Direct synthesis of terminally "Clickable" linear and hyperbranched polyesters

Article abstract of DOI:10.1002/pola.24108

1,3-Dipolar cycloaddition of an organic azide and an acetylenic unit, often referred to as the "click reaction", has become an important ligation tool both in the context of materials chemistry and biology. Thus, development of simple approaches to directly generate polymers that bear either an azide or an alkyne unit has gained considerable importance. We describe here a straightforward approach to directly prepare linear and hyperbranched polyesters that carry terminal propargyl groups. To achieve the former, we designed an ABtype monomer that carries a hydroxyl group and a propargyl ester, which upon self-condensation under standard transesterification conditions yielded a polyester that carries a single propargyl group at one of its chain-ends. Similarly, an AB₂ type monomer that carries one hydroxyl group and two propargyl ester groups, when polymerized under the same conditions yielded a hyperbranched polymer with numerous "clickable" propargyl groups at its molecular periphery. These propargyl groups can be readily clicked with different organic azides, such as benzyl azide, ω-azido heptaethyleneglycol monomethylether or 9-azidomethyl anthracene. When an anthracene chromophore is clicked, the molecular weight of the linear polyester could be readily estimated using both UV-visible and fluorescence spectroscopic measurements. Furthermore, the reactive propargyl end group could also provide an opportunity to prepare block copolymers in the case of linear polyesters and to generate nanodimensional scaffolds to anchor a variety of functional units, in the case of the hyperbranched polymer.

Full text of DOI:10.1002/pola.24108

Direct Synthesis of Terminally ‘‘Clickable’’ Linear and Hyperbranched
Polyesters
S. G. RAMKUMAR, K. A. AMALA ROSE, S. RAMAKRISHNAN
Department of Inorganic and Physical Chemistry, Indian Institute of Science, Bangalore 560012, Karnataka, India
Received 9 March 2010; accepted 27 April 2010
DOI: 10.1002/pola.24108
Published online in Wiley InterScience (www.interscience.wiley.com).
ABSTRACT: 1,3-Dipolar cycloaddition of an organic azide and an
acetylenic unit, often referred to as the ‘‘click reaction’’, has
become an important ligation tool both in the context of mate-
rials chemistry and biology. Thus, development of simple
approaches to directly generate polymers that bear either an
azide or an alkyne unit has gained considerable importance.
We describe here a straightforward approach to directly pre-
pare linear and hyperbranched polyesters that carry terminal
propargyl groups. To achieve the former, we designed an AB-
type monomer that carries a hydroxyl group and a propargyl
ester, which upon self-condensation under standard transester-
ification conditions yielded a polyester that carries a single pro-
pargyl group at one of its chain-ends. Similarly, an AB2 type
monomer that carries one hydroxyl group and two propargyl
ester groups, when polymerized under the same conditions
yielded a hyperbranched polymer with numerous ‘‘clickable’’
propargyl groups at its molecular periphery. These propargyl
groups can be readily clicked with different organic azides,
such as benzyl azide, x-azido heptaethyleneglycol monomethy-
lether or 9-azidomethyl anthracene. When an anthracene chro-
mophore is clicked, the molecular weight of the linear
polyester could be readily estimated using both UV–visible and
fluorescence spectroscopic measurements. Furthermore, the
reactive propargyl end group could also provide an opportu-
nity to prepare block copolymers in the case of linear polyest-
ers and to generate nanodimensional scaffolds to anchor a
variety of functional units, in the case of the hyperbranched
C
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polymer.
2010 Wiley Periodicals, Inc. J Polym Sci Part A:
Polym Chem 48: 3200–3208, 2010
KEYWORDS: functionalization of polymers; hyperbranched; pol-
ycondensation; polyesters
INTRODUCTION
have undergone cyclization. The use of single monomer self-
condensation polymerizations gained prominence after the
advent of hyperbranched polymers, which are typically pre-
pared by the self-condensation of an AB2 type monomer to
generate highly branched polymers that carry numerous
B-type terminal groups;5 postfunctionalization of which results
in a variety of interesting systems, such as core-shell struc-
tures.6 A particularly noteworthy elaboration of the AB-type
self-condensation is the study by Yokozawa and coworkers7
who demonstrated pseudo-chain growth condensation poly-
merizations using suitably designed AB monomers.
Chain-end functionalization of polymers is important for a
variety of reasons, such as for the preparation of block
copolymers, macromonomers and graft copolymers, and for
surface grafting.1,2 Furthermore, incorporation of functional
units, such as a chromophore, at the polymer chain-ends per-
mits one to probe solution structure and dynamics of the
chains.3 In the case of dendrimers and hyperbranched poly-
mers, selective incorporation of suitable chromophores also
opens up the possibility of creating interesting light seques-
tering systems.4 Chain-end functionalization of polymers is
generally achieved using chain polymerization processes, in
particular using those that exhibit ‘‘living’’ characteristics.1
Step-growth polymerizations, on the other hand, are not par-
ticularly useful in this context because majority of them uti-
lize an A-A þ B-B type polycondensation, wherein all the
chain-ends are not identically functionalized; some would be
symmetric and carry two A (or B) type functionalities
whereas others could carry one each of A and B type groups.
The self-condensation of an AB-type monomer, however,
would always result in chains that carry an A-group at one
chain end and a B-group at the other, barring those that
Among the various postpolymerization functionalization
approaches, the Cu-catalyzed Huisgen type 1,3-dipolar cycload-
dition,8 popularly referred to as the ‘‘click reaction’’, has gained
enormous attention because it can be carried out under very
mild reaction conditions and in a nearly quantitative fashion.9
Several examples of the use of click reaction in the context of
block copolymers,10 surface grafting,11 dendrimers and hyper-
branched polymers,12 peptidomimetics,13 bioconjugation,14 etc.,
have been described in the literature. Thus, development of pol-
ymerizations that permits the direct incorporation of clickable
functionality either at one or both chain-ends of linear polymers,
Additional Supporting Information may be found in the online version of this article.
K. A. Amala Rose is a MSc Project student from M.G. University, Kerala, India
Correspondence to: S. Ramakrishnan (E-mail: raman@ipc.iisc.ernet.in)
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Journal of Polymer Science: Part A: Polymer Chemistry, Vol. 48, 3200–3208 (2010) 2010 Wiley Periodicals, Inc.
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and polymers are given in the Supplementary Information.
UV-Vis measurements were carried out using a Cary 300-Bio
spectrophotometer and fluorescence spectra were recorded
using a Jobin Yvon Fluorolog 3 instrument. DSC measurements
were carried out on a DSC-Q100 –TA instrument. Gel permeation
chromatography (GPC) was carried out with a Viscotek TDA
model 300 system, coupled refractive-index, differential viscometer,
and light scattering detectors in series. The separation was
achieved using two mixed-bed PLgel columns (5 lm, mixed C)
SCHEME 1 Synthesis of linear polyester (LP) and hyper-
branched polyester (HP) from linear monomer (LM) and hyper-
branched monomer (HBM), respectively, under melt-
transesterification conditions.
ꢀ
maintained at 30 C, with tetrahydrofuran (THF) as the eluent.
The molecular weights were determined with a conventional
calibration curve constructed with polystyrene standards.
Synthesis of Monomers
Compound 1
or at the numerous chain-ends of hyperbranched polymers
would be of immense value. Recently, we described a single-step
preparation of hyperbranched polyethers, that carry numerous
propargyl groups at their chain-ends, by the melt self-condensa-
tion of an AB2 monomer having two benzyl propargyl ethers
groups and one alcohol group;15 the polymerization occurred via
a novel transetherification process.16 In this melt-condensation
process, which was carried out at around 150 ꢀC, propargyl alco-
hol is removed as a condensate, which in turn drives the equilib-
rium toward polymer formation. By analogy, therefore, one
should be able to carry out melt-transesterification polymeriza-
tions by a similar self-condensation of suitably designed mono-
mers that carry an alcohol and propargyl ester functionality.
Transesterification, being a commercially important process, the
adaptation of this approach in the context of polyesters would
be important. Earlier work by Du Prez and coworkers17 demon-
strated the stability of the propargyl group under the high tem-
perature conditions used for polyester formation, suggesting
that our proposed strategy could be feasible. Other significant
reports of pendant-clickable polyesters include clickable poly-
caprolactones by Emrick18 and clickable polyglycolides by
Baker.19 In this article, we describe the design of two monomers
on the basis on 4-hydroxybenzoic acid and 5-hydroxyisophthalic
acid, which upon polymerization directly yielded a linear polyes-
ter carrying a single propargyl ester group at one of their chain-
ends or a hyperbranched polyester that bear numerous periph-
eral propargyl units, respectively, as depicted in Scheme 1. Fur-
ther, we show that these propargyl groups can be readily
‘‘clicked’’ with different organic azides to yield nearly quantita-
tively end-functionalized polymers.
4-Hydroxy benzoic acid (10 g) and 150 mL of dry methanol
were taken in a 250 mL round bottom flask fitted with a
reflux condenser and a guard tube. 5 mL concentrated sul-
phuric acid was added as catalyst and the contents were
refluxed for 12 h. The reaction mixture was cooled and
excess methanol was removed using a rotary evaporator. The
residue obtained was dissolved in chloroform and washed
thoroughly with 10% sodium bicarbonate solution. The or-
ganic layer was dried over anhydrous Na2SO4 and cꢀoncen-
trated to give the product in 97% yield. mp: 122–124 C.
1H NMR (CDCl3, d ppm): 7.973–7.951 (d, 2H, ArAmAOH),
6.887–6.865 (d, 2H, ArAoAOH), 5.8 (s, 1H, ArAOH), 3.896
(s, 3H, COOCH3)
Compound 2
Methyl, 4-hydroxy benzoate (2.0 g, 13.1 mmol) was taken in
25 mL dry DMF, along with potassium carbonate (5.4 g, 39.4
mmol) and a catalytic amount of KI. 6-Bromohexanol (3.6,
19.8 mmol) was added to it and the contents were stirred at
ꢀ
90 C for 48 h. The reaction mixture was concentrated under
reduced pressure, poured into ice-cold water and extracted
thrice with ethyl acetate (3ꢁ 20 mL). The combined organic
layer was dried over anhydrous Na2SO4 and concentrated to
obtain a white solid in 86% yield.
1H NMR (CDCl3, d ppm): 7.990–7.968 (d, 2H, ArAmAOH), 6.911–
6.889 (d, 2H, ArAoAOH), 4.027–3.994 (t, 2H, ArAOCH2), 3.883
(s, 3H, COOCH3), 3.682–3.654 (t, 2H, ACH2CH2OH), 2.050 (s, 1H,
OH), 1.839–1.802 (t, 2H, ArAOCH2CH2A), 1.802–1.685 (t, 2H,
ACH2CH2OH), 1.512–1.432 (m, 4H, rest of aliphatic protons).
EXPERIMENTAL
Compound 3
Compound 2 (2.0 g, 7.9 mmol) was dissolved in 25 mL
methanol and stirred with potassium hydroxide (1.5 g, 27.7
mmol) at 50 ꢀC for 12 h. Subsequently, methanol was
removed using a rotary evaporator and the residue was dis-
solved in water and acidified with dilute HCl to give a white
precipitate, which was washed thoroughly with distilled
Materials and Methods
4-Hydroxy benzoic acid, 1,6-hexanediol, 5-hydroxy isophthalic
acid, propargyl alcohol, dicyclohexyl carbodimide (DCC), N,N-di-
methyl aminopyridine (DMAP), 9-formyl anthracene, sodium
borohydride, and copper bromide were procured from Sigma-
Aldrich chemical company. Aqueous HBr (48%), copper
sulfate pentahydrate, sodium ascorbate, and triphenylphos-
phine were procured from Spectrochem Pvt. Ltd. Common or-
ganic solvents were locally procured and distilled before use.
1H NMR spectra were recorded on a 400 MHz Bruker spec-
trometer using CDCl3 as solvent unless otherwise mentioned
and TMS as a reference. 13C NMR spectra of the monomers
ꢀ
water to afford the product in 85% yield. mp: 134–136 C.
1H NMR (CD3OD, d ppm): 7.955–7.933 (d, 2H, ArAmAOH),
6.965–6.943 (d, 2H, ArAoAOH), 4.055–4.024 (t, 3H,
ArAOCH2A), 3.572–3.539 (t, 2H, ACH2CH2OH), 1.882–1.787
(t, 2H, ArAOCH2CH2A), 1.583–1.431 (m, 6H, rest of aliphatic
protons).
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JOURNAL OF POLYMER SCIENCE: PART A: POLYMER CHEMISTRY DOI 10.1002/POLA
Compound 4
The contents were cooled and methanol was completely
removed at rotary evaporator. The residue was dissolved in
water and acidified with dilute HCl. The precipitated com-
pound was extracted with ethyl acetate (4ꢁ 20 mL) and the
combined organic layer was dried over anhydrous Na2SO4
and concentrated to obtain the product as white powder.
Compound 3 (2.0 g, 8.4 mmol) was taken in 15 mL of dry
dichloromethane (DCM) along with 1 mL of dry DMF. Pro-
pargyl alcohol (2.3 g, 41.1 mmol) and DMAP (10 mol %)
were added, the contents were cooled in an ice-water bath
and stirred for 1 h under nitrogen atmosphere. DCC (5.2 g,
25.1 mmol) taken in 15 mL of dry DCM was slowly added
using a dropping funnel. The contents were allowed to grad-
ually attain room temperature and stirred for 12 h. The pre-
cipitate formed was filtered and the supernatant was con-
centrated. The concentrate was dissolved in diethylether and
filtered again to remove residual traces of the urea by-prod-
uct. The organic layer was washed thrice with 10% aqueous
bicarbonate solution, dried over anhydrous ꢀNa2SO4, and con-
centrated. The residue was distilled at 220 C under reduced
ꢀ
Overall yield from previous step: 80%. mp: 177–180 C.
1H NMR (CD3OD, d ppm): 8.218 (s, 1H, ArAH pAOH), 7.730
(s, 2H, ArAH, oAOH), 4.092–4.060 (t, 2H, ArAOCH2A),
3.583–3.551 (t, 2H, ACH2CH2OH), 1.854–1.818 (t, 2H,
ArAOCH2CH2A), 1.615–1.451 (m, 6H, rest of aliphatic
protons).
Compound 8
ꢀ
pressure in Kugelrohr apparatus. Yield: 86%. mp: 59 C.
7 (3.0 g, 10.6 mmol) was taken in dry DCM with 1 mL of
dry DMF. Propargyl alcohol (3.6 g, 63.8 mmol) and DMAP
(20 mol %) were added; the contents were cooled in an ice-
water bath and stirred for 1 h under dry nitrogen atmos-
phere. DCC (6.5 g, 31.6 mmol) in 15 mL of dry DCM was
slowly added drop-wise and the contents were allowed to
gradually attain room temperature and further stirred for 12
h. The precipitate formed was filtered and the supernatant
was concentrated. The concentrate was dissolved in diethyl
ether and filtered again to remove residual traces of the
urea. The organic layer was washed thrice with 10% aque-
ous bicarbonate solution, concentrated and the residue was
purified on a basic alumina column using chloroform as elu-
ent to afford the product in 65% yield as a liquid.
1H NMR (CDCl3, d ppm): 8.024–8.002 (d, 2H, ArAmAOH),
6.921–6.899 (d, 2H, ArAoAOH), 4.899–4.893 (d,
2H,COOCH2CCH), 4.021–4.018 (t, 2H, ArAOCH2A), 3.576–
3.471 (t, 2H, ACH2CH2OH), 2.513–2.50 (t, 1H,COOCH2CCH),
2.052 (s, 1H, ACH2CH2OH), 1.837–1.807 (t, 2H,
ArAOCH2CH2A), 1.635–1.609 (t, 2H, ACH2CH2OH), 1.495–
1.446 (m, 4H, rest of aliphatic protons).
Compund 5
5-Hydroxy isophthalic acid (10 g) and 150 mL of dry metha-
nol were taken in a 250 mL round bottom flask fitted with
reflux condenser and guard tube. Concentrated sulphuric
acid (5 mL) was added as catalyst and the contents were
refluxed for 12 h. The reaction mixture was cooled and
excess methanol was removed using a rotary evaporator. The
residue was dissolved in chloroform and washed thoroughly
with 10% aqueous sodium bicarbonate solution. The organic
layer was dried over anhydrous Na2SO4 andꢀconcentrated to
afford the product. Yield: 80% and mp: 164 C
1H NMR (CDCl3, d ppm): 8.317 (s, 1H, ArAH pAOH), 7.780
(s, 2H, ArAH, oAOH), 4.950–4.944 (d, 2H,COOCH2CCH),
4.070–4.038 (t, 2H, ArAOCH2A), 3.689–3.657 (t, 2H,
ACH2CH2OH), 2.552–2.541 (t, 1H,COOCH2CCH), 1.852–1.835
(t, 2H, ArAOCH2CH2A), 1.635–1.430 (m, 6H, rest of aliphatic
protons).
1H NMR (CDCl3, d ppm): 8.265 (s, 1H, ArAH pAOH), 7.735 (s,
2H, ArAH, oAOH), 5.666 (s, 1H, ArAOH), 3.945 (s, 6H, COOCH3).
The detailed synthetic procedures for the various organic
azides used for the ‘click’ reactions are provided in the Sup-
porting Information.
Compound 6
Compound 5 (3.0 g, 14.3 mmol) was taken in dry DMF, along
with potassium carbonate (11.8 g, 85.6 mmol) and a cata-
lytic amount of KI. 6-Bromohexanol (7.8 g, 42.8 mmol) was
added to it; the contents were purged with dry nitrogen and
stirred at 90 ꢀC for 48 h. After cooling the DMF was
removed under reduced pressure; the resulting paste was
dissolved in ethyl acetate and washed with ice-cold dilute
HCl solution (3ꢁ 15 mL). The organic layer was dried over
anhydrous Na2SO4 and concentrated to obtain the product.
The crude product was taken directly for the next step of
the synthesis.
Typical Polymerization
Polymerization under melt transesterification was carried
out in two stages. Compound 4 (600 mg, 2.1 mmol) along
with (26 mg) ꢂ2 mol % of dibutyltin dilaurate were taken
in a test tube shaped polymerization vessel and stirred at
150 ꢀC under continuous dry N2 purge until highly viscous
oligomers are formed (ca. 2–3 h). The polymerization vessel
was then connected to a Kugelrohr apparatus and stirred by
gradual rotation at 150 ꢀC, under dynamic vacuum, for an
additional 2 h. Vigorous bubbling from the melt was seen
indicating loss of the volatile propargyl alcohol. After cooling,
the polymer was dissolved in chloroform and precipitated in
petroleum ether to obtain a fibrous white polymer. The poly-
mer was purified once again by dissolution in chloroform
and reprecipitation in methanol. Yield: 71 %.
1H NMR (CDCl3, d ppm): 8.261 (s, 1H, ArAH pAOH), 7.737 (s,
2H, ArAH, oAOH), 4.342–4.031 (t, 2H, ArAOCH2A),3.945 (s, 6H,
COOCH3), 3.689–3.657 (t, 2H, ACH2CH2OH), 1.877–1.848 (t, 2H,
ArAOCH2CH2A), 1.608–1.451 (m, 6H, rest of aliphatic protons).
Compound 7
Compound 6 from the previous step was taken in methanol
and stirred with four equivalents of KOH at 50 ꢀC for 12 h.
The hyperbranched polymer was synthesized similarly using
the AB2 monomer 8.
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SCHEME 2 Synthesis of the AB and AB2
type monomers.
Click Reactions
would be readily amenable to postpolymerization click
reactions.
Azide-alkyne click reactions were carried out following
standard protocol.9 In a typical click reaction, 100 mg of
polymer LP1 was dissolved in 10 mL of chloroform along
with 12 mg of 9-azidomethylanthracene (ꢂ3-fold excess with
respect to the propargyl end-group based on DP obtained
from NMR), 2 mg of bromo tris(triphenylphosphine) cop-
per(I) (ꢂ10 mol %) and 8 mg of diisopropylethyl amine (ꢂ3
mol equivalents). The contents were purged with nitrogen
for 5 min, stoppered and stirred at 50 ꢀC for 3 days. For
compounds soluble in THF, click reactions were performed
using 5 mol % of aqueous copper sulfate pentahydrate (5
mg in 100 lL) along with 10 mol % of aqueous sodium
ascorbate (8 mg in 100 lL). For further experimental details
refer Supplementary Information.
Clickable Linear Polyesters
Polymerization of the AB monomer was carried out in the
melt at 150 ꢀC. Thus, compound 4 was taken along with 2
mol % of the catalyst (dibutyltin dilaurate) and heated with
stirring under a continuous dry-N2 purge. Vigorous evolution
of the condensate, propargyl alcohol, was evident during the
polymerization leading to an increase in the melt viscosity.
In the second stage, the polymerization was continued for an
additional 3 h, under reduced pressure using a Kugelrohr ap-
paratus to ensure uniform mixing of the melt. Two aliquots
were taken at different stages of the polymerization to
obtain samples of two different molecular weights. The pro-
ton NMR spectra of the monomer and those of the two poly-
mer samples are shown in Figure 1, along with their peak
assignments. The salient features of the spectra are – (i) a
visible decrease in the relative intensity of the propargyl
peaks (c & f) as a function of polymerization time, reflecting
the loss of the propargyl units which in turn implies an
increase in the polymer molecular weight, and (ii) a substan-
tial shift in the peak position of the methylene protons adja-
cent to the hydroxyl group in the monomer (peak e moves
from 3.7 ppm in the monomer to 4.2 ppm in the polymer)
upon polymerization. From the relative intensities of the
peaks because of the propargyl end groups (see the
expanded regions of the spectra) and those of the aromatic
protons, the average degree of polymerization (DPn) was
RESULTS AND DISCUSSIONS
The required AB and AB2 type monomers were readily syn-
thesized using a series of simple steps as shown in scheme
2. Methyl, 4-hydroxybenzoate (1) is coupled with 6-bromo-
hexanol to yield 2, which is then hydrolyzed and esterified
with propargyl alcohol to yield the required AB monomer 4.
Similarly, the AB2 monomer 8, was synthesized from 5-
hydroxyisophthalic acid in a series of steps as depicted in
scheme 2. A six-carbon spacer (C6) was incorporated in both
the momomers to ensure that the resulting polymers were
readily soluble in common organic solvents and, therefore,
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JOURNAL OF POLYMER SCIENCE: PART A: POLYMER CHEMISTRY DOI 10.1002/POLA
FIGURE 1 1H NMR spectra of linear monomer (LM), polymer
after stage 1 (LP1), and after stage 2 (LP2). The end-group sig-
nals of the polymers are y-expanded to different extents as
indicated. # - peaks due to residual dibutyltin dilaurate.
FIGURE 2 1H NMR spectra of the nascent linear polymer (LP1),
after clicking with benzyl azide (LP1-BENZ) and 9-azidomethyl
anthracene (LP1-ANTH), in CDCl3. # - peaks due to dibutyl tin-
dilaurate. Y-expanded regions confirm the absence of propar-
gyl end groups after clicking.
calculated and the values thus obtained are listed in Table 1.
The spectra were in accordance with the expected polymer
structure, and clearly demonstrate that the propargyl ester
monomer can indeed undergo transesterification under the
Lewis-acid catalyzed melt-polycondensation conditions; in
addition it also confirms that the propargyl groups are stable
under the high temperature conditions used for the polymer-
ization, as previously observed by Du Prez.17 The 13C NMR
spectra of the monomer and the polymers were in accord-
ance with the expected structure, although the propargyl
end-group signals were not easily detectable (Supporting In-
formation Fig. S4).
cases, also clearly reveal that the reaction has proceeded in
a nearly quantitative fashion. Using the chromophore, 9-azi-
domethyl anthracene, the DPn of the polymers after clicking
could be readily estimated. To do so, a model compound was
prepared by clicking the AB monomer (4) with 9-azido-
methyl anthracene, and the molar extinction coefficient of
the resulting product in chloroform was determined and was
found to be 6830 Mꢃ1cmꢃ1 at 389 nm (Figure S5 in Sup-
porting Information).
The propargyl end group can be readily functionalized using
a variety of organic azides under the standard Cu-catalyzed
click reaction conditions. The linear polyesters, of two differ-
ent molecular weights (LP1 & LP2), were first clicked with
simple benzyl azide, as a control, and subsequently with
9-azidomethyl anthracene. The latter served as a useful chro-
mophore for molecular weight estimation using end-group
analysis, as will be discussed later. The proton NMR spectra
of the one of the linear polymers LP1, along with those
clicked with the two different azides are stack plotted in Fig-
ure 2. The complete disappearance of the propargyl peak
protons (see expanded spectrum), along with a concomitant
appearance of peaks because of the clicked moiety, confirms
the near quantitative nature of the clicking process. The rela-
tive intensities of the peaks due to the clicked unit, in both
The absorption and fluorescence spectra of pristine LP1 and
the anthracene-clicked polymer LP1-ANTH are shown in Fig-
ure 3. The presence of the anthracene end group is evident
from the absorption spectrum, which shows the typical
vibration fine-structure that seen for anthracene. Using the
extinction coefficient of model compound, the molar concen-
tration of the anthracene end group in the clicked polymers
was determined, from which the DPn of the polymers were
estimated (see Table 1). Similarly, the fluorescence spectra of
the model compound was also measured at lM concentra-
tions (excitation wavelength of 350 nm); in this concentra-
tion range the emission intensity is seen to vary linearly
with concentrations and the slope provided an apparent
emission constant, which was estimated to be around
7.47Eþ10 Mꢃ1cmꢃ1 at 416 nm (Supporting Information Fig.
S6). Following the procedure adopted for the UV-visible stud-
ies, the DPn of the polymers were estimated from the fluo-
rescence intensity and the values are also listed in Table 1.
TABLE 1 Degree of Polymerization Values Estimated from
Various Spectroscopic Techniques of Linear Polyester
DPn of Nascent
Polymer
DPn After Clicking with
It is clear that there is good agreement between the values
obtained using the different methods, although the values
obtained postclicking are a little higher. This may be due to
inadvertent fractionation that may have occurred during the
recovery of the polymer (by precipitation) after the click
reaction. It is important to recognize that the ability to
9-Azidomethyl anthracene
Polymer
1H NMR
1H NMR
UV
Fluorescence
LP1-ANTH
LP2-ANTH
29
34
34
36
110
145
153
155
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FIGURE 3 Left: absorption spectra
of linear polymer before (LP1) and
after (LP1-ANTH) functionalization
with 9-azidomethyl anthracene.
Right: Fluorescence spectra of lin-
ear polymer before (LP1) and after
(LP1-ANTH) functionalization with
9-azidomethyl anthracene. All the
measurements were done using
chloroform solutions at concentra-
tions of 1 mg/mL.
quantitatively introduce a fluorescent tag at the chain-end
permits the accurate determination of the molecular weight
even at significantly higher DP values because of the inher-
ently higher sensitivity of the method; this is especially true
while using the click reaction to functionalize the chain-ends,
given its established effectiveness in quantitative ligation.
neglycol monomethylether. As in the earlier case, here too
complete disappearance of the propargyl peaks is evident, as
is the appearance of peaks corresponding to the clicked unit.
The UV-visible spectra of the hyperbranched polyesters
before and after clicking with 9-azidomethyl anthracene are
shown in Figure 5. The spectrum of the anthracene-clicked
polymer clearly reveals the presence of the anthracene chro-
mophore and the spectral fine-structure suggests that there
Clickable Hyperbranched Polyesters
The AB2 monomer was polymerized similarly under melt
transesterification conditions to yield a hyperbranched poly-
ester carrying a large number of propargyl ester groups at
its molecular periphery. Given the tendency for hyper-
branched polymers to adopt a globular shape, this approach
of directly generating hyperbranched polyesters carrying
clickable terminal groups is particularly attractive because
they can function as molecular scaffolds for placement of a
variety of functional units. The NMR spectra of the AB2
monomer and the corresponding hyperbranched polyester
are shown in Figure 4. Here again, it is evident that the poly-
merization proceeds smoothly leading to a loss of ca. one
mole of the propargyl group. This is apparent from the rela-
tive intensities of the peaks due to the propargyl group and
the aromatic protons; the intensity ratio of peaks f:a
decreases from 2:1 in the monomer to nearly 1:1 (m:h is
1.09:1.0) in the polymer. The intensities of the rest of the
peaks are in accordance with the expected polymer structure
confirming the absence of any side reactions during the poly-
merization. The 13C NMR spectra of the monomer and the
HB polymer were in accordance with the expected structure
(Supporting Information Fig. S4).
The numerous terminal propargyl groups in the hyper-
branched polyester were ‘‘clicked’’ using three different or-
ganic azides. The polymer was first clicked using simple ben-
zyl azide to demonstrate the efficacy of the process. The
spectrum of the clicked polymer clearly reveals that the
reaction is nearly quantitative; the y-expanded spectrum in
the relevant regions shows the complete disappearance of
the propargyl groups (Fig. 4). Furthermore, the relative
intensities of peaks due to the clicked unit are also in ac-
cordance with the expected value for complete reaction. Sim-
ilar click reactions were conducted using two other azides,
namely 9-azidomethyl anthracene and x-azido heptaethyle-
FIGURE 4 1H NMR spectra of the AB2 monomer (HBM), hyper-
branched polymer (HP), after clicking with benzyl azide (HP-
BENZ), with 9-azidomethyl anthracene (HP-ANTH), and with
heptaethyleneglycol monomethylether monoazide (HP-7OEG).
Solvent used is CDCl3.
SYNTHESIS OF TERMINALLY ‘‘CLICKABLE’’ POLYESTERS, RAMKUMAR, ROSE, AND RAMAKRISHNAN
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JOURNAL OF POLYMER SCIENCE: PART A: POLYMER CHEMISTRY DOI 10.1002/POLA
FIGURE 5 Left: Absorption spectra
of hyperbranched polymer before
(HP) and after functionalization
with 9-azidomethyl anthracene
(HP-ANTH). Right: Fluorescence
spectra of hyperbranched polymer
before (HP) and after functionali-
zation with 9-azidomethyl anthra-
cene
(HP-ANTH).
Excitation
wavelength is 350 nm.
is very little ground state aggregation of the chromophores
even though the chromophore density is very high. It is
interesting that the fluorescence spectrum of the clicked
polymer also does not exhibit a significant excimer band,
although small changes in the spectrum when compared to
the model compound are evident; the highest energy peak at
394 nm is largely suppressed and a weak tail in the higher
wavelength region is seen (see Fig. S5). One other unex-
pected observation is that the pristine hyperbranched poly-
mer also exhibited a fluorescence spectrum which, at first
sight, is similar to that of HP-ANTH. In an effort to explain
this observation the excitation spectra of HP and HP-ANTH
were recorded at the emission wavelength of 433 nm (Sup-
porting Information Fig. S7). While excitation spectrum of
HP-ANTH resembled its absorption spectrum, that of HP
exhibited a broad featureless peak in the region 320–400
nm. On the basis of these observations it is clear that the flu-
orescence in the case of the nascent HP has some rather
uncommon origins. To probe this further, we measured the
fluorescence spectra of both the AB2 monomer (8) and an
analogous hyperbranched polymer, devoid of the propargyl
end groups, prepared from the dimethyl ester AB2 mono-
mer.20 Whereas the monomer did not exhibit any significant
fluorescence, the hyperbranched polyester bearing methyl
ester end groups exhibited a spectrum (Supporting Informa-
tion Fig. S8) similar to that of HP, suggesting that the fluo-
rescence is intrinsic to the hyperbranched polyester back-
bone itself. The exact origin of the fluorescence in the pure
HBP is presently unclear and further experiments are
required to understand this. It may, however, be relevant to
note that several perfectly branched dendrimers have been
shown to exhibit such unusual fluorescence even in the ab-
sence of a standard chromophore.21
the incorporation of anthracene units caused a dramatic
increase in the Tg to about 106 C. The considerably higher Tg
ꢀ
of the anthracene containing polymer suggests the presence of
strong interactions between the anthracene units in the solid
state. The presence of such interactions was confirmed by the
broad excimer emission seen in the spectrum of thin films of
HP-ANTH (Supporting Information Fig. S9).
The peripherally PEGylated HP was completely soluble in
water and exhibited a lower critical solution temperature
(LCST), as was earlier seen in peripherally PEGylated hyper-
branched polyethers prepared via the AB2 þ A-R type
copolymerization approach.23 A plot of the percent transmis-
sion (at 600 nm) as a function of temperature (Fig. 7) clearly
depicts the LCST, which was estimated to be around 64 ꢀC.
This is significantly higher than the previously studied analo-
gous PEGylated polyethers, which had an LCST of around 35
ꢀC; one of the reasons for the lower value in the HP poly-
ether is the lower level of peripheral PEGylation (ca. 66
mole-percent) in them.23
It is well known that the nature of the terminal groups
strongly affect the thermal properties and the solubility charac-
teristics of hyperbranched polymers.22 The DSC thermograms
of the parent hyperbranched polyester, along with those clicked
with different organic azides are shownꢀin Figure 6. The parent
polyester HP exhibits a clear Tg at 18 C, while the PEGylated
polymer prepared by reaction with x-azido heptaethylenegly-
col monomethylether exhibited a significantly lower Tg at
FIGURE 6 DSC run of hyperbranched polyester (HP), function-
alized with benzyl azide (HP-BENZ), 9-azidomethyl anthracene
(HP-ANTH), and heptaethyleneglycol monomethyl ether (HP-
7OEG).
ꢀ
around ꢃ32 C. On the other hand, the polymers clicked with
ꢀ
benzyl azide caused the Tg to increase slightly to 45 C, while
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ARTICLE
interesting and potentially useful functional units. We have
demonstrated the efficacy of ligation using different organic
azides, such as an anthracene azide which serves as a chro-
mophore, and a PEG-azide that renders the parent hydropho-
bic polyester completely water-soluble. The latter is an
example of a core-shell type polymer that has been demon-
strated to contain hydrophobic pockets that can sequester
relatively hydrophobic small molecules, such as dyes, from
aqueous solutions.25 The use of these peripherally clickable
polyesters for a variety of such applications by suitable mod-
ification of their molecular periphery is currently under
investigation in our laboratory.
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In conclusion, we have developed a simple and direct route
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