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grafting was also confirmed by the FTIR spectrum with bands for
NeH stretching at 3400 cmꢁ1, C]N stretching of the triazole ring at
1626 cmꢁ1, and C]O stretching of the polyester polymer and ester
bond of the pendent PABA, at 1700 and 1725 cmꢁ1, respectively
(Fig. 4B).
degradation peak appeared at around 335 ꢀC followed by a small
degradation peak, a moderate degradation peak at 370 ꢀC, and by
a small broad degradation peak starting at 460 ꢀC. In contrast, P
(aN33CL-ran-3
CL) showed a small degradation peak at 270 ꢀC
attributed to the initial rupture of azide (NeN2) [36,37] and an
extensive weight loss was found at 350 ꢀC followed by moderate
degradation peaks at 400 ꢀC. In case of the grafted copolymers, the
3.5.3. Grafting of phthaloyltryptophan by means of 3(2-N-
phthalimido-2-(prop-2-ynyl acetayl)ethyl)indole (3) along the
thermal degradation pattern of P((Nico-g-
as that of P( 33CL-ran- CL). The thermogram of P((PABA-g-
ran- CL exhibited only two main degradation peaks, an extensive at
320 ꢀC and a moderate one at 370 ꢀC. the latter one being stronger
than that of P( 33CL-ran- CL) at comparable temperature. For P
((Phatryp-g- CL)-ran- CL, the extensive degradation started at
3CL)-ran-3CL was the same
P(
3CL) backbone
aN
3
3CL)-
The phthaloyltryptophan by means of 3(2-N-phthalimido-2-
3
(prop-2-ynyl acetayl)ethyl)indole (3) was used as a large and bulky
representative to investigate the limitation of grafting onto P( CL)
backbone through click reaction. However, this compound could be
completely attached along P( CL) after 4 h using the same condi-
3
aN
3
3
3
3
370 ꢀC while the second degradation step was shifted to about
550 ꢀC. According to these results all copolymers and grafted
copolymers are thermally stable to about 200 ꢀC in dried state.
From these combined results it can be concluded that the
thermal properties of the grafted copolymers are largely governed
by the type of grafted bioactive model compound at the polymer
backbone. The larger bioactive molecule altered the thermal
properties stronger than the smaller type. In addition, an increasing
amount of grafted model compound changed the structure of the
grafted copolymer to the amorphous form.
tions as for engrafting of nicotinic acid. The 1H NMR spectrum
showed the characteristic signal of triazole proton (Fig. 5C),
together with the typical set of signal groups of phthaloyl-
tryptophan between 6.9 and 8.0 ppm coinciding with the absence
of methyne proton signal of the former azide (CHeN3) at 3.85 ppm.
The FTIR spectrum (Fig. 4C) also confirmed the successful click
reaction by means of the NeH stretching peak at 3400 cmꢁ1 and
the two C]O stretching bands at 1710 and 1774 cmꢁ1 of the
phthaloyl group.
The molecular weight of the grafted copolymer calculated from
1H NMR and GPC gradually increased according to the increasing
number of grafted units. Its distribution was narrower than that of P
4. Conclusion
(aN33CL-ran-3CL) (Table 2). Unlike to the grafted PABA, DBU did not
Three bioactive model compounds (nicotinic acid, PABA, and
phthaloyltryptophan) were successively grafted onto the P(3CL)
cause any severe chain degradation according to GPC results, since
the indole ring proton is less acidic and sterically hindered by the
phenyl ring and hardly converted to the nucleophilic species.
However, this steric effect did not disturb the completeness of
grafting reaction. In contrast, Riva et al. [12] were only able to
backbone through copper-catalyzed Huisgen’s 1,3-dipolar cyclo-
addition or the “click reaction”. Under very mild conditions, the
reaction could preserve the length of the polymer backbone.
However, reflecting the type of the model compound containing
either a protic or a nucleophilic group the type of base used in the
reaction is the critical issue since in combination they may
possibly lead to intra- or intermolecular transesterification and
thus induce the polymer chain degradation. Several types of
model compounds could be grafted along the polymer backbone
engraft a linear macromolecule, PEO, on the P(3CL) backbone to just
40% probably due to stronger sterical interaction between two
macromolecules than in the case of phthaloyltryptophan with
complete of engrafting.
3.6. Thermal properties of the copolymers and grafted copolymers
by varying amounts of the
aCl3CL units on the backbone. The
molecular size of the compounds modified the physicochemical
and thermal properties of the grafted copolymers compared to
the copolymer. The grafted copolymers could be identified by
FTIR, NMR, and GPC analysis. Derived from this accomplishment,
various kinds of drugs including cytotoxic drugs, peptides and
proteins, could probably be grafted along the polymer backbone
in ongoing research in order to modify the physicochemical
properties of drugs and also of macromolecular carriers to be
more suitable for drug delivery applications. The conjugation of
these grafted copolymers with other polymeric carriers such as
PEG and nanoparticles prepared from these grafted copolymers
are being under investigation to gain more efficient drug delivery
systems.
The thermal properties of the grafted copolymers were
measured with DSC and TGA and compared to those of the original
P(aN33CL-ran-3CL) and P(aCl3CL-ran-3CL). The glass transition
temperature Tg and melting temperature Tm values characterizing
the polymorphic properties of the copolymers are summarized in
Table 3 indicating their semisolid form. In case of an undetectable
Tms the polymer is amorphous. In some cases of destructible
polymers Tgs cannot be detected. The Tgs values of P(
aN33CL-ran-
3
CL) and of P( Cl CL-ran- CL) tend to increase with increasing
a
3
3
molar ratio of substituted units, meanwhile their Tms tend to
decline.
The increase of grafted units in the copolymer resulted in the
change of the polymorphic form from semi-crystalline to amorphous,
altering their thermal properties. At 10% grafting of nicotinic acid and
PABA, respectively, the Tm was observablewhile at higher ratios itwas
undetectable. In case of grafting phthaloyltryptophan, Tm was not
detected at all grafting ratios. Thus, conversion from polymorphic to
amorphous form of these kinds of copolymers goes with their size
and/or with the increasing number of substituted units.
Acknowledgements
Financial support from the Thailand Research Fund (TRF)
through the Royal Golden Jubilee Ph.D. Program (Grant No. PHD/
0189/2547) and the Thai Research Fund and Commission of Higher
Education, Thailand for the research funding (RMU5180019) is
gratefully acknowledged. The authors are very pleased to
acknowledge the National Metal and Materials Technology Center
(MTEC, Pathumthani, Thailand) for GPC experiment. The authors
thank Professor Dr. AW Frahm, Department of Pharmaceutical and
Medicinal Chemistry, Institute of Pharmaceutical Sciences, Freiburg
University, Freiburg, Germany, for language and writing approval.
To investigate the thermal degradation of the copolymers in
comparison with the grafted copolymers, TGA profiles were recor-
ded. Fig. 7 illustrates TGA profiles of copolymers and grafted copol-
ymers at 20% molar ratio. The thermograms of P(
and P( Cl CL-ran- CL) show different thermal degradation pattern.
Although, the starting degrading temperature of both copolymers at
around 200 ꢀC was similar, in case of P(
Cl CL-ran- CL) the main
aN33CL-ran-3CL)
a
3
3
a
3
3