Amine functionalized polyglycerols obtained by copolymerization of cyclic carbonate monomers

Article abstract of DOI:10.1016/j.polymer.2018.07.055

Hyperbranched aliphatic polyethers containing hydroxyl and amine end groups were produced from glycerol carbonate (4-hydroxymethyl-1,3-dioxolan-2-one) and cyclic carbonate bearing phthalimide moieties. The new monomer N-[(2-oxo-1,3-dioxolan-4-yl)methyl]phthalimide was synthesized in a simple two-step, one-pot process. The structure of the monomer was proved by means of NMR, FTIR and X-ray techniques. Anionic polymerization of cyclic carbonate monomers, which proceeds with simultaneous decarboxylation, was performed using a simple catalyst - potassium carbonate and trimethylolpropane (TMP) or glycerol carbonate as an initiator. The polymerization conditions were investigated and optimized. The polymers were characterized by means of nuclear magnetic resonance, FTIR, MALDI-TOF, GPC and elemental analysis. It was shown that during the process of polymerization an intermediate - glycidol is formed and acts as initiator or monomer.

Full text of DOI:10.1016/j.polymer.2018.07.055

Accepted Manuscript
Amine functionalized polyglycerols obtained by copolymerization of cyclic carbonate
monomers
Paweł G. Parzuchowski, Aleksandra Świderska, Marlena Roguszewska, Tomasz
Frączkowski, Mariusz Tryznowski
PII:
S0032-3861(18)30661-X
10.1016/j.polymer.2018.07.055
JPOL 20774
DOI:
Reference:
To appear in: Polymer
Received Date: 26 April 2018
Revised Date: 16 July 2018
Accepted Date: 20 July 2018
Please cite this article as: Parzuchowski PawełG, Świderska A, Roguszewska M, Frączkowski T,
Tryznowski M, Amine functionalized polyglycerols obtained by copolymerization of cyclic carbonate
monomers, Polymer (2018), doi: 10.1016/j.polymer.2018.07.055.
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ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
Amine functionalized polyglycerols obtained by copolymerization of cyclic
carbonate monomers
*
Paweł G. Parzuchowski, Aleksandra Świderska, Marlena Roguszewska,
Tomasz Frączkowski, Mariusz Tryznowski
Warsaw University of Technology, Faculty of Chemistry, Noakowskiego 3, 00-664 Warsaw,
Poland
ABSTRACT: Hyperbranched aliphatic polyethers containing hydroxyl and amine end groups
were produced from glycerol carbonate (4-hydroxymethyl-1,3-dioxolan-2-one) and cyclic
carbonate bearing phthalimide moieties. The new monomer N-[(2-oxo-1,3-dioxolan-4-
yl)methyl]phthalimide was synthesized in a simple two-step, one-pot process. The structure of
the monomer was proved by means of NMR, FTIR and X-ray techniques. Anionic
polymerization of cyclic carbonate monomers, which proceeds with simultaneous
decarboxylation, was performed using a simple catalyst - potassium carbonate and
trimethylolpropane (TMP) or glycerol carbonate as an initiator. The polymerization
conditions were investigated and optimized. The polymers were characterized by means of
nuclear magnetic resonance, FTIR, MALDI-TOF, GPC and elemental analysis. It was shown
that during the process of polymerization an intermediate - glycidol is formed and acts as
initiator or monomer.
Key words: glycerol carbonate; hyperbranched polyglycerol; cyclic carbonate monomer;
amine groups
1
. Introduction
Using biomass for the production of polymers can produce both environmental and
economic benefits. In last decades it has been observed a strong desire to replace polymers
from fossil fuels with more environmentally friendly polymers generated from renewable
resources.
In one of our recent articles we proposed a simple way of synthesis of hyperbranched
polyglycerols based on an environmentally benign monomer cyclic glycerol carbonate.[1],
*
correspondence to: P. G. Parzuchowski e-mail: pparzuch@ch.pw.edu.pl, phone: + 48 22 234 7317, fax: + 48
2
2 628 2741.
1

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Glycerol carbonate is easily available with quantitative yield from glycerol and dimethyl
carbonate. Since glycerol is produced in large quantities during the biodiesel production, it
becomes a non-expensive and easily available starting material for the synthesis of new
monomers and polymers.[2] Whereas cyclic carbonate functionality can be attained with the
use of carbon dioxide – a cheap, easily available but environmentally burdensome starting
material. Therefore glycerol carbonate can be considered an environmentally friendly and
"
green"chemical.[3],[4] Five-membered cyclic carbonates can be synthesized directly from
oxiranes and carbon dioxide, or indirectly in the reaction of vicinal diols with ethylene
carbonate or dialkyl carbonates.[5] In combination with diamines bis(cyclic carbonates)
provide a convenient way to the formation of non-isocyanate polyurethanes.[6] Moreover,
cyclic carbonates bearing substituents containing free hydroxyl groups can alone be a source
of many valuable compounds and polymers.
Hyperbranched polymers can be prepared from an AB -type monomers according to a
n
single step synthetic procedure.[7] To obtain polymers containing hydroxyl terminal groups
glycidol [8], 3-(hydroxymethyl)-3-alkyl oxetanes [9] or glycerol carbonate are typically used
in ring opening polymerization reactions. Glycerol carbonate belongs to the class of
monomers which is considered a latent AB -type monomer since the release of the second B
2
functionality occurs as a result of reaction of the A group.[10] The polymerization of glycerol
carbonate occurs with decarboxylation leading to the hyperbranched polyether.[1]
Hyperbranched polyglycerols (HBPGs) are structurally defined, biocompatible
macromolecular scaffolds, that have an aliphatic polyether backbone, and possess multiple
hydroxyl terminal groups. The hydroxyl groups in polyglycerol not only increase the
hydrophilicity of this polymer but also allow for its modification, leading to polymers with
carboxyl, amine, and vinyl groups, as well as to polymers with bonded aliphatic and
perfluorated chains, sugar moieties, and covalently immobilized bioactive compounds in
particular proteins.[11] Cyclic carbonate derivatives of hyperbranched polyethers have also
been reported.[12]
Functional HBPGs have recently gained considerable interest due to their potential in
biomedical applications.[13],[14],[15],[16],[17], Particularly interesting are branched
polymers containing amine groups. A comprehensive review of amine containing
hyperbranched polyglycerols as gene carriers was given by Fischer et al.[18] However,
hyperbranched polymers have also a high potential as additives and modifiers in engineering
materials.[19] The specific advantages of the hyperbranched polymers and their influence on
mechanical properties in modification of thermoset resin systems have been discussed in
2

ACCEPTED MANUSCRIPT
detail by Månson et al.[20] For such applications a simple, reliable and environmentally
friendly synthetic procedure allowing polymerization in a large scale is needed.
Currently, all of the literature reports concerning synthesis of functional HBPGs,
particularly amine containing hyperbranched polyglycerol (A-HBPG) are based on the use of
epoxy monomers, mainly products of modification of glycidol based polymers. Various
synthetic methodologies were used. The most popular pathway leading to A-HBPGs involves
the use of azide intermediates.[21],[22],[23],[24] In this approach polyglycerols were surface
modified with amine groups in a three-step protocol involving: mesylation of hydroxyl
groups, a nucleophilic substitution with sodium azide and the final reaction with
triphenylphosphine.[21] Such architectures containing amine groups showed ability to
complex DNA and functioned as cellular delivery systems of low cytotoxicity. A-HBPGs
obtained in the same way were also used as coatings for resistant to protein and bacteria
attachment polypropylene surfaces.[25] Oupicky et al. reported hyperbranched polyglycerol
modified with a polyamine shell by the reaction of hydroxyl groups of HBPG activated with
phenyl chloroformate with large excess of norspermine or N,N-bisethylnorspermine. [26] Another
way to attach amine-functional molecules to the HBPG’s outer sphere involved oxidation of
hydroxyl groups with sodium periodate followed by the reaction with polyamine.[27]
Majority of literature reports concerning preparation of A-HBPGs includes the
modification of existing HBPG macromolecules. The examples of preparation of these
structures via copolymerization are particularly rare and based only on epoxy monomers.
Such approach was presented by Kim et al.[13],[28] The Boc-protected alkylamine glycidyl
ether monomers were copolymerized with glycidol through anionic ring-opening
multibranching polymerization. The copolymerization and subsequent deprotection chemistry
allowed the incorporation of an adjustable fraction of primary amine, hydroxyl and alkyl
moieties within the HBPG backbones.
Another method of obtaining HBPGs containing amine functionalities which has just
emerged in the literature is the use of the Gabriel synthesis. Phthalimide monofunctional
HBPGs were synthesized by applying a (phthalimide)/(potassium phthalimide) initiating
system for the anionic ring-opening multibranching polymerization of glycidol.[29] The
phthalimide group was then quantitatively cleaved by hydrazinolysis to form a monoamine
functional HBPG. Phthalimide functional groups were also introduced to the HBPG structure
by post-polymerization modification with N-hydroxy phthalimide.[30] Similar, well-defined,
precisely monofunctional hyperbranched polyglycerol-based structures were reported by Frey
3

ACCEPTED MANUSCRIPT
et al.[31] For the introduction of the amino functionality the authors used a new initiator -
di(benzyl)aminoethanol obtained from ethanolamine and benzyl bromide.
The objective of this work was the synthesis of a new type of hyperbranched polyethers
by introduction of amine groups to the polyglycerol via copolymerization of environmentally
friendly monomer - glycerol carbonate with a cyclic carbonate monomer bearing phthalimide
moiety. Moreover, we expected that the synthesis could be performed using cheap and safe in
use catalyst potassium carbonate, instead of burdensome metal alkoxide used in our previous
report.[1] We expect that the presence of two types (amine and hydroxyl) of functional groups
of different reactivity in the structure of hyperbranched polymer will allow building larger
molecular systems with different types of substituents not only for biomedical applications
but also as modifiers of mechanical properties of other polymeric materials.
2
. Experimental
2
.1 Materials
All the reagents were purchased from Sigma-Aldrich (Poznań, Poland) and used as received.
Solvents were purchased from POCh (Gliwice, Poland). THF was distilled over potassium
benzophenone ketyle and immediately transferred to the reaction vessel under inert
atmosphere. DMF was dried using molecular sieves (0.4 nm) for at least 48h and used without
further purification. DMSO was dried by azeotropic distillation with toluene and stored over
molecular sieves (0.4 nm). Other solvents were used without further purification.
2
.2 Instrumentation
FTIR spectra were recorded on a Nicolet iS5 Mid Infrared FT-IR Spectrometer equipped with
1
13
iD7 ATR Optical Base or Biorad FTS-165 FT-IR Spectrometer. H NMR and C NMR
spectra were recorded on a Varian VXR 400 MHz or Bruker AVANCE 500 MHz
spectrometers using tetramethylsilane as an internal standard and deuterated solvents (CDCl3,
DMSO-d ). The average molecular masses of polymers were determined based on integration
6
1
of signals in H NMR spectra. The integral of the CH group signal coming from the core
3
trimethylolpropane (TMP) molecule was used as a reference. MALDI-TOF spectra were
measured on a Bruker UltraFlex (Bremen, Germany) spectrometer using DCTB (trans-2-[3-
(4-tert-butylphenyl)-2-methyl-2-propenylidene]malononitrile) as a matrix and analyzed with
flexAnalysis v.3.3 (Bruker Daltonik GmbH) and Polymerix v. 2.0 (Sierra Analytics Inc.)
software. Rheological measurements were performed with Malvern Kinexus Pro rheometer in
4

ACCEPTED MANUSCRIPT
the parallel plate geometry (φ20 mm, spacing gap 0.5 mm) within the shear rate 0.1–100 1/s.
Elemental analysis was performed with Elementar Vario EL III CHNS analyzer. The molar
mass and molar mass distribution of acetylated samples of polymers were determined by a
GPC on a Viscotek system comprising GPCmax and TDA 305 unit equipped with one guard
and two DVB Jordi gel columns (102-107, linear, mix bed) in CH Cl as an eluent at 35 °C at
2
2
a flow rate of 1.0 mL/min using the RI detector and PS calibration.
2
.3 Syntheses
N-(2,3-dihydroxypropyl)phthalimide (1) was prepared according to modified patent
procedure.[32]
3
-Chloro-1,2-propnediol (40 g, 0.362 mol) and potassium phthalimide (80 g, 0.430
mol) were heated to reflux in ethanol (400 ml) for 24 h in a nitrogen atmosphere. The
resulting mixture was cooled down and evaporated to dryness. Dichloromethane (400 ml) was
added to the residue. The solid salts were filtered off, and the solution evaporated to dryness
yielding crude N-(2,3-dihydroxypropyl)phthalimide that was used without further
purification.
o
1
Yield 80 g (99.9%), mp= 122-124 C; H NMR (400 MHz, CDCl , δ): 7.90-7.84 (m,
3
2
H, H ), 7.78-7.71(m, 4H, H ), 4.02-3.95 (m, 1H, CH CHCH ), 3.93 (dd, 1H, CH OH,
ar
ar
2
2
2
J =14.2 Hz, J =5.9 Hz), 3.85 (dd, 1H, CH OH, J =14.2 Hz, J =5.1 Hz), 3.67 (dd, 1H, CH N,
1
2
2
1
2
2
13
J =11.8 Hz, J =4.1 Hz), 3.60 (dd, 1H, CH N, J =11.8 Hz, J =4.8 Hz), 2.24 (bs, 2H, OH); C
1
2
2
1
2
NMR (400 MHz, DMSO-d , δ): 168.1 (C=O), 134.2 (C ), 131.8 (C ), 122.9 (C ), 68.5
6
Ar
Ar
Ar
-1
(
CHOH), 64.2 (CH OH), 41.7 (CH N). FTIR (KBr): ν (cm ) = 3300, 2942, 1780, 1717, 1433,
2 2
1
392, 1192, 719.
N-[(2-oxo-1,3-dioxolan-4-yl)methyl]phthalimide (2)
Crude N-(2,3-dihydroxypropyl)phthalimide (1) 80g, 0.361 mol), dimethyl carbonate
(DMC) (187 g, 200 ml, 2.075 mol) and potassium carbonate (1.6 g, 11.6 mmol) were placed
in a 1000 ml round bottom flask equipped with a reflux condenser. The reaction mixture was
heated at reflux for 48h. The excess of DMC and ethanol were removed on a rotary
evaporator. Addition of 10 ml of THF caused crystallization of the residue. Crystals were
washed with water to remove the catalyst and dried. The product was purified by extraction
and crystallization with hot THF performed in a Soxhlet apparatus.
5

ACCEPTED MANUSCRIPT
o
1
Yield 59.8 g (66.9 %), mp= 178-179 C, H NMR (DMSO, 500 MHz, δ): 7.93-7.89 (m,
2
H, H ), 7.89-7.84 (m, 2H, H ), 5.06-4.99 (m, 1H, CH), 4.60 (dd, 1H, OCH , J =8.6 Hz,
Ar
Ar
2
1
J =8.0 Hz), 4.35 (dd, 1H, OCH J =8.6 Hz, J =6.2 Hz), 3.97 (dd, 1H, NCH , J =14.8 Hz,
2
2,
1
2
2
1
13
J =6.4 Hz), 3.92 (dd, 1H, NCH , J =14.8 Hz, J =4.9 Hz); C NMR (DMSO, 125 MHz, δ):
2
2
1
2
1
3
67.8 (NC=O), 154.4 (C=O), 134.6 (C ), 131.5 (C ), 123.3 (C ), 74.2 (OCH), 67.5 (OCH ),
Ar Ar Ar 2
-1
9.4 (NCH ); FTIR (ATR): ν (cm ) = 1775, 1705, 1390, 1310, 1169, 1046, 716; MALDI-
2
+
TOF (DCTB, m/z): [M + K ] calcd for C H NO K, 286.012; found 286.015.
1
2
9
5
4
-Hydroxymethyl-1,3-dioxolan-2-one (3) - Glycerol carbonate was synthesized according to
literature procedure.[1]
Determination of the catalyst amount needed for preparation of glycerol carbonate
In a round bottom flask equipped with a reflux condenser, a thermometer and a
magnetic stirrer 28,26 g (0.3 mol) of glycerol was placed followed by a certain amount of
◦
catalyst - potassium carbonate. The mixture was heated at 40 C. Then 81g (0.9 mol) of
◦
◦
dimethyl carbonate was added. The temperature was then increased up to 70 C. At 60 C the
dissolution of the catalyst was observed. The time needed for homogenization of the reaction
mixture measured from the moment of addition of dimethyl carbonate was registered. A blank
experiment without addition of the catalyst showed no reaction progress (no homogenization)
◦
after heating for 2h at 70 C.
Determination of the catalyst amount needed for polymerization of glycerol carbonate
To get rid of the catalyst, glycerol carbonate solution in dry ethyl acetate was filtered
several times through a bed of silica gel until neutral pH. Then the solvent was removed under
vacuum.
In a round bottom flask equipped with a thermometer, magnetic stirrer and a gas outlet
connected to a gas burette (filled with CO saturated water) 5g (0,04 mol) of glycerol
2
◦
carbonate was placed and heated at 155 C. Then a certain amount of catalyst - K CO was
2
3
◦
added and heating continued at 155 C. The amount of collected CO was measured in time.
2
General procedure of co-polymerization of glycerol carbonate and N-[(2-oxo-1,3-
dioxolan-4-yl)methyl]phthalimide
6

ACCEPTED MANUSCRIPT
To a 25 mL three-neck round bottom flask equipped with a magnetic stirrer, nitrogen
inlet and thermometer, trimethylolpropane (TMP, 1 equivalent, see Tab.1) was added,
followed by glycerol carbonate (50-29 equivalents, see Tab. 1) and N-[(2-oxo-1,3-dioxolan-4-
o
yl)methyl]phthalimide (2) (0-21 equivalents). The reaction mixture was stirred at 80 C to
o
obtain a homogeneous solution, then K CO was added and the reaction carried out at 155 C.
2
3
Reaction progress was monitored by FT-IR spectroscopy. It was finished when the absorption
-1
band at 1795 cm corresponding to C=O of cyclic carbonate groups disappeared, usually after
2
4-48 h. Copolymers HBPG0-HBPG9 were obtained as brown viscous oils. Exact amounts
1
of reagents are placed in Table 1. The method of calculation of molecular weights by H
NMR is provided in supplementary materials.
Table 1. Amounts of reagents used for polymerization and the reaction yields.
Mn
NMR
calc.
value
Da
Mn
theoret.
calc.
value
Da
TMP /
Glycerol
Monomer
Monomer
Polymer
*
TMP
K CO3 Yield Yield
2
g.c. / 1
carbonate
1
1
molar
ratio
g
g
mol %
g
mg
g
%
HBPG-0
HBPG-1
HBPG-2
HBPG-3
HBPG-4
HBPG-5
HBPG-6
HBPG-7
HBPG-8
HBPG-9
1/50/0 0.160
1/47/2 0.167
1/46/4 0.148
1/46/5 0.150
1/43/6 0.158
1/41/8 0.165
1/40/10 0.170
1/37/12 0.182
1/33/17 0.239
1/29/21 0.270
6.99
6.98
5.99
6.01
5.99
6.01
6.02
6.00
7.60
7.60
0
0
41
9
4.49
4.73
4.66
4.76
4.77
5.65
5.39
6.29
9.79
11.96
98.8 3800
91.9 3800
99.0 4200
96.0 4300
88.4 4000
94.2 4600
82.5 4300
85.2 4600
88.7 5500
88.8 5900
3800
4100
4300
4400
4600
4900
5200
5400
6200
6700
4.7
0.73
0.97
1.26
1.80
2.51
3.14
4.19
7.33
10.26
7.0
8
8.9
39
40
42
45
28
13
14
12.3
16.3
19.6
24.5
31.0
38.5
*
g.c.- glycerol carbonate
General procedure of hydrazinolysis of copolymers of glycerol carbonate and N-[(2-oxo-
1
,3-dioxolan-4-yl)methyl]phthalimide
The amine groups of the HBPG polymers were deprotected using modified literature
procedures.[33],[34],[35] In a 100 ml round bottom flask equipped with a magnetic stirrer and
a reflux condenser 5 g of HBPG copolymer followed by approx. 25 ml of ethanol were placed.
The mixture was heated at reflux to dissolve the polymer. Then 25% molar excess (in respect
to the amount of phthalimide groups) of hydrazine hydrate 65% water solution was added and
7

ACCEPTED MANUSCRIPT
the resulting solution stirred at reflux for 20 h. The mixture was cooled down to room
temperature, evaporated to dryness and re-dissolved in methanol. Diluted hydrochloric acid
was added drop-wise to a stable acidic pH. The mixture was then heated at reflux for an
additional 30 min. The resulting precipitate was filtered off. The filtrate was condensed almost
to dryness under reduced pressure and the residue was dissolved in water. Any white
precipitate was filtered off and the clear aqueous solution was made alkaline (pH = 10) by
addition of Na CO . The solvent was removed using rotary evaporator. The residue was
2
3
purified by multiple precipitation from methanol/ethanol mixture to remove any inorganic
salts. Amounts of the reagents and yields are given in Table 2.
Table 2. Amounts of reagents used for hydrazinolysis and the reaction yields.
6
5%
Phthalimide
content
Polymer
Polymer
Hydrazine
hydrazine Ethanol Yield Yield
hydrate
g
mmol
2.37
mmol
3.00
g
ml
g
%
A-HBPG-1
A-HBPG-2
A-HBPG-3
A-HBPG-4
A-HBPG-5
A-HBPG-6
A-HBPG-7
A-HBPG-8
A-HBPG-9
5.20
0.15
26
3.47
71
5.00
2.72
3.48
4.83
5.30
5.35
5.00
5.25
3.36
2.27
3.88
6.87
8.78
10.6
11.9
14.6
4.20
2.84
4.85
8.59
11.0
13.3
14.9
18.3
0.21
0.14
0.24
0.42
0.54
0.66
0.73
0.90
25
14
17
24
27
27
25
26
3.14
1.72
2.17
2.63
3.02
1.52
2.23
2.22
69
71
73
67
73
68
65
67
2
.4 Crystallography
The X-ray measurement of OE was performed at 100(2)K on a Bruker D8 Venture Photon
00 CMOS diffractometer equipped with a mirror monochromator and a CuKα INCOATEC
1
IµS micro-focus source (λ = 1.54178 Å). A total of 3052 frames were collected with Bruker
APEX2 program [36]. The frames were integrated with the Bruker SAINT software package
[
37] using a narrow-frame algorithm. The integration of the data using a monoclinic unit cell
yielded a total of 1897 reflections to a maximum θ angle of 67.99° (0.83 Å resolution), of
which 1895 were independent (average redundancy 1.001, completeness = 98.8%, Rsig
=
2
1
.77%) and 1756 (92.66%) were greater than 2σ(F ).The final cell constants of a = 6.9447(5)
3
Å, b = 17.0186(12) Å, c = 9.1872(7) Å, β = 104.177(2)°, V = 1052.76(13) Å , are based upon
8

ACCEPTED MANUSCRIPT
the refinement of the XYZ-centroids of 9920 reflections above 20 σ(I) with 10.39° < 2θ <
1
36.5°. Data were corrected for absorption effects using the multi-scan method (TWINABS)
[
38]. The calculated minimum and maximum transmission coefficients (based on crystal size)
are 0.7450 and 0.7960.
The structure was solved and refined using the Bruker SHELXTL Software Package [39, 40],
using the space group P2 /n , with Z = 4 for the formula unit, C H NO .The final anisotropic
1
12
9
5
2
full-matrix least-squares refinement on F with 163 variables converged at R1 = 3.10%, for
the observed data and wR2 = 7.93% for all data. The goodness-of-fit was 1.065. The largest
-
3
peak in the final difference electron density synthesis was 0.261 e /Å and the largest hole was
-
3
-
3
-
0.175 e /Å with an RMS deviation of 0.041 e /Å . On the basis of the final model, the
3
-
calculated density was 1.560 g/cm and F(000), 512 e .
The crystal is twinned by pseudomerohedry with two domains. Some of the reflections are
separated whereas the other are overlapped. At the initial stages structure was refined with
HKLF 5 option. The refined ratio of the twin components is equal to 0.643(2):0.357(2). After
the refinement converged data were processed using WinGX software [41] to regular HKLF 4
format.
The non-hydrogen atoms were refined anisotropically. All hydrogen atoms were placed in
calculated positions and refined within the riding model. The temperature factors of hydrogen
atoms were not refined and were set to be equal to 1.2 times larger than Ueq of the
corresponding heavy atom. The atomic scattering factors were taken from the International
Tables [42]. Molecular graphics was prepared using program Diamond 3.2. [43] Thermal
ellipsoids parameters are presented at 50% probability level.
3
. Results and discussion
3
.1 Monomer synthesis and characterization
Glycerol carbonate is one of the most valuable derivatives that could be obtained from
glycerol and CO and it is considered a green chemical with a broad spectrum of uses, for
2
instance a substitute for petro-derivative compounds such as ethylene or propylene carbonate.
This monomer and its derivatives are also key compounds in the synthesis of multiple cyclic
carbonates which are used for preparation of non-isocyanate polyurethanes [6] or
polyglycerols.[1]
9

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The number of functional five-membered cyclic carbonates that could be co-
polymerized with glycerol carbonate is very limited. In majority those compounds posses
aliphatic or aromatic hydrocarbon side groups, however a chloromethyl, vinyl, allyl or
methacrylic ester derivatives were also reported.[5] So far there were no reports on five-
membered cyclic carbonates containing protected amine substituents.
(iii)
(iv)
(i)
(ii)
1
2
(v)
(vi)
Scheme 1. Synthesis of N-[(2-oxo-1,3-dioxolan-4-yl)methyl]phthalimide; (i) 3-chloro-1,2-
propanediol; (ii) DMC, K CO , overall (i+ii) yield 67%; (iii) 4-chloromethyl-2,2-dimethyl-
2
3
+
1
,3-dioxolane, 31%; (iv) H , H O, 18%; (v) phthalimide, epichlorohydrin, DMF, 58%; (vi)
2
NaHCO , DMSO, 16%.
3
In this work we proposed a synthesis of a new cyclic carbonate monomer N-[(2-oxo-
,3-dioxolan-4-yl)methyl]phthalimide (2) that allows production of amine containing
1
hyperbranched polyglycerol (A-HBPGs) using Gabriel synthesis. N-[(2-oxo-1,3-dioxolan-4-
yl)methyl]phthalimide cannot be considered a "green chemical". However, it allows easy
functionalization of polyglycerol obtained from glycerol carbonate. There are two main
synthetic routes leading to five-membered cyclic carbonates: the reaction of a respective
oxirane with carbon dioxide or 1,2-diol with dialkyl or diphenyl carbonate. Instead of
carbonic acid esters, phosgene or its derivatives can also be used.[44]
1
0

ACCEPTED MANUSCRIPT
We tried several approaches to synthesize monomer 2 shown in Scheme 1. The
preferred synthetic way consisted of two solvent free steps: a reaction of potassium
phthalimide with 3-chloro-1,2-propanediol followed by transesterification of crude product 1
with excess of dimethyl carbonate in presence of potassium carbonate. Since the final product
2
readily crystallized and was relatively easy to purify, there was no need to purify the
intermediate 1. The monomer 2 was synthesized with the overall yield 67%.
The halohydrin pathway [45] (v+vi, Scheme 1) was less preferred due to the low
effectiveness. It required the use of difficult to remove polar aprotic solvents (DMSO, DMF),
extended reaction times and multiple step purification procedures. Intermediate 1 was also
available via protection-deprotection procedure using ketal derivative (4-chloromethyl-2,2-
dimethyl-1,3-dioxolane). However, since we had realized that final product 2 could be
reached from crude compound 1 the synthetic steps iii and iv (Scheme 1) became no longer
relevant.
Monomer 2 has been characterized using NMR, FT-IR, X-ray and MALDI-TOF
techniques.
1
Figure 1. H NMR spectrum of N-[(2-oxo-1,3-dioxolan-4-yl)methyl]phthalimide (2).
1
1

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1
3
Figure 2. C NMR spectrum of N-[(2-oxo-1,3-dioxolan-4-yl)methyl]phthalimide (2).
1
13
1
Figures 1 and 2 show high resolution H and C NMR spectra of monomer 2. The H NMR
spectrum of 2 contains two symmetrical multiplets (d, Fig.1) at approx. 7.9 ppm that were
assigned to aromatic protons of phthalimide ring. The protons of aliphatic part of the molecule
are represented by a pattern consisting of five groups of signals, typical for unsymmetrically
substituted glycerol derivatives, where each proton can be assigned to a separate signal group
due to the presence of the asymmetry center in the molecule. The c protons of the methylene
group linked to a nitrogen atom show two overlaping doublets of doublets at approx. 3.9 ppm
with the coupling constants equal 14.8, 6.4 and 4.9 Hz, grouped in a symmetrical multiplet.
The methylene group of the 1,3-dioxolan-2-one ring (b, b' protons at 4.7-4.3 ppm) is also
represented by two doublets of doublets. However in this case one pair of doublets appears as
a triplet due to the overlapping of peaks. The coupling constants are equal 8.6, 8.0 and 6.2 Hz.
The a proton signal of the 1,3-dioxolan-2-one ring appears at approx. 5.0 ppm as a multiplet.
1
3
C NMR spectrum shown in Fig. 2 confirmed that the final product contained two types of
carbonyl carbons: an imide one at 167.8 ppm and a five-membered cyclic carbonate at 154.4
ppm, three types of aromatic carbons (134.6, 131.5, 123.3 ppm) and three types of aliphatic
carbons (74.2, 67.5, 39.4 ppm) which is in agreement with the designed structure.
1
2

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Figure 3. X-Ray structure of N-[(2-oxo-1,3-dioxolan-4-yl)methyl]phthalimide (2).
Figure 3 shows the X-Ray crystal structure of 2. The structure of 2 was determined by single
crystal X-ray diffraction. Single crystals of 2 were obtained by recrystallization from the ethyl
acetate solution by slow evaporation of the solvent. Monomer 2 crystallized in a monoclinic
crystal system with space symmetry P2 /m. In the crystal phase phthalimide structures were
1
parallel to each other and formed planes.
-1
The FT-IR spectrum of 2 showed multiple absorption bands below 2000 cm . The
-1
presence of the carbonyl absorption band at 1775 cm confirmed formation of the five-
-1
membered cyclic carbonate ring, while the 1705 cm presence of the imide ring. The molar
mass of 2 was measured with MALDI-TOF spectrometer using CDTB as a matrix. The
measured value of 286.015 m/z was in agreement with the molecular formula: C H NO K,
1
2
9
5
where K stands for potassium ionization cation.
.2 Determination of the catalyst amount needed for polymerization of cyclic carbonates
3
1
3

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K CO3
K2CO3
2
-
CH OH
3
-
CO2
3
Scheme 2. Process of production of hyperbranched polyglycerols.
By now, synthesis of hyperbranched polyglycerols starting from glycerol carbonate
has been performed using strong base catalysts: potassium methoxide [1] or sodium
hydroxide.[46] However, we have found that the process can be completed using easily
available, cheap and safe in operation potassium carbonate. The use of K CO is also
2
3
convenient from the technological point of view, since the same catalyst is used for glycerol
carbonate synthesis. (Scheme 2)
To match glycerol carbonate and subsequent polyglycerol syntheses, the amount of
catalyst was optimized. In case of glycerol carbonate synthesis the fastest reaction rates were
obtained for K CO to glycerol molar ratio equal 0.01 and higher. This stands for 0.33g of
2
3
K CO in 100g of the reaction mixture containing glycerol and dimethyl carbonate in the
2
3
molar ratio 1 to 3.
1
4

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Figure 4. Changes in the amount of CO released during polymerization of glycerol carbonate
2
in time, depending on the amount of catalyst (A); Time needed to reach 10% conversion
depending on the amount of catalyst (B); g.c.=glycerol carbonate.
To follow the reaction of polymerization of glycerol carbonate, a setup containing a
gas burette connected to the polymerization reactor was applied. The polymerization of
glycerol carbonate took place with decarboxylation. Its rate could be estimated by the amount
of CO released in time. The fastest reaction rates were reached for the 0.00055 potassium
2
carbonate to glycerol carbonate molar ratio and higher (see Fig. 4) This stands for 0.06% of
wt
the catalyst in glycerol carbonate, which is a lower value than in case of glycerol carbonate
synthesis. This result opens a way to a one-pot production of polyglycerols from glycerol and
dimethyl carbonate with a single catalyst common for both synthetic steps, added once, at
1
5

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3
.3 Co-polymerization of glycerol carbonate with N-[(2-oxo-1,3-dioxolan-4-yl)methyl]-
phthalimide (2)
2
3
(i)
(ii)
Scheme 3. The synthesis of amine containing hyperbranched polyglycerols; (i) TMP, K CO ,
2
3
1
55 °C, 83-91%, (ii) 65% hydrazine hydrate, ethanol, reflux, 24h, 65-73%.
Amine functionalized polyglycerols were synthesized in a simple two-step procedure shown
in Scheme 3. In the first step monomer 2 was copolymerized with glycerol carbonate 3 in a
ring opening polymerization-decarboxylation process using trimethylolpropane (TMP) as a
core molecule (initiator) and potassium carbonate as a catalyst. Application of a core
molecule (TMP) made it possible to control the molar masses of the products and helped to
reduce the dispersity of the molar masses of hyperbranched polymers.[47],[48] Presence of
1
the ethyl group in the core allowed determination of an average molar mass using H NMR
spectroscopy (Tab.1). The resulting polymers containing phthalimide groups were then
reacted with hydrazine hydrate to yield final hyperbranched amino-polyglycerols.
1
6

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Figure 5. Changes in FT-IR spectra during synthesis of polymer HBPG-1 containing 4.7% of
phthalimide monomer units.
Hyperbranched polymers HBPG-0−HBPG-7 were prepared by a modified procedure
previously reported by us.[1] However, to allow the CO release studies the slow addition of
2
monomers was not used. Such methodology in case of hyperbranched polymers usually
results in high dyspersity index of the product. The ring-opening copolymerization of 2 and
glycerol carbonate was carried out in bulk, in the presence of TMP and a catalytic amount of
o
potassium carbonate at 155 C. The molar ratio of the carbonate monomers to TMP was equal
5
0 to yield in the final step A-HBPGs of the average molar mass of approx. 3800 g/mol that
could be easily characterized with spectroscopic methods. For analytical purposes, mainly to
simplify MALDI-TOF spectrograms, samples without the core molecule were also
synthesized. The progress of the reaction was monitored by disappearance of the cyclic
-1
carbonate absorption band at 1795 cm in the FT-IR spectrum. (Fig. 5) The process was
usually finished within 48h. Copolymers HBPG-0−HBPG-9 were obtained as dark yellow
viscous oils.
The copolymerization rate was dependent on the content of 2 in the mixture with
glycerol carbonate. Fig. 6 shows the amount of carbon dioxide released from the reactor in
time for the reaction system containing from 0 to 100%mol of 2 and constant amount of
catalyst.
1
7

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Figure 6. The CO release during copolymerization of glycerol carbonate and monomer 2 in
2
time, depending on the amount of 2 in the reaction mixture (molar per-cents of 2 given); inset
shows a full CO release curve for HBPG-1 polymer containing 4.7% of 2.
2
Surprisingly, the highest polymerization rates were observed for samples containing
highest amounts of sterically hindered monomer 2. It seems that electron withdrawing effect
of imide nitrogen atom, activating the cyclic carbonate ring is of large importance.
1
8

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1
Figure 7. H NMR (400MHz, DMSO-d ) spectra of the HBPG-0-HBPG-9 polymers.
6
Theoretical amount of phthalimide monomer 2 shown.
1
Fig. 7 shows a comparison of H NMR spectra of synthesized polymers. They show no
signals of unreacted monomer 2. The a and b peaks located between 1.5 and 0.5 ppm are
assigned to the ethyl group of the core molecule (TMP). The integrals ratio of other signals to
these signals allowed to calculate the average molar mass of the polymers and their
composition. The calculated values of molar masses placed in Tab.1 may be overestimated.
As shown below, due to the occurrence of autoinitiation, it is not guaranteed that every
polymer molecule bears a TMP moiety. The phthalimide aromatic ring signals are located at
approx. 8 ppm. Their intensity grows with the growing amount of the monomer 2 in the post-
reaction mixture. The signals in the range of 3.7 to 3 ppm are assigned to methylene and
methine groups attached to oxygen atoms and are overlapping. The signals in the range of 5 to
4
.3 ppm are assigned to the hydroxyl groups.
1
9

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1
3
Figure 8. C NMR (400MHz, DMSO-d ) spectra of the HBPG-8 polymer.
6
1
3
The C NMR spectrum shown in Fig. 8 confirmed the incorporation of phthalimide
monomer into the structure of the polymer. Due to a high complexity of the structure of
hyperbranched polymers (presence of core, linear, branching and terminal units) precise
1
3
assignment of signals in the C NMR spectra was difficult. The signals in Fig. 8 were
assigned according to a publication by Sunder et al.[8] containing detailed chemical shifts of
carbons in the polyglycerol structure and confirmed by the HSQC and HMBC analyses (see
supplementary materials Figures 5s-7s). Fig. 8 shows the structures of possible repeating units
and their signals in the range of 80-40 ppm. In addition to the units typical for polyglycerol
the spectrum contains the signals of phthalimide containing repeating units. The most intense
2
0

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signals in the spectrum come from linear and terminal units while the dendritic subunits are in
minority. It may be caused by the sterical hindrance of the bulky phthalimide residues.
MALDI-TOF technique allows to observe the mass of repeating units of the polymers
and their end groups. In case of homo-polymers, the analysis of the spectrum is usually
simple. However, when copolymers and products of polymer modifications are considered the
analysis becomes tedious.[49] To simplify the MALDI-TOF spectrum a copolymer of 2 and
glycerol carbonate (molar ratio 1:2) was synthesized without the TMP core molecule.
+
Figure 9. MALDI-TOF (DCTB, K ) spectrum of polyglycerol obtained from glycerol
carbonate (3) and N-[(2-oxo-1,3-dioxolan-4-yl)methyl]phthalimide (2) used in the molar ratio
1
:2.
Its spectrum is shown in Fig.9. All the signals in the spectrum can be assigned to a
combination of masses of repeating units produced from glycerol carbonate and phthalimide
monomer 2 and the mass of potassium cation. The core molecule (residual mass 74.08 m/z)
was glycidol of the same molar mass as the repeating unit A. As shown in the monomer
distribution plot in the inset of Fig. 9, the molar masses of majority of macromolecules
2
1

ACCEPTED MANUSCRIPT
corresponded to approx. 10 glycerol (A) or phthalimide (B) repeating units where the numbers
of A and B units are on the comparable levels. One would expect higher unit A content.
However, the aromatic structures absorb the laser light and undergo excitation more easily
than aliphatic ones. Therefore the population of signals corresponding to aromatic structures is
higher than expected. For comparison reasons a sample MALDI-TOF spectrum of a HBPG-3
polymer containing initiator molecule (TMP) is available in supplementary materials (Figure
8
s).
As stated above, the glycidol molecule was found at the core of hyperbranched
structure. In fact, it was produced in the reaction mixture and could act as an initiator or an
intermediate leading to hyperbranched polymer. Thus, the growth of the polymer could be
achieved according to the reaction (1) (Scheme 4) or by anionic polymerization of glycidol.
The formation of glycidol in the reaction mixture is explained in Scheme 4.
(1)
CO2
etc.
(2)
or
CO2
Scheme 4. Polymerization with decarboxylation of glycerol carbonate (3) (reaction 1) and
formation of glycidol under reaction conditions (reaction 2).
The formation of glycidol from glycerol carbonate under reaction conditions was also
1
confirmed by H NMR spectroscopy. The reaction mixture containing glycerol carbonate and
potassium carbonate was heated at reduced pressure allowing the volatile molecules to distill
off the mixture. The distillate was collected and investigated. As shown in Fig. 10 it consisted
of glycerol carbonate and glycidol in the molar ratio 1 to 1.5 (60 % mol. of glycidol).
2
2

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1
Figure 10. H NMR (400 MHz, DMSO-d ) spectrum of a distillate obtained from the mixture
6
of glycerol carbonate and K CO .
2
3
3
.4 Hydrazinolysis of glycerol carbonate - N-[(2-oxo-1,3-dioxolan-4-yl)methyl]phthalimide
copolymers
The final aminated polyglycerols (A-HBPGs) were obtained in the reaction of synthesized
in the first step copolymers with 65% aqueous hydrazine hydrate performed in ethanol for 20
h at reflux. This method produced a precipitate of phthalhydrazide along with the primary
amine groups in the polymer. The precipitate was removed by filtering acidified methanol
solution of the polymers. Then the solution was alkalized (pH = 10) by addition of Na CO3
2
and evaporated to dryness. Inorganic salts were removed from the polymers by multiple
precipitation from the methanol/ethanol mixtures. Attempts to purify the polymers by dialysis
were not effective due to low yields of this process.
2
3

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Figure 11. FT-IR (ATR) spectra of polyglycerol HBPG-0 and copolymers HBPG-8
(containing phthalimide residues) and A-HBPG-8 (deprotected one) based on mixture
containing 34% mol of 2.
The procedure of removal of phthalimide residues described above was effective which was
confirmed by spectral data. Fig. 11 shows a set of three FTIR spectra of reference polymer
HBPG-0, copolymer HBPG-8 based on a mixture of glycerol carbonate and 33%mol of 2 and
its deprotected counterpart A-HBPG-8. The removal of aromatic rings was accompanied by
-1
disappearance of characteristic imide carbonyl absorption band at 1705 cm , aromatic ring
–
1
-1
CH bending vibrations band at 724 cm and 530 cm O=C-N out of plane rocking vibration
band.
1
Figure 12. H NMR (400MHz, DMSO-d ) spectrum of deprotected A-HBPG-7 polymer
6
containing 24.5% of amine containing repeating units.
2
4

ACCEPTED MANUSCRIPT
1
Similarly, the H NMR spectrum shown in Fig. 12 showed disappearance of aromatic protons.
Because the spectrum does not give a definitive proof of amine group presence in the
structure, the polymer was reacted with acetic anhydride. Such modification revealed
1
presence of two amide proton signals at 5.14 i 5.04 ppm in the H NMR spectrum. Moreover,
13
the C NMR spectrum of A-HBPG-8 showed presence of CH NH aliphatic carbon signal at
2
2
4
8.7 ppm. The spectra are given in supplementary materials (Figures 2s and 3s).
The MALDI-TOF spectrum (Fig. 13) of deprotected polyglycerol obtained from glycerol
carbonate (3) and N-[(2-oxo-1,3-dioxolan-4-yl)methyl]phthalimide (2) in the molar ratio 1:2
also confirmed successful removal of phthalimide moieties.
+
Figure 13. MALDI-TOF (DCTB, K ) spectrum of polyglycerol obtained from glycerol
carbonate (3) and N-[(2-oxo-1,3-dioxolan-4-yl)methyl]phthalimide (2) in the molar ratio 1:2
with deprotected amine groups.
The spectrum contains several series of signals that are overlapping. They all can be assigned
to one core molecule: glycerol (residual mass 92.09 m/z). This type of core molecule results
from a glycidol one that was hydrolized under hydrazinolysis reaction conditions. Each series
of signals can be assigned to molecules containing one molecule of glycerol and multiple
units containing hydroxyl (derived from glycerol carbonate) and amine (derived from
2
5

ACCEPTED MANUSCRIPT
phthalimide monomer 2) (A and B in Fig. 13) repeating units. The molar mass difference
between those two types of repeating units is equal 1, therefore the peaks are grouped in sets
and overlaping. The small signals seen close to the baseline were identified as molecules
containing one or two phthalimide groups. This is in agreement with NMR data, since small
quantity of the phthalimide residues are also seen in Fig. 14 at approx. 7.5 ppm.
The distribution plot present in tn Fig. 13 shows that both A and B units are evenly distributed
in copolymer macromolecules.
Typically, GPC is used for the analysis of the molar masses of polymeric materials. In
case of hyperbranched polymers the NMR calculated results are more precise. For comparison
purposes acetylated samples of copolymers of 2 and glycerol carbonate in a molar ratio 1 to 2
were measured by GPC using polystyrene standards. The sample containing phthalimide
residues showed molar mass M =1560 g/mol and dispersity D=2.13, while the deprotected,
w
amine containing polymer 790 g/mol and dispersity D=2.13. A sample GPC curve is available
in supplementary materials (Figure 4s).
Finally, we confirmed the presence of nitrogen in the deprotected polymer samples by
elemental analysis. The results showed slightly lower content of nitrogen than expected. The
sample A-HBPG-7 showed 6.53% of N (7.43% theoret.) while the A-HBPG-8 7.47% N
(8.32% theoret.). This confirmed that described synthetic procedure was correct.
4
. Conclusions
Hyperbranched aliphatic polyethers with hydroxyl and amine end groups were produced from
glycerol carbonate (4-hydroxymethyl-1,3-dioxolan-2-one) and cyclic carbonate bearing
phthalimide moiety. Anionic polymerization of cyclic carbonate monomers, which proceeds
with simultaneous decarboxylation, was performed using a simple catalyst - potassium
carbonate and trimethylolpropane (TMP) or glycerol carbonate as an initiator. The
polymerization conditions were optimized. The polymers were characterized by means of
NMR, FTIR, MALDI-TOF, GPC and elemental analysis.
It was shown that during the process of polymerization an intermediate - glycidol is formed
and acts as initiator or monomer. The easy production and purification of phthalimide - cyclic
carbonate monomer enables multigram synthesis of amine functionalized polyglycerols that
will be investigated as biomolecules carriers, antibacterial agents, carbon dioxide scavengers
or modifiers of mechanical properties of epoxy resins and polyurethanes.
2
6

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5
. Acknowledgments
This paper is based upon work supported by the Polish National Science Centre research grant
OPUS UMO-2015/17/B/ST5/00350. Prof. G. Rokicki is kindly acknowledged for many
helpful remarks during preparation of this work. The X-ray structure was determined in the
Advanced Crystal Engineering Laboratory (aceLAB) at the Chemistry Department of the
University of Warsaw by dr. Ł. Dobrzycki.
References
[
1] G. Rokicki, P. Rakoczy, P. Parzuchowski, M. Sobiecki, Hyperbranched aliphatic
polyethers obtained from environmentally benign monomer: glycerol carbonate, Green
Chemistry 7(7) (2005) 529-539.
[
2] A. Behr, J. Eilting, K. Irawadi, J. Leschinski, F. Lindner, Improved utilisation of
renewable resources: new important derivatives of glycerol, Green Chemistry 10(1) (2008)
3-30.
3] M.O. Sonnati, S. Amigoni, E.P.T. de Givenchy, T. Darmanin, O. Choulet, F. Guittard,
1
[
Glycerol carbonate as a versatile building block for tomorrow: synthesis, reactivity, properties
and applications, Green Chemistry 15(2) (2013) 283-306.
[
4] J.R. Ochoa-Gómez, O. Gómez-Jiménez-Aberasturi, C. Ramírez-López, M. Belsué, A brief
review on industrial alternatives for the manufacturing of glycerol carbonate, a green
chemical, Organic Process Research & Development 16(3) (2012) 389-399.
[
5] G. Rokicki, P. Parzuchowski, ROP of Cyclic Carbonates and ROP of Macrocycles–Latest
Developments, in: S. Hashmi (Ed.), Reference Module in Materials Science and Materials
Engineering,, Elsevier2016, pp. 1-92.
[
6] G. Rokicki, P.G. Parzuchowski, M. Mazurek, Non-isocyanate polyurethanes – synthesis,
properties and applications, Polymers for Advanced Technologies 26(7) (2015) 707-761.
7] D. Yan, C. Gao, H. Frey, Hyperbranched polymers: synthesis, properties, and applications,
John Wiley & Sons2011.
8] A. Sunder, R. Hanselmann, H. Frey, R. Mulhaupt, Controlled synthesis of hyperbranched
polyglycerols by ring-opening multibranching polymerization, Macromolecules 32(13) (1999)
240-4246.
9] T. Biedron, M. Bednarek, P. Kubisa, Cationic polymerization of 3-ethyl-3-
hydroxymethyloxetane in an ionic liquid, Macromolecular Rapid Communications 25(8)
[
[
4
[
(2004) 878-881.
[
10] A. Sunder, J. Heinemann, H. Frey, Controlling the growth of polymer trees: concepts and
perspectives for hyperbranched polymers, Chemistry-A European Journal 6(14) (2000) 2499-
506.
11] M. Gosecki, M. Gadzinowski, M. Gosecka, T. Basinska, S. Slomkowski, Polyglycidol,
2
[
Its Derivatives, and Polyglycidol-Containing Copolymers—Synthesis and Medical
Applications, Polymers 8(6) (2016) 227.
[
12] P.G. Parzuchowski, M. Kizlinska, G. Rokicki, New hyperbranched polyether containing
cyclic carbonate groups as a toughening agent for epoxy resin, Polymer 48(7) (2007) 1857-
865.
1
2
7

ACCEPTED MANUSCRIPT
[
13] S. Song, J. Lee, S. Kweon, J. Song, K. Kim, B.S. Kim, Hyperbranched Copolymers
Based on Glycidol and Amino Glycidyl Ether: Highly Biocompatible Polyamines Sheathed in
Polyglycerols, Biomacromolecules 17(11) (2016) 3632-3639.
[
14] M. Schömer, C. Schüll, H. Frey, Hyperbranched aliphatic polyether polyols, Journal of
Polymer Science Part A: Polymer Chemistry 51(5) (2013) 995-1019.
15] R. Haag, F. Kratz, Polymer therapeutics: concepts and applications, Angew Chem Int Ed
Engl 45(8) (2006) 1198-215.
16] D. Wilms, S.-E. Stiriba, H. Frey, Hyperbranched polyglycerols: from the controlled
[
[
synthesis of biocompatible polyether polyols to multipurpose applications, Accounts of
chemical research 43(1) (2010) 129-141.
[
17] G. Kasza, G. Gyulai, Á. Ábrahám, G. Szarka, B. Iván, É. Kiss, Amphiphilic
hyperbranched polyglycerols in a new role as highly efficient multifunctional surface active
stabilizers for poly (lactic/glycolic acid) nanoparticles, RSC Advances 7(8) (2017) 4348-
4
352.
[
18] W. Fischer, M. Calderon, R. Haag, Hyperbranched Polyamines for Transfection, in: W.
Bielke, C. Erbacher (Eds.), Nucleic Acid Transfection, Springer-Verlag Berlin, Berlin, 2010,
pp. 95-129.
[
19] G. Kasza, T. Stumphauser, A. Nádor, Z. Osváth, G. Szarka, A. Domján, J. Mosnáček, B.
Iván, Hyperbranched polyglycerol nanoparticles based multifunctional, nonmigrating
hindered phenolic macromolecular antioxidants: Synthesis, characterization and its
stabilization effect on poly (vinyl chloride), Polymer 124 (2017) 210-218.
[
20] R. Mezzenga, L. Boogh, J.-A.E. Månson, A review of dendritic hyperbranched polymer
as modifiers in epoxy composites, Composites Science and Technology 61(5) (2001) 787-
95.
21] S. Roller, H. Zhou, R. Haag, High-loading polyglycerol supported reagents for
Mitsunobu- and acylation-reactions and other useful polyglycerol derivatives, Mol Divers
(4) (2005) 305-16.
22] A.M. Staedtler, M. Hellmund, F.S. Mehrabadi, B.N.S. Thota, T.M. Zollner, M. Koch, R.
7
[
9
[
Haag, N. Schmidt, Optimized effective charge density and size of polyglycerol amines leads
to strong knockdown efficacy in vivo, Journal of Materials Chemistry B 3(46) (2015) 8993-
9
000.
[
23] F.S. Mehrabadi, O. Hirsch, R. Zeisig, P. Posocco, E. Laurini, S. Pricl, R. Haag, W.
Kemmner, M. Calderon, Structure-activity relationship study of dendritic polyglycerolamines
for efficient siRNA transfection, Rsc Advances 5(96) (2015) 78760-78770.
[
24] M. Hellmund, H.X. Zhou, O. Samsonova, P. Welker, T. Kissel, R. Haag, Functionalized
Polyglycerol Amine Nanogels as Nanocarriers for DNA, Macromolecular Bioscience 14(9)
(2014) 1215-1221.
[
25] M.C. Lukowiak, S. Wettmarshausen, G. Hidde, P. Landsberger, V. Boenke, K.
Rodenacker, U. Braun, J.F. Friedrich, A.A. Gorbushina, R. Haag, Polyglycerol coated
polypropylene surfaces for protein and bacteria resistance, Polymer Chemistry 6(8) (2015)
1
350-1359.
[
26] Y. Zhu, S. Hazeldine, J. Li, D. Oupicky, Dendritic polyglycerol with secondary amine
shell as an efficient gene delivery vector with reduced toxicity, Polymers for Advanced
Technologies 25(9) (2014) 940-947.
[
27] E. Moore, B. Delalat, R. Vasani, H. Thissen, N.H. Voelcker, Patterning and
Biofunctionalization of Antifouling Hyperbranched Polyglycerol Coatings,
Biomacromolecules 15(7) (2014) 2735-2743.
28] G. Ahn, S. Kweon, C. Yang, J.E. Hwang, K. Kim, B.S. Kim, One-pot synthesis of
[
hyperbranched polyamines based on novel amino glycidyl ether, Journal of Polymer Science
Part a-Polymer Chemistry 55(24) (2017) 4013-4019.
2
8