λ-Orthogonal pericyclic macromolecular photoligation

Article abstract of DOI:10.1002/anie.201410789

A photochemical strategy enabling λ-orthogonal reactions is introduced to construct macromolecular architectures and to encode variable functional groups with site-selective precision into a single molecule by the choice of wavelength. λ-Orthogonal pericy

Full text of DOI:10.1002/anie.201410789

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Chemie
DOI: 10.1002/anie.201410789
Polymer Photoreactions
l-Orthogonal Pericyclic Macromolecular Photoligation**
Kai Hiltebrandt, Thomas Pauloehrl, James P. Blinco, Katharina Linkert, Hans G. Bçrner, and
Christopher Barner-Kowollik*
Abstract: A photochemical strategy enabling l-orthogonal
reactions is introduced to construct macromolecular architec-
tures and to encode variable functional groups with site-
selective precision into a single molecule by the choice of
wavelength. l-Orthogonal pericyclic reactions proceed inde-
pendently of one another by the selection of functional groups
that absorb light of specific wavelengths. The power of the new
concept is shown by a one-pot reaction of equimolar quantities
of maleimide with two polymers carrying different maleimide-
reactive endgroups, that is, a photoactive diene (photoenol) and
a nitrile imine (tetrazole). Under selective irradiation at l =
310–350 nm, any maleimide (or activated ene) end-capped
compound reacts exclusively with the photoenol functional
polymer. After complete conversion of the photoenol, subse-
quent irradiation at l = 270–310 nm activates the reaction of
the tetrazole group with functional enes. The versatility of the
approach is shown by l-orthogonal click reactions of complex
maleimides, functional enes, and polymers to the central
polymer scaffold.
deactivation methods.[1] Such polymers find widespread
applications in areas such as drug delivery,[2] self-healing
materials,[3] organic solar cells (OSCs),[4] and microelectron-
ics.[5] Click chemistry is also an excellent method for the
synthesis of macromolecular materials.[6] The concept of click
chemistry was introduced by Sharpless in 2001.[7] Fast reaction
kinetics, quantitative yield, stereoselectivity, equimolarity,
orthogonal reactivity and no purification of the obtained
products are unique features of click chemistry.[8] Never-
theless, thermally induced click reactions lack spatial and
temporal control. Light-triggered click reactions offer a pos-
sibility to overcome these disadvantages.[9] In general, photo-
chemistry is environmentally friendly, can be orthogonal, and
offers the possibility of uphill photosensitization.[10] Herein
we define l-orthogonality of click reactions as the (kinetic)
preference of one reaction channel by using a specific wave-
length regime. Importantly, we wish to impart this orthogon-
ality using cheap, simple, and readily available radiation
sources.
There are examples of wavelength-dependent reactions;
for example, Del Campo et al. synthesized different photo-
active protecting groups consisting of aromatic chromo-
phores. These photoactive groups were then attached to
surfaces. After irradiating one of these chromophores with an
appropriate wavelength, small aromatic molecules and
carbon dioxide are released.[11] Franking et al. demonstrated
the wavelength-dependent (254 nm vs. 350 nm) photochem-
ical grafting of a set of alkenes onto single-crystal TiO2
samples.[12] Inui et al. addressed the wavelength-dependent
cleavage of azirine rings forming nitrile ylides at l > 300 nm
and acetonitrile oxides at l = 300 nm in the presence of
oxygen.[13] All the above studies either successfully establish
the photo-triggered attachment of molecules onto surfaces,
the release of small molecules from surfaces by irradiation, or
the decomposition of photoactive molecules into smaller
fragments. Until now, however, there is no description of
a chemical system that employs orthogonal wavelength-
dependent pericyclic click reactions in a one-pot fashion.
The key to achieve orthogonality in photo-induced click
reactions is to choose appropriate moieties that are kinetically
preferred by a specific wavelength as illustrated in Scheme 1.
Initial kinetic studies of two polymers each carrying
a different photoactive endgroup were performed in the
presence of maleimide in varying ratios. A poly(ethylene
glycol) methyl ether (PEG) chain is capped with 4-((2-formyl-
3-methylphenoxy)methyl)benzoic acid (“photoenol”, a diene
that can be photoactivated) to form compound 1 (Supporting
Information, Figure S3) and capped with 4-(2-phenyl-2H-
tetrazol-5-yl) benzoic acid (“tetrazole”, a nitrilamine that can
be photoactivated) to form compound 2 (Supporting Infor-
mation, Figure S4). Choosing the appropriate irradiation
T
he synthesis of polymers with tailored material properties
has been revolutionized with the advent of reversible
[*] K. Hiltebrandt, Dr. T. Pauloehrl, Prof. Dr. C. Barner-Kowollik
Preparative Macromolecular Chemistry
Institut fꢀr Technische Chemie und Polymerchemie
Karlsruhe Institute of Technology (KIT)
Engesserstrasse 18, 76128 Karlsruhe (Germany)
and
Institut fꢀr Biologische Grenzflꢁchen (IBG)
Karlsruhe Institute of Technology (KIT)
Hermann-von-Helmholtz-Platz 1
76344 Eggenstein-Leopoldshafen (Germany)
E-mail: christopher.barner-kowollik@kit.edu
Dr. T. Pauloehrl
Current address: Institute for Complex Systems
Eindhoven University of Technology
Post Office Box 513, 5600 MD Eindhoven (The Netherlands)
Dr. J. P. Blinco, Prof. Dr. C. Barner-Kowollik
School of Chemistry, Physics and Mechanical Engineering
Queensland University of Technology (QUT)
2 George St, Brisbane, Queensland 4001 (Australia)
K. Linkert, Prof. Dr. H. G. Bçrner
Laboratory for Organic Synthesis of Functional Systems
Humboldt-Universitꢁt zu Berlin
Brook-Taylor-Strasse 2, 12489 Berlin (Germany)
[**] C.B.K. acknowledges continued funding from the Karlsruhe Institute
of Technology (KIT) in the context of the Helmholtz STN program.
K.H.’s PhD studies are funded by the Fonds der Chemischen
Industrie (FCI). H.G.B. acknowledges funding from the ERC (ERC
305064).
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201410789.
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To achieve irradiation in these discrete regions, the
compact fluorescent lamp PL-L with an absorbance maxi-
mum at 370 nm for activating the photoenol-capped polymer
and the compact fluorescent lamp Arimed B12 (Supporting
Information, Figure S1) with an absorbance maximum of
310 nm for activating polymers carrying the tetrazole compo-
nent were employed. When the photoenol or tetrazole
component are activated by the respective UV lamps,
a maleimide acting as dienophile will then undergo selective
reaction with only the activated species (Scheme 1).
In the first kinetic study, eight samples containing an
equimolar mixture of 1 and 2 and a 10.7 equiv excess of
maleimide in dichloromethane were irradiated with the PL-L
lamp for various times from 0 to 15 min (see the Supporting
Information). Next, six samples containing the same mixture
of 1, 2, and maleimide were all initially irradiated for 15 min
with the PL-L lamp and subsequently with the Arimed B12
lamp for 0 to 240 min (see the Supporting Information). To
determine the ratios of each species, the samples were
analyzed by electrospray ionization mass spectrometry. The
evolution of the relative intensities of the substances 1, 2, 3,
and 4 in the mass spectrum were compared after the
irradiation with the PL-L lamp and the Arimed B12 lamp,
respectively (Figure 2; the complete procedure for the
determination of the kinetic data is described in detail in
the Supporting Information). The kinetic data of the samples
that were irradiated only with the PL-L lamp (Figure 2a)
displays an exponential decay of the photoenol capped PEG
1 in combination with the exponential increase of the
corresponding cycloadduct 3. After an irradiation time of
15 min with the PL-L lamp, the conversion is quantitative.
Furthermore, the orthogonal transformation of 1 into 3 after
an irradiation time of 15 min was traced by 1H NMR
spectroscopy (Supporting Information, Figure S26) in excel-
lent agreement with the MS data. The decay of 1 follows
pseudo first-order kinetics, giving a rate coefficient of (8.88 Æ
0.37) ꢀ 10À3 sÀ1 under the chosen conditions (Supporting
Information, Figure S28a). Furthermore, a very slow increase
of the tetrazole-capped PEG 2 in combination with a slow
decrease of the corresponding cycloadduct 4 is detectable.
After 15 min of irradiation with the PL-L lamp, less than 3%
of compound 2 were converted into compound 4. However, if
the tetrazole is irradiated under identical conditions with the
Arimed B12 lamp for 15 min, a significantly higher conver-
sion results than with the PL-L lamp (4% vs 30% determined
Scheme 1. Evidencing l-orthogonal pericyclic reactions. The system
consists of a photoenol derivative 1, a tetrazole derivative 2, and
a dienophile such as maleimide in a true one-pot system. Irradiating
the system with the PL-L lamp selectively affords the photoenol
cycloadduct 3. Subsequently, compound 2 can be transformed into
compound 4 with the Arimed B12 lamp.
wavelength leads to l-orthogonal reactivity. Both the photo-
enol and the tetrazole exhibit an intensive absorption in the
range between 250 and 290 nm. The photoenol shows
a further, less-intense absorption between 290 and 360 nm.
Within this absorption range, the photoenol can be excited
selectively since the tetrazole moiety only has a negligible
absorption in the range between 310 and 350 nm (Figure 1).
The discrete absorption enables the photochemical orthogon-
ality between the photoenol and the tetrazole and leads to an
orthogonal light-triggered reactivity with dienophiles. How-
ever, orthogonality between photoenol and tetrazole can only
be achieved when the photoenol is activated prior to the
tetrazole compound.
1
by H NMR; Supporting Information, Figure S27). Thus, the
addition of the maleimide moiety to an equimolar mixture of
the photoenol containing polymer 1 and the tetrazole capped
polymer 2 is rapid and highly orthogonal. The mass spectra
reveal that maleimide was selectively added to compound 1,
whereas the conversion of compound 2 within this one-pot
reaction is negligible. The kinetic data of the remaining 6
samples that were first irradiated with the PL-L lamp for
15 min and subsequently with the Arimed B12 lamp at
variable times (Figure 2b) display the exponential decay of
the tetrazole capped PEG 2 in combination with the
exponential increase of the corresponding cycloadduct 4.
After an irradiation time of 240 min with the Arimed B12
lamp, compound 2 is quantitatively converted into compound
Figure 1. UV/Vis absorption spectrum of photoenol 1 and tetrazole 2
superimposed with the emission spectra of the PL-L lamp
(lmax =370 nm) and the Arimed B12 lamp (lmax =310 nm). The absorp-
tion area of tetrazole has negligible overlap with the PL-L emission
area, whereas the photoenol can be activated in the wavelength range
of 310–350 nm by the PL-L lamp.
2
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Figure 2. Kinetic data plot showing the evolution of the relative intensities of 1 (1 equiv), 2 (1 equiv), and maleimide (10.7 equiv) when irradiated
following the sequence depicted in Scheme 1. A zoom (m/z=1218.50 À1278.50) of the mass spectra in the double charged region is included for
each data point in the kinetic plot: a) eight samples were irradiated at l=310–350 nm for 15 min. The intensity of the mass spectrum signal of
1 decreases subsequently in combination with a signal intensity increase of 3. The signal intensity of 2 decreases negligibly. The quantitative
conversion of 1 into 3 was also determined by 1H NMR spectroscopy and is marked in the kinetic plot by the orange star. b) All six of the samples
were initially irradiated at l=310–350 nm for 15 min. The kinetic data plot was determined by irradiating the six samples at l=270–310 nm for
240 min. A decrease in the relative abundance of 2 and an increase of cycloadduct 4 is observed. Compound 1 was completely converted into
compound 3 prior to irradiation at l=310–350 nm.
4. The decay of 2 follows first-order kinetics, giving a rate
coefficient of (2.03 Æ 0.02) ꢀ 10À4 sÀ1 under the chosen con-
ditions (Supporting Information, Figure S28b). A key criteria
of polymer click chemistry is equimolarity.[14] Thus, a second
kinetic study was performed under the same conditions (that
is, sequential irradiation of a solution containing 1 and 2 in
equimolar ratios with the PL-L lamp and subsequent
irradiation of the solution with the Arimed B12 lamp at
different irradiation times). However, the relative amount of
maleimide was reduced from 10.7 equiv close to 2 equiv
(Supporting Information, Figure S24), providing one equiv-
alent of maleimide for each photoactive end group. The decay
of 1 and 2, respectively, follows pseudo first-order kinetics,
affording a rate coefficient for 1 of (7.96 Æ 0.21) ꢀ 10À3 sÀ1 and
for 2 of (1.92 Æ 0.14) ꢀ 10À4 sÀ1 under the chosen conditions
(Supporting Information, Figure S25). The data clearly evi-
dence that a system consisting of an equimolar ratio of
a photoenol-capped polymer and a tetrazole-capped polymer
is able to react selectively with a maleimide when the system
is initially activated in the range of 310–350 nm.
The second fundamental aspect of l-orthogonal click
chemistry is demonstrating the l-orthogonal principle on
a macromolecular dilinker carrying l-orthogonal functions at
each chain end. Initially, l-orthogonality was demonstrated
by the selective addition of maleimide towards the a,w-
functional dilinker 9. A mixture of 9 with a 2.5 equiv excess of
maleimide in dichloromethane was irradiated for 15 min with
the PL-L lamp. One sample was subsequently irradiated for
4 h with the Arimed B6 lamp. The molecules 9, 12, and 13
were analyzed by ESI-MS as illustrated in Figure 3. The ESI-
MS data show that 9 was completely converted into 12 after
the first irradiation and only a small amount of 13 was formed
(3% conversion). The second irradiation step leads to
a complete conversion into 13.
The l-orthogonality principle was above demonstrated for
the site-specific attachment of maleimide in a system of two
photoactive polymers as well as a dilinker system. Highly
important, however, is the selective l-orthogonal attachment
of enes with variable and complex chemical functionality to
the a,w-functional dilinker, demonstrating the wide applic-
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Figure 3. A system consisting of the dilinker 9 and maleimide was
irradiated for 15 min at l=310–350 nm leading to a regioselective
addition of maleimide towards the end group carrying photoenol 12.
The system was subsequently irradiated for 4 h at l=270–310 nm
forming 13.
Figure 4. A system consisting of the dilinker 9 and fluorescein 5-
maleimide 19 was irradiated for 20 min at lmax =370 nm leading to
a regioselective addition of fluorescein towards the end group carrying
the photoenol 22. The system was subsequently irradiated for 4 h at
lmax =310 nm forming 24 that carries an acid functionality at the
tetrazole chain end.
ability and robustness of the system. Thus, complex malei-
mide capped molecules carrying the fluorescent dye fluores-
cein[15] or the antimicrobial peptide magainin were employed
as reaction partners[16] as well as species featuring electron-
poor double bonds, such as acrylates and acrylic acid, in order
to show the power of the ligation approach (see the
Supporting Information).
A mixture of 9 with an equimolar amount of fluorescein
maleimide 19 in dichloromethane was irradiated for 20 min
with the PL-L lamp. One sample was subsequently mixed with
an excess of acrylic acid and irradiated for 4 h with the
Arimed B6 lamp. The molecules 9, 22, and 24 were analyzed
by ESI-MS (Figure 4). The ESI-MS data unambiguously show
that 9 was completely converted into 22 after the first
irradiation sequence. The second irradiation step leads to
a complete conversion into 24.
Importantly, dilinker 9 was also shown to quantitatively
react in a l-orthogonal fashion with the fluorescein derivate
19 on both termini (Supporting Information, Figure S29)
along with maleimide and methyl acrylate (Supporting
Information, Figure S30) on the photoenol and tetrazole
terminus.
Furthermore, on the basis of the small molecule studies,
a l-orthogonal polymer/peptide hybrid triblock synthesis
starting from the a,w-functional dilinker 9, a maleimide
terminal magainin peptide, and a maleimide terminal poly-
lactide 16 (see the Supporting Information) was carried out.
The light-induced l-orthogonal click reaction sequence is
illustrated in Scheme 2.
A mixture of 9 with an equimolar amount of magainin
maleimide 21 in dry DMF was irradiated for 30 min in the
wavelength range of l = 310–350 nm (see the Supporting
Information and Figure S31 for the MS analysis). Subse-
Scheme 2. Stepwise construction of a triblock polymer/peptide hybrid
starting from the a,w-functional dilinker 9. The irradiation with the PL-
L lamp of 9 and an equimolar amount of the maleimide-capped
magainin 21 leads to the site-specific formation of the magainin-PEG
diblock 26. The subsequent irradiation of the diblock with an equimo-
lar amount of the maleimide terminal polylactide with the Arimed B6
lamp forms the hybrid triblock macromolecule 27.
quently, the solution was mixed with a maleimide-capped
polylactide (Mn = 8000 gmolÀ1) and irradiated for 6 h (l =
4
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270–310 nm). The macromolecules 9, 16, 26, and 27 were
analyzed by GPC to confirm the l-orthogonal formation of
the hybrid triblock in two steps (Figure 5).
maleimides, with enes featuring electron-poor double bonds
such as acrylates and acrylic acid, which extends the site-
specific l-orthogonality of the dilinker to also include
a chemical orthogonality. These combined aspects constitute
a chemical method that is easy to handle and very powerful
for selectively addressing l-orthogonal end groups. Thus,
based on light-induced reactions performed at specific wave-
lengths, l-orthogonal pericyclic photochemistry offers an
efficient and fast avenue to synthesize complex (macro)-
molecules by addressing individual parts of a macromolecule
with light of different wavelengths. We envisage that l-
orthogonal pericyclic reactions will not only find applications
in complex syntheses, but also in fields such as functional
photoresist design. Thus, l-orthogonal pericyclic photochem-
istry combines the features of classic photochemistry (no
catalyst required, no by-products formed, and thus no
purification necessary) with light-induced orthogonality,
making it a prime tool for site specific macromolecular
ligation.
Figure 5. A system consisting of the dilinker 9 and an equimolar
amount of magainin maleimide was irradiated for 30 min with the PL-
L lamp selectively forming the peptide-PEG diblock 26. The system
was subsequently mixed with the maleimide capped polylactide 16 and
irradiated for 6 h with the Arimed lamp forming the hybrid triblock 27.
GPC reported relative to a PMMA calibration.
Received: November 5, 2014
Published online: && &&, &&&&
Keywords: click reactions · orthogonal reactivity ·
.
photochemistry · photoenol · tetrazole
The GPC data reveal a successful block formation,
indicated by a clear shift of the maleimide capped polylactide
peak after the irradiation with the PL-L lamp and a second
shift after the irradiation with the Arimed B6 lamp. Fur-
thermore, the l-orthogonal block formation was carried out in
an all-polymer system, that is, employing two polylactide
blocks (Mn = 4800 gmolÀ1). Close inspection of the GPC trace
of 14 (Supporting Information, Figure S22) indicates sub-
structuring: A first shoulder is located at a retention time of
31 min and is associated with the residual equivalent of
maleimide-capped polymer 11. A second very small shoulder
is visible at 34 min and belongs to a small amount of non-
[1] a) K. Matyjaszewski, J. Xia, Chem. Rev. 2001, 101, 2921; b) G.
Moad, E. Rizzardo, S. H. Thang, Aust. J. Chem. 2005, 58, 379.
[2] M. Allmeroth, D. Moderegger, D. Gꢁndel, K. Koynov, H.-G.
Buchholz, K. Rausch, F. Roesch, R. Zentel, O. Thews, Biomac-
romolecules 2013, 14, 3091.
[3] C N. K. Guimard, K. K. Oehlenschlaeger, J. Zhou, S. Hilf, F. G.
Schmidt, C. Barner-Kowollik, Macromol. Chem. Phys. 2012, 213,
131 – 143.
[4] N. M. C. Tria, K.-S. Liao, N. Alley, S. Curran, R. Advincula, J.
Mater. Chem. 2011, 21, 10261.
[5] K. Matyjaszewski, N. V. Tsarevsky, Nature Chem. 2009, 1, 276 –
288.
[6] C. Barner-Kowollik, A. J. Inglis, Macromol. Chem. Phys. 2009,
210, 987.
converted dilinker 9. The irradiation of compound 14 at lmax
=
[7] a) H. C. Kolb, M. G. Finn, K. B. Sharpless, Angew. Chem. Int.
Ed. 2001, 40, 2004; Angew. Chem. 2001, 113, 2056; b) J.-F. Lutz,
Angew. Chem. Int. Ed. 2007, 46, 1018; Angew. Chem. 2007, 119,
1036; c) C. E. Hoyle, C. N. Bowman, Angew. Chem. Int. Ed.
2010, 49, 1540; Angew. Chem. 2010, 122, 1584.
310 nm subsequently leads to the triblock polymer 15. The l-
orthogonal triblock synthesis is additionally evidenced via
1H NMR spectroscopy (Supporting Information, Figure S21).
Similarly, the l-orthogonal block formation functions cleanly
with two polylactide blocks of 8000 gmolÀ1 (Supporting
Information, Figure S23). Thus, each end of the dilinker 9
can be selectively addressed by a specific wavelength regime
for the attachment of a macromolecular chain, be it a synthetic
polymer or a peptide sequence.
In summary, we have demonstrated the high efficiency of
l-orthogonal pericyclic reactions on two polymers carrying
a different photoactive endgroup each with maleimide in
a one-pot reaction and on an a,w-functionalized orthogonal
dilinker that reacts selectively with maleimides. Importantly,
we verify that complex maleimides can be site-selectively
attached to the dilinker in a l-orthogonal fashion, including
those featuring biologically applicable functionalities (for
example, peptides and fluorescent labels) as well as synthetic
polymers. The tetrazole compound is able to react, along with
[8] E. P. Espeel, F. E. Du Prez, Macromolecules 2015, 48, 2 – 14.
[9] a) B. Adzima, Y. J. Tao, C. Kloxin, C. A. J. DeForest, K. S.
Anseth, C. N. Bowman, Nat. Chem. 2011, 3, 256; b) T. Pauloehrl,
G. Delaittre, V. Winkler, A. Welle, M. Bruns, H. G. Bçrner,
A. M. Greiner, M. Bastmeyer, C. Barner-Kowollik, Angew.
Chem. Int. Ed. 2012, 51, 1071; Angew. Chem. 2012, 124, 1096;
c) T. Pauloehrl, A. Welle, M. Bruns, K. Linkert, H. G. Bçrner, M.
Bastmeyer, G. Delaittre, C. Barner-Kowollik, Angew. Chem. Int.
Ed. 2013, 52, 9714; Angew. Chem. 2013, 125, 9896; d) M. A.
Tasdelen, Y. Yagci, Angew. Chem. Int. Ed. 2013, 52, 5930;
Angew. Chem. 2013, 125, 6044; e) A. Bogdanova, V. V. Popik, J.
Am. Chem. Soc. 2003, 125, 14153; f) A. A. Poloukhtine, N. E.
Mbua, M. A. Wolfert, G. J. Boons, V. V. Popik, J. Am. Chem. Soc.
2009, 131, 15769.
[10] N. J. Turro, V. Ramamurthy, J. S. Scaiano, Modern Molecular
Photochemistry of Organic Molecules, University Science Books,
University of California, 2010.
Angew. Chem. Int. Ed. 2015, 54, 1 – 7
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www.angewandte.org
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These are not the final page numbers!

.
Angewandte
Communications
[11] V. San Miguel, C. G. Bochet, A. del Campo, J. Am. Chem. Soc.
2011, 133, 5380.
[12] R. Franklin, H. Kim, S. A. Chambers, A. Scott, A. N. Mangham,
R. J. Hamers, Langmuir 2012, 28, 12085.
[13] H. Inui, S. Murata, J. Am. Chem. Soc. 2005, 127, 2628.
[14] C. Barner-Kowollik, F. E. Du Prez, P. Espeel, C. J. Hawker, T.
Junkers, H. Schlaad, W. Van Camp, Angew. Chem. Int. Ed. 2011,
50, 60; Angew. Chem. 2011, 123, 61.
Chan, Y. Bruemmel, M. Seydack, K. Sin, L. Wong, E. Merisko-
Liversidge, D. Trau, R. Renneberg, Anal. Chem. 2004, 76, 3638.
[16] a) L. Ryan, B. Lamarre, T. Diu, J. Ravi, P. J. Judge, A. Temple, M.
Carr, E. Cerasoli, B. Su, H. F. Jenkinson, G. Martyna, J. Crain, A.
Watts, M. G. Ryadnov, J. Biol. Chem. 2013, 288, 20162; b) O.
Cirioni, C. Silvestri, R. Ghiselli, F. Orlando, A. Riva, F.
Mocchegani, L. Chiodi, S. Castelletti, E. Gabrielli, V. Saba, G.
Scalise, A. Giacometti, J. Antimicrob. Chemother. 2008, 62, 1332.
[15] a) N. Saruyama, Y. Sakukara, T. Asano, T. Nishiuchi, H.
Sasamoto, H. Kodama, Anal. Biochem. 2013, 441, 58; b) C. P.
6
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Polymer Photoreactions
It’s up to the wavelength: The concept of
l-orthogonal photochemistry is pre-
sented using light-induced pericyclic
photoreactions. A functionalized elec-
tron-poor alkene is reacted with various
selectively photoactive groups on a poly-
mer; the selectivity depends on the
wavelength of the light used.
K. Hiltebrandt, T. Pauloehrl, J. P. Blinco,
K. Linkert, H. G. Bçrner,
C. Barner-Kowollik*
&&& — &&&
l-Orthogonal Pericyclic Macromolecular
Photoligation
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