Homopolymerization and copolymerization kinetics of trimethylene carbonate bearing a methoxyethoxy side group

Article abstract of DOI:10.1002/pola.27805

The polymerization kinetics of 5-[2-{2-(2-methoxyethoxy)ethyoxy}-ethoxymethyl]-5-methyl-trimethylene carbonate (TMCM-MOE3OM) synthesized using the organocatalyst 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) were studied and compared to those with the commonly used catalyst/initiator for ring-opening polymerization of cyclic carbonates and esters, stannous 2-ethylhexanoate. Further, the utility of each of these catalysts in the copolymerization of TMCM-MOE3OM with trimethylene carbonate (TMC) and l-lactide (LLA) was examined. Regardless of conditions with either catalyst, homopolymerization of TMCM-MOE3OM yielded oligomers, having number average molecular weight less than 4000 Da. The resultant molecular weight was limited by ring-chain equilibrium as well as through monomer autopolymerization. Interestingly, autopolymerization of TMC was also achieved with DBU as the catalyst. Copolymerization with TMC using stannous 2-ethylhexanoate as the catalyst yielded random copolymers, while diblock copolymers were formed by copolymerization with LLA. With DBU as the catalyst, copolymers with LLA could not be formed, while blocky copolymers were formed with TMC. These findings should be useful in the incorporation of this monomer in the design of polymer biomaterials.

Full text of DOI:10.1002/pola.27805

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Homopolymerization and Copolymerization Kinetics of Trimethylene
Carbonate Bearing a Methoxyethoxy Side Group
Fei Chen, Brian G. Amsden
Department of Chemical Engineering and Human Mobility Research Centre, Queen’s University, Kingston, Ontario, Canada
Correspondence to: B. G. Amsden (E-mail: amsden@queensu.ca)
published online 00 Month 2015
DOI: 10.1002/pola.27805
ABSTRACT: The polymerization kinetics of 5-[2-{2-(2-methoxye-
thoxy)ethyoxy}-ethoxymethyl]-5-methyl-trimethylene carbonate
(TMCM-MOE3OM) synthesized using the organocatalyst 1,8-
diazabicyclo[5.4.0]undec-7-ene (DBU) were studied and com-
pared to those with the commonly used catalyst/initiator for
ring-opening polymerization of cyclic carbonates and esters,
stannous 2-ethylhexanoate. Further, the utility of each of these
catalysts in the copolymerization of TMCM-MOE3OM with tri-
methylene carbonate (TMC) and L-lactide (LLA) was examined.
Regardless of conditions with either catalyst, homopolymeriza-
tion of TMCM-MOE3OM yielded oligomers, having number
average molecular weight less than 4000 Da. The resultant
molecular weight was limited by ring-chain equilibrium as well
as through monomer autopolymerization. Interestingly, auto-
polymerization of TMC was also achieved with DBU as the
catalyst. Copolymerization with TMC using stannous 2-
ethylhexanoate as the catalyst yielded random copolymers,
while diblock copolymers were formed by copolymerization
with LLA. With DBU as the catalyst, copolymers with LLA could
not be formed, while blocky copolymers were formed with
TMC. These findings should be useful in the incorporation of
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this monomer in the design of polymer biomaterials.
2015
Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem.
2015, 00, 000–000
KEYWORDS: biomaterials; degree of polymerization; kinetics
(polym.); polycarbonates; ring-opening polymerization
tion of a 5,5-dimethyl-trimethylene carbonate monomer with
pendant methyoxyethoxy (MOE) groups.11 Homopolymers of
this monomer exhibited an LCST in water, which was adjust-
able by modifying the length of the MOE group. In particular,
poly(5-[2-{2-(2-methoxyethoxy)ethyoxy}-ethoxymethyl]-5-methyl-
1,3-dioxa-2-one), or poly(TMCM-MOE3OM), was soluble in
water at 25 8C but exhibited an LCST at 33 and 43 8C for
reported molecular weights of 7400 and 960 Da,
respectively.11
INTRODUCTION Hydrogels have been extensively investigated
as both drug and cell delivery vehicles for biomedical appli-
cations. This interest stems from their high water content,
which provides for control over the diffusion of drugs for
controlled release situations, and nutrients and/or immuno-
modulating proteins for cell delivery purposes,1,2 as well as
endowing them with mechanical properties that are similar
to soft tissues, thereby minimizing inflammation due to
mechanical irritation.3 Hydrogels that can be formed in situ
following minimally invasive injection are especially advanta-
geous as this implantation strategy reduces healing time and
scarring while reducing the risk of infection,4,5 and the
hydrogel formed can conformally fill the implantation site.6–8
This polymer was synthesized using the organocatalyst 1,8-
diazabicyclo[5.4.0]undec-7-ene (DBU). DBU as a catalyst has
potential advantages for the polymerization of cyclic carbo-
nates such as TMCM-MOE3OM in that polymerization can
occur at low temperatures, thereby eliminating side reactions
and decarboxylation associated with polymerization at high
temperatures, and it is easily removed from the resulting
polymer and thus potential toxicity issues are mitigated.12
For example, using DBU as a catalyst the alcohol-initiated
polymerization of trimethylene carbonate (TMC) at 50 8C
was complete in 8 h with good control over molecular
weight and weight distribution and yielded polymers with
high end group fidelity. However, the molecular weights of
the poly(TMCM-MOE3OM) obtained by Ajiro et al. using DBU
Polymer-in-water solutions that undergo a phase transition
when warmed from room temperature to body temperature
are of particular interest as in situ gelling systems because
the mild nature of the gelation process ensures cell survival
and maintenance of biotherapeutic activity.9,10 These poly-
mers are soluble in water at a given concentration and ambi-
ent temperature, and, upon warming to above a threshold
temperature referred to as the lower critical solution tem-
perature (LCST), their solubility decreases, and they form
physical gels. Recently, Ajiro et al. have reported the prepara-
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SCHEME 1 Synthesis pathway for the preparation of TMCM-MOE3OM.
as the catalyst were lower than the theoretical, suggesting
poor control over the polymerization with this catalyst.11 We
hypothesized that the reason for the apparent lack of control
over poly(TMCM-MOE3OM) molecular weight was due to the
formation of a ring-chain equilibrium during polymerization.
Ring-chain equilibrium has been reported in the polymeriza-
tion of other functionalized cyclic carbonates,13–15 with the
equilibrium molecular weight achieved dependent on the
degree and type of substitution on the TMC as well as the
catalyst/initiator system used. For example, high molecular
weight poly(2,2-dimethyl carbonate) can be obtained with
stannous 2-ethylhexanoate as the catalyst/initiator,14
whereas for the same monomer the use of a 2-stanna-1,3-
dioxacycloalkane catalyst yielded high monomer conversions
but very low molecular weights.16 Of relevance to this study,
the presence of a large (1900 Da) methoxy-poly(ethylene
glycol) substituent onto 5-methyl, 5-carboxylate TMC, caused
ring-chain equilibrium to dominate such that a high molecular
weight polymer could not be formed with DBU as a catalyst.12
More recently, a DBU and 1-(3,5-bis(trifluoromethyl)phenyl-3-
cyclohexyl-2-thiourea (TU) co-catalyst system was reported for
the ring-opening polymerization of 1000 Da methoxy-PEG sub-
stituted trimethylolpropane carbonate.17 In this latter paper,
the PEG was coupled to the monomer through a carbonate
linkage. Although a relatively low molecular weight (10 kDa)
polymer was targeted, a molecular weight of only 6.6 kDa was
achieved along with a broad dispersity of 2.1.
anhydrous dimethylformamide (DMF) were purchased from
Sigma-Aldrich, Canada, and used as received. Benzyl alcohol
and DBU were purchased from Aldrich and dried with 3 Å
molecular sieves. Tetrahydrofuran (THF) and dichlorome-
thane (DCM) for monomer synthesis and polymerization
were distilled with calcium hydride (CaH2) before use.
Monomer Synthesis
5-[2-{2-(2-Methoxyethoxy)ethyoxy}-ethoxymethyl]-5-methyl-
trimethylene carbonate (TMCM-MOE3OM) was synthesized
via a five-step process (Scheme 1) based on the protocol
described by Ajiro et al.,11 with the exception that the final
crude mixture was dissolved in DCM and extracted with
1 M HCl and saturated NaCl solution to remove the byprod-
uct imidazole salt without using silica gel chromatography.
The organic layer was collected and dried by MgSO4. A final
yield of 47% (2.4 g) of TMCM-MOE3OM was obtained after
evaporation of the DCM.
Polymerization Conditions
Homo- and copolymerizations of TMCM-MOE3OM were per-
formed using the organocatalyst DBU as well as with stan-
nous 2-ethylhexanoate. A typical polymerization procedure is
described here for TMCM-MOE3OM homopolymerization
using DBU as the catalyst. 0.206 g of TMCM-MOE3OM (0.7
mmol) was dissolved in 1 mL of anhydrous DCM with CaH2
particles and left to stir overnight. The CaH2 was removed
using a 0.2-lm nylon filter and the monomer solution was
then transferred to a flame-dried glass vial in which the
DCM was evaporated under reduced pressure. Then, 0.35-mL
anhydrous DCM under argon atmosphere was introduced to
re-dissolve the monomer. Into the monomer solution,
0.76 mg of benzyl alcohol (0.007 mmol) as initiator and
1.07 mg of DBU (0.007 mmol) were added to start the poly-
merization at room temperature for 24–48 h. At specific
time points, the reaction was stopped by adding a few drops
of acetic acid. The solvent was removed under a flow of
The utilization of poly(TMCM-MOE3OM) as a biomaterial
requires an understanding of the degree to which its degree of
homo- and copolymerization can be controlled. One of the objec-
tives of this study was therefore to ascertain whether pol-
y(TMCM-MOE3OM) with controllable molecular weight and high
end group fidelity was achievable using either DBU or stannous
2-ethylhexanoate, generally referred to as stannous octoate, as a
catalyst. A further objective was to examine the utility of each of
these catalysts in the copolymerization of TMCM-MOE3OM with
TMC and L-lactide (LLA) as a means of obtaining copolymers
with varying functionalities as polymer biomaterials.
1
argon, then directly analyzed for monomer conversion via H
NMR spectroscopy. For purification, the reaction mixture was
poured into 20 mL of cold hexane/2-propanol (9/1, v/v).
The resultant product was recovered by decantation of the
supernatant and dried under vacuum at room temperature.
EXPERIMENTAL
Triethylene glycol monomethyl ether, p-toluenesulfonyl chlo-
ride, benzaldehyde, p-toluenesulfonic acid, trimethylolethane,
2-methyoxyethyl p-toluenesulfonate, sodium hydride in oil
(20%w/w), 1,10-carbonyldiimidazole (CDI), acetic acid, and
Homo- and copolymerization of TMCM-MOE3OM with stan-
nous 2-ethylhexanoate (SnOct2) as the catalyst were carried
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synthesized materials were dissolved in chloroform-d (Fluka,
Canada) at 10 mg/mL and their chemical shifts were meas-
ured relative to the methyl proton resonance of an internal
tetramethylsilane reference. The number average molecular
weight (Mn), weight-average molecular weight (Mw), and
-
molar-mass dispersity (DM) were measured using size exclu-
sion chromatography (SEC) on a Viscotek GPCmax VE2001
Separation Module equipped with a refractive index (RI)
detector. Two porous PAS-106M columns (PolyAnalytik
SupeRes Series) were used in series. The calibration curve
based on the RI detector was constructed using narrow
molecular weight polystyrene standards ranging from 890 to
3.28 3 106 g/mol. THF at 40 8C was used as the mobile
phase at a flow rate of 1 mL/min with the polymer sample
dissolved in THF at a concentration of 5 mg/mL. The results
were analyzed and fitted in Astra v4.90.07 software (Wyatt
Technology). The number average molecular weights were
also analyzed using a Waters/Micromas MALDI micro MX in
linear ion mode using sinnapinic acid as a matrix with capa-
bility to detect mass range from 100 Da to at least 200 kDa.
FIGURE 1 Representative 1H NMR spectra of the TMCM-
MOE3OM monomer, and its homopolymer, following polymer-
ization for different reaction times using DBU as the catalyst.
The reaction conditions were as follows: monomer concentra-
tion of 2 M, monomer to initiator ratio of 200:1, monomer to
catalyst ratio of 100:1, a temperature of 25 8C, and using benzyl
alcohol as the initiator. [Color figure can be viewed in the
online issue, which is available at wileyonlinelibrary.com.]
RESULTS AND DISCUSSION
TMCM-MOE3OM Synthesis
The TMCM-MOE3OM synthesis followed the previously
reported protocol11 (Scheme 1) with a single modification.
Unlike in the previous protocol, time-consuming column
chromatography was avoided, and instead extraction with
dilute HCl (1 M) and water was used to remove the
unreacted CDI and resultant imidazole salt. The structure
and purity of TMCM-MOE3OM was confirmed by 1H NMR
(Fig. 1). The extraction proved to be efficient in removing
impurities, with the yield reaching 47%, which was higher
than the 34% reported previously.11
out by bulk melt polymerization at 130 8C. In a typical poly-
merization, 0.2 g of TMCM-MOE3OM (0.68 mmol), 0.74 mg
of benzyl alcohol (0.0068 mmol) and 0.8 mg of Sn(Oct)2
were loaded into a 10-mL glass ampoule. The ampoule was
then purged with argon twice, sealed under vacuum, and
placed in an oven at 130 8C for 24 h. After cooling, the prod-
uct was dissolved in DCM and precipitated in an excess of
hexane/2-propanol (9/1, v/v). The resultant product was
recovered by decantation of the supernatant and dried under
vacuum at room temperature.
Homopolymerization of TMCM-MOE3OM with DBU
The results of the homopolymerization using the DBU cata-
lyst are summarized in Table 1. The effect of reaction time
and monomer to initiator ratio on the monomer conversion
and final molecular weight were investigated. Figure 1 shows
representative 1H NMR spectra of the TMCM-MOE3OM
Characterization
Compositions were determined from 1H NMR spectra
obtained from a Bruker Avance 400 MHz spectrometer. The
TABLE 1 Summary of TMCM-MOE3OM Polymerization Kinetics at 25 8C Using DBU as Catalyst, a Monomer to Catalyst Ratio of
100:1, a Monomer Concentration of 2 M, and Benzyl Alcohol as the Initiator
Reaction
Time (h)
M0/I0
Monomer
Mn (Da)a
a
-
DM
Run
(mol/mol)
Conversion (%)
1
2
3
4
5
6
7
8
2
200:1
200:1
200:1
200:1
200:1
100:1
25:1
31
54
66
92
96
93
93
94
1,800
2,300
2,700
3,700
3,300
3,500
2,900
4,100
1.40
1.45
1.47
1.58
1.71
1.67
1.64
1.70
5
8
24
48
48
48
48
No I
a
Determined by SEC using THF as mobile phase calibrated with PS standard.
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FIGURE 2 Representative MALDI-TOF spectra of poly(TMCM-
MOE3OM): (A) M/I 5 100/1, Run 6 in Table 1, (B) without initia-
tor, Run 8 in Table 1.
monomer and poly(TMCM-MOE3OM) synthesized using the
DBU catalyst and benzyl alcohol as initiator, respectively, as
a function of time. After polymerization, the peaks at
d 5 4.37 ppm (Peak b) and 3.44 ppm (Peak c) corresponding
to the methylene protons near the carbonate group and eth-
ylene glycol pendant group in the monomer, respectively, dis-
appeared, while a peak at d 5 4.05–4.1 ppm appeared,
corresponding to the methylene protons near the carbonate
group in the opened ring of poly(TMCM-MOE3OM). The con-
version of the TMCM-MOE3M was calculated using,
FIGURE 4 1H NMR spectrum of P(TMCM-MOE3OM) prepared
with benzyl alcohol following purification. (Table 1, Run 6).
increasing reaction time, reaching a monomer conversion of
92%, a dispersity of 1.58 and an Mn of 3650 Da by 24 h
(Table 1). Increasing the reaction time to 48 h improved
monomer conversion to 96%, but Mn decreased slightly to
3300 Da while dispersity increased to 1.71. These molecular
weights are far below the theoretical molecular weight,
which is approximately 56 kDa, as calculated assuming every
initiator molecule initiates a single chain and all chains have
the same molecular weight. As these SEC molecular weight
results were calculated relative to poly(styrene) standards,
they were confirmed by MALDI-TOF measurements. In each
case, the SEC measurements and the MALDI-TOF measure-
ments were in good agreement (Fig. 2).
ðI4:072I4:35Þ=4
Monomer conversion5
3100%
I
4:35=21ðI4:072I4:35Þ=4
wherein I represents the integration of the peak correspond-
1
ing to the subscript H NMR ppm.
Under polymerization conditions wherein the monomer to
initiator ratio was maintained constant (Runs 1–5), mono-
-
mer conversion, molar-mass dispersity (DM), and number
average molecular weight (Mn) increased gradually with
FIGURE 3 1H NMR spectra of TMCM-MOE3OM polymerization
with different monomer to benzyl alcohol ratios (2 M, mono-
mer to catalyst ratio 5 100:1, 25 8C. DBU catalyst, reaction time:
48 h). [Color figure can be viewed in the online issue, which is
available at wileyonlinelibrary.com.]
FIGURE 5 1H NMR spectra of TMCM-MOE3OM monomer (top),
purified poly(TMCM-MOE3OM) (middle), and the poly(TMCM-
MOE3OM) mixed with DBU for 3 days (bottom). Peak assign-
ments are as shown in Figure 1. [Color figure can be viewed in
the online issue, which is available at wileyonlinelibrary.com.]
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FIGURE 6 1H NMR spectrum of poly(trimethylene carbonate)
prepared using DBU as catalyst and benzyl alcohol as the ini-
tiator (Table 2, Run 2, no purification).
SCHEME 2 Proposed mechanism for autopolymerization of
TMCM-MOE3OM in the presence of DBU.
The possibility of ring-chain equilibrium was assessed by first
purifying the oligo(TMCM-MOE3OM) by precipitation from
DCM into hexane/2-propanal (9:1) twice, followed by drying
under vacuum, then re-dissolution in anhydrous DCM contain-
ing 6.67 mg/L DBU and leaving the polymer in this solution
for 72 h at room temperature. After 72 h, the solution was
directly analyzed via 1H NMR. The 1H NMR spectra clearly
showed the appearance of monomer Peaks (a and c) in the
resulting polymer solution (Fig. 5). Moreover, the ratio of the
area of the peak corresponding to the pendant methyl group
in the repeating unit (d 5 1.02 ppm) to that in the terminal
group (d 5 0.89 ppm) clearly decreased, indicative of a
decrease in number average molecular weight.
Control over molecular weight was then attempted by
adjusting the monomer to initiator ratio. However, decreas-
ing the monomer to initiator ratio while maintaining a reac-
tion time of 48 h resulted in no significant change in the
obtainable Mn, as measured by SEC before any purification.
The Mn remained between roughly 3000–4200 Da (Table 1,
1
Runs 5–7). Further, there were no differences in the H NMR
spectra of the resultant oligomers (Fig. 3).
Following purification, the calculated Mn from the 1H NMR
spectra based on integration of the peaks corresponding to
the phenyl group of the initiator (benzyl alcohol), assuming
it was present at one terminus of the oligomer chain, yielded
much larger values than the theoretical feed ratio. This find-
ing indicated a loss of benzyl alcohol in the purification pro-
cess. For example, the resulting monomer to initiator ratio
for Run 6 was 322:1 (Fig. 4) whereas the starting ratio was
100:1. These results suggested that the degree of polymer-
ization of TMCM-MOE3OM was not controlled by the ratio of
monomer to initiator, and that poor end group fidelity was
achieved. As noted in the above experimental section, water
was absent during the polymerizations, and so initiation by
adventitial water did not affect the polymerization. Both find-
ings, therefore, may have resulted from either backbiting
during the polymerization leading to ring-chain equilibrium,
or from monomer autopolymerization.
To test whether the TMCM-MOE3OM was capable of autopoly-
merization, the polymerization reaction was run in the absence
of benzyl alcohol. An oligomer with high monomer conversion
(94%), but only slightly higher Mn (4100 Da) (Table 1, Run 8)
was obtained, demonstrating that TMCM-MOE3OM is capable
of autopolymerization in the presence of DBU. A possible
mechanism for the autopolymerization, adapted from a mecha-
nism determined for the DBU-catalyzed ring-opening polymer-
ization of 5,5-(bicyclo[2.2.1]hept-2-en-5,5-ylidene)-1,3-dioxan-
2-one,18 is given in Scheme 2. The process is initiated by
a reaction between DBU and TMCM-MOE3OM, forming an
alkoxide anion. Once the alkoxide anion forms it serves as the
initiator that can attack the carbonyl group of remaining
TABLE 2 Summary of TMC Polymerization Kinetics Using DBU as Catalyst and Benzyl Alcohol as the Initiator
Monomer
Run
Time (h)
M0:I0 (mol/mol)
Conversion (%)
Mn (Theor) (Da)
Mn (1H NMR) (Da)
a
1
2
3
4
24
24
24
72
17:1
20:1
No I
200:1
94
91
19
80
1,700
1,960
–
1,740
2,250
1,380
16,800
16,400
a
Polymerizations were done at 25 8C, using a monomer to catalyst ratio
Mo and Io are the initial monomer and initiator concentrations,
of 100:1 and a monomer concentration of 2 M.
respectively.
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TABLE 3 Polymerization of TMCM-MOE3OM in Different Sol-
Homopolymerization of TMCM-MOE3OM with Sn(Oct)2
Bulk melt polymerizations of TMCM-MOE3OM with Sn(Oct)2
initiated with benzyl alcohol were carried out at 130 8C. A
similar trend was observed as for the DBU-catalyzed poly-
merizations; the Mn first increased with increasing monomer
conversion then reached a maximum Mn of about 3300 Da
(Table 4). High monomer conversion was obtained, but as
vents at Room Temperature
a
M0:I0
Monomer
Mn
a
-
DM
Solvent
(mol/mol)
Conversion (%)
(Da)
THF
100:1
100:1
100:1
100:0
68
36
95
94
2,100
1,650
3,040
3,450
1.51
1.30
1.44
1.40
DMF
DCM
DCM
polymerization proceeded,
a higher dispersity resulted.
These results are again attributed to backbiting reactions
that would predominate in the later stages of polymerization
under high temperature, leading to ring-chain equilibrium.
In each case, the reaction time was 48 h, the monomer to catalyst ratio
was 100:1, and the monomer concentration was 2 M.
a
Thus, it is not possible to obtain a homopolymer of TMCM-
MOE3OM with a molecular weight greater than about 4000
Da with a low dispersity using either of these common cata-
lysts. These results are in contrast to those of Ajiro et al.,
who reported that Mn could be controlled by the monomer
Determined by SEC with THF as the mobile phase and calibrated with
PS standards.
TMCM-MOE3OM, forming the polymer. Thus, it is likely that
both backbiting and monomer autopolymerization of TMCM-
MOE3OM limit the maximum molecular weight that can be
obtained when using DBU as the catalyst.
As a control, TMC was polymerized using DBU as catalyst
and benzyl alcohol as the initiator under the same reaction
conditions as TMCM-MOE3OM. The monomer conversion
and final Mn of PTMC was monitored by 1H NMR (Fig. 6).
Compared to TMCM-MOE3OM, the final molecular weights of
PTMC were close to the theoretical values and the molecular
weight was controlled to a high degree by changing the
monomer to initiator ratio (Table 2). Notably, TMC was also
capable of autopolymerization (Table 2, Run 3), but the poly-
merization proceeded more slowly than in the presence of
the benzyl alcohol initiator.
Finally, a series of polymerizations of TMCM-MOE3OM was
run with different solvents at the same reaction conditons.
With or without benzyl alcohol initiator, high monomer con-
versions were obtained in DCM (ꢀ94%), while low monomer
conversion was observed in THF and DMF (Table 3). These
results are probably due to hydrogen bonding betweeen DBU
and THF or DMF, which inhibited the polymerization.19 The
polymerization behavior in different solvents also implies that
through hydrogen bonding DBU was able to activate the
monomer and this activation was essential for polymerization.
TABLE 4 Summary of TMCM-MOE3OM Polymerization Kinetics
with Sn(Oct)2 as Catalyst, Benzyl Alcohol as Initiator, and Bulk
Polymerization at 130 8C
Monomer
a
a
-
DM
Time (h)
Conversion (%)
Mn (Da)
1
20
31
38
54
71
1,630
2,000
2,280
2,700
3,300
1.14
1.24
1.26
1.36
1.51
3
5
8
24
FIGURE 7 Monomer conversion during copolymerization of
TMC and TMCM-MOE3OM using (A) DBU and (B) Sn(Oct)2 as
catalyst.
a
Determined by SEC using THF as the mobile phase calibrated with PS
standard.
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TABLE 5 Summary of Copolymerization Results of TMC with TMCM-MOE3OM
a
b
TMCM:TMC
(mol/mol)
Monomer
Temperature
M0:I0
M0:C0
Copolymer
TMCM:TMC
Mn
b
-
Run
Concentration (M)
(8C)
(mol/mol)
(mol/mol)
(Da)
DM
1
2
3
4
50:50
33:67
90:10
50:50
2
R.T
R.T
R.T
130
300:1
100:1
100:1
200:1
300:1
100:1
100:1
300:1
54:46
29:71
92:8
4,400
2,200
3,100
2,700
2.08
1.28
1.34
1.64
1
2
bulk
50:50
b
Runs 1–3 were catalyzed with DBU, 4 with Sn(Oct)2. All reactions were
for 48 h.
Determined by SEC using THF as the mobile phase calibrated with
PS standard.
a
Mo:Co represents the initial monomer to catalyst molar ratio.
TABLE 6 Summary of LLA Polymerization Kinetics by DBU
TMC-MOE1OM when measured using SEC with different
polymer standards.20 Our SEC molecular weight results are
consistent, however, with those we have obtained from
mass spectrometry.
Monomer
Concentration
(M)
Monomer
Conversion
(%)
Reaction
Time (h)
Run
Copolymerization of TMC and LLA with TMCM-MOE3OM
Catalyzed by DBU and Sn(Oct)2
1
2
3
4
5
6
7
0.7
0.7
0.7
0.7
0.7
0.7
0.7
0.5
1
78
89
95
97
98
99
99
TMC and LLA are both widely used monomers for making
biodegradable polymers. Copolymerization of TMCM-
MOE3OM with these monomers is potentially of interest as
doing so might introduce thermoresponsive properties and
increase the hydrophilicity of these polymers, and therefore
serve as a means of adjusting their degradation via hydroly-
sis. The copolymerization of TMCM-MOE3OM with each of
these monomers was therefore investigated, again using DBU
and Sn(Oct)2 as catalysts.
2
5
8
24
48
to initiator ratio, although lower than theoretical molecular
weight was obtained, using DBU as the catalyst and benzyl
alcohol as the initiator, under the same reaction conditions
of solvent and temperature we have used.11 Ajiro et al. also
reported a maximum Mn of 11 kDa in contrast to the
approximately 4 kDa obtained in this study, along with a
dispersity of 1.4. These differences may be attributable to
the fact that Ajiro et al. first purified their homopolymers
before measuring the molecular weight. The purification
step likely removed the low molecular weight fraction, thus
increasing the average molecular weight and reducing the
dispersity. Further, Ajiro et al. utilized PMMA as standards
in their universal calibration for their SEC measurements,
whereas we have used polystyrene standards. Ajiro et al.
also have reported different molecular weights for
The copolymerization of TMC with TMCM-MOE3OM using
Sn(Oct)2 but not DBU yielded random copolymers (Fig. 7). In
each case, the final copolymer composition was close to the tar-
get feed ratio, but the resultant Mn was still lower than the theo-
retical value (Table 5). This latter result indicates that ring-chain
equilibrium still occurs in the late stage of copolymerization.
The homopolymerization of LLA was first examined as a
basis to study the reaction kinetics profile of the copolymer-
ization of TMCM-MOE3OM with LLA. Compared to TMC and
TMCM-MOE3OM, LLA polymerized much faster when cata-
lyzed by DBU under the same reaction conditions. At rela-
tively low monomer concentration (0.7 M), the monomer
conversion reached to greater than 95% within 2 h (Table 6)
TABLE 7 Summary of Copolymerization of LLA with TMCM-MOE3OM
Monomer
Concentration
(M)
M0:I0
(mol/
mol)
M0:C0
(mol/
mol)
TMCM
Conversion
(%)
LLA
LLA:TMCM
(mol/mol)
Reaction
Time (h)
Temperature
Conversion
(%)
Run
(8C)
1
2
3
50:50
67:33
50:50
2
48
48
48
200:1
100:1
200:1
100:1
100:1
300:1
R.T.
R.T.
130
0
95
91
97
1
0
Bulk
50
Runs 1 and 2 were with DBU, 3 was with Sn(Oct)2.
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Interestingly, the maximum molecular weight that was
obtained with DBU was independent of the monomer to
initiator ratio, which suggests that it can serve as both an
initiator and a catalyst. Copolymers could be obtained by
copolymerizing TMCM-MOE3OM with TMC with either DBU
or Sn(Oct)2 as catalyst, but only with Sn(Oct)2 as the cata-
lyst when TMCM-MOE3OM was copolymerized with LLA,
albeit with the formation of a diblock copolymer as the LLA
is consumed rapidly while the conversion of TMCM-
MOE3OM is far slower. The failure to obtain high molecular
weight copolymers of TMCM-MOE3OM and LLA using DBU
as the catalyst was due to the large differences in the reac-
tivity of each monomer; with LLA reacting much faster than
TMCM-MOE3OM. This study indicates that catalyst selection
for the polymerization of substituted TMCs must be care-
fully investigated to obtain polymers with controlled molec-
ular weights and end group fidelity.
FIGURE 8 Monomer conversion during copolymerization of
LLA and TMCM-MOE3OM using Sn(Oct)2 as catalyst.
ACKNOWLEDGMENTS
Funding for this project was provided by the Natural Sciences
and Engineering Research Council of Canada through a Discov-
ery Grant and the CREATE Biointerfaces Training Program,
CREATE Training Program in Bone and Joint Health
Technologies.
and a high molecular weight product (29.8 kDa) was
obtained. These findings are in agreement with those of
others for this polymerization system.21–23
As shown in Table 7, LLA did not effectively copolymerize
with TMCM-MOE3OM when DBU was used as the catalyst.
With targeted 50/50 and 67/33 molar feed ratios (LLA/
TMCM-MOE3OM), only LLA was predominantly polymerized
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