Degradable poly(ester triazole)s based on renewable resources

Article abstract of DOI:10.1002/pola.27710

The copper(I)-catalyzed alkyne-azide cycloaddition (CuAAC) click polymerization has been used to obtain novel linear poly(ester triazole)s by reaction of bis-alkyne having ester linkage and bis-azido monomers, most of them derived from carbohydrates, such

Full text of DOI:10.1002/pola.27710

JOURNAL OF
POLYMER SCIENCE
WWW.POLYMERCHEMISTRY.ORG
ARTICLE
Degradable Poly(ester triazole)s Based on Renewable Resources
ꢀ
Khalid Hakkou, Manuel Bueno-Martınez, Inmaculada Molina-Pinilla, Juan A. Galbis
ꢀ
ꢀ
ꢀ
Departamento de Quımica Organica y Farmaceutica. Facultad de Farmacia, Universidad de Sevilla, 41012-Sevilla, Spain
ꢀ
Correspondence to: M. Bueno-Martınez (E-mail: mbueno@us.es)
Received 27 March 2015; accepted 14 May 2015; published online 16 June 2015
DOI: 10.1002/pola.27710
ABSTRACT: The copper(I)-catalyzed alkyne-azide cycloaddition
(CuAAC) click polymerization has been used to obtain novel
linear poly(ester triazole)s by reaction of bis-alkyne having
ester linkage and bis-azido monomers, most of them derived
from carbohydrates, such as glucose, arabinose, and erythrose,
and therefore coming from natural renewable resources. The
resulting polyesters had weight-average molecular weights in
the 11,500–148,000 range and were characterized by GPC, IR,
and NMR spectroscopies. Thermal studies revealed them to be
amorphous and stable up to 200 8C under nitrogen. Degrada-
tion studies showed that they were hydrolytically degradable.
These studies were carried out at 50 8C in phosphate buffer
solution at pH 7.4, and were monitored by GPC, and NMR
spectroscopy. Finally, novel network hydrogels were obtained
by crosslinking reaction of the poly(ester triazole) chains with
hexamethylene diisocyanate. The water absorption and the
C
V
kinetic parameters of the networks were studied. 2015 Wiley
Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015, 53,
2481–2493
KEYWORDS: carbohydrate-based polymers; click polymerization;
crosslinking; degradation; network; polyesters
mers, can be performed without the need to protect the
remaining alcohol functions in the carbohydrate monomer and
without producing byproducts, among other advantages. In
recent years, click chemistry has been successfully utilized as
a modular15,16 synthetic approach to prepare a large variety of
materials in different areas.17–22 However, in the case of the
synthesis of linear triazole-linked polymers it has been more
limited. In this respect, polyaddition of small bis-azide and
bis-alkyne monomers has been used for the preparation of
different polytriazoles by us23–25 and others.26–34 We are
particularly interested in degradable materials, such as
poIy(ester triazole)s. Polyesters constitute one of the largest
classes of biodegradable materials, with very well-known
examples, such as polylactide and polycaprolactone. Because
synthetic polyesters usually lack functionalities, functionalized
polyesters hold greater potential interest for biomedical appli-
cations than do their nonfunctionalized counterparts. In this
paper, we present the synthesis and characterization of several
linear poly(ester triazole)s prepared using the copper(I)-cata-
lyzed azide-alkyne cycloaddition (CuAAC) reaction to combine
bis-azide and bis-alkyne monomers, some of them derived
from carbohydrates, such as glucose, arabinose, and erythrose,
and therefore coming from a natural renewable resource. As
expected, these poly(ester triazole)s could be degraded under
mild conditions such as phosphate buffer at pH 7.4 (50 8C).
Moreover, all of them contain, along their repeating units, at
least two free secondary alcohol functions which could be sub-
sequently transformed, providing an efficient way to tailor the
INTRODUCTION Most of the polymers used for both dispos-
able and durable materials have been synthesized from
petroleum-based monomers.1 Despite their success, prob-
lems such as environmental pollution and the rapid deple-
tion of the petroleum reserves, raising questions about
future sustainability,2,3 have driven the development of alter-
natives such as biobased monomers.4–6 Today, polymer syn-
theses from renewable and biomass resources constitute a
steadily growing field of interest.7 Carbohydrates are very
interesting starting materials because they are readily avail-
able8 with a large functionality and great stereochemical
diversity. However, there are some issues. One is that their
water uptake is much higher than that of the monomers
derived from petrochemical feedstock.9 This could be a draw-
back in certain applications, although the hydrophilicity can be
modified by blocking the free alcohol functions. Also, because
of their multifunctionality, and in order to circumvent the
problem of controlling the reactivity of many different
hydroxyl groups, selective protection-deprotection chemistry
would be required. This last difficulty could be overcome by
first introducing relatively stable functional groups, such as
alkyne and azido, and then using “click” chemistry as polymer-
ization method. The 1,3-dipolar cycloaddition of an azide moi-
ety and a triple bond (Huisgen reaction)10,11 or the highly
efficient, orthogonal and regiospecific copper(I)-catalyzed
azide-alkyne cycloaddition (CuAAC)12–14 have received signifi-
cant attention in the last decade, because these reactions,
apart from requiring stoichiometric amounts of starting mono-
C
V
2015 Wiley Periodicals, Inc.
WWW.MATERIALSVIEWS.COM
JOURNAL OF POLYMER SCIENCE, PART A: POLYMER CHEMISTRY 2015, 53, 2481–2493
2481

JOURNAL OF
POLYMER SCIENCE
ARTICLE
WWW.POLYMERCHEMISTRY.ORG
properties of the polymers. We illustrate the use of the free
hydroxyl groups present in the poly(ester triazole) chain by
preparing diverse network hydrogel materials. Hydrogels are
macromolecular materials that can be obtained with a large
variety of structures and find practical applications in many
fields such as medicine, agriculture, pharmacy, or the food
industry. The properties of hydrogels depend on their molecu-
lar structure, and for this reason the synthesis of hydrogels
with new molecular structures is an area of great academic
and industrial interest. We report on the synthesis and proper-
ties of three network hydrogels obtained by reaction of differ-
ent poly(ester triazole)s with hexamethylene diisocyanate as
the crosslinking agent. The polymers used to prepare the net-
works were chosen based on the importance that poly(ethyl-
ene glycol) (PEG) and isosorbide have in the synthesis of
materials. PEG is a hydrosoluble polymer with a great stability
and high biocompatibility, and thus an attractive candidate for
biomedical applications. It has frequently been used in the
synthesis of biocompatible hydrogels, and has been exploited
in many fields, such as tissue engineering35–39 or drug deliv-
ery40–47 among others. Isosorbide (1,4:3,6-dianhydro-D-gluci-
tol) is a biomass monomer derived from glucose and is
currently produced on an industrial scale. The presence of the
isosorbide units should provide stiffness to the polymer chain,
and also to the network. Because of its rigid molecular struc-
ture, chirality, and nontoxicity, isosorbide has been used in a
multitude of polymer applications.48–51
using a Bruker HR-MAS probe with an external lock. The
sample was loaded in a 4 mm ZrO2 cylindrical rotor, treated
with DMSO-d6, and spun at a spinning rate of 4 kHz. H HR-
1
MAS spectrum was recorded accumulating 32 scans with
64 k data points and using a spectral width of 12.5 ppm. A
4.95 ms 90o excitation pulse was used with a relaxation delay
of 10 s. Diffusion NMR spectra were recorded on a Bruker
Avance III 700 MHz spectrometer equipped with a 5 mm
QCI cryoprobe at 300 K. All DOSY experiments were per-
formed using the bipolar pulse longitudinal eddy current
delay pulse sequence (BPPLED). Spoil gradients were also
applied at the diffusion period and the eddy current delay.
The gradient duration and the diffusion time were optimized
to obtain ꢀ95% signal attenuation for the slowest diffusion
species at the last step experiment. Values of 1.2, 1.5, and
2.0 ms were used for the gradient duration (d=2), 175 ms
for the diffusion time (D), and the gradient strength was var-
ied from 2 to 95% of the maximum strength in 32 steps.
The pulse repetition delay between each scan was 1 s. Data
acquisition and analyses were performed using the Bruker
Topspin software (version 3.1). Elemental analyses were car-
ried out in the Microanalysis Laboratories of the CITIUS
Service at the University of Seville. Chemical ionization (CI)
and fast-atom bombardment mass spectra were performed
on a Micromass Autospec spectrometer. FABMS spectra were
obtained using thioglycerol–NaI as a matrix. The thermal
properties of the polymers were determined by differential
scanning calorimetry (DSC) using a TA Instruments DSC
Q200, calibrated with indium. Samples of about 2–3 mg
were heated at a rate of 10 8C min21 under a nitrogen
atmosphere (flow rate of 20 mL min21) and cooled to room
temperature. Thermogravimetric analyses (TGA) were per-
formed with an SDTQ600 TA instrument at a heating rate of
10 8C min21 under a nitrogen flow of 100 mL min21. Gel
permeation chromatography (GPC) analyses were performed
using a Waters apparatus equipped with a Waters 2414
refractive-index detector and two Styragel HR columns (7.8
3 300 mm) linked in series, thermostatted at 60 8C, using
NMP–LiBr or N, N-dimethylformamide–LiBr as the mobile
phase, at a flow rate of 1.0 mL min21. Calibration was per-
formed using 12 polystyrene samples of narrow molecular
weight distribution.
EXPERIMENTAL
Materials
Chemicals were all used as purchased from Aldrich Chemical
Co. Solvents were dried and purified when necessary, by
appropriate standard procedures. 1,4-Diazido-1,4-dideoxyery-
thritol (7) and 1,5-diazido-1,5-dideoxy-3-benzyl-L-arabinitol
(5) were obtained according to the procedures described by
Glac¸on52 and Boehm,53 respectively. Propiolates 254 and 323
were prepared according to the procedure reported in the
bibliography.
Measurements
Thin-layer chromatography (TLC) was performed on Silica
Gel 60 F254 (E. Merck) with detection by UV light or char-
ring with H2SO4 or phosphomolybdic acid. Flash column
chromatography was performed using E. Merck Silica Gel 60
(230–400 mesh). IR spectra (films or KBr disks) were
recorded with a JASCO FT/IR-4200 spectrometer. The Raman
spectra of the samples were acquired on a LabRAM HORIBA
Jobin Yvon spectrometer, using an excitation wavelength of
785 nm. The wavelength range of recording was from 800
to 3000 cm21, using a 320 magnification objective. 1H and
13C NMR spectra were recorded with a Bruker AMX-500 or
Bruker AV300 spectrometer. Chemical shifts are reported as
parts per million downfield from tetramethylsilane. Two-
dimensional 1HA1H homonuclear and 13CA1H heteronuclear
shift correlation spectra were recorded with the COSY and
HETCOR pulse sequences, respectively. HR-MAS experiments
were performed on a Bruker AVANCE 500 spectrometer,
Synthesis
3,6,9,12-Tetraoxatetradecane-1,14-diyl dipropiolate (1)
A mixture of 3,6,9,12-tetraoxatetradecane-1,14-diol (1.73 mL,
8.17 mmol), propiolic acid (1.036 mL, 16.8 mmol), and
p-toluensulfonic acid (0.076 g) in toluene (65 mL) was
heated to reflux through a Dean–Stark apparatus for 48 h.
Toluene was evaporated under reduced pressure, and the
residue was diluted with dichloromethane (30 mL), washed
with saturated NaHCO3 (2 3 15 mL), water (1 3 20 mL),
and dried over anhydrous MgSO4. Filtration and evaporation
of the solvent gave a colorless residue which crystallized on
cooling (2.0 g, 60%), m.p. 66–68 8C, IR: mmax 3241 (HCBC),
1
2108 (CBC), 1712 cm21 (CO); NMR data (CDCl3): H, d 4.36–
4.30 (m, 4H, H-1, H-10), 3.75–3.70 (m, 4H, H-2, H-9), 3.64
(s, 12H, H-3, H-4, H-5, H-6, H-7, H-8), 2.91 (s, 2H, H-CB); 13C,
2482
JOURNAL OF POLYMER SCIENCE, PART A: POLYMER CHEMISTRY 2015, 53, 2481–2493

JOURNAL OF
POLYMER SCIENCE
WWW.POLYMERCHEMISTRY.ORG
ARTICLE
TABLE 1 GPCa Data of the Polymers 8–15
d 152.57(CO), 75.14 (H-CBC), 74.49 (H-CBC),.70.65, 70.60,
70.52 (C-3, C-4, C-5, C-6, C-7, C-8), 68.50 (C-2, C-9), 65.19
(C-1, C-10). Anal. Calcd for C16H22O8: C, 56.14; H, 6.48. Found:
C, 56.44; H, 6.27.
b
b
c
c
Polymer
Mn
Mw
Mn
Mw
P8
55,000
107,000
95,000
160,500
58,000
32,000
76,000
35,500
73,000
128,000
135,000
208,000
81,500
40,000
106,000
45,000
10,000
24,000
36,000
66,500
16,000
11,000
19,000
7,000
20,000
48,000
72,000
148,000
32,000
26,000
39,000
11,500
P9
3-O-Benzyl-1,5-di-O-propiolyl-L-arabinitol (4)
P10
P11
P12
P13
P14
P15
To a stirred solution of 1,2:4,5-dianhydro-3-O-benzyl-L-arabi-
nitol55 (0.248 g, 1.2 mmol) in dry dichloromethane (5 mL)
cooled to around 278 8C and under argon atmosphere, hex-
amethylphosphoramide (HMPA, 1.25 mL, 7.2 mmol) was
added. After 15 min of stirring, propiolic acid (0.446 mL, 7.0
mmol) was added dropwise. Once the addition was com-
pleted, the reaction mixture was allowed to warm to room
temperature and then heated at about 30 8C for 48 h. The
solvent was removed under reduced pressure, and the resi-
due was purified by column chromatography (tert-butyl
methyl ether:hexane, 1:1), giving after evaporation of the sol-
vents 4 as a syrup (0.22 g, 53%), IR: mmax 3429 (OH), 3267
(HCBC), 2115 (CBC), 1712 cm21 (CO); NMR data (CDCl3):
1H, d 7.36 (m, 5H, phenyl), 4.69–4.57 (2 d, 2H, CH2Ph), 4.48
(dd, 1H, H-1a), 4.38-4.23 (m, 3H, H-5, H-1b), 4.20–4.07 (m,
2H, H-2, H-4), 3.60 (dd, 1H, H-3), 2.96 and 2.93 (2 s, 2H,
HCBC); 13C, d 152.61, 152.49 (CO), 136.75, 128.72, 128.48,
128.35 (Phenyl), 76.98 (C-3), 75.86, 75.65 (HCBC), 74.29,
74.20, (HCBC), 74.08 (CH2Ph), 69.84, 68.94 (C-2, C-4),
67.32, 66.87 (C-1, C-5). Anal. Calcd for C18H19O7 1= H O: C,
a
Determined by GPC analysis with polystyrene standards.
Measured in DMF/LiBr.
b
c
Measured in NMP/LiBr.
trated to dryness under reduced pressure to obtain a syrupy
residue which was purified by column chromatography (tert-
butyl methyl ether:hexane, 1:1), giving after evaporation of the
solvents 6 as a solid (3.2 g, 68%), m.p. 56–58 8C, IR: mmax 3400
(OH), 2087 cm21 (N3); NMR data (CDCl3): 1H, d 3.99–3.88 (m,
2H, H-2, H-11), 3.55–3.30 (m, 12H, H-3, H-5, H-8, H-10, H-1,
H-12), 2.72 (d, 2H, OH), 1.69–1.63 (m, 4H, H-6, H-7); 13C, d
71.92, 71.30 (C-3, C-5, C-8, C-10), 69.65 (C-2, C-11), 53.41
(C-1, C-12), 26.27 (C-6, C-7). Anal. Calcd for C10H20N6O4: C,
41.66; H, 6.99; N, 29.15. Found: C, 41.58; H, 6.99; N, 29.12.
2
2
60.84; H, 5.39. Found: C, 60.91; H, 5.42. HRMS: m/z
347.1124 (calcd. for [M]1: 347.1131).
General Procedure for the Synthesis of
1,5-Diazido-1,5-dideoxy-3-O-benzyl-L-arabinitol (5)
Poly(ester triazole)s
A stirred mixture of 1,2:4,5-dianhydro-3-O-benzyl-L-arabinitol
(1.0 g, 4.85 mmol), tetrabutylammonium sulfate (0.2 g, 0.6
mmol), and sodium azide (3.94 g, 60 mmol) in water-
dioxane (1:1, 60 mL) was refluxed for 4 h. Then, the reaction
mixture was concentrated to about half its volume and
extracted with ethyl acetate (3 3 50 mL). The combined
organic phase was dried with anhydrous sodium sulfate, fil-
tered, and concentrated to dryness under reduced pressure
to obtain a syrupy residue which was purified by column
chromatography (tert-butyl methyl ether:hexane, 1:1), giving
after evaporation of the solvents 5 as a solid (0.6 g, 42%),
m.p. 72–74 8C, IR: mmax 3327 (OH), 2087 cm21 (N3); NMR
data (CDCl3): 1H, d 7.43–7.29 (m, 5H, Phenyl), 4.66, 4.60 (d,
2H, CH2Ph), 4.06–3.93 (m, 2H, H-20, H-40), 3.60–3.29 (m, 5H,
H-10, H-30, H-50); 13C, d 137.01 (quaternary, Ph), 128.72,
128.45, 128.23 (CH, Ph), 77.81 (C-30), 74.11 (CH2Ph), 70.84,
70.41 (C-20, C-40), 53.86, 53.50 (C-10, C-50). Anal. Calcd for
C12H16N6O3: C, 49.31; H, 5.52; N,.28.75 Found: C, 49.71; H,
5.56; N, 28.87.
The above bifunctional monomers were reacted in (1:1) tert-
butanol:H2O at room temperature for 24 h in the presence
of 5% CuSO4 and 10% sodium ascorbate. Poly(ester tria-
zole)s P8–P15 were isolated and purified as follows: after
the polymerization period, the suspended polymer was
recovered by filtration on a glass filter and washing with
(1:1) tert-butanol:H2O. The polytriazoles were dissolved in
dimethylsulfoxide and precipitated in acetone. The gel per-
meation chromatography data and the thermal characteris-
tics of the polymers are given in Tables 1 and 2, respectively.
The isolated yields and their spectroscopic properties (IR
and NMR spectra) are described below.
Poly(ester triazole) P8
Yield: 92%. IR: mmax 3355 (OH), 1727 cm21 (CO); NMR data
(DMSO-d6): 1H, d 8.69, 8.66 (s, Ha-triazole), 7.50-7.28 (m,
5H, phenyl), 5.49, 5.22 (d, 2H, OH), 4.80-4.43 (m, 6H, CH2Ph,
H-10, H-50), 4.37 (m, 4H, H-1, H-10), 4.22–4.10 (m, 2H, H-20,
H-40), 3.70 (m, 4H, H-2, H-9), 3.55 (m, 4H, H-3, H-8), 3.52–
3.43 (m, 9H, H-30, H-4, H-5, H-6, H-7); 13C, d 160.38, 160.36
(CO), 138.34, 138.22 (Cb triazole, quaternary Ph), 130.17,
129.97 (Ca triazole), 128.28, 128.07, 127.68 (CH, Ph), 81.03
(C-30), 73.86 (CH2Ph), 69.80-69.64 (C-20, C-40, C-3-C-8), 68.28
(C-2, C-9), 63.75 (C-1, C-10), 53.46, 53.11 (C-10, C-50).
1,12-Diazido-4,9-dioxadodecan-2,11-diol (6)
Treatment of a mixture of 1,4-butanediol diglycidyl ether
(3.3 g, 16.0 mmol), tetrabutylammonium sulfate (0.68 g, 2.0
mmol), and sodium azide (13 g, 200 mmol) in water-dioxane
(1:1, 200 mL) was refluxed for 4 h. Then, the reaction mixture
was concentrated to about half its volume and extracted with
ethyl acetate (3 3 100 mL). The combined organic phase was
dried with anhydrous sodium sulfate, filtered, and concen-
Poly(ester triazole) P9
Yield: 80%. IR: mmax 3390 (OH), 1727 cm21 (CO); NMR data
1
(DMSO-d6): H, d 8.63 (s, Ha-triazole), 5.31 (d, 2H, OH), 4.60-
WWW.MATERIALSVIEWS.COM
JOURNAL OF POLYMER SCIENCE, PART A: POLYMER CHEMISTRY 2015, 53, 2481–2493
2483

JOURNAL OF
POLYMER SCIENCE
ARTICLE
WWW.POLYMERCHEMISTRY.ORG
70.09 (C-20, C-40), 64.77 (C1, C-6), 53.91, 53.56 (C10, C-50),
28.55 (C-2, C-5), 25.50 (C-3, C-4).
TABLE 2 Thermal Analysis Data of the Polymers 8–15
a
b
b
Polymer
Tg (8C)
T10% (8C)
Tdes (8C)
Poly(ester triazole) P13
Yield: 96%. IR: mmax 3395 (OH), 1732 cm21 (CO); NMR data
(DMSO-d6): 1H, d 8.77–8.69 (d, Ha-triazole), 7.50–7.28 (m,
5H, phenyl), 5.55–5.47, 5.27–5.21 (m, 2H, OH), 5.40 (m, 1H,
H-2), 5.34 (s, 1H, H-5), 4.97 (m, 1H, H-3), 4.83–4.45 (m, 6H,
CH2Ph, H-10, H-50), 4.58 (d, 1H, H-4), 4.28–4.09 (m, 2H, H-20,
H-40), 4.05-3.88 (m, 4H, H-1, H-6), 3.50 (m, 1H, H-30); 13C, d
159.63 (CO), 138.27, 138.09, 137.93 (Cb triazole, quaternary
Ph), 130.57, 130.40, 130.29, 130.14 (Ca triazole), 128.31,
128.10, 127.71 (CH, Ph), 85.68 (C-4), 81.19 (C-30), 80.86 (C-
3), 78.09 (C-5), 74.24 (C-2), 73.64 (CH2Ph), 72.59, 70.62 (C-
1, C-6), 69.77, 69.67 (C-20, C-40), 53.56, 53.18 (C-10, C-50).
P8
54
6
279
287
229
258
172
287
277
303
244
194
325
321
316
289
289
320
311
329
334
277
P9
P9B
P10
P10B
P11
P12
P13
P14
P15
13
50
55
36
87
152
94
110
a
Measured by DSC, second heating.
Determined by TGA.
Poly(ester triazole) P14
b
Yield: 98%. IR: mmax 3360 (OH), 1730 cm21 (CO); NMR data
1
(DMSO-d6): H, d 8.68, 8.66 (s, 2H, Ha-triazole), 5.39 (m, 1H,
4.30 (m, 8H, H-10, H-100, H-1, H-10), 4.03 (m, 2H, H-20, H-90),
3.72 (m, 4H, H-2, H-9), 3.60–3.20 (m, 20H, H-3, H-4, H-5, H-
6, H-7, H-8, H-30, H-40, H-70, H-80), 1.55 (bs, 4H, H-50, H-60);
13C, d 160.31 (CO), 138.27 (Cb triazole), 129.93 (Ca triazole),
72.02 (C-30, C-80), 70.48 (C-40, C70), 69.77, 69.73, 69.70 (C-3,
C-4, C-5, C-6, C-7, C-8), 68.25 (C-2, C-9), 67.97 (C-20, C-90),
63.69 (C-1, C-10), 53.22 (C-10, C-100), 25.82 (C-50, C-60).
H-2), 5.35–5.30 (m, 3H, H-5, OH), 4.97 (t, 1H, H-3), 4.58 (d,
1H, H-4), 4.56–4.32 (m, 4H, H-10, H-100), 4.06–3.89 (m, 6H,
H-20, H-90, H-1, H-6), 3.50–3.26 (m, 8H, H-30, H-40, H-70, H-80),
1.56 (m, 4H, H-50, H-60); 13C, d 159.63, 159.61 (CO), 138.04,
137.93 (Cb triazole), 130.39, 130.17 (Ca triazole), 85.67 (C-
4), 80.84 (C-3), 78.10 (C-5), 74.24 (C-2), 72.57, 72.10, 72.04,
70.63, 70.53 (C-1, C-30, C-80, C-6, C-40, C-70), 68.05, 68.01 (C-
20, C-90), 53.32 (C-10, C-100), 25.89 (C-50, C-60).
Poly(ester triazole) P10
Yield: 92%. IR: mmax 3350 (OH), 1715 cm21 (CO); NMR data
(DMSO-d6): 1H, d 8.64 (s, Ha-triazole), 5.64 (d, 2H, OH),
4.74–4.36 (m, 8H, H-10, H-40, H-1, H-10), 3.73 (m, 6H, H-20,
H-30, H-2, H-9), 3.78-3.48 (m, 12H, H-3, H-4, H-5, H-6, H-7,
H-8); 13C, d 160.32 (CO), 138.30 (Cb triazole), 130.11 (Ca
triazole), 70.75 (C-20, C-30), 69.77, 69.74, 69.72 (C-3, C-4, C-5,
C-6, C-7, C-8), 68.27 (C-2, C-9), 63.70 (C-1, C-10), 53.05
(C-10, C-40).
Poly(ester triazole) P15
Yield: 80%. IR: mmax 3355 (OH), 1724 cm21 (CO); NMR data
1
(DMSO-d6): H, d 8.70–8.60 (s, 2H, Ha triazole), 7.40-7.20 (m,
5H, Ph), 5.18 (s, 2H, OH), 5.32, 5.07 (d, 2H, OH), 4.80–4.50
(m, 4H, H-1a, H-4a, CH2Ph), 4.50-4.22 (m, 6H, H-1b, H-4b, H-
10, H-50), 4.20–4.00 (m, 2H, H-20, H-40), 3.78 (m, 2H, H-2, H-
3), 3.62 (m, 1H, H-30); 13C, d 160.94, 160.80 (CO), 139.05,
138.92, 138.79 (Cb triazole, quaternary Ph), 130.66 (Ca tria-
zole), 128.69, 128.33, 128.04 (Ph), 80.34 (C-30), 74.00
(CH2Ph), 71.30 (C-2, C-3), 68.76, 68.55 (C-20, C-40), 67.08,
66.44 (C-10, C-50), 53.57 (C-1, C-4).
Poly(ester triazole) P11
Yield: 94%. IR: mmax 3414 (OH), 1721 cm21 (CO); NMR data
(DMSO-d6): 1H, d 8.60 (s, 2H, Ha-triazole), 5.31 (d, 2H, OH),
4.51 (dd, 2H, H-10a, H-100a), 4.35 (dd, 2H, H-10b, H-100b),
4.25 (t, 4H, H-1, H-6), 4.05–3.96 (m, 2H, H-20, H-90), 3.50–
3.26 (m, 8H, H-30, H-40, H-70, H-80), 1.69 (m, 4H, H-2, H-5),
1.54 (m, 4H, H-50, H-60), 1.41 (m, 4H, H-3, H-4); 13C, d
160.48 (CO), 138.51 (Cb triazole), 129.90 (Ca triazole), 72.07
(C-30, C-80), 70.53 (C-40, C-70), 68.03 (C20, C-90), 64.37 (C-1,
C-6), 53.28 (C10, C-100), 28.12 (C-2, C-5), 25.88 (C-50, C-60),
25.08 (C-3, C-4).
Hydrolytic Degradation
Hydrolysis experiments were carried out on films prepared
by dissolving 15–20 mg of the selected poly(ester triazole)
in DMF. The solvent was subsequently evaporated with a
rotary evaporator under reduced pressure, and finally the
polymer coated on the inside surface of the bottom of the
flask was dried to constant weight in an oven under vacuum.
Then, 3 mL of a phosphate buffer (pH 7.4) was added to the
flask, which was kept at 50 8C for a designated time. Next,
the buffer solution was separated by filtration, and the resid-
ual film was washed with deionized water and dried in vac-
uum. The filtered buffer solution was also concentrated to
dryness. All the residues were analyzed by GPC and NMR
spectroscopy.
Poly(ester triazole) P12
Yield: 98%. IR: mmax 3414 (OH), 1721 cm21 (CO); NMR data
(DMSO-d6): 1H, d 8.69, 8.66 (s, Ha triazole), 7.50–7.28 (m,
5H, phenyl), 5.49, 5.22 (d, 2H, OH), 4.80–4.43 (m, 6H, CH2Ph,
H-10, H-50), 4.27 (m, 4H, H-1, H-6), 4.25–4.10 (m, 2H, H-20,
H-40), 3.49 (m, 1H, H-30), 1.70 (m, 4H, H-2, H-5), 1.42 (m,
4H, H-3, H-4); 13C, d 160.93 (CO), 138.95, 138.94 (Cb tria-
zole, quaternary Ph), 130.49, 130.30 (Ca triazole), 128.72,
128.51, 128.12 (CH, Ph), 81.50 (C-30), 74.06 (CH2Ph), 70.18,
Crosslinking Hydrogels
Hexamethylene diisocyanate (HMDI) was employed as a
crosslinking agent. HDMI (15 mL) was added to a solution of
the polymer (0.1 g) in dry DMF at room temperature. After
2484
JOURNAL OF POLYMER SCIENCE, PART A: POLYMER CHEMISTRY 2015, 53, 2481–2493

JOURNAL OF
POLYMER SCIENCE
WWW.POLYMERCHEMISTRY.ORG
ARTICLE
applied to obtain monomer 7, which was prepared from
erythritol in two steps involving tosylation of the primary
alcohols and subsequent nucleophilic substitution by sodium
azide.23
All these monomers were fully characterized using 1H and
13C NMR spectroscopy and elemental analysis. The mono-
mers were polymerized by copper(I)-catalyzed azide-alkyne
cycloaddition reaction (CuAAC) to obtain the poly(ester tria-
zole)s 8–15 (Fig. 3) in high yields, although separation of
the polymer could be observed in some cases. Concerning
the polymerization reaction, the stoichiometry of the end
groups is of major importance to attain high degrees of poly-
merization and thereby high molecular masses. Thus, polyad-
dition reactions were carried out with stoichiometric
mixtures of the diazido- and dialkyne-monomers, in (1:1)
tBuOH:H2O mixtures, and catalyzed by copper sulfate in the
presence of sodium ascorbate (sharpless classical conditions)
(Fig. 4). Although the CuAAC reaction is fast, all the polymer-
ization reactions were run for 24 h to ensure similar conver-
sion. Changing the solvent mixture (e.g., DMSO-H2O) did not
prevent the separation of the polymer in cases where this
occurs.
FIGURE 1 Structures of the monomers.
The chemical constitution of the resulting polymers was con-
1
firmed by FTIR and H and 13C NMR spectroscopies. Infrared
15 min, a gel was obtained which was heated at 50 8C for
24 h. The gel was removed from the bottle and placed in dis-
tilled water (50 mL) at 8 8C for 6 days. The water was
changed each day. Finally, the hydrated gel was dried under
vacuum to obtain a film.
spectroscopy showed the characteristic absorption bands of
the ester and alcohol functions. The absorption bands at
about 3400 and 1730 cm21 were assigned to the stretching
band of the OH and to the carbonyl group of the ester func-
tions, respectively. The H and 13C NMR data detailed in the
1
RESULTS AND DISCUSSION
Experimental Section were consistent with the chemical con-
stitution anticipated for these poly(ester triazole)s. The 1H
and 13C NMR spectra (Figs. 5 and 6, respectively) of poly(es-
ter triazole)s P13 and P11, recorded in DMSO-d6, are shown
with the assignments of the peaks appearing in both types
of spectrum, for illustration. The assignment of the signals
was possible on the basis of data correlation provided by
two-dimensional COSY and HETCOR NMR spectra. The 1H
NMR spectrum of P13 [Fig. 5(A)] showed four signals
between 8.80 ppm and 8.70 ppm, which were assigned to
the Ha protons of the aromatic 1,4-triazole ring formed dur-
ing the click polymerization catalyzed by copper ions. These
Ha protons appear as narrow multiplets because of the long-
Seven alkyne- and azido-terminated monomers have been
prepared from diol- or diepoxide-terminated compounds
(Fig. 1).
Dialkyne monomers 1, 2, and 3 were obtained by refluxing
the corresponding diol with propiolic acid and p-toluensul-
fonic acid in toluene (Fig. 2), as described elsewhere.23,54
A different route for introducing alkyne groups that takes
advantage of the reaction between carboxylic acid and epox-
ides56,57 was also tested to prepare the dialkyne-capped
monomer 4. The synthesis of this monomer by reaction of
1,2:4,5-dianhydro-3-O-benzyl-L-arabinitol55 and propiolic
acid is illustrated in Scheme 1.
The alkyne functions present in these monomers was intro-
duced by reaction with propiolic acid because it is known
that acetylene groups connected to electron-withdrawing
groups showed better activities than, for instance, ethers
that need higher temperature and/or catalyst to react with
azides.58 Azido-terminated monomers were also prepared by
two different routes. One method consists of the nucleophilic
opening of epoxide rings with sodium azide. Thus,
5
(Scheme 1) and 6 were prepared by this method from
1,2:4,5-dianhydro-3-O-benzyl-L-arabinitol55 and 1,4-butane-
diol diglycidyl ether, respectively. A second procedure was
FIGURE 2 Synthesis of monomers 1–3.
WWW.MATERIALSVIEWS.COM
JOURNAL OF POLYMER SCIENCE, PART A: POLYMER CHEMISTRY 2015, 53, 2481–2493
2485

JOURNAL OF
POLYMER SCIENCE
ARTICLE
WWW.POLYMERCHEMISTRY.ORG
SCHEME 1 Synthesis of monomers 4 and 5.
range coupling with the diastereotopic protons on C–10 or C–
50, displaying small coupling constants (4J < 2 Hz). We could
also observe that the two secondary alcohol functions pres-
ent in the repeating unit of the polymer chain appeared as
two signals, more complex than expected, centered at 5.50
and 5.25 ppm. These signals can be considered as being
formed by the union of several doublet signals correspond-
ing to the proton of the alcohol functions coupled with their
respective methynic protons.
triazole ring a single signal which appeared at 8.60 ppm in
the proton spectrum [Fig. 5(B)]. Its 13C NMR confirmed this
assignation, showing only one signal at 129.90 ppm, corre-
sponding to the Ca of the 1,4-disubstituted 1,2,3-triazole
ring, as expected taking into account the regioselectivity of
the CuAAC polymerization [Fig. 6(B)].
The poly(ester triazole)s described were not soluble in non-
aggressive oxygenated solvents such as ethyl acetate or ether,
or in polar protic solvents such as methanol or water,
despite their containing hydrophilic functions along the poly-
mer backbone. Conversely, they were readily soluble in polar
aprotic solvents such as dimethylsulfoxide, N,N-dimethylfor-
mamide, or N-methylpyrrolidone.
The 13C NMR spectrum of P13 [Fig. 6(A)] also supports
what has been discussed above. Thus, it showed four differ-
ent signals at 130.57, 130.40, 130.29, and 130.14 ppm for
the Ca of the 1,4-triazole ring. The presence of four signals,
which are assigned to the same proton or carbon, is inter-
preted considering that both monomers 3 and 5, used for
the synthesis of P13, are chiral and are introduced in the
polymer chain in a nonstereoselective manner, yielding four
diastereoisomeric possibilities: two for each carbon. In
contrast, the polymer P11 showed for the Ha proton of the
The stoichiometry of the monomers is of major importance
not only to obtain high molecular masses but also to prevent
unwanted reactions. Thus, if the polymerization of the mono-
mers 1 and 6 is carried out with a small excess of the
dialkyne-terminated monomer 1 with respect to 6, under the
FIGURE 3 Structures of the described poly(ester triazole)s.
2486
JOURNAL OF POLYMER SCIENCE, PART A: POLYMER CHEMISTRY 2015, 53, 2481–2493

JOURNAL OF
POLYMER SCIENCE
WWW.POLYMERCHEMISTRY.ORG
ARTICLE
FIGURE 4 Synthesis of poly(ester triazole)s.
standard click reaction conditions described in the experi-
mental section, a gel P9B is obtained which could not be dis-
solved in any common organic solvents. A similar result was
obtained when a small excess of 1 was subjected to the click
polymerization with 7; the polymerization reaction also
ended with the formation of an insoluble gel (P10B). The
observed gelation in the click polymerization reaction has
been explained59 by saying that either the polymerization
could be very efficient in forming high-molecular-weight
polymer, or because triazole is a good electron donor, and
may interact with Cu(I) and form physical crosslinks during
the polymerization process. In other cases, the isolation of
insoluble materials during the click polymerization reaction
has been explained60 considering that after the termination
of the polymerization process, some unreacted azido and
alkyne groups could remain and react with each other to
give final insoluble products during the purification process.
Moreover, under certain conditions, homocoupling (Hay cou-
pling) of the terminal alkynes could be also observed.31,61 In
our case, in the experiments in which the insoluble poly-
mers, P9B and P10B, were isolated, the presence of an
excess of the dialkyne-terminated monomer 1 allows some
FIGURE 6 13C NMR spectra of (A) P13; (B) P11.
Hay acetylenic homocoupling between the terminal alkyne
groups of the polymer generated by the click reaction, which
could explain the formation of insoluble high-molecular-
weight polymer. The 1H and 13C NMR spectra (Fig. 7) of
poly(ester triazole)s P9 (soluble in DMSO-d6) and P9B
(insoluble, HR-MAS in DMSO-d6) are shown for illustration.
As this figure shows, the structure of the two polymers
should be very similar, without the bridging diacetylene
units being able to be observed, probably due to the
expected low content, as also noted by other authors.31 For-
tunately, Raman spectroscopy could reveal the presence of
these diacetylene units in the polymers.
Thus, Raman spectra of P9B and P10B [Fig. 8(A,B), respec-
tively] showed a signal at 2260 cm21, which could be
assigned to the triple-bond vibration of the diacetylene moi-
eties.62,63 The presence of this band could support the
notion that some acetylene homocoupling occurred during
the preparation of these polymers as a side reaction when
the click polymerization was carried out with an excess of
alkyne, as in the case of these two experiments. This signal
was not detected in the Raman spectra of the soluble poly-
mers, P9 and P10 [Fig. 8(C,D)], respectively).
Gel Permeation Chromatography
The polymer molecular-weight distributions were determined
by gel permeation chromatography (GPC) using mStyragel col-
umns calibrated with polystyrene standards. All the chromato-
grams were unimodal, and the weight-averaged molecular
weights (Mw) ranged from 40,000 to 208,000 using DMF-LiBr
as the mobile phase or from 11,500 to 148,000 when NMP–
LiBr was used as the carrier solvent (Table 1).
Thermal Analysis
Thermal properties of poly(ester triazoles) P8–P15 were
studied by differential scanning calorimetry (DSC); the ther-
mal values obtained in this study are given in Table 2. The
FIGURE 5 1H NMR spectra of (A) P13 and (B) P11.
WWW.MATERIALSVIEWS.COM
JOURNAL OF POLYMER SCIENCE, PART A: POLYMER CHEMISTRY 2015, 53, 2481–2493
2487

JOURNAL OF
POLYMER SCIENCE
ARTICLE
WWW.POLYMERCHEMISTRY.ORG
FIGURE 8 Raman spectra of (A) P9B; (B) P10B; (C) P9; (D) P10.
[Color figure can be viewed in the online issue, which is avail-
able at wileyonlinelibrary.com.]
In general, it could be observed that the dialkyne-terminated
monomers enhance mobility of the polymer chain following
the trend 3, 4, 2, and 1. Although it could be thought that
monomers 5 and 7 would induce a similar rigidity to the
polymer chain, since polymers P8 and P10 have similar Tg
(Table 2), in fact, taking into account that the molecular
weight of P8 is significantly lower than that of P10, it could
be concluded that of the diazido-terminated monomers, 5
will be the one causing most rigidity in the polymer chain.
In the cases of poly(ester triazole)s P9B and P10B, their Tg
are higher than the corresponding values of P9 and P10;
this difference may be explained by the expected higher
molecular-weight distribution of polymers P9B and P10B.
FIGURE 7 (A) 1H NMR spectrum of P9 recorded in DMSO-d6;
(B) 1H HR-MAS spectrum of P9B recorded in DMSO-d6; (C) 13C
NMR spectrum of P9; (D) 13C HR-MAS spectrum of P9B.
glass-transition temperatures (Tg) were measured with a
heating rate of 10 8C min21; the upper limit of these meas-
urements was fixed at about 200 8C to avoid decomposition,
because all Tg values were determined from the second heat-
ing trace. Well-defined slope changes due to second-order
thermal transitions were observed for all the polymers on
the heating DSC traces of samples previously quenched from
the melt (Fig. 9). Annealing experiments at different temper-
atures did not result in the crystallization of the samples.
This could suggest that intermolecular forces resulting from
possible hydrogen bonds between triazole units and/or
hydroxyl groups are not sufficient to induce crystallization
within the polymers, under the conditions tested. Poly(ester
triazole) P13 has the highest Tg value (152 8C), as a result of
combining the relatively high rigidity of the dianhydrohexitol
3 with monomer 5 which, besides two hydroxyl groups, has
a benzyl substituent that should hamper the mobility of the
polymer chain.
Thermal stabilities were studied by thermogravimetric analy-
ses (TGA), heating the sample at a rate of 10 8C min21 under
a nitrogen atmosphere from room temperature to 600 8C.
The decomposition temperature corresponding to 10%
weight loss and the temperature for the maximum degrada-
tion rate are compared in Table 2. All the polymers were
stable up to 200 8C. The poly(ester triazole) P15, which
Polymers P9 and P11 have the lowest Tg values (6 and 36
8C, respectively), due to the polymethylene segments present
along the polymer chain, which is consistent with the gener-
ally accepted concept that longer linear methylene chains in
a polymer alter the macromolecular dynamics because of
increasing flexibility.
FIGURE 9 DSC thermograms of the described poly(ester
triazole)s.
2488
JOURNAL OF POLYMER SCIENCE, PART A: POLYMER CHEMISTRY 2015, 53, 2481–2493

JOURNAL OF
POLYMER SCIENCE
WWW.POLYMERCHEMISTRY.ORG
ARTICLE
FIGURE 10 Remaining weight versus incubation time. Hydroly-
sis at 50 8C in buffer solution at pH 7.4: (A) P8, (B) P13, (C) P12.
derived from two carbohydrate monomers, has the lowest
stability, while polymers which have the isosorbide moiety in
the repeating units have the highest temperature for the
maximum decomposition rate.
Hydrolytic Degradation
The hydrolytic degradation of poly(ester triazole)s P8, P12,
and P13, prepared by click polymerization of the dialkyne-
terminated monomers 1, 2, and 3 with 1,5-diazido-1,5-
dideoxy-3-O-benzyl-L-arabinitol (5), respectively, has been
carried out by submerging samples in aqueous buffer solu-
tions (pH 7.4) at 50 8C. The hydrolytic degradation was fol-
lowed by determination of the loss of mass of the samples.
The data revealed different behavior in the three samples.
The mass of the poly(ester triazole)s P8 and P13 decreased
continuously with time after the onset of the experiment,
with P8 losing mass faster [Fig. 10(A,B)].
FIGURE 11 1H NMR spectra of (A) P8 before degradation; (B)
P8 solid residue after 51 days of degradation; (C) residue from
the stock solution; (D) commercial pentaethylene glycol.
the hydrolysis of these two polymers is characterized by a
continuous decrease in both number- and weight-average
molecular weight during the degradation study. However,
poly(ester triazole) P12 showed an unusual behavior. The
apparent molecular weight determined by GPC as a function
of immersion time increased during the first two months of
degradation, and then decreased as the degradation pro-
ceeded (Fig. 14).
This could be explained considering that degradation pro-
duces water-soluble compounds. Pentaethylene glycol and D-
isosorbide are the expected degradation products in the
hydrolysis of P8 and P13 respectively, and are water-
soluble. In this regard, the 1H NMR spectra for the degrada-
tion experiment of poly(ester triazole) P8 are shown in Fig-
ure 11. As can be observed, pentaethylene glycol is clearly
detected in the 1H NMR spectrum [Fig. 11(C)] of the buffer
solution obtained after filtration of the degraded sample.
This assignation was corroborated by comparison with the
spectrum of a commercial sample of pentaethylene glycol
[Fig. 11(D)]. In contrast, Figure 10(C) shows that practically
no mass losses occur during the hydrolysis of poly(ester tria-
zole) P12 at 50 8C in phosphate buffer (pH 7.4). In this case,
the fragments produced by the hydrolytic process are not
soluble in the medium, and therefore are not able to exit
from the sample.
Degradation of these poly(ester triazole)s was also moni-
tored by gel permeation chromatography (GPC) analysis, to
determine the changes in molecular weight and molecular-
weight distribution. The evolution of the apparent molecular
weights of poly(ester triazole) P8 and P13 as a function of
immersion time is shown in Figs. 12 and 13. As expected,
FIGURE 12 Number-average molecular weight versus incuba-
tion time. Hydrolysis at 50 8C in buffer solution at pH 7.4:
(A) P8 and (B) P13.
WWW.MATERIALSVIEWS.COM
JOURNAL OF POLYMER SCIENCE, PART A: POLYMER CHEMISTRY 2015, 53, 2481–2493
2489

JOURNAL OF
POLYMER SCIENCE
ARTICLE
WWW.POLYMERCHEMISTRY.ORG
FIGURE 13 Weight-average molecular weight versus incuba-
tion time. Hydrolysis at 50 8C in buffer solution at pH 7.4:
(A) P8 and (B) P13.
This behavior, observed in both DMF and NMP as mobile
phase, might tentatively be explained considering that the
initial degradation products of the polymer form aggregates.
In this regard, the possible formation of macromolecular
aggregates was studied by DOSY NMR experiments. The sig-
nals belonging to a sample of polymer P12 after about 50
days of degradation at 50 8C in buffer solution (pH 7.4)
appear in Figure 15(B) with a diffusion coefficient lower
than that of the original sample of poly(ester triazole) P12
[Fig. 15(A)].
FIGURE 15 DOSY NMR spectra recorded in DMF-d7 of (A) P12
before degradation; (B) after 51 days of degradation; (C) after
106 days of degradation. [Color figure can be viewed in the
online issue, which is available at wileyonlinelibrary.com.]
This observation is consistent with the GPC data, as the
apparent molecular weight, Mn, of the sample degraded for
50 days is approximately 1.4 times that of the initial sample.
However after about 100 days of degradation, the apparent
molecular weight of the degraded sample P12, determined
by GPC, was lower than that of the nondegraded polymer.
This observation can also be confirmed by DOSY NMR, since
the sample of P12 degraded for 106 days had a diffusion
coefficient [Fig. 15(C)] higher than that of the nondegraded
sample [Fig. 15(A)].
Crosslinking Hydrogels
The alcohol functions present in the poly(ester triazole)
chains could be chemically modified to obtain a greater
diversity in the resulting polymers. In this sense, we are
interested in the synthesis of hydrogels, a kind of macromo-
lecular structure of great importance, and currently consid-
erable scientific effort is being made in this area due to their
numerous applications in various fields.
As a proof of principle, we used polymers P10, P11, and
P14 to prepare polymeric networks by reacting the hydroxyl
groups, present in the repeating units of these polymers,
with hexamethylene diisocyanate (HMDI). The crosslinking
reaction proceeded readily, without the need to add a cata-
lyst. The structures of these hydrogels were studied by 1H
and 13C NMR spectroscopies. As an example, the 1H NMR
spectrum of the crosslinked polymer P11U is displayed in
Figure 16(A).
It can be observed, by comparison with the 1H NMR spec-
trum of the polymer P11 [Fig. 16(B)], that all resonance sig-
nals of P11 are present in the spectrum of the crosslinked
gel. Furthermore, new signals corresponding to the crosslink-
ing agent and to the protons belonging to the chemical
FIGURE 14 GPC chromatogram evolution of P12 degradation
as a function of immersion time in buffer solution at pH 7.4:
(A) before degradation; (B) after 20 days; (C) after 51 days; and
(D) after 106 days.
2490
JOURNAL OF POLYMER SCIENCE, PART A: POLYMER CHEMISTRY 2015, 53, 2481–2493

JOURNAL OF
POLYMER SCIENCE
WWW.POLYMERCHEMISTRY.ORG
ARTICLE
TABLE 3 Crosslinking and Swelling Parameters
Network
[Polymer]a
(%)b
W
1
K
R2
P11U
P10U
P14U
60
43
48
50
n.d.
n.d.
n.d.
1.00
0.99
158
170
0.440
0.014
0.275
0.199
a
Concentration of polymer in DMF (mg mL21).
Determined by NMR analysis.
b
carbon atoms. Thus, the signal corresponding to C2’ and C9’
appeared at 68.06 ppm and at 70.22 ppm; similarly, the sig-
nals corresponding to C10, C100, C30, and C80 appear at 53.32
and 72.07 ppm, and at 50.58 and 69.14 ppm, respectively,
depending on whether the alcohol function is free or as ure-
thane. These assignments were confirmed by two-
dimensional HSQC and COSY experiments. A semiquantitative
estimation of the crosslinking degree was obtained by com-
parison of the integral of the resonance signal at 2.86 ppm,
labeled b in the spectrum [Fig. 16(B)], due to the four
hydrogen atoms of the two methylene groups directly
attached to the nitrogen atoms of the urethane groups [I(A)],
with the resonance signal appearing at 4.25 ppm, which was
assigned to the four hydrogen atoms of the two methylene
groups, labeled 1 and 6 in the spectrum, present in the
repeating unit of the polymer chain [I(B)]. The crosslinking
degree of the gel is obtained according to the equation:
FIGURE 16 (A) 1H NMR spectrum of P11 recorded in DMSO-d6;
(B) 1H HR-MAS spectrum of P11U recorded in DMSO-d6.
I½ðAÞꢁ
% crosslinking5
3 100543
functions which link the chains are detected. The urethane
linkage in the gel is confirmed by the signal labeled b
appearing at 2.86 ppm [Fig. 16(B)] which is assigned to the
hydrogen atoms of the methylene group directly attached to
the nitrogen atom of the urethane group. The signal that
appears at 7.16 ppm was assigned to the proton of the ure-
thane functions, labeled a in the spectrum. The four remain-
ing methylene groups appear as two broad signals at 1.27
and 1.11 ppm (labeled c and d, respectively). All these
assignments were confirmed by COSY and HSQC experi-
ments. The signals corresponding to the crosslinking agent
were also detected in the 13C NMR spectrum of the cross-
linked gel. Thus, peaks appearing at 40.04, 29.14, and 25.17
ppm were assigned to the methylene groups, b, c, and d of
the crosslinking agent. The presence of crosslinking units
causes a chemical shift of the signals of the protons and car-
bons of the polymer chain which are close to the urethane
functions. Thus the signal appearing at 4 ppm [Fig. 16(A,B)]
as a multiplet, and assigned to the protons H-2’ and H-9’ of
the repeating units with alcohol functions unsubstituted,
undergoes a downfield shift when the alcohol functions react
with isocyanate to give the urethane functions. In this case,
the signal of these protons appears at 5.14 ppm as a broad
singlet [Fig. 16(B)]. The proton signals H-1’ and H-10’, which
appear at 4.51 and 4.36 ppm when the alcohol functions of
the repeating unit are free, were also shifted to lower field,
appearing as a multiplet between 4.74 and 4.60 ppm when
the crosslinking reaction occurs. The 13C NMR spectrum of
the crosslinked gel also displayed duplicate signals for some
I½ðBÞꢁ
This degree of crosslinking can be further confirmed by
other resonance signals. Thus, the two alcohol functions
present in the repeating unit of P11, which appeared as a
doublet at 5.31 ppm, reduced to about half its integral in the
crosslinked polymer P11U. Similarly it could be established
that the degree of crosslinking of hydrogels P10U and P14U
was 48% and 50%, respectively (Table 3). The dry gels were
rehydrated in distilled water to determine the extent and
kinetics of swelling. Thus, from time to time the gel was
taken out, gently wiped, and weighed. The degree of swelling
(DS) was calculated from the following equation:
DS5ðWh2WcÞ=Wc 3 100
where Wh is the weight of the swollen gel and Wc that of the
corresponding dry film.
Figure 17 shows the kinetics of swelling: an increase in the
crosslinks produces, as could be expected, a decrease in the
amount of swelling of the hydrogel. However, it is also neces-
sary to bear in mind that the hydrogels have different com-
positions, which can also affect the swelling ratio of the
hydrogel. As the crosslinking increases, the resultant net-
work should be less flexible, and therefore the capacity of
the hydrogel to swell decreases.64,65
The dynamics of the water sorption process was investigated
by monitoring the amount of water imbibed by hydrogels in
WWW.MATERIALSVIEWS.COM
JOURNAL OF POLYMER SCIENCE, PART A: POLYMER CHEMISTRY 2015, 53, 2481–2493
2491

JOURNAL OF
POLYMER SCIENCE
ARTICLE
WWW.POLYMERCHEMISTRY.ORG
ACKNOWLEDGMENTS
ꢀ
We thank the Ministerio de Economıa y Competitividad of Spain
ꢀ
(Grant MAT2012–38044-C03-01) and the Junta de Andalucıa
(Grant P12-FQM-1553) for financial support. The authors
also thank the Instituto de Ciencias de Materiales (ICMS) and
ꢀ
ꢀ
~
Mr. Miguel Angel Aviles Escano for the Raman spectra.
REFERENCES AND NOTES
1 E. Elliott, In Polymers and People: An Informal History,
Beckman Center for the History of Chemistry: Philadelphia,
2005.
FIGURE 17 Water sorption of crosslinked gels versus time: ٗ,
P14; ‡, P10; ᭺, P11. [Color figure can be viewed in the online
issue, which is available at wileyonlinelibrary.com.]
2 L. D. DeSimone, F. Popoff, In Eco-efficiency: The Business
link to sustainable Development; MIT Press: Cambridge, 2000.
3 A. Azapagic, A. Emsley, I. Hamerton, In Polymers: The
Environment and Sustainable Development; Wiley: West
Sussex, 2003.
various time periods. The kinetics of the swelling process was
evaluated by Schott’s pseudo-second-order kinetic model.66
€
€
4 U. Biermann, W. Friedt, S. Lang, W. Luhs, G. Machmuller, J.
ꢀ
ꢁ
€
O. Metzger, M. R. G. Klass, H. J. Schafer, M. P. Schneider,
t
1
1
5
1
t
Angew. Chem. Int. Ed. 2000, 39, 2206–2224.
Wt
K
W
1
5 Bozell, J. J. Patel, M., Eds.; Feedstocks for the Future: Renew-
ables for the Production of Chemicals and Materials; ACS Sym-
posium Series 921; American Chemical Society: Washington,
DC, 2006.
where Wt is the water absorption of the hydrogels at time t,
W the water content at equilibrium, and K the swelling rate
1
constant. According to this equation, the experimental data
must fit a straight line when t/Wt versus t is plotted. As can
be seen from the linear correlation coefficient R2 (Table 3),
the pseudo-second-order model can be effectively used to
evaluate swelling kinetics of hydrogels. From these graphs
ꢁ
ꢀ
6 J. C. Ronda, G. Lligadas, M. Galia, V. Cadiz, Eur. J. Lipid Sci.
Technol. 2011, 113, 46–58.
7 A. Gandini, Green Chem. 2011, 13, 1061.
8 F. Lichtenthaler, Ullmann’s Encycl. Ind. Chem. 2010, 583–616.
9 G. Marosi, Express Polym. Lett. 2013, 8, 219–219.
10 R. Huisgen, Angew. Chem. Int. Ed. 1963, 2, 565–598.
11 R. Huisgen, Angew. Chem. Int. Ed. 1963, 2, 633–645.
the water content at equilibrium (W ) could be determined
1
from the slope, and the kinetics rate constants (K) from the
intercept of each straight line. The swelling kinetics parame-
ters and the linear correlation coefficients (R2) for hydrogels
P10U and P14U are shown in Table 3. The swelling kinetics
parameters for hydrogel P11U were not determined because
the sample did not reach complete saturation after 350 h of
immersion in distilled water at 8 8C. This hydrogel has the
lowest crosslinking degree and, in addition, it is prepared
from P11, which has the lowest Tg of the three polymers
studied. These two factors should facilitate relaxation of the
polymer chain and the diffusion of water molecules into the
network. A parallel explanation can be given regarding the
results displayed for P10U and P14U hydrogels in Table 3.
Thus, P14U has the highest degree of crosslinking and a
composition that also includes isosorbide units, which are
known to increase the rigidity of the polymer chain, confer-
ring a greater physical restriction in the network that finally
causes the swelling rate to decrease.
12 H. C. Kolb, M. G. Finn, K. B. Sharpless, Angew. Chem. Int.
Ed. 2001, 40, 2004–2021.
13 V. V. Rostovtsev, L. G. Green, V. V. Fokin, K. B. Sharpless,
Angew. Chem. Int. Ed. 2002, 41, 2596–2599.
14 C. W. Tornøe, C. Christensen, M. Meldal, J. Org. Chem.
2002, 67, 3057–3064.
15 C. Barner-Kowollik, A. J. Inglis, Macromol. Chem. Phys.
2009, 210, 987–992.
16 C. Barner-Kowollik, F. E. Du Prez, P. Espeel, C. J. Hawker, T.
Junkers, H. Schlaad, W. Van Camp, Angew. Chemie Int. Ed.
2011, 50, 60–62.
€
17 R. K. Iha, K. L. Wooley, A. M. Nystrom, D. J. Burke, M. J.
Kade, C. J. Hawker, Chem. Rev. 2009, 109, 5620–5686.
18 B. S. Sumerlin, A. P. Vogt, Macromolecules 2010, 43, 1–13.
19 O. Altintas, U. Tunca, Chem. Asian J. 2011, 6, 2584–2591.
20 P. L. Golas, K. Matyjaszewski, Chem. Soc. Rev. 2010, 39,
1338–1354.
21 G. K. Such, S. T. Gunawan, K. Liang, F. Caruso, Macromol.
Rapid Commun. 2013, 34, 894–902.
CONCLUSIONS
22 S. Hvilsted, Polym. Int. 2012, 61, 485–494.
The results of this work have shown that the CuAAC polymer-
ization of dialkynes containing ester linkages and diazides can
lead to high-molecular-weight poly(ester triazole)s, and that
these novel biobased polyesters can be hydrolyzed under mild
conditions: at 50 8C in buffer solution at pH 7.4. In addition,
these functionalized polymers can be easily converted into
network structures by crosslinking reaction of the secondary
alcohol functions with hexamethylene diisocyanate.
23 M. Bueno, I. Molina, J. A. Galbis, Polym. Degrad. Stab.
2012, 97, 1662–1670.
ꢀ
24 I. Molina-Pinilla, M. Bueno-Martınez, K. Hakkou, J. A. Galbis,
J. Polym. Sci., Part A: Polym. Chem. 2014, 52, 629–638.
ꢀ
25 M. Bueno-Martınez, I. Molina-Pinilla, K. Hakkou, J. A. Galbis,
J. Polym. Sci., Part A: Polym. Chem. 2015, 53, 413–421.
26 A. R. Katritzky, N. K. Meher, S. Hanci, R. Gyanda, S. R. Tala,
S. Mathai, R. S. Duran, S. Bernard, F. Sabri, S. K. Singh, J.
2492
JOURNAL OF POLYMER SCIENCE, PART A: POLYMER CHEMISTRY 2015, 53, 2481–2493

JOURNAL OF
POLYMER SCIENCE
WWW.POLYMERCHEMISTRY.ORG
ARTICLE
Doskocz, D. A. Ciaramitaro, J. Polym. Sci., Part A: Polym.
Chem. 2008, 46, 238–256.
47 B. Chertok, M. J. Webber, M. D. Succi, R. Langer, Mol.
Pharm. 2013, 10, 3531–3543.
27 S. Binauld, F. Boisson, T. Hamaide, J. P. Pascault, E.
Drockenmuller, E. Fleury, J. Polym. Sci., Part A: Polym. Chem.
2008, 46, 5506–5517.
48 W. C. Shearouse, L. M. Lillie, T. M. Reineke, W. B. Tolman,
ACS Macro Lett. 2015, 284–288.
49 H. Kang, M. Li, Z. Tang, J. Xue, X. Hu, L. Zhang, B. Guo, J.
Mater. Chem. B 2014, 2, 7877–7886.
28 R. M. Meudtner, S. Hecht, Macromol. Rapid Commun. 2008,
29, 347–351.
50 X. Feng, A. J. East, W. B. Hammond, Y. Zhang, M. Jaffe,
Polym. Adv. Technol. 2011, 22, 139–150.
29 A. Qin, L. Tang, J. W. Y. Lam, C. K. W. Jim, Y. Yu, H. Zhao,
J. Z. Sun, B. Z. Tang, Adv. Funct. Mater. 2009, 19, 1891–1900.
51 F. Fenouillot, a. Rousseau, G. Colomines, R. Saint-Loup, J.
P. Pascault, Prog. Polym. Sci. 2010, 35, 578–622.
30 Y. Nagao, A. Takasu, J. Polym. Sci., Part A: Polym. Chem.
2010, 48, 4207–4218.
52 V. Glac¸on, M. Benazza, A. El Anzi, D. Beaupe`re, G. Demailly,
J. Carbohydr. Chem. 2004, 23, 95–110.
31 A. Soules, B. Ameduri, B. Boutevin, G. Calleja,
Macromolecules 2010, 43, 4489–4499.
53 G. Dreyer (Smith-Kline Beecham Co.) U.S. Patent 9104757,
January 23, 1992.
32 H.-F. Chow, T.-K. Chui, Q. Qi, Synlett 2014, 25, 2246–2255.
33 M. Abid, M. Aden Ali, J. Bernard, S. Abid, E. Fleury, R. El
Gharbi, Polym. Sci. Ser. B 2014, 56, 290–297.
54 L. Balas, B. Jousseaume, B. Langwost, Tetrahedron Lett.
1989, 30, 4525–4526.
€
34 V. Bretzler, M. Grubel, S. Meister, B. Rieger, Macromol.
55 L. M. H. Leung, V. Gibson, B. Linclau, Tetrahedron
Asymmetry 2005, 16, 2449–2453.
Chem. Phys. 2014, 215, 1396–1406.
35 Y. C. Kuo, I. N. Ku, Biomacromolecules 2008, 9, 2662–2669.
56 H. Kakiuchi, Y. Tanaka, J. Org. Chem. 1966, 31, 1559–1564.
36 J. Kim, K.-W. Lee, T. E. Hefferan, B. L. Currier, M. J.
Yaszemski, L. Lu, Biomacromolecules 2008, 9, 149–157.
57 E. Soto-Cantu, B. S. Lokitz, J. P. Hinestrosa, C. Deodhar, J.
M. Messman, J. F. Ankner, S. M. Kilbey, Langmuir 2011, 27,
5986–5996.
37 J. Zhu, Biomaterials 2010, 31, 4639–4656.
58 A. R. Katritzky, L. Wang, Y. M. Song, R. Gyanda, R. Sakhuja,
N. K. Meher, S. Hanci, K. Gyanda, S. Mathai, F. Sabri, D. A.
Ciaramitaro, C. D. Bedford, R. S. Duran, J. Appl. Polym. Sci.
2010, 117, 2612–2621.
38 F. Tan, X. Xu, T. Deng, M. Yin, X. Zhang, J. Wang, Biomed.
Mater. 2012, 7, 055009.
ꢁ
39 P. Brun, F. Ghezzo, M. Roso, R. Danesin, G. Palu, A. Bagno,
M. Modesti, I. Castagliuolo, M. Dettin, Acta Biomater. 2011, 7,
59 X. M. Liu, A. Thakur, D. Wang, Biomacromolecules 2007, 8,
2526–2532.
2653–2658.
40 I. Savva, A. D. Odysseos, L. Evaggelou, O. Marinica, E.
Vasile, L. Vekas, Y. Sarigiannis, T. Krasia-Christoforou,
Biomacromolecules 2013, 14, 4436–46.
60 Z. Li, Z. Li, G. Yu, P. Hu, C. Ye, Y. Liu, J. Qin,
Macromolecules 2009, 42, 1589–1596.
61 C. J. Duxbury, D. Cummins, A. Heise, J. Polym. Sci. Part A:
Polym. Chem. 2009, 47, 3795–3802.
41 K. Knop, R. Hoogenboom, D. Fischer, U. S. Schubert,
Angew. Chemie Int. Ed. 2010, 49, 6288–6308.
62 H. Gan, H. Liu, Y. Li, Q. Zhao, Y. Li, S. Wang, T. Jiu, N. Wang,
X. He, D. Yu, D. Zhu, J. Am. Chem. Soc. 2005, 127, 12452–12453.
42 P. Kallinteri, S. Higgins, G. A. Hutcheon, C. B. S. Pourcain,
M. C. Garnett, Biomacromolecules 2005, 6, 1885–1894.
63 E. Jahnke, I. Lieberwirth, N. Severin, J. P. Rabe, H.
Frauenrath, Angew. Chemie Int. Ed. 2006, 45, 5383–5386.
43 J. Stukel, S. Thompson, L. Simon, R. Willits, J. Biomed.
Mater. Res. Part A 2015, 103A, 604–613.
64 P. E. M. Allen, D. J. Bennett, D. R. G. Williams, Eur. Polym.
J. 1992, 28, 347–352.
44 J. M. Harris, R. B. Chess, Nat. Rev. Drug Discov. 2003, 2,
214–221.
45 C. C. Lin, K. S. Anseth, Pharm. Res. 2009, 26, 631–643.
65 C. S. Brazel, N. A. Peppas, Polymer (Guildf). 1999, 40, 3383–
3398.
46 U. Wattendorf, H. P. Merkle, J. Pharm. Sci. 2008, 97, 4655–
4669.
66 H. Schott, J. Macromol. Sci. 1992, 31, 1–9.
WWW.MATERIALSVIEWS.COM
JOURNAL OF POLYMER SCIENCE, PART A: POLYMER CHEMISTRY 2015, 53, 2481–2493
2493