Synthesis and adhesive property study of polyoxetanes grafted with catechols via Cu(I)-catalyzed click chemistry

Article abstract of DOI:10.1016/j.polymer.2014.01.028

Mussel-inspired catechol-containing polymers have drawn great attention due to their outstanding adhesive properties. Catechol-containing polyethylene glycol (cPEG) is a well-studied catechol-containing polymer used for tissue repair. Nevertheless, catechols can only be attached to the chain ends of polyethylene glycols thus the bonding strength of the resulting polymers is limited. Aiming at solving the problem, a series of clickable polyoxetane copolymers with grafted catechol moieties were synthesized in an efficient manner. Upon addition of FeCl₃ as the cross-linker, strong bonding strength of the adhesive was achieved. Polymer containing 15.5 molar percent of catechol showed the strongest bonding strength up to 5.59 MPa on sanded stainless steel. It was found that the triazole groups also contributed to the overall adhesive performance. This polyoxetane-based adhesive also displayed strong bonding ability to a variety of other substrates including porcine skin.

Full text of DOI:10.1016/j.polymer.2014.01.028

Polymer 55 (2014) 1160e1166
Contents lists available at ScienceDirect
Polymer
journal homepage: www.elsevier.com/locate/polymer
Synthesis and adhesive property study of polyoxetanes grafted
with catechols via Cu(I)-catalyzed click chemistry
,
,
,
c
a,
Mingchen Jia a b, Ailei Li a b, Youbing Mu a , Wei Jiang , Xiaobo Wan
*
*
a Key Laboratory of Biobased Materials, Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Sciences, 189 Songling Road,
Qingdao, Shandong Province 266101, PR China
b University of Chinese Academy of Sciences, 19A Yuquan Road, Beijing 100049, PR China
c National Engineering Research Center for Organic Pollution Control and Resource Reuse, State Key Laboratory of Pollution and Resource Reuse,
School of the Environment, Nanjing University, 22 Hankou Road,Nanjing, Jiangsu Province 210093, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
Mussel-inspired catechol-containing polymers have drawn great attention due to their outstanding
adhesive properties. Catechol-containing polyethylene glycol (cPEG) is a well-studied catechol-con-
taining polymer used for tissue repair. Nevertheless, catechols can only be attached to the chain ends of
polyethylene glycols thus the bonding strength of the resulting polymers is limited. Aiming at solving the
problem, a series of clickable polyoxetane copolymers with grafted catechol moieties were synthesized
in an efficient manner. Upon addition of FeCl3 as the cross-linker, strong bonding strength of the adhesive
was achieved. Polymer containing 15.5 molar percent of catechol showed the strongest bonding strength
up to 5.59 MPa on sanded stainless steel. It was found that the triazole groups also contributed to the
overall adhesive performance. This polyoxetane-based adhesive also displayed strong bonding ability to
a variety of other substrates including porcine skin.
Received 22 October 2013
Received in revised form
10 January 2014
Accepted 22 January 2014
Available online 31 January 2014
Keywords:
Mussel-inspired adhesive
Polyoxetane
Click chemistry
Ó 2014 Elsevier Ltd. All rights reserved.
1. Introduction
depth, an obvious shortcoming of PEG is that the polymer can
only be modified at its chain ends. The highest catechol content of
The catechol-containing polyethylene glycol (cPEG) has found
its application in tissue repairing due to its biocompatibility and
underwater bonding ability. The inspiration comes from a marine
mollusk named blue mussel which uses catechol-containing pro-
teins to stick on rocks and ship hulls [1e3]. Lee et al. reported the
preparation of a series of catechol-containing PEGs and studied
their gelation behavior in the presence of oxidizing agents. They
demonstrated that the PEGs containing more than one catechol can
undergo oxidative polymerization to form polymeric network [4].
Then Burke et al. used the four-arm PEG with a catechol moiety
attached to each end for tissue adhesion study. This adhesive
formed strong bonding on porcine skin (35.1 kPa) when being
oxidized at 37 ꢀC, which was several times stronger than a fibrin
glue control [5]. Brubaker et al. further interrogated the in-vivo
performance of cPEG in a murine model of islet transplantation,
in which cPEG was mixed with sodium periodate to efficiently
immobilize transplanted islets and minimize inflammatory
response [6]. Although PEG-based adhesives were studied in-
cPEG used for adhesive was only about 1.7 mol% when four cate-
chols were attached to a 4-arm PEG (10 kDa). However, the molar
percent of catechol moiety in mussel foot protein (mfp) can be as
high as 30% [7]. As a result, the strength of the bond formed by cPEG
is limited. There is still a need for stronger tissue adhesives, espe-
cially in the case of bone repairing and moving organs bonding.
Oxetanes can undergo ring-opening polymerization to generate
polyoxetanes, which have similar polyether backbone as PEG but
with modifiable side chains. Feng and co-workers synthesized
homo- and copolymers from 3-(2-cyanoethoxy) methyl- and 3-
(methoxy (triethylenoxy)) methyl-30-methyloxetane through
cationic ring-opening polymerization. These polyoxetanes have
low Tg (ꢁ27 ꢀC to ꢁ47 ꢀC) and high heat decomposition tempera-
ture (about 300 ꢀC) [8]. Wynne and co-workers employed co-
polymers of 3, 30-substituted oxetanes as the soft blocks in
polyurethanes to produce various functional polyurethanes [9e11].
Polyoxetane is also considered to be biocompatible like PEG but
more versatile. Recently, Yang and co-workers developed a new
platform for drug delivery based on clickable polyoxetanes. PEGs
were grafted onto the backbone of polyoxetanes via Cu(I)-catalyzed
alkyne-azide cycloaddition click chemistry (CuAAC) to improve its
water-solubility. Anti-cancer drugs, fluorescent agents and other
functional groups were clicked onto the backbone in an efficient
* Corresponding authors.
E-mail addresses: muyb@qibebt.ac.cn (Y. Mu), wanxb@qibebt.ac.cn, wanxiaob@
sas.upenn.edu (X. Wan).
0032-3861/$ e see front matter Ó 2014 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.polymer.2014.01.028

M. Jia et al. / Polymer 55 (2014) 1160e1166
1161
manner. In cytotoxicity assessment study, the PEG-grafted poly-
oxetanes are compatible with human dermal fibroblasts at con-
centrations up to 2 mg/l [12,13]. Inspired by the work mentioned
above, we envisioned that a catechol-containing polyoxetane might
be an adjustable platform for alternative adhesive polymers to
cPEG.
(5.21 g, 0.04 mol) and EPOMO (1.54 g, 0.01 mol) in 3 mL of CH2Cl2
was added dropwise through the addition funnel into the solution
in an hour. The mixture was stirred at 0 ꢀC for another 5 h. Water
(10 mL) was then added to terminate the polymerization. The
product was extracted with CH2Cl2 (2 ꢂ 30 mL) and washed with
brine (2 ꢂ 30 mL). The CH2Cl2 layer was concentrated and the
residue was added drop-wise into 200 mL of methanol under
stirring. The precipitate was dissolved in CH2Cl2 (20 mL), concen-
trated and precipitated out again in methanol (200 mL). The pre-
cipitate was dried under reduced pressure to afford the copolymer
(5.56 g) as a solid. Yield: 66.8%.
Taking advantage of the efficiency of click chemistry, various
amounts of catechols can be graft onto the backbone of a polymer
without lowering the degree of polymerization. However, click
chemistry is seldom used in the literature to synthesize catechol-
containing polymers. Hawker and coworkers introduced cate-
chols to polysiloxanes via thiol-ene click chemistry. The loading of
catechols in the polysiloxanes ranged from 0 mol % to 50 mol %, in
good consistency with the catechol feeding ratio [14]. Müller and
coworkers utilized an alkyne-modified catechol-derivative to
functionalize Fe3O4 nanoparticles. Azido-end group functionalized
PEGs were then grafted onto the functionalized nanoparticles via
CuAAC [15]. Moreover, triazoles formed in CuAAC are chemically
and biochemically invisible, ensuring the stability and biocompat-
ibility of the adhesive polymers under conditions where they are
used [16].
As far as we know, there has not been any report on the syn-
thesis of catechol-containing polyoxetanes via CuAAC. We herein
wish to report the synthesis of catechol-containing polyoxetane
and its adhesive properties under dry conditions. The new adhesive
showed strong bonding strength on varies substrates, and we
believe that further modification on this novel platform (such as to
increase its solubility in aqueous solution and to lower its poly-
dispersity) will lead to stronger tissue adhesives.
2.3. Synthesis of 3,4-bis-(tert-butyl-dimethyl-silanyloxy)-benzyl
azide
3,4-Bis-(tert-butyl-dimethyl-silanyloxy)-benzyl bromide was
synthesized according to the method developed by Nicolaou
(Supplementary Information, Scheme S2) [18]. Sodium azide
(4.38 g, 0.067 mol) was added to a stirred solution of 3,4-bis-
(tert-butyl-dimethyl-silanyloxy)-benzyl bromide (14.60 g,
0.034 mol) in acetone and the resulting mixture was heated at
reflux for 8 h. Water (20 mL) was then added to the reaction
mixture and acetone was evaporated. The resulting mixture was
extracted with CH2Cl2 (2 ꢂ 100 mL) and the extract was washed
with water (100 mL) and brine (100 mL), dried over anhydrous
MgSO4 and concentrated. The crude product was subjected
to silica column chromatography (petroleum ether/CH2Cl2: 20/1
v/v) to afford the benzyl azide (12.00 g) as a colorless oil. Yield:
93%. 1H NMR (CDCl3, 600 MHz):
d (ppm) 0.20 (s, 6H), 0.21 (s, 6H),
0.99 (s, 9H), 0.10 (s, 9H), 4.19 (s, 2H), 6.75e6.83 (m, 3H) (Sup-
2. Experimental section
plementary Information, Fig. S3). 13C NMR (CDCl3, 300 MHz):
d
(ppm) 147.2, 147.1, 128.4, 121.2, 121.3, 121.2, 54.5, 25.9, 18.47,
2.1. Materials and methods
18.45 (Supplementary Information, Fig. S4).
All the starting materials were purchased from Sigmae
Aldrich and used as received unless otherwise stated. Substrates
for lap shear test were purchased from the local stores. BF3$Et2O
was fresh distilled under reduced pressure before use. THF and
CH2Cl2 were dried and distilled before use. 3-ethyl-3-
2.4. Synthesis of protected catechol grafted (PCG)-P(EMOMOx-co-
EPOMOy)
Using the polyoxetane obtained at the feeding ratio of 4:1
(EMOMO:EPOMO) as an example: 3,4-bis-(tert-butyl-dimethyl-
silanyloxy)-benzyl azide (1.3 g, 3.3 mmol), CuSO4$5H2O (54.9 mg,
0.22 mmol), ascorbic acid (77.5 mg, 0.44 mmol) were added to a
solution of copolymer (1.5 g, 0.09 mmol) in 20 mL of THF. The
resulting mixture was heated at reflux overnight under argon at-
mosphere. THF was evaporated and to the residue was added 50 mL
of CH2Cl2. The resulting mixture was washed with water (50 mL)
and brine (3 ꢂ 50 mL). The aqueous layer was extracted with CH2Cl2
(3 ꢂ 50 mL). The combined CH2Cl2 layer was concentrated and
added drop-wise into 200 mL of methanol under stirring to pre-
cipitate the polymer. The crude product was purified by repeating
precipitation. The precipitate was dried under vacuum to afford the
PCG-P(EMOMO84.5%-co-EPOMO15.5%) as a viscous solid (8.50 g).
Yield: 91.4%.
methoxymethyl-oxetane
(EMOMO)
and
3-ethyl-3-
propargyloxymethyl-oxetane (EPOMO) were synthesized ac-
cording to an article with modifications (Supplementary Infor-
mation, Scheme S1) [17], which were distilled over CaH2 before
use. 1H NMR and 13C NMR spectra were recorded on a Bruker
AV600 using tetramethylsilane (TMS) as an internal standard. Gel
permeation chromatography (GPC) data were obtained on a
Polymer Laboratories PL-GPC 120 system equipped with
a
refractive index detector. A combination of two polystyrene gel
columns of PL gel-MIXED C was used, with tetrahydrofuran as an
eluent at a flow rate of 1.0 mL/min and a temperature of 40 ꢀC.
The columns were calibrated using polystyrene standards. Lap
shear test was conducted on a TY-8000 universal materials
testing system equipped with a 5000 N load cell.
2.5. Synthesis of catechol-grafted (CG)-P(EMOMOx-co-EPOMOy)
2.2. Synthesis of P(EMOMOx-co-EPOMOy)
In a general procedure, concentrated HCl (5 equiv. to catechol)
was added to a solution of PCG-P(EMOMOx-co-EPOMOy) in THF
(0.25 g/mL) under argon atmosphere at room temperature. The
resulting mixture was stirred at room temperature overnight. The
resulting mixture was concentrated and added dropwise into
200 mL of n-hexane under stirring. The precipitate was dissolved in
THF (20 mL), concentrated and precipitated out again in n-hexane
(200 mL). The precipitate was dried under reduced pressure to
afford the CG-P(EMOMOx-co-EPOMOy) as a viscous solid (5.50 g).
Yield: 91.0%.
The polyoxetanes with various content of EPOMO were syn-
thesized by adjusting the feeding ratio of the two monomers. The
polymerization was carried out according to a reported procedure
with slight modifications [8]. For example, the copolymer with the
EMOMO:EPOMO feeding ratio at 4:1׃was synthesized using the
following method: To 2 mL of CH2Cl2 in a 50 mL two-neck flask
equipped with a 50 mL addition funnel under argon atmosphere,
were added BF3$Et2O (63.1 mL, 0.5 mmol) and ethylene glycol
(13.9 mL, 0.25 mmol) at 0 ꢀC. After 20 min, a mixture of EMOMO

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M. Jia et al. / Polymer 55 (2014) 1160e1166
2.6. Adhesion experiments
such monomers was relatively low. EMOMO was then selected due
to its relatively high reactivity in copolymerization, leading to co-
polymers with higher molecular weight.
The substrates were cut into rectangular pieces with 10 cm long
and 2.5 cm wide. Metal and plastic pieces were sanded with a 50-
grit sandpaper, cleaned, washed with water and ethanol and then
dried. The poplar pieces were bonded without any pretreatment.
The glass pieces were cleaned, washed with water and ethanol and
dried. Two aluminum pieces were then bonded on the glass
adherends using Krazy Glue before test. The porcine skin was
washed with detergent and water, then air-dried, and bonded on
the outside surface. In the adhesion process, 20 mL of CG-P(EMO-
MOx-co-EPOMOy) solution in ethanol (0.3 g/mL) was spread on two
adherends with an area of 3 cm2[2]. Then 10 mL of FeCl3 in ethanol
was added on one of the adherends. The molar feeding ratio of Fe3þ
to catechol was 1:3. The ends of the two adherends were over-
lapped after being dried by a blower. The two adherends were
fastened by two binder clips and placed under room temperature
for 1 h. Then a load of 50 N was applied on the samples, and the
samples were cured at 55 ꢀC for 22 h to evaporate the solvent and
cross-link the adhesive polymers. Lap shear adhesion measure-
ments were conducted on a universal materials testing system.
Adherends were pulled apart at a rate of 10 mm/min. At least five
samples were measured for each test and the average value of the
bonding strength was adopted, with the error bar showing the
maximum deviation of the measured data.
EMOMO and EPOMO were copolymerized at different feeding
ratios (9:1, 4:1, 7:3, 3:2 and 1:1 molar ratio) using BF3$Et2O as the
catalyst and ethylene glycol as the initiator. The polymerization was
carried out at 0 ꢀC to achieve fast polymerization rate and depress
side reactions [19,20]. A typical 1H NMR spectrum of the copolymer
with the molar feeding ratio of 4:1 was shown in Fig. 1. As can be
seen in the spectrum, the characteristic peaks of oxetane (Supple-
mentary Information, Figs. S1eS2) disappeared, and the appear-
ance of a singlet at 3.19 ppm confirmed the occurrence of the
polymerization. The peaks at w0.84 and 1.38 ppm (a and b) were
assigned to the protons on ethyl groups from both monomers, since
they shared similar chemical environment in the polymer chains.
The signal at 3.23 ppm (d) was assigned to the methylene group on
the side chain of EMOMO moiety and the one at 3.38 ppm (e) was
assigned to that of EPOMO. The peak at 2.39 ppm (h) was assigned
to the acetylene proton and the peak at 4.09 ppm (g) was assigned
to the methylene protons adjacent to the alkynyl group. The
incorporation ratio of EPOMO into the copolymer was calculated
according to the integral ratio of peak h to peak b. Generally, the
incorporation ratio of EPOMO into the copolymer increased with
the increase of its feeding ratio, but was slightly lower than the
feeding ratio, as shown in Table 1, indicating the difference in the
reactivity of the two monomers.
The molecular weights of the copolymers fell between 10 kDa
and 20 kDa and decreased gradually as the content of EPOMO
increased (Table 1). The molecular weights of the polyoxetanes
were higher than PEGs used in mussel-inspired adhesive polymers
(10 kDa), which implies that the adhesives based on polyoxetanes
might show better adhesive properties, since polymeric adhesives
sharing similar structures but with higher molecular weight usually
form stronger bonds than those with lower one.
We noticed that the polydispersity index (PDI) of the poly-
oxetanes is around 2.0, which is larger than the PDI of PEG (approx.
1.00). As biomedical applications generally need polymers with low
PDI, the PDI of polyoxetanes at this stage might not be suitable for
3. Results and discussion
3.1. Synthesis of the adhesive polymer
The synthetic route towards the catechol-containing poly-
oxetane is shown in Scheme 1. Two oxetane derivatives, EMOMO
and EPOMO, were synthesized for copolymerization. EPOMO con-
tains a clickable terminal alkynyl group that is suitable for post-
polymerization modification. They are then copolymerized to give
the corresponding polyoxetanes. Oxetanes with longer alkyl chain
were also synthesized and tested for copolymerization, however,
the degree of polymerization (DP) of the polymers obtained from
Scheme 1. Synthetic route to catechol-containing polyoxetane adhesive polymer.

M. Jia et al. / Polymer 55 (2014) 1160e1166
1163
Fig. 1. 1H NMR of the copolymer of EMOMO and EPOMO in CDCl3 at the molar feeding ratio of 4:1.
direct biomedical use. However, if controlled ring-opening poly-
merization methods are used, polyoxetanes with relatively low
PDIs can be obtained. Till to date, only the controlled coordinate
polymerization of unsubstituted oxetane is reported. Aida and co-
workers reported the living anionic polymerization of oxetane in
the presence of bulky organoaluminum diphenolates and onium
salts. The PDI of the resulting polyoxetanes were around 1.10 when
the molecular weights were below 20 kDa [21]. The controlled
polymerization of substituted oxetanes will be helpful to meet the
requirement of biomedical applications and is our next goal.
inferred from 1H NMR was 4.5%, 15.5%, 24%, 31% and 46% respec-
tively, which is in accordance with the EPOMO content in the
copolymer, indicating a full conversion of the alkynyl groups.
The TBS groups on catechols were easily removed using
concentrated HCl. As can be seen from 1H NMR spectrum of the
final adhesive polymer (Fig. 3), characteristic peaks of TBS groups
disappeared and the other peaks showed little change. Considering
that the ether bonds in the polymer may be sensitive to acid, we
also treated the unmodified polyoxetane copolymer with HCl under
the same conditions to test the stability of the backbone. GPC re-
sults of the polyoxetane before and after acid treatment did not
show any noticeable evidence of degradation. So the ether bonds in
the polyoxetanes are stable during the deprotection process. Thus,
the influence of the acid treatment on the molecular weight of the
final polymer could be ruled out.
Since free-catechol containing polymers might adhere to the
column to make GPC results unauthentic [22], the molecular
weights of the final catechol-containing polyoxetanes were esti-
mated from the GPC results of the unmodified polyoxetanes. As can
be seen from the results, the five adhesive polymers have similar
molecular weights (w19 kDa for Mn). CG-P(EMOMO95.5%-co-
EPOMO4.5%) and CG-P(EMOMO54%-co-EPOMO46%) have a slightly
higher molecular weight than the other three polymers (Supple-
mentary Information, Table S1).
3.2. Post-polymerization modification to introduce catechol moiety
Nevertheless, catechol moiety was grafted onto the polyoxetane
with broad PDI to test its adhesive properties. TBS (tert-butyldi-
methylsilyl) group protected catechols with an azide group were
synthesized in high yield and the method is readily scalable. It was
then grafted onto the polyoxetane backbone via CuAAC chemistry.
CuSO4$5H2O and ascorbic acid were chosen to form cuprous ion
in situ as the catalysts for the graft reaction, which could be easily
removed by washing the obtained polymer with abundant water
and repeating precipitation. Successful grafting was verified in the
1H NMR spectrum (Fig. 2, Supplementary Information, Figs. S6eS9).
The peak of the acetylene proton disappeared completely and a
new peak at 7.37 ppm appeared, which was assigned to the proton
on the triazole group (h). The peak of methylene protons adjacent
to the triazole group was located at 4.55 ppm. The peak i was
assigned to the methylene protons adjacent to the benzene ring.
The peaks at w6.70 ppm (j) and the peaks characteristic of TBS (k,
k0, l, l0) were assigned to the protons of TBS-protected catechol. The
peaks of the other protons showed little change. The ratio between
the integral value of peak i and peak b was calculated to determine
the molar percent of protected catechol attached to the poly-
oxetane. The molar percent of protected catechol in the copolymers
3.3. Characterization of the adhesive properties
In mussel adhesives, there is an unusually high content of
transition metal ions which are involved in the curing of the ad-
hesive proteins. Wilker and coworkers found that, among all the
transition metal ions presented in mussel adhesives, Fe3þ plays the
most important role in cross-linking, in which Fe3þ ions act as the
metal center for complexation and the oxidant for covalently cross-
linking [23]. So in our experiments, FeCl3 was used as the cross-
Table 1
Characterization data for P(EMOMOx-co-EPOMOy) copolymers.
Feeding ratio(%)
EMOMO
Polymer composition(%)
Mn (KDa)
Mw (KDa)
PDI
Monomer conversion (%)
Yield (%)
EPOMO
EMOMO
EPOMO
90
80
70
60
50
10
20
30
40
50
95.5
84.5
76
69
54
4.5
15.5
24
31
46
19.9
16.5
15.5
13.7
14.4
38.9
37.1
31.3
32.0
31.7
2.0
2.2
2.1
2.3
2.2
96.1
98.3
97.8
90.3
93.9
64.9
66.8
59.7
44.3
45.0

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M. Jia et al. / Polymer 55 (2014) 1160e1166
Fig. 2. 1H NMR of PCG-P(EMOMO84.5%-co-EPOMO15.5%) in CDCl3.
Fig. 3. 1H NMR of CG-P(EMOMO84.5%-co-EPOMO15.5%) in CDCl3.
linker to form an adhesive with the catechol-containing poly-
oxetane and lap shear test was conducted to measure the bonding
strength of the resulting adhesives. A 3:1 catechol/FeCl3 ratio was
employed in the adhesion process since it was speculated that
under this ratio Fe3þ might form tris-complex with catechol and
result in efficient cross-linking.
exhibit better bonding behavior than that containing 15 mol%
catechol [14]. The optimal catechol content for best adhesive
strength was 33 mol% for catechol containing polystyrene type
adhesives [22].
The results of lap shear tests showed that FeCl3 was effective in
improving the adhesive strength of catechol-containing poly-
oxetanes, as shown in Fig. 4. For instance, without the addition of
FeCl3, the adhesive strength of CG-P(EMOMO84.5%-co-EPOMO15.5%
)
on stainless steel was only around 1.40 MPa. This number increased
three times upon addition of FeCl3 to an average of 4.87 MPa with
the maximum up to 5.59 MPa. This result is consistent with the
previous reports showing that addition of Fe3þ greatly enhances
the mechanical properties of mussel-inspired materials [24,25].
The relationship between bonding strength and the content of
catechols in the polymers was investigated using stainless steel as
the substrate and the results are illustrated in Fig. 5. Best adhesion
strength was achieved using polyoxetanes containing 15.5 mol%
catechol moiety. Although it is generally accepted that higher
catechol content does not always leads to better adhesion strength,
we noticed that the optimal catechol moiety content was obviously
lower that other artificial mussel-inspired adhesives. For instance,
although no optimal catechol content was given, for a polysiloxane-
based adhesive polymer, the polymer containing 20 mol% catechol
Fig. 4. Results of lap shear test using stainless steel as the substrate, where Cat-Pox
refer to CG-P(EMOMO84.5%-co-EPOMO15.5%).

M. Jia et al. / Polymer 55 (2014) 1160e1166
1165
Fig. 7. Lap shear strength of CG-P(EMOMO84.5%-co-EPOMO15.5%) on different
substrates.
Fig. 5. Lap shear strength of CG-P(EMOMOx-co-EPOMOy) on stainless steel as
a
function of the content of catechol.
average lap shear strength was 4.87 MPa and 3.70 MPa for stainless
steel and aluminum respectively. The adhesive also performed well
on poplar (2.69 MPa) and glass substrates (2.10 MPa). The bonding
strength for polypropylene (PP) substrates was 0.77 MPa. Porcine
skin, which is similar to human tissues, was bonded together with
an average strength of 0.41 MPa. Overall, the performance of this
mussel-inspired polymer is comparable to previously reported
mussel-inspired adhesives. For example, a synthetic polypeptide
mimic of mussel adhesive developed by Deming’s group displayed
a bonding strength of 2.8 ꢃ 0.7 MPa on steel, 4.1 ꢃ 0.7 MPa on
aluminum, 2.3 ꢃ 0.3 MPa on glass, lower than 0.1 MPa on poly-
ethylene [30]. The poly[(3,4-dihydroxystyrene)-co-styrene] adhe-
sive bonded sanded steel at 5 ꢃ 1 MPa, aluminum at 7 ꢃ 1 MPa, red
oak at 10 ꢃ 1 MPa and polytetrafluorethylene at 0.4 ꢃ 0.1 MPa [22].
Adhesion strength on porcine skin is commonly below 0.1 MPa
using PEG-based adhesives [31]. However, the comparison must be
done cautiously in view of the different testing methods used.
Although at current stage, the catechol-containing polyoxetane
we have synthesized is not water soluble so it is not applicable to
test its biocompatibility, it could be converted into a water-soluble
polymer by grafting PEG side chains onto its backbone, as reported
by Yang and coworkers [13]. That will provide us an opportunity to
test its biocompatibility. It is our next goal.
Based on these results, we examined the reason for lower
catechol content requirement to achieve better adhesive strength
of catechol-containing polyoxetanes. We notice that the catechol
might not be the only group that has coordination ability in our
polyoxetane-based adhesive, and the triazole group formed via
CuAAC could also form networks by forming triazole-metal com-
plex [26,27], which might also contributes to the enhancement of
the cohesive strength and adhesive strength. Also, the triazole
group is structurally similar to the imidazole moiety in histidine,
another important amino acid moiety in mfps that has the coor-
dination ability [28,29]. Thus we speculated that one possible
reason for lower catechol content requirement to achieve excellent
bonding strength in our case is the coordination ability of triazole
groups towards Fe3þ. To test the speculation, a polyoxetane grafted
with alkyl chains via CuAAC was synthesized (Supplementary In-
formation, Scheme S3) and tested for its bonding strength in the
presence of FeCl3. The bonding strength of catechol-free poly-
oxetanes bearing triazole groups is three-times stronger than that
of unmodified polyoxetanes, as shown in Fig. 6, which supports our
hypothesis. To the best of our knowledge, the synergy effect of
catechol and triazole groups to improve the adhesive properties of
mussel-inspired adhesives has not been reported.
We also tested the lap shear strength of CG-P(EMOMO84.5%-co-
EPOMO15.5%) on different substrates using FeCl3 as the cross-linker
(Fig.7). As expected, the adhesive showed highest bonding on metal
substrates because of the high affinity of catechols to metal. The
4. Conclusions
In conclusion, catechol-containing polyoxetane adhesive poly-
mers were synthesized as alternatives to catechol-modified PEGs.
Catechols were grafted onto polyoxetanes at various composition
ratios via Cu(I)-catalyzed click chemistry in an efficient manner.
The adhesive showed a strong adhesion to a variety of substrates
when FeCl3 was used as the cross-linker, with the maximum of
bonding strength when the molar percent of catechol was around
15.5%. Besides the catechols, the triazoles formed via click reaction
might also contribute to the adhesion. Our work demonstrated that
the polyoxetane is an adjustable platform for strong mussel-
inspired adhesive design. Although the curing method used in
the current experiments is not applicable in biomedical situations,
the polymers could be further modified to be more suitable for
biomedical use. The synthesis of a water-soluble adhesive polymer
based on polyoxetane that is more suitable for biomedical use is
currently underway in our laboratory. We believe that the
biocompatibility and versatility of the polyoxetane backbone will
eventually make it possible to be used for biomedical applications.
Fig. 6. Results of lap shear test using stainless steel as the substrate, where Pox refers
Notes
to
a polyoxetane without triazole groups, C8-Pox refers to P(EMOMO85.5%-co-
EPOMO15.5%) grafted with octyl groups via triazole moiety. Both polymers have similar
molecular weight.
The authors declare no competing financial interest.

1166
M. Jia et al. / Polymer 55 (2014) 1160e1166
[12] Zolotarskaya OY, Wagner AF, Beckta JM, Valerie K, Wynne KJ, Yang H. Mol
Acknowledgment
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The authors thanks the financial support from the “100 Talents”
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Appendix A. Supplementary data
Supplementary data related to this article can be found at http://
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