 2 allows the high molec-
ular weight labeled polyphosphoester 6 to be generated
(Mw 170 000 g/mol, GPC polystyrene standards in THF
PDI = 2.1). By this approach, we were able to increase the
amount of fluorescent comonomer into the polymer chain
6a to seven times that in 6. This tunable labeling keeps the
properties of the mother polymer less affected, demon-
strating with 6a the possibility of obtaining a bright
material with a high extinction coefficient and strong
fluorescence without self-quenching (Table 1).
Acknowledgment. The authors thank Prof. Dr. Katharina
Landfester (Max Planck Institute for Polymer Research,
Mainz, Germany) for support. F.M. thanks Material
Science in Mainz and the Max Planck Society for financial
support. F.R.W. thanks the Max Planck Graduate Center
for support.
Supporting Information Available. Full experimental
details and characterization data. This material is avail-
able free of charge via the Internet at http://pubs.acs.org.
In summary, two new BODIPY 2 and 3 derivatives have
been synthesized which can be used to label polymers and
The authors declare no competing financial interest.
Org. Lett., Vol. 15, No. 15, 2013
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