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Liu et al.,25,26 RAFT polymerization has proven to be an effi-
cient method to synthesize hyperbranched polymers.26–37
Several hyperbranched polymers, such as polystyrene and
poly(methyl methacrylate), were prepared via RAFT poly-
merization in the presence of divinyl crosslinkers25–32 or
polymerizable RAFT agents (inimers).22–24,33–37 To the best
of our knowledge, there is no reported synthesis of hyper-
branched glycopolymers using RAFT inimers and glycan
monomers.
MS Analysis
Positive ion EI mass spectra were obtained on a Thermo-
Quest MAT95XL mass spectrometer using an ionization
energy of 70 eV. Accurate mass measurements were con-
ducted with a resolution of 5000–10,000 using perfluoroker-
osene as the reference compound.
Synthesis of Inimers 2-(Methacryloyloxy)ethyl
4-cyano-4-(phenylcarbonothioyl-thio)pentanoate (1) and
2-(3-(Benzylthiocarbonothioylthio)propanoyloxy)
Ethyl Acrylate (2)
Our aim was to prepare potentially bioactive hyperbranched
glycopolymers through RAFT polymerization. The use of
RAFT inimers provided a relatively simple methodology by
which the hyperbranched polymers were prepared in a one-
pot reaction without the disadvantages of multistep synthe-
ses typically required to prepare polysaccharides. Our pre-
liminary work on the synthesis of hyperbranched galactose
glycopolymers, both protected and deprotected, via direct
RAFT polymerization is reported here. It differs from the
work of Semsarilar et al.,38 in which click chemistry was
used to conjugate saccharides onto the polymer backbone af-
ter RAFT polymerization. Polymerization and kinetic studies
of two different types of galactose monomers using different
polymerizable RAFT agents (inimers) are discussed.
Preparation of 2-(methacryloyloxy)ethyl 4-cyano-4-(phenylcar-
bonothioylthio)pentanoate (MAE-CPP) (1) is described below.
CPAD (1.0 g, 3.6 mmol) and HEMA (0.51 g, 4 mmol) were dis-
solved in dry toluene (10 mL), followed by the addition of
DMAP (44 mg, 0.36 mmol). After the dissolution of DMAP,
1,3-dicyclohexyl carbodiimide (DCC; 0.82 g, 4 mmol) was
added and the mixture was stirred for 12 h at room tempera-
ture. The reaction mixture was then filtered and the solution
was dried on a rotary evaporator to afford the crude product.
The crude product was further purified through a silica gel
column (eluent: ethyl acetate:hexane, 1:3 v/v) to afford inimer
MAE-CPP (1) as a pink liquid on drying (1.1 g, 75% yield).
1H NMR (400 MHz, CDCl3, d, ppm): 1.61 (s, 3H, C(CH3)(CN)),
1.95 (s, 3H, CH3AC¼¼C), 2.38 (s, 1H, C(CH3)(CN)ACHH), 2.68
(t, 2H, CH2(CO)O), 2.79 (s, 1H, C(CH3)(CN)ACHH), 4.35 (m,
4H, (CO)OCH2CH2O(CO)), 5.61 (s, 1H, C¼¼C-Hb), 6.13 (s, 1H,
C¼¼C-Ha), 7.28–7.95 (m, 5H, U). 13C NMR (75 MHz, CDCl3, d,
ppm): 18.2, 24.1, 29.7, 33.3, 45.7, 62.2, 62.7, 76.4, 77.0, 77.6,
126.2, 126.6, 128.6, 133.0, 135.8, 144.5, 171.3. FTIR (NaCl,
thin film, cmꢂ1): 2957, 1738, 1636, 1445, 1381, 1296, 1161,
1048, 945, 868, 763, 688, 650. HRMS (EI, m/z): calculated
for C19H21O4NS2 [M]þ: 391.0907; found: 391.0903.
EXPERIMENTAL
Materials
2-Hydroxyethyl methacrylate (HEMA, inhibited with 20 ppm
MEHQ; Ubichem), 2-hydroxyethyl acrylate (HEA; Sigma),
methacrylic acid, vinyl azlactone, 4-(N,N-dimethylamino)pyri-
dine (DMAP, 99%; Merck), toluene (99.9%; Merck), and 4,40-
azobis(cyanopentanoic acid) (98%; Fluka) were used as
received without purification. Other chemicals used in this
work were purchased from Aldrich and used without purifi-
cation. 4-Cyano-4-(phenylcarbonothioylthio)pentanoic acid
(CPAD) and 3-((benzylthio)carbonothioyl)thio)propanoic acid
(BCPA) were synthesized as described in the literature.39–41
The procedure for preparing 2-(3-(benzylthiocarbono-
thioylthio)propanoyloxy)ethyl acrylate (BCP-EA) (2) was the
same as that of MAE-CPP (1), except CPAD and HEMA were
substituted with BCPA and HEA, respectively. The final prod-
uct was a yellow liquid (82% yield).
Characterization and Instrumentation
NMR Analysis
1H NMR (400 MHz, CDCl3, d, ppm): 2.80 (t, 2H, CH2(CO)O),
3.63 (t, 2H, S(S¼¼C)SACH2), 4.36 (m, 4H, (CO)OCH2 and U-
CH2), 4.60 (s, 2H, CH2O(CO)), 5.85–5.88 (d, 1H, C¼¼C-Hc),
6.10–6.17 (tetra, 1H, Hb-C¼¼C), 6.41–6.46 (d, 1H, C¼¼C-Ha),
7.26–7.33 (m, 5H, U). 13C NMR (75.4 MHz, CDCl3, d, ppm):
31.2, 33.0, 41.5, 62.1, 62.6, 76.7, 77.0, 77.3, 127.8, 127.9,
128.7, 129.2, 131.5, 134.8, 138.2, 165.8, 171.2, 222.9. FTIR
(NaCl, thin film, cmꢂ1): 3062, 3030, 2956, 1731, 1635, 1494,
1453, 1407, 1373, 1348, 1182, 1065, 982, 900, 888, 802,
730, 680, 638. HRMS (EI, m/z): calculated for C16H18O4S3
[M]þ: 370.0362; found: 370.0360.
All the products were analyzed by 1H and 13C NMR on
a
400 MHz Bruker Ultrashield spectrometer (Bruker,
Germany).
Size Exclusion Chromatography Analysis
The dried polymer (ꢀ10 mg) was dissolved in tetrahydrofu-
ran (THF, 4 mL) and filtered through a 0.22 lm pore-size dis-
posable filter prior to analysis. Size exclusion chromatography
(SEC) data were collected from a system consisting of a series
of four ‘‘PLGel’’ columns (3 ꢁ 5 lm Mixed-C and 1 ꢁ 3 lm
Mixed-E; Polymer Laboratories, Church Stretton, Shropshire,
UK) and a Waters (Milford, MA) 2414 refractive index detec-
tor. THF was used as the mobile phase at a flow rate of 1.0
mLꢃminꢂ1. Measurement was conducted at a temperature of
25 C with an injection volume of 10 lL. The SEC instrument
was calibrated with narrow polydispersity polystyrene stand-
ards with peak molecular weight (Mp) in the range of 256–
264,000 g molꢂ1 (Polymer Laboratories), and the molecular
weights were reported as polystyrene equivalents.
Synthesis of 6-O-Methacryloyl-1,2:3,4-di-O-
isopropylidene-D-galactopyranose (3)
1,2:3,4-Di-O-isopropylidene-D-galactopyranose (3.12 g, 12
mmol), methacrylic acid (1.12 mL, 13.2 mmol), and DMAP
(0.16 g, 1.32 mmol) were dissolved in dichloromethane (30
mL). The solution was immersed in an ice bath and DCC
(2.72 g, 13.2 mmol) was added. The reaction was then
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JOURNAL OF POLYMER SCIENCE PART A: POLYMER CHEMISTRY 2012, 000, 000–000