The 2-acetylthioethyl ester group: A versatile protective group for P-OH-groups

Article abstract of DOI:10.1016/j.tet.2018.11.002

Phosphodiesters are bridging elements in nucleic acids. In nature and synthesis, their negative charge protects them from hydrolysis and controls their solubility profile. RNA is a promising material for gene technology but cellular uptake is low due to negative charges. Synthetic oligonucleotides were delivered into cells by a prodrug approach relying on the enzymatic release of the polyphosphodiester oligonucleotides. In synthetic chemistry, a protective group for the P–OH functionality is often necessary, e.g. due to solubility or chemical incompatibility. Several methods for P–OH protection were proposed, but often with low selectivity or harsh conditions. Here, we present the 2-acetylthioethyl group as a versatile protective group for low molecular weight or polymeric phosphodiesters, which can be cleaved under acidic conditions in water or by hydrazine in THF to release the P–OH-functionality, but olefins remain intact. This straightforward use allows designing various synthetic polyphosphodiesters, e.g. for flame-retardant or dispersants.

Full text of DOI:10.1016/j.tet.2018.11.002

Accepted Manuscript
The 2-acetylthioethyl ester group: A versatile protective group for P-OH-groups
Jens C. Markwart, Frederik R. Wurm
PII:
S0040-4020(18)31329-2
https://doi.org/10.1016/j.tet.2018.11.002
TET 29913
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 28 September 2018
Revised Date: 1 November 2018
Accepted Date: 3 November 2018
Please cite this article as: Markwart JC, Wurm FR, The 2-acetylthioethyl ester group: A versatile
protective group for P-OH-groups, Tetrahedron (2018), doi: https://doi.org/10.1016/j.tet.2018.11.002.
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to
our customers we are providing this early version of the manuscript. The manuscript will undergo
copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please
note that during the production process errors may be discovered which could affect the content, and all
legal disclaimers that apply to the journal pertain.

ACCEPTED MANUSCRIPT
Graphical Abstract
To create your abstract, type over the instructions in the template box below.
The 2-acetylthioethyl ester group: A versatile
protective group for P-OH-groups
Leave this area blank for abstract info.
Jens C. Markwart, Frederik R. Wurm
Max-Planck-Institut für Polymerforschung (MPIP), Ackermannweg 10, 55128 Mainz
Fonts or abstract dimensions should not be changed or altered.

1
ACCEPTED MANUSCRIPT
Tetrahedron
journal homepage: www.elsevier.com
The 2-acetylthioethyl ester group: A versatile protective group for P-OH-groups
Jens C. Markwarta,b and Frederik R. Wurma,
aMax-Planck-Institut für Polymerforschung (MPIP), Ackermannweg 10, 55128 Mainz, Germany, wurm@mpip-mainz.mpg.de
bGraduate School Materials Science in Mainz, Staudinger Weg 9, 55128 Mainz, Germany
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
Phosphodiesters are bridging elements in nucleic acids. In nature and synthesis, their negative
charge protects them from hydrolysis and controls their solubility profile. RNA is a promising
material for gene technology but cellular uptake is low due to negative charges. Synthetic
oligonucleotides were delivered into cells by a prodrug approach relying on the enzymatic
release of the polyphosphodiester oligonucleotides. In synthetic chemistry, a protective group
for the P-OH functionality is often necessary, e.g. due to solubility or chemical incompatibility.
Several methods for P-OH protection were proposed, but often with low selectivity or harsh
conditions. Here, we present the 2-acetylthioethyl group as a versatile protective group for low
molecular weight or polymeric phosphodiesters, which can be cleaved under acidic conditions in
water or by hydrazine in THF to release the P-OH-functionality, but olefins remain intact. This
straightforward use allows designing various synthetic polyphosphodiesters, e.g. for flame-
retardant or dispersants.
Available online
Keywords:
Polyphosphoester
Protective group
ADMET
Adhesive
Phosphorus
2009 Elsevier Ltd. All rights reserved
.
———
Corresponding author. Tel.: +49-6131-379-581; fax: +0-000-000-0000; e-mail: wurm@mpip-mainz.mpg.de

2
Tetrahedron
ACCEPTED MANUSCRIPT
1. Introduction
We propose the 2-acetylthioethyl ester group as a protective
group for the P-OH functionality in low molecular weight
phosphates as well as polyphosphates. In contrast to the above-
mentioned strategies, the protected materials are accessible by
straightforward chemistry and possess long shelf lives with fast
purifications. The cleavage was possible both in organic solvents
as well as in water and did not interfere with olefins. All these
factors render the 2-acetylthioethyl phosphoester an attractive
protective group for synthetic (poly)phosphodiesters.
Phosphodiesters build the backbone of DNA or RNA. Their
negative charge protects DNA from hydrolytic degradation.2,3 In
modern medicine, oligonucleotides are promising gene
therapeutics, but due to the negative charge are only poorly
internalized by cells.1 To increase cellular uptake, prodrug
approaches were developed.1 One method used
a
2-
acetylthioethyl group, which masks the negative charge of the
phosphate by creating a neutral phosphotriester. Those neutral
oligonucleotides could be internalized by cells, but the
thioacetate is cleaved enzymatically by intracellular
carboxyesterases to release the free thiol-group, which then forms
the phosphodiester under the release of thiirane.1
2. Results and Discussion
Phosphoryl chloride was first reacted with 2-bromoethanol
followed by a reaction with hex-5-en-1-ol to yield 2-bromoethyl
di (hex-5-en-1-yl)phosphate (2), which was then reacted with
potassium thioacetate to give 2-acetylthioethyl di(hex-5-en-1-
yl)phosphate (3, Figure 1). This compound was used as an
unsaturated model compound for the cleavage of the 2-
acetylthioethyl phosphoester to di(hex-5-en-1-yl) hydrogen
phosphate (4).
Besides biomedical applications, polyphosphodiesters are also
interesting for synthetic chemistry, e.g. for the generation of
potentially biocompatible and biodegradable materials4-7 or to
increase polymer hydrophilicity. However, the direct preparation
of polyphosphodiesters is not possible. Polycondensation with
phosphoryl chloride results in ill-defined branched or cross-
linked structures or acyclic diene metathesis polymerization
(ADMET) only produced oligomeric PPEs8. Also, the ring-
opening polymerization of cyclic phospholanes does not tolerate
free P-OH-groups and makes protective groups inevitable.9 We
recently used a diene monomer containing a P-Cl bond for
ADMET, followed by hydrolysis to the respective
polyphosphodiester.8,10 However, the high electrophilicity of the
P-Cl makes handling difficult and working under strictly dry
conditions is essential to prevent short shelf life and cross-linking
reactions during polymerization. Other protective groups could
be removed by hydrogenation, e.g. benzylesters.9 This method
however, would also remove olefins in the desired polymers.9
Other reports used dealkylation of an alkoxy sidechain by
treating the phosphate with a strong nucleophilic reagent, which
however is plagued by backbone degradation.11-13 The third
method utilized the different pH-stability of phosphoramidates
and phosphates, in which the acid-labile phosphoramidate bond
was cleaved under relatively mild acidic conditions.14,15 Other
Thioesters are often used as a protective group for the highly
nucleophilic thiols, which can be cleaved under acidic or basic
conditions.18-20 However, if a 2-acetylthioethyl group is linked
via a phosphoester, the hydrolysis of the thioester to the thiol will
be followed by a complete removal of the alkyl chain from the
phosphate and releases a phosphodiester.21,1 This strategy was
extensively used in solid-phase oligonucleotide synthesis,
followed by enzymatic cleavage of the thioester.21,1 We used
either hydrazine (method a (Experimental)) or hydrochloric acid
(method
b
(Experimental)) to successfully release the
PO(OR)2OH (compounds 4 or Poly-4). The successful formation
of the P-OH group was proven by 31P{H} and 1H NMR
spectroscopy and mass spectrometry. The first indication for a
successful removal of the 2-acetylthioethyl ester was the down-
field shift in the 31P NMR from -1.17 ppm in compound 3 to 1.30
ppm in compound 4 (Figure 1 f). The release of the P-OH-group
was further supported by the integral of the methylene groups
16
1
routes rely on the oxidation of H-phosphonates with N2O4 or
next to the phosphoesters at ca. 4 ppm in the H NMR spectra,
which corresponded to four instead of six (Figure 1 c – e). This
indicates that there are only two alkyl chains attached to the
thermolysis of tert-butyl esters. 17
Fig. 1. a) Synthesis of 2-acetylthioethyl ester–protected unsaturated phosphate 3 and removal of the protective group to 4 according to b) the proposed
mechanism.1 c) 1H NMR spectrum (300 MHz, CDCl3, T = 298K) of 3. d, e) 1H NMR (300 MHz, CDCl3, T = 298K) of reaction of 3 with HCl (d) and hydrazine
(e). f) 31P NMR spectra (121 MHz, CDCl3, T = 298K) of the 2-acetylthioethyl ester–protected compound (3) and the reaction product (4) after treatment with HCl
or hydrazine.

3
phosphate. Furthermore, the resonances for the methylene groups
next to the thioester at 3.15 ppm vanished and no new resonances
for a free thiol group are detected (Figure 1 d, e). When we used
K2CO3 in methanol to remove the 2-acetylthioethyl group
(another typical procedure for the cleavage of thioesters20), we
found partial formation of 4, but also the formation of the methyl
ester via transesterification with methanol. The 1H NMR
spectrum of the crude reaction mixture showed a typical doublet
with a J=11.1 Hz for a methyl-ester (“P-O-CH3”) due to the
coupling with phosphorus (Figure S8).
common organic solvents.8 Thus, a solubilizing protective
ACCEPTED MANUSCRIPT
group is a desirable intermediate. We used monomer 2 to prepare
a
polyphosphate by ADMET polymerization (Poly-2,
Mn=5100 g mol-1 D=1.68) according to a modified literature
procedure.10 After the polymerization, the alkyl bromide in the
pendant chains was reacted with potassium thioacetate (in
acetone, r.t., 12h) to produce the 2-acetylthioethyl ester protected
PPE (Poly-3). The product shows two characteristic resonances
1
in the H NMR spectrum at 2.28 ppm, which were attributed to
the methyl group of the thioacetate, and the methylene group at
3.10 ppm next to the thioester. The polymer (Poly-3) was bench-
stable at room temperature for at least several weeks. In the final
step, the polymer was treated with hydrazine in THF at r.t. to
release the polyphosphodiester (Poly-4). During the reaction, the
polymer precipitated from solution. The crude product Poly-4
was soluble in CDCl3/MeOD and the removal of the 2-
acetylthioethyl ester was proven as the resonance of the
methylene group next to the thioester at 3.17 ppm vanished and
the signal of the leaving group shifts to 1.73 ppm. In addition a
down-field shift in the 31P NMR from -1.16 ppm to 0.55 ppm was
observed, which is indicative for the cleavage of the pendant
ester. Purification of Poly-4 was achieved by precipitation into
diethyl ether and obtained as an off-white viscous liquid in 84%
The mechanism for the enzymatic removal of the 2-
acetylthioethyl ester in synthetic oligonucleotides was reported to
release the phosphodiesters.21,1 After hydrolysis of the thioester to
the thiol, a nucleophilic attack by the thiol on the methylene
group next to the ester group was postulated to release the
phosphodiester and thiirane, which probably will be hydrolyzed
to mercaptoethanol or react with the nucleophilic
hydrazine.1,21We propose the same mechanism on the synthetic
phosphates as shown in Figure 1 b, which retains the olefins in
the molecule for further functionalization. Mass spectrometry
analysis of the crude reaction from 3 to 4 proves the formation of
the product 4 and the cleaved side chain with further adducts with
hydrazine (cf. Supp. Info.). The reaction was also monitored by
1
yield. The H DOSY-NMR spectrum additionally proves the
1
real-time H NMR spectroscopy as the disappearance of the
formation of Poly-4 (Figure 2 e).
thioacetate resonance gives a direct insight to the reaction
kinetics (cf. Supp. Info. for further details). The successful
3. Conclusion
formation of
4
was proven by the reaction with
We demonstrated the use of the 2-acetylthioethyl ester group
for the protection of (poly)phosphodiesters. The protective group
guarantees solubility in common organic solvents and the
compounds show high shelf-lives. The 2-acetylthioethyl ester
was successfully removed either by hydrazine (in THF) or
trimethylsilyldiazomethane to convert the hydroxyl group to a
methyl ester. The typical doublet for the methyl ester due to
coupling with phosphorus can be appreciated in the H NMR
1
spectrum (J=11.1 Hz, Figure S1).
Fig. 2. Polymer Examples: a-c) 1H NMRs (300 MHz, CDCl3, T = 298K) of the polymers a) poly-2, b) poly-3 after introducing the thioacetate group, and c) of
1
the polyphosphodiester (poly-4, measured at 300 MHz, in CDCl3:MeOD 7:3, T = 298K). d) Reaction scheme. e) H DOSY (700 MHz, CDCl3:MeOD 7:3, T =
298K) spectrum of poly-4 underlining the successful removal of the pendant chains.
After the successful preparation of low molecular weight
phosphodiesters, we studied the synthesis of polyphosphodiesters
by the 2-acetylthioethyl ester protective group. The synthesis of
polyphosphodiesters with a hydrophobic backbone is often
plagued by the low solubility of oligomers or polymers in
hydrochloric acid (in water) and additional double bonds in the
(macro)molecule remained untouched during the procedure. The
2-acetylthioethyl ester can be used as a soluble precursor for P-
OH-containing polymers which are appealing for adhesives,
dispersants, or flame-retardants.

4
Tetrahedron
ACCEPTED MANUSCRIPT
4. Acknowledgments
To a 100 mL round bottom flask 500 mg of 2-Bromoethyl di
(hex-5-en-1-yl)phosphate (1.35 mmol; 1.0 eq.) and 170.11 mg of
potassium thioacetate (1.49 mmol; 1.1 eq.) were added under
argon atmosphere in 5 mL of acetone and stirred for 20 h at room
temperature.
The authors thank Prof. Dr. Katharina Landfester (MPIP) for
her support. J.M. is recipients of a fellowship through funding of
the Excellence Initiative (DFG/GSC 266) in the context of the
graduate school of excellence “MAINZ” (Material Sciences in
Then, the mixture was filtered through Celite 501 to remove
the salt. The acetone was removed by rotary evaporation. The
crude mixture was dissolved in diethyl ether and washed three
times with brine. The organic layer was dried over anhydrous
sodium sulfate, filtered, and concentrated on the rotary
evaporator. The purified product was recovered as a viscous oil
(yield: 0.4 g, 82%). The purity and chemical structure were
determined by 1H NMR and 31P {H} NMR spectroscopy.
Mainz).
J.M.
and
F.R.W.
thank
the
Deutsche
Forschungsgemeinschaft (DFG WU 750/8-1) for support.
5. Experimental
All chemicals were purchased from commercial suppliers as
reagent grade and used without further purification. H and 31P
1
nuclear magnetic resonance (NMR) spectra were recorded on
Bruker AV 300 at 300 MHz (1H) and 121.50 MHz (31P) or
Bruker AV 700 spectrometers at 700 MHz (1H). The temperature
of measurement is indicated in the corresponding figure captions.
Chemical shifts are reported in ppm using the residual non-
deuterated solvent signals as an internal reference.
1H NMR (300 MHz, 298K, chloroform-d): δ [ppm] = 5.81 –
5.68 (m, 2H); 5.02 – 4.93 (m, 4H); 4.16 – 3.99 (m, 6H); 3.15 (t,
2H); 2.33 (s, 3H); 2.08 – 2.01 (td, 4H); 1.71 – 1.62 (tt, 4H); 1.50
– 1.40 (tt, 4H).
31P {H} NMR (121 MHz, 298K, chloroform-d): δ [ppm] = -
1.17 (s, 1P).
2-Bromoethyl phosphorodichloridate (1)
To a dried three-necked, 250 mL round-bottomed flask fitted
with a dropping funnel, 61.35 mL of phosphoryl chloride (672.19
mmol; 7.0 eq.) were added under an argon atmosphere in 300 mL
of dry toluene. Then 13.31 mL of triethylamine (96.03 mmol; 1.0
eq.) and 12 g of 2-bromoethanol (96.03 mmol; 1.0 eq.) dissolved
in 50 mL of dry toluene were added dropwise to the above-
mentioned flask at 0 °C. The reaction was allowed to stir
overnight at room temperature. Afterward, the crude mixture was
filtered to remove the triethylammonium chloride and
concentrated at reduced pressure. Then, all by-products and
starting material were removed at reduced pressure (R.T., 5 * 10-2
mbar). The product was used without further purification. 87%
(20.2 g) yield.
Di(hex-5-en-1-yl) hydrogen phosphate (4)
a) 3 (1 g), 5 mL of 1M hydrazine solution in THF were mixed
and 10 mL dichloromethane and stirred overnight at r.t. in an
argon atmosphere. The solvent was removed at reduced pressure
and the crude product redissolved in dichloromethane and the
organic phase was washed with 10% HCl, saturated NaHCO3 and
again 10% HCl. The organic phase was dried over MgSO4 and
the solvent removed at reduced pressure to yield the product
(yield: 736 mg, 83%).
b) 3 (200 mg) was dissolved in 0.66 mL methanol. Then
0.5 mL (10 eq.) of 37% HCl was added and the solution was
stirred at 65°C overnight. The solvent was removed at reduced
pressure and the crude product was dissolved in diethyl ether and
washed two times with brine. The organic phase was dried over
MgSO4 to yield the pure product (yield: 0.2 g, 87%).
1H NMR (300 MHz, 298K, chloroform-d): δ [ppm] = 5.85 –
5.71 (m, 2H; 5.04 – 4.95 (m, 4H, f); 4.06 – 4.00 (q, 4H); 2.12 –
2.05 (td, 4H); 1.74 – 1.65 (tt, 4H); 1.54 – 1.44 (tt, 4H).
2-Bromoethyl di (hex-5-en-1-yl)phosphate (2)
To a dried three-necked, 250 mL round-bottomed flask fitted
with
a
dropping funnel, 7.00 g of 2-bromoethyl
phosphorodichloridate (28.95 mmol; 1.0 eq.) were added under
an argon atmosphere in 40 mL of dry toluene. Then 7.30 mL of
hex-5-en-1-ol (60.79 mmol; 2.1 eq.) and 8.43 mL of
triethylamine (60.79 mmol; 2.1 eq.) were dissolved in 20 mL of
dry toluene and added dropwise to the mixture at 0 °C. The
reaction was allowed to warm up to room temperature, stirred for
an additional 12 h and filtered. The toluene was removed on the
rotary-evaporator and the crude product was dissolved in toluene
to wash it with 10% aqueous hydrochloric acid solution, a
saturated solution of calcium carbonate and brine. The organic
layer was dried over anhydrous magnesium sulfate, filtered, and
dried at reduced pressure. 82% (8.6 g) yield.
1H NMR (300 MHz, 298K, chloroform-d): δ [ppm] = 5.81 –
5.68 (m, 2H); 4.98 – 4.89 (m, 4H); 4.29 – 4.22 (q, 2H); 4.06 –
4.00 (q, 4H); 4.49 (t, 2H); 2.08 – 2.01 (td, 4H); 1.71 – 1.62 (tt,
4H); 1.50 – 1.40 (tt, 4H).
31P {H} NMR (121 MHz, 298K, chloroform-d): δ [ppm] = -
1.23 (s, 1P).
31P {H} NMR (121 MHz, 298K, chloroform-d): δ [ppm] =
1.30 (s, 1P).
Poly-2
In a Schlenk tube equipped with a stir bar, 500 mg of 2 with
10 mg (0.6 mol%) of Grubbs I catalyst were added. The reaction
was allowed to procede at reduced pressure over night at 40 °C,
then the temperature was increased to 60 °C for another 4 hours
to give the product in quantitative yield (439 mg).
1H NMR (300 MHz, 298K, chloroform-d): δ [ppm] = 5.39 (m,
2H); 4.28 (q, 2H); 4.05 (q, 4H); 3.53 (m, 2H); 2.02 (m, 4H); 1.68
(m, 4H); 1.43 (m, 4H).
31P {H} NMR (121 MHz, 298K, chloroform-d): δ [ppm] = -
1.26 (s, 1P).
2-Acetylthioethyl di (hex-5-en-1-yl)phosphate (3)
Poly-3
The synthesis of 2-acetylthioethyl di (hex-5-en-1-yl)phosphate
was carried out adopting a procedure previously described by
Liras et al.22
Poly-2 (150 mg), 51.03 mg of potassium thioacetate
(0.447 mmol; 1.1 eq.) and 2 mL of acetone were stirred overnight
at r.t. under an argon atmosphere. The solution was filtered

5
17.
Yasuda,
H.;
Sumitani,
M.;
Nakamura,
A.
through a syringe filter and the solvent was removed under
reduced pressure to give the product in quantitative yield
(148 mg)
1H NMR (300 MHz, 298K, chloroform-d): δ [ppm] = 5.39 (m,
2H); 4.09 (q, 2H); 4.02 (q, 4H); 3.17 (m, 2H); 2.35 (s, 3H); 2.00
(m, 4H); 1.67 (m, 4H); 1.43 (m, 4H).
ACCEPTED MANUSCRIPT
Macromolecules 1981, 14, 458-60.
18.
Kang, J.; Miyajima, D.; Itoh, Y.; Mori, T.; Tanaka, H.;
Yamauchi, M.; Inoue, Y.; Harada, S.; Aida, T. Journal of
the American Chemical Society 2014, 136, 10640-10644.
Toulemon, D.; Pichon, B. P.; Leuvrey, C.; Zafeiratos, S.;
Papaefthimiou, V.; Cattoën, X.; Bégin-Colin, S. Chemistry
of Materials 2013, 25, 2849-2854.
Chauvin, J.-P. R.; Griesser, M.; Pratt, D. A. Journal of the
American Chemical Society 2017, 139, 6484-6493.
Tosquellas, G.; Alvarez, K.; Dell'Aquila, C.; Morvan, F.;
Vasseur, J.-J.; Imbach, J.-L.; Rayner, B. Nucleic Acids
Research 1998, 26, 2069-2074.
19.
31P {H} NMR (121 MHz, 298K, chloroform-d): δ [ppm] = -
1.16 (s, 1P).
20.
21.
Poly-4
22.
Liras, M.; Garcia, O.; Guarrotxena, N.; Palacios-Cuesta,
M.; Quijada-Garrido, I. Polymer Chemistry 2013, 4, 5751-
5759.
Poly-3 (150 mg), 0.6 mL 1M hydrazine solution in THF and
2.5 mL DCM were stirred overnight at room temperature under
an argon atmosphere. The polymer precipitated during the
reaction and the solvent was removed at reduced pressure. The
polymer could be redissolved in chloroform:methanol 7:3. It was
then precipitated into diethyl ether for purification. 84%
(90.7 mg) yield.
1H NMR (300 MHz, 298K, chloroform-d: methanol-d4 7:3): δ
[ppm] = 5.20 (m, 2H); 3.66 (m, 4H); 1.83 (m, 4H); 1.43 (m, 4H);
1.24 (m, 4H).
31P {H} NMR (121 MHz, 298K, chloroform-d: methanol-d4
7:3): δ [ppm] = 0.55 (s, 1P).
1.
2.
3.
Debart, F.; Dupouy, C.; Vasseur, J.-J. Beilstein Journal of
Organic Chemistry 2018, 14, 436-469.
Zhao, Z.; Wang, J.; Mao, H.-Q.; Leong, K. W. Advanced
Drug Delivery Reviews 2003, 55, 483-499.
Marks, F.; Klingmüller, U.; Müller-Decker, K. Cellular
Signal Processing: An Introduction to the Molecular
Mechanisms of Signal Transduction; CRC Press, 2017.
Yilmaz, Z. E.; Jérôme, C. Macromolecular Bioscience
2016, 16, 1745-1761.
Wang, Y.-C.; Yuan, Y.-Y.; Du, J.-Z.; Yang, X.-Z.; Wang,
J. Macromolecular Bioscience 2009, 9, 1154-1164.
Steinbach, T.; Wurm, F. R. Angewandte Chemie
International Edition 2015, 54, 6098-6108.
4.
5.
6.
7.
8.
Bauer, K. N.; Tee, H. T.; Velencoso, M. M.; Wurm, F. R.
Progress in Polymer Science 2017.
Becker, G.; Ackermann, L.-M.; Schechtel, E.; Klapper, M.;
Tremel, W.; Wurm, F. R. Biomacromolecules 2017, 18,
767-777.
9.
Yasuhiko, I.; Takashi, K.; Shin-ichi, Y. Chemistry Letters
2009, 38, 1054-1055.
10.
11.
12.
Steinmann, M.; Markwart, J.; Wurm, F. R.
Macromolecules 2014, 47, 8506-8513.
Zeynep, E. Y.; Antoine, D.; Brice, C.; Frank, B.; Jerome,
C. Journal of Materials Chemistry B 2015, 3, 7227-7236.
Wan, A. C. A.; Mao, H.-Q.; Wang, S.; Phua, S. H.; Lee, G.
P.; Pan, J.; Lu, S.; Wang, J.; Leong, K. W. Journal of
Biomedical Materials Research Part B: Applied
Biomaterials 2004, 70B, 91-102.
13.
14.
Hirano, Y.; Iwasaki, Y. Colloids and Surfaces B:
Biointerfaces 2017, 153, 104-110.
Zhang, S.; Wang, H.; Shen, Y.; Zhang, F.; Seetho, K.; Zou,
J.; Taylor, J.-S. A.; Dove, A. P.; Wooley, K. L.
Macromolecules 2013, 46, 5141-5149.
15.
16.
Cankaya, A.; Steinmann, M.; Bulbul, Y.; Lieberwirth, I.;
Wurm, F. R. Polymer Chemistry 2016, 7, 5004-5010.
Biela, T.; Penczek, S.; Slomkowski, S.; Vogl, O. Die
Makromolekulare Chemie, Rapid Communications 1982,
3, 667-671.