Star polymer synthesis: Via λ-orthogonal photochemistry

Article abstract of DOI:10.1039/c6cc03848d

We introduce a light induced sequence enabling λ-orthogonal star polymer formation via an arms-first approach, based on an α,ω-functional polymer carrying tetrazole and o-methyl benzaldehyde moieties, which upon irradiation can readily undergo cycloaddition with a trifunctional maleimide core. Depending on the wavelength, the telechelic strand can be attached to the core at either photo-reactive end.

Full text of DOI:10.1039/c6cc03848d

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DOI: 10.1039/C6CC03848D
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Star Polymer Synthesis via 흀-Orthogonal Photochemistry
ab
ab
a
a
c
Kai Hiltebrandt, Michael Kaupp, Edgar Molle, Jan P. Menzel, James P. Blinco,* and
abc
Received 00th January 20xx,
Accepted 00th January 20xx
Christopher Barner-Kowollik*
DOI: 10.1039/x0xx00000x
www.rsc.org/
We introduce a light induced sequence enabling 흀-orthogonal star have termed this process 흀-orthogonal chemistry. The first 흀-
polymer formation via an arms-first approach, based on an α,ω- orthogonal system featured a tetrazole and photoenolisable o-
functional polymer carrying tetrazole and o-methyl benzaldehyde methyl benzaldehyde as the photoactive moieties that
moieties, which upon irradiation can readily undergo underwent cycloadditions with electron poor enes such as
cycloaddition with a trifunctinal maleimide core. Depending on maleimides. Irradiation in the wavelength range between 260
the wavelength, the telechelic strand can be attached to the core and 320 nm triggerd transformation of the tetrazole moiety
1
3
at either photo-reactive end.
into a nitrile imine reactive intermediate that subsequently
undergoes a [3+2] cycloaddition reaction with an ene yielding
Star shaped polymers find widespread applications in various
scientific and industrial fields. The physical and mechanical
14
a 4,5-dihydro-pyrazole. The benzaldehyde moiety is activated
in the complimentary wavelength range of 320-360 nm in
1
properties of the majority of polymers are strongly influenced
by the degree of branching of the polymer backbone, thus the
properties of star and branched polymers can differ from
those of their linear analogues. For example, hyperbranched
which a highly reactive diene (o-quinodimethane) is formed
that undergoes a [4+2]-cycloaddition Diels-Alder reaction.
15
The above system allows for an orthogonal reaction sequence
in which benzaldehyde terminated polymers were selectively
activated in the presence of tetrazole capped polymers and an
2
macromolecules show viscoelastic properties and are used in
3
4
polymer blends and coatings. In addition, end group
modified star polymers have been selectively crosslinked to
generate networks via irradiation in discrete wavelength
16
equimolar amount of maleimides.
5
regimes. Well defined star polymers have previously been
synthesised using controlled polymerisation techniques such
6
as atom transfer radical polymerisation (ATRP) , reversible
7
addition-fragmentation chain transfer (RAFT) polymerisation
8
and nitroxide mediated polymerisation (NMP) directly via
multi-arm initiators, yet also in combination with modular
9
ligation strategies. An extension of this concept has been
introduced which exploits the advantages of photo-driven click
chemistry – high yields, equimolarity, fast reaction kinetics,
1
0
11
simple product isolation , eco-friendly reactions and uphill
photosensitization
12
– yet additionally allows for the
independent reaction of multiple photo-click ligations in one
pot based solely on the employed activation wavelength. We
a.Preparative Macromolecular Chemistry, Institut für Technische und
Polymerchemie, Karlsruhe Institute of Technology (KIT), Engesserstraße 18, 76128
Karlsruhe, Germany. Email: christopher.barner-kowollik@kit.edu
Figure 1: UV/vis absorption spectra of the o-methyl benzaldehyde and a
tetrazole moiety. The absorption of both photoactive compounds shows a
negligible overlap area between 320-360 nm leading to a selective activation of
the benzaldehyde in the presence of tetrazole in the indicated wavelength
regime (blue box).
b.
Institut für Biologische Grenzflächen (IBG), Karlsruhe Institute of Technology (KIT),
Hermann-von Helmholtz-Platz 1, 76344 Eggenstein-Leopoldshafen, Germany.
School of Chemistry, Physics and Mechanical Engineering, Queensland University
c.
of Technology (QUT), 2 George St, Brisbane, QLD 4000, Australia.
Email: christopher.barnerkowollik@qut.edu.au, email: j.blinco@qut.edu.au
†
Electronic Supplementary Information (ESI) available: Comprehensive
experimental and analytical information. See DOI: 10.1039/x0xx00000x
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DOI: 10.1039/C6CC03848D
Scheme 1: Light induced orthogonal star polymer synthesis by the selective addition of an α,ω-functional molecule
2
carrying a benzaldehyde (red) and a tetrazole
(
green) functionality to the trifunctional maleimide centre
1
. The irradiation of
1
(1 eq.) and the imine protected telechelic
is terminated with an aryl imine. Subsequent imine hydrolysis results in the re-activation of
(1 eq.) and PEG-maleimide (3 eq.) are irradiated at = 300-440 nm
(left part). The reaction strategy – selective benzaldehyde activation before tetrazole activation – was performed by the photochemical
= 300-440 nm according to the photoenol centre attached precursor . The subsequent irradiation of with pL-maleimide 10 at = 280-
4 (3 eq.) at 흀 = 280-440 nm leads to the
selective tetrazole attachment to
the aldehyde end groups
yielding the star polymer
1. The resulting star shaped structure 5
6. The star shaped structure containing benzaldehyde end groups
6
7
흀
8
ligation of
2
towards
1
at
흀
9
9
흀
4
40 nm leads to the star polymer 11 (right).
However, the reverse reaction path – in which the tetrazole sequence with the novel reaction path constitute a one pot
polymer is activated first – is not possible within this reaction system allowing the synthesis of two different star polymers
sequence due to overlapping absorbances in the UV range from identical starting materials in an orthogonal fashion
below 320 nm. A fully
that the two reaction paths be activated independently of one The irradiation of
another using mutually exclusive wavelengths in a one pot eq.) at = 310-370 nm leads to the selective attachment via
reaction system. the benzaldehyde moiety of the maleimide core yielding the
The present contribution closes this critical gap, allowing star shaped structure . Maleimide terminated polylactide 10
tetrazole activation prior to the benzaldehyde by the (3 eq.) and (1 eq.) are subsequently irradiated at = 270-
흀-orthogonal ligation system requires (Scheme 1).
1
(1 eq.) and the α,ω-functional polymer 2 (3
흀
1
9
9
흀
reversible deactivation of the aldehyde species with 310 nm leading to the 3 arm star shaped polymer 11 (right
hexylamine yielding an imine prior the irradiation process. As part). This was then followed by the tetrazole activation – the
the formed imine is inert to any light induced reactions, the complimentary photoreaction with the 흀-orthogonal system –
tetrazole is able to react without competition in the range affording a 3 arm star polymer with benzaldehyde at the core
between 260-320 nm. After the complete conversion of the and polylactide terminated chains. A collation of the star
tetrazole functionality in the one pot system, the deprotection shaped polymers is depicted in Scheme 2.
of the imine via a fast hydrolysis step freeing the photoactive The choice of an appropriate light source is key to achieve a
aldehyde is performed allowing subsequent reaction when selective activation in the aforementioned absorption regions.
irradiated at
The combination of the
including the original wavelength dependent reaction tetrazole end group functionality
흀
= 320-360 nm.
To demonstrate, tris(2-maleimidoethyl)amine
-orthogonal chemistry concept α,ω-functional polymer carrying a benzaldehyde and a
1 (1 eq.) and the
흀
2
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Scheme 2: Star polymer structures
9 and 11, obtained by the initial
benzaldehyde activation and a subsequent tetrazole activation.
Scheme 3: Overview of the star polymer structures
5, 6, and 8 which are
obtained from initial tetrazole activation and subsequent benzaldehyde
activation.
centre by deactivating the benzaldehyde moiety through
transformation to an imine. In general, protecting groups in
photochemical applications show a photolabile behaviour,
where they are removed upon irradiation revealing various
17
functionalities. In addition, systems containing wavelength-
selective photolabile protecting groups have been reported.18
However, the example presented here is not photolabile. The
photoactive benzaldehyde species is transformed into an
imine leading to the temporary photochemical deactivation of
the compound. A shift in the light absorption between the
α,ω-functional polymer carrying the benzaldehyde and the
subsequently yielded imine end group was recorded via UV/vis
spectroscopy (refer to ESI Figure S13).
The benzaldehyde modification of the α,ω-functional polymer
is key for the novel 흀-orthogonal reaction sequence – so the
tetrazole moiety can react prior to the benzaldehyde
activation – before the irradiation procedure can actually start.
Figure 2: A system consisting of the trifunctional maleimide
1 and the α,ω-
functional
was irradiated for 3 h with the PL-L lamp leading to the selective formation of
The star shaped oligomer was subsequently mixed with the maleimide
2, carrying the benzaldehyde and tetrazole end group functionalities,
9.
9
terminated polylactide 10 and irradiated for 13 h at
흀 = 280-440 nm forming the
star polymer 11. GPC reported to a PS calibration.
In this context, the α,ω-functional polymer
2 (1 eq.) and
2
3
(3 eq.) were irradiated for 3 h in the wavelength range of
10-440 nm in dichloromethane (ESI Figure S1). Evidence for
hexylamine (2.8 eq.) were dissolved in dry THF for 3 h
3
yielding quantitative imine formation. The successful imine
the successful ligation between the benzaldehyde moiety and
the maleimide centre resulting in the star shaped structure
terminated with tetrazole moieties
1
transformation was evidenced via H NMR (refer to ESI Figure
S10), Orbitrap ESI-MS (refer to ESI Figure S11), and GPC (refer
to ESI Figure S12). The light induced tetrazole reaction was
then performed by irradiating tris(2-maleimidoethyl)amine
9
was obtained via GPC.
1
The quantitative conversion is illustrated in Figure 2. H NMR
analysis also evidences the complete benzaldehyde conversion
after irradiation, yet it should be noted that a small amount of
tetrazole attachment to the maleimide centre (< 4 %
conversion) is detectable (refer to ESI S17). Finally, the
photoenol cored star precursor
groups was used as starting material for the final ligation step.
In this case, and the maleimide terminated polylactide 10
were irradiated for 13 h at = 280-440 nm (refer to ESI Figure
1
(
1 eq.) and the imine containing polymer (3 eq.) for 13 h with
4
the Arimed B6 lamp (refer to ESI Figure S1) in the wavelength
range of 280-440 nm in dichloromethane. Evidence for the
successful ligation between the tetrazole moiety and the
maleimide core resulting in the star shaped structure
9 carrying three tetrazole end
terminated with aryl imine moieties
5 was determined via
9
GPC. The quantitative conversion is illustrated in Figure 3.
흀
1
H NMR underpins the complete and selective tetrazole
S1) in the wavelength range of 280-440 nm in
dichloromethane. The macromolecular star shaped structure
1
conversion after the irradiation, whereas the benzaldehyde
compound remained unreacted (refer to ESI Figure S14). The
stability of the imine protection group under irradiation was
additionally demonstrated via the selective addition of
maleimide to a benzaldehyde terminated poly(ethylene glycol)
with and without hexylamine (refer to ESI Figure S19). The
1
was analysed via GPC in order to evidence the
흀-orthogonal
1
ligation steps (refer to Figure 2). A H NMR indicates a
quantitative NITEC reaction of the tetrazole end groups of
with the maleimide functionality of the polylactide 10 (refer to
ESI S18). Our novel, inverse -orthogonal method allows for
the tetrazole attachment initially to the trifunctional
maleimide
9
흀
imine hydrolysis was performed by dissolving
dichloromethane and adding wet molecular sieves. The
5
in
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hydrolysis overnight led to the benzaldehyde terminated star
precursor and according
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DOI: 10.1039/C6CC03848D
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1
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4
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functional polymer was selectively attached to the maleimide
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– allowing wavelength-dependant ligation –
1
demonstrates that the photochemical synthesis of complex
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C.B-K. acknowledges funding from the Karlsruhe Institute of
Technology (KIT) in the context of the Helmholtz STN program.
K.H.’s PhD studies were partly funded by the Fond der
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Star Polymer Synthesis via 흀-Orthogonal Photochemistry
흀
-Orthogonal photo-induced ligation in two directions is
introduced via a modular, light driven selective star shaped
polymer formation.
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