Investigation of the telomerization kinetics of N-isopropylacrylamide using 3-mercaptopropionic hydrazide as chain transfer agent

Article abstract of DOI:10.1021/ma0484882

The telomerization (chain transfer polymerization) kinetics of N-isopropylacrylamide were investigated in various (hydro)organic solvents using 3-mercaptopropionic hydrazide as chain transfer agent (telogen). Except for the dioxane/water system telogen consumption rates were similar for all cases, while solvent effects could be observed for the monomer consumption rates. Chain transfer constants, as defined by the ratio of the rate constants for chain transfer and chain propagation (C_T = k_tr/k_p), were highest in DMF (10.3), a solvent unable to form hydrogen bonds or dipole-dipole interactions with the monomer, while a more promising value of C_T = 1.7 was found for the 6:4 methanol/water mixture. The highest monomer consumption rates were observed for the 1:1 dioxane/water mixture. However, in this particular case the telogen consumption was also found to increase, as we propose due to a "hydrophobic effect" whereby polymer microaggregates serve to locally increase the concentration of telogen and/or monomer once a certain water concentration has been passed. As a result a comparatively high C_T of 3.2 characterizes the dioxane/water system.

Full text of DOI:10.1021/ma0484882

3630
Macromolecules 2005, 38, 3630-3637
Investigation of the Telomerization Kinetics of N-Isopropylacrylamide
Using 3-Mercaptopropionic Hydrazide as Chain Transfer Agent
Matteo D. Costioli,† D. Berdat,† Ruth Freitag,*,†,‡ Xavier Andre´,§ and
Axel H. E. Mu1 ller§
Laboratory of Chemical Biotechnology, Faculty of Basic Science, Swiss Federal Institute of Technology,
Lausanne, Switzerland, Process Biotechnology, University of Bayreuth, 95440 Bayreuth, Germany, and
Macromolecular Chemistry II, University of Bayreuth, 95440 Bayreuth, Germany
Received July 23, 2004; Revised Manuscript Received December 16, 2004
ABSTRACT: The telomerization (chain transfer polymerization) kinetics of N-isopropylacrylamide were
investigated in various (hydro)organic solvents using 3-mercaptopropionic hydrazide as chain transfer
agent (telogen). Except for the dioxane/water system telogen consumption rates were similar for all cases,
while solvent effects could be observed for the monomer consumption rates. Chain transfer constants, as
defined by the ratio of the rate constants for chain transfer and chain propagation (CT ) ktr,/kp), were
highest in DMF (10.3), a solvent unable to form hydrogen bonds or dipole-dipole interactions with the
monomer, while a more promising value of CT ) 1.7 was found for the 6:4 methanol/water mixture. The
highest monomer consumption rates were observed for the 1:1 dioxane/water mixture. However, in this
particular case the telogen consumption was also found to increase, as we propose due to a “hydrophobic
effect” whereby polymer microaggregates serve to locally increase the concentration of telogen and/or
monomer once a certain water concentration has been passed. As a result a comparatively high CT of 3.2
characterizes the dioxane/water system.
Introduction
conveniently employed for the construction of biocon-
jugates.8-12 For such applications, the ability to control
the size and heterogeneity of the polymer is the most
important aspect besides the presence of a reactive end
group. It is known that the degree of polymerization and
therefore the molecular mass of the telomer can be
controlled via the initial ratio of the telogen and
monomer concentration.5,6 However, to take advantage
of this, the kinetics of a given telogen/monomer couple
and in particular their chain transfer constants have
to be known. To date, few kinetic studies on telomer-
ization reactions have been reported, mostly by Boutevin
and co-workers, cf. Tables 1 and 2.5,7,13-20 In particular,
these authors studied the behavior of various telogens
in the telomerization of (meth)acrylates. A detailed
study of PNIPAAm is still missing, which is unfortunate
given the overwhelming importance of this compound
in the area of stimuli-responsive macromolecules and
materials.8-10
The mechanistic steps of chain transfer polymeriza-
tion differ little from those in conventional radical
polymerization; cf. Scheme 1. Ideally, chain growth
starts with the addition of the telogen radical to the first
monomer rather than a radical stemming from the
initiator. Propagation is by the addition of a certain
number of monomers, while chain termination is typi-
cally by chain transfer. The higher the growth rate
relative to the transfer rate, the higher the number of
monomer units present in the telomer before chain
transfer occurs. To produce macromolecules the reaction
rates of chain growth, Rp, and chain transfer, Rtr, should
differ by one to 2 orders of magnitude. If Rp . Rtr,
predominantly conventional polymers are formed and
the chain transfer effect on the size is lost. If Rp is too
small compared to Rtr, 1:1 adducts and oligomers are
formed. In addition to these reactions, all reactions
known from conventional free radical polymerization
Controlled chain transfer, i.e., the calculated shift of
the radical from the growing polymer chain to another
molecular species, which in turn can reinitiate chain
growth, is a convenient way to control the molar mass
and the polydispersity of polymers produced by free
radical polymerization.1-4 If the rate of reinitiation is
in the same order of magnitude as the original rate of
propagation, the overall polymerization rate is not
affected, while a larger number of polymers (or oligo-
mers) albeit with smaller molecular mass, is formed.
When the reinitiation rate is slow compared to the
propagation, the size of the polymers as well as the rate
of the polymerization is decreased in chain transfer
polymerization (also called telomerization) compared to
the same reaction in the absence of the chain transfer
agent. Many compounds can be used as chain transfer
agents (telogens) in free radical polymerization; the
most popular are halogens and mercaptans. Besides
their capacity to react as chain transfer agents, these
molecules also supply a well-defined end group to the
final polymer (telomer). Vinyl monomers that are suit-
able for conventional radical chain polymerization, such
as ethylene, styrenes, acrylamides, or (meth)acrylates,
can be used in telomerization.4-7
Chain transfer polymerization of N-isopropylacryl-
amide (NIPAAm) is increasingly used for the synthesis
of defined oligomers bearing a particular functional
(ester, carboxylic acid, amino) end group that can be
* Corresponding author. Chair for Process Biotechnology, Fac-
ulty of Engineering Science, University of Bayreuth, 95440
Bayreuth, Germany. Fax: 0049 921 55-7375. E-mail ruth.freitag@
uni-bayreuth.de.
† Swiss Federal Institute of Technology.
‡ Process Biotechnology, University of Bayreuth.
§ Macromolecular Chemistry II, University of Bayreuth.
10.1021/ma0484882 CCC: $30.25 © 2005 American Chemical Society
Published on Web 04/09/2005

Macromolecules, Vol. 38, No. 9, 2005
Investigation of Telomerization Kinetics 3631
Table 1. Chain Transfer Constants of Linear Thiols with Alkylacrlyamides, Alkylmethacrylamide, and Acrylic Acids
monomer
thiols
CT
T (°C)
solvent
ref
acrylic acid
acrylamide
thioglycolic acid
3.2
65
65
THF
THF/water
water
14
14
42
43
44
44
44
[44
15
31
31
31
31
45
33
32
thioglycolic acid
0.5-3.2
0.49
0.38
1.7-2.3
1.7
3-mercaptopropionic acid
1-ethyldecanethiol
70
45
45
45
45
80
50
50
50
50
60
70
65
65
65
65
65
65
dichlorobenzene
2-propanol
methanol
methanol
methanol
acetonitrile
methanol
methanol
methanol
methanol
methanol
DMF
1-dodecanethiol
1-dodecanethiol
1-octanethiol
1.65-1.70
1.70
0.65
0.08
0.32
0.38
0.8
1-octadecanethiol
C6F13-C2H4-SH
N-(2-hydroxypropyl)methacrylamide
2-mercaptoethylamine
3-mercaptopropionic acid
methyl 3-mercaptopropionate
3-mercaptopropionic hydrazide
n-alcanethiols
tris(hydroxymethyl)acrylamidomethane
N-isopropylacrylamide
1
3-mercaptopropionic acid
methyl 3-mercaptopropionate
3-mercaptopropionic hydrazide
3-mercaptopropionic hydrazide
3-mercaptopropionic hydrazide
3-mercaptopropionic hydrazide
3-mercaptopropionic hydrazide
0.006 63
4.1
ethanol
6.0
10.3
5.5
1.7
3.2
dioxane
this study
this study
this study
this study
this study
DMF
methanol
methanol/water 6:4
dioxane/water 1:1
Table 2. Values of the Propagation/Termination Rate Constant Ratio Determined from Telomerization Different
Monomers in Different Solvents
monomer
acrylic acid
thiols
kp/ k [(L mol s)-0.5
]
T [°C]
solvent
ref
x
t
thioglycolic acid
5
50a
29a
29a
29a
80
65
65
65
65
65
45
80
80
65
65
65
65
65
65
water
water
42
14
14
14
46
14
14
14
14
14
44
47
47
32
thioglycolic acid
2.02
0.42
0.11
0.75
0.48
0.54
1.56
2.09
2.48
2.5
thioglycolic acid
formamide
DMSO
CH3CN
thioglycolic acid
thioglycolic acid
thioglycolic acid
THF
thioglycolic acid
THF/water 9:1
THF/water 5:5
THF/water 2:8
water
methanol
CH3CN
thioglycolic acid
thioglycolic acid
thioglycolic acid
alkylacrylamide
1-dodecanethiol
1-dodecanethiol
0.66
0.23
0.53
0.24
0.58
0.53
1.42
8.30
1-dodecanethiol
CH3CN
ethanol
N-isopropylacrylamide
methyl 3-mercaptopropionate
3-mercaptopropionic hydrazide
3-mercaptopropionic hydrazide
3-mercaptopropionic hydrazide
3-mercaptopropionic hydrazide
3-mercaptopropionic hydrazide
DMF
this study
this study
this study
this study
this study
dioxane
methanol
methanol/water 6:4
dioxane/water 1:1
a H2O2 was used as initiator.
can also take place, e.g., the direct initiation of a
polymer chain by an initiator rather than a telogen
radical. Several other side reactions, e.g., a termination
by recombination of a chain initiated by a telogen radical
and a chain initiated by an initiator radical further add
to the complexity of chain transfer polymerization. The
kinetics of a telomerization are hence extremely com-
plicated. Moreover, the rate constants of the early events
in telomerization, which are the most crucial ones, are
difficult to access experimentally.4,21
O’Brien et al.25 proposed a method for the determi-
nation of the chain transfer constant CT in which the
telogen concentration is connected to the reaction
progress. From the average degree of polymerization,
DPn, and under the assumption that termination is
exclusively due to the transfer of the radical to the
telogen, we can formulate
•
kp[M][Pn ]
d[M]/dt
DPn )
)
•
d[T]/dt
ktr[T][Pn ]
In the case of a homopolymerization, the chain
transfer constant CT ()ktr,/kp) can be used to character-
ize the system. In such a case the chain propagation
rate, Rp, is proportional to (kp/(ki/kt))0.5, i.e., the rate
constants for the chain propagation, initiation, and
termination reactions respectively, while the chain
transfer rate, Rtr, is proportional only to ktr, i.e., the rate
constant for chain transfer. Since initiation and termi-
nation show little dependency on the solvent, save for
a possible viscosity effect, they can be assumed to be
constant and the ratio of chain propagation and chain
transfer is proportional to the ratio of the two remaining
rate constants, i.e., CT.
which in turn allows the determination of CT from the
following relationship:
[T]
[M]0
[M]
ln 0 ) CT ln
[T]
or
ln(1 - RT) ) CT ln(1 - RM)
where the subscript of 0 denotes initial concentrations
and RM (RT) is the monomer (telogen) conversion.

3632 Costioli et al.
Macromolecules, Vol. 38, No. 9, 2005
Scheme 1. Schematic Presentation of the Reactions
Involved in Chain Transfer Polymerization
(Telomerization)a
dissolved in a minimal volume of the same solvent and added
with a syringe to the reaction vessel (N2 atmosphere). In both
cases, samples were taken at different time intervals using a
disposable syringe. The samples were immediately immersed
in liquid nitrogen and stored at -20 °C until analysis.
Analytics. The consumption of the chain transfer agent,
3-mercaptopropionic hydrazide, was followed by the Ellman
test.26 Briefly, 50 µL of sample from the reaction mixture was
diluted several times in a 0.1 M phosphate buffer pH 8 to reach
a final concentration of approximately 0.1 µmol/mL in terms
of the sulfhydryl group in a total volume of 1.5 mL. Then 50
µL of a freshly prepared 5,5′-dithio(2-nitrobenzoic acid) (DTNB)
solution (4 mg/mL) was added to the sample mixture and the
mixture left to stand for 20 min. The concentration of the
sulfhydryl group was calculated from the UV signal recorded
at 410 nm using 1.5 mL buffer containing 50 µL of the DTNB
solution as reference.
1H NMR spectra for monitoring of the monomer conversion
were obtained on a Bruker AC 250 at an operating frequency
of 250 MHz. As an internal standard, the residual proton
signal of the deuterated solvent was used. Samples were
analyzed after dilution in deuterated DMSO (telomerization
in DMF) or methanol (telomerization in methanol or dioxane).
The degree of conversion, RΜ, was determined by a comparison
of the signal stemming from the three vinylic protons of the
monomer (Ha′, 5.7 ppm and Hb′, 6.3 ppm) with the broad peak
stemming from the methin proton of the polymer (Hc, between
2.05 and 2.35 ppm), according to the following formula:
Hc
RM
)
(Ha′ + Hb′)
+ Hc
3
a
Key: I ) initiator, R ) radical, XY ) chain transfer agent,
and M ) monomer. Possible competitive reaction steps due to
conventional radical polymerization are indicated in brackets.
Fourier transform near-infrared (FT-NIR) spectroscopy was
performed in situ using a Nicolet Magna 560 FT-IR optical
bench equipped with a white-light source and a PbS detector.
The fiber-optic immersion probe (Hellma, quartz glass Suprasil
300) with an optical path length of 10 mm was connected to
the FT-NIR instrument by 2 m fiber-optical cables. Data
processing was performed with Nicolet’s OMNIC Series soft-
ware. Each spectrum was constructed from 32 scans with a
resolution of 4 cm-1. The total collection time per spectrum
was approximately 22 s. Prior to the measurements, a blank
spectrum was recorded with the solution of the corresponding
chain transfer agent in the indicated solvent. FT-NIR spectra
were recorded every 30 s and the variation in time of the
intensity of the NIPAAm monomer bands at 6157 cm-1 (the
vinylic stretching overtone of NIPAAm) was followed for the
evaluation of the monomer consumption. The monomer con-
version, RM, was extrapolated from the intensities of the FT-
NIR absorbance peaks at zero monomer conversion and at total
conversion using the following equation:
Experimental Procedures
Materials. Chemicals were obtained from Sigma-Aldrich.
The initiator 2,2′-azoisobutyronitrile (AIBN) and the monomer
N-isopropylacrylamide (NIPAAm) were recrystallized from
methanol and hexane, respectively, prior to use. Solvents were
from Fluka and Carlo-Erba. Diethyl ether was dried by reflux
over sodium using benzophenone as indicator. DMF and
dichlomethane were dried on calcium hydride and distilled
over 3 Å molecular sieves. Water was purified with an Elix-3
water purification system (Millipore, USA). Deuterated sol-
vents were from Deutero, Germany.
Syntheses. The chain transfer agent 3-mercaptopropionic
hydrazide was prepared as follows. First, 10 g (83 mmol) of
methyl 3-mercaptopropionate was added dropwise to an excess
of hydrazine monohydrate (10 g, 200 mmol) dissolved in 30
mL of methanol at ambient temperature. The reaction mixture
was stirred at room-temperature overnight. Thin-layer chro-
matography was used to follow the reaction (Rf ) 0.62;
methanol/diethyl ether 1:4). Methanol was removed under
vacuum by rotary evaporator and the product purified by
chromatography on a silica gel column eluted with methanol/
diethyl ether (1:4). The fraction containing the product was
collected and the solvent removed under vacuum by rotary
evaporator. The final oily 3-mercaptopropionic hydrazide was
dried under vacuum; yield 8.4 g (84%). 1H NMR (CDCl3,
ppm): 1.57 (t, 2H, SH), 2.43 (t, 2H, COCH2), 2.76 (m, 2H,
CH2SH), 3.96 (sh, 1H, NH). ESI-MS, m/z: 121.54 (H+).
For the synthesis of poly(N-isopropylacrylamide), PNIPAAm,
12.0 g of the monomer (0.11 mol) was dissolved in 70 mL of
the indicated degassed solvent. The mixture was heated to 65
°C. Then, 174.0 g AIBN (1.06 mmol) and 318.1 g of the chain
transfer agent (2.65 mmol) were dissolved together in 1 mL of
the same solvent. Both solutions were injected into the reaction
vessel (N2 atmosphere) with a syringe. The reaction was
A0 - At
A0 - A∞
RM
)
Here At is the absorbance at time t, A0 is the initial absorbance,
and A∞ is the absorbance at full conversion.
ESI-TOF mass spectra were acquired on a LCT mass
spectrometer from Micromass (Manchester, U.K.). This instru-
ment combines an electrospray ionization source with a TOF
(time-of-flight) mass analyzer. The LCT mass spectrometer
was used in the positive ionization mode for all experiments.
The ES+ Source parameters were adjusted as a function of
the tested products.
Results
We undertook an investigation of the telomerization
kinetics of NIPAAm considering mainly the possible
effect of various solvents. Since we have recently
introduced 3-mercaptopropionic hydrazide as a chain
transfer agent particularly suitable for bioconjugate
synthesis by chemical ligation,27 telomerization of
1
monitored by FT-NIR. In the case of H NMR monitoring 1.7
g of monomer (15.02 mmol) were dissolved in the indicated
degassed solvent and heated to 65 °C. 24.7 g AIBN (0.15 mmol)
and 72.1 g chain transfer agent (0.60 mmol) were individually

Macromolecules, Vol. 38, No. 9, 2005
Investigation of Telomerization Kinetics 3633
Scheme 2. Idealized Scheme of Telomerisation of NIPAAm Using 3-Mercaptopropionic Hydrazide as Chain
Transfer Agent
NIPAAm using this particular chain transfer agent was
taken as an example in our studies. However, the
conclusions drawn in regard to the influence of the
solvent on the telomerization kinetics of NIPAAm
should be of general applicability.
the respective chain transfer constants, CT ) ktr/kp,
according to the method proposed by O’Brien outlined
in the Introduction. For this purpose, the consumption
of the monomer and chain transfer agent were followed
as a function of time. In the case of the monomer this
was achieved by in situ FT-NIR and/or by 1H NMR. FT-
NIR is a powerful tool for this type of investigation, as
it allows the in situ monitoring of the monomer conver-
sion.29,30 The intensity of the NIPAAm monomer bands
at 6157 cm-1 (the vinylic stretching overtone of NIPAAm)
was followed with time. This band does not significantly
overlap with those at other wavelengths, in particular
those of the polymer (e.g., the band at 6727 cm-1, which
increases during the telomerization) or more impor-
tantly, the bands of most of the investigated solvents.
As an example of the FT-NIR measurements, the
evolution of the spectra with time for a telomerization
of NIPAAm in dioxane as solvent is shown in Figure 1.
1H NMR was used for the determination of the monomer
conversion, especially when the solvent employed in the
telomerization showed NIR absorption bands overlap-
ping with those of the monomer. Figure 2 shows an
example of an 1H NMR spectrum recorded for a NIPAAm
The reactions involved in the telomerization of
NIPAAm using 3-mercaptopropionic hydrazide as chain
transfer agent are shown in Scheme 2. In principle, any
solvent should be suitable for telomerization as long as
the monomer and the telogen are well dissolved and,
more importantly, as long as the solvent does not act
itself as chain transfer agent. When an efficient chain
transfer agent, e.g., a thiol, is chosen, the chain transfer
properties of most solvents should be negligible by
comparison. However, as in any radical polymerization,
the solvent may exert a pronounced effect on the
monomer reactivity, especially in the case of polar
monomers, monomers containing atoms with a free
electron pair, and/or those capable of forming hydrogen
bonds. Examples include acrylates, methacrylates, and
acrylamides such as the NIPAAm central to this study.28
The influence of the nature of the solvent on the
telomerization kinetics was investigated by calculating
Figure 1. Evolution of the FT-NIR-spectrum (after 0.4, 4, 9, 21, 36, and 80 min) in the telomerization of NIPAAm in dioxane,
using 3′-mercaptopropionic hydrazide as chain transfer agent.

3634 Costioli et al.
Macromolecules, Vol. 38, No. 9, 2005
Figure 2. 1H NMR spectrum of the PNIPAAm obtained through telomerization at 65 °C in DMF in the presence of the 3′-
mercaptopropionic hydrazide as transfer agent.
Figure 3. Monomer consumption (followed by FT-NIR) as a function of time for the telomerization of NIPAAm at 65 °C in
different solvents in the presence of 3′-mercaptopropionic hydrazide as chain transfer agent (telogen). Key: (s) dioxane; (2)
methanol; (]) methanol/water (4:6, v/v); (×) DMF; (b) dioxane/water (1:1, v/v); [M] monomer concentration at the given time;
[Mo] initial monomer concentration.
telomerization in DMF. The consumption of the chain
transfer agent was followed by titrating aliquots of the
samples taken during the reaction with Ellman’s re-
agent.26 This colorimetric essay allows the detection of
primary thiols by a reaction with 5,5′-dithiobis[2-nitro-
benzoic acid] (DTNB). Under mildly alkaline conditions,
the displaced nitrobenzoate anion shows a characteristic
absorbance at 410 nm, which can be correlated to the
sulfudryl group of the transfer agent.
The influence of the solvent on the monomer and
telogen consumption can be seen in Figures 3 and 4.
Differences can be observed for the monomer consump-
tion rate, cf. Figure 3. Propagation is most rapid in the
dioxane/water mixture. In contrast, only small changes
are observed for the telogen consumption, except for the
dioxane/water mixture. The chain transfer constant, CT
) ktr/kp, should vary accordingly. In fact, as summarized
in Table 1, the CT values vary between a value of about

Macromolecules, Vol. 38, No. 9, 2005
Investigation of Telomerization Kinetics 3635
Figure 4. Telogen consumption as a function of time for the telomerization of NIPAAm at 65 °C in different solvents in the
presence of 3′-mercaptopropionic hydrazide as chain transfer agent (telogen). Key: (0) dioxane; (2) methanol; (]) methanol/
water (4:6, v/v); (×) DMF; (O) dioxane/water (1:1, v/v); [T] telogen concentration at a given time; [To] initial telogen concentration.
Figure 5. Relationship between the telogen and the monomer consumption in the telomerization of NIPAAm (monomer) at 65
°C in different solvents in the presence of 3′-mercaptopropionic hydrazide as chain transfer agent (telogen). Key: (0) dioxane; (2)
methanol; (]) methanol/ water (4:6, v/v); (×) DMF; (O) dioxane/water (1:1, v/v). Straight lines represent linear regressions. According
to the relationship proposed in ref 25 (O’Brien and Gornick) the slopes of the plots give the CT value of the reaction.
10 found for DMF and a value of 1.7 found for the
mixture of methanol and water. Values were calculated
from 4 to 7 data points in each case. The correlation
coefficient of the linear relationship (R2) was 0.99 or
higher in all cases as shown in Figure 5.
study. The value found by Tekei et al.33 for the telom-
erization of NIPAAm in DMF using 3-mercaptopropionic
acid as chain transfer agent, on the other hand, is
several orders of magnitude lower. The observed diver-
gence of the CT value could be partially explained by
differences in the telogen reactivity. It has been reported
that the acidic character of the thiol group, which
corresponds to its telogen activity, is increased by
electron-drawing groups.14,19,31,33 Lu et al.31 showed, e.g.,
that for a series of telogens (HSCH2CH2R) the reactivity
increased for R ) -NH2 < -COOCH3 < COOH <
-CONHNH2. We can therefore expect the 3-mercapto-
propionic hydrazide used by us to have a higher CT then
methyl-3-mercaptopropionate used in ref 31.
Discussion
Chain transfer constants vary with the type of
monomer and telogen.31 It is therefore difficult to
compare our results with the CT values found in the
literature. However, the values measured for a range
of solvents in these experiments are in the same order
of magnitude as those found by Desponds and Freitag
(ref 32, Table 1), who observed a CT ) 4.1 for the
telomerization of NIPAAm in pure ethanol using methyl
3-mercaptopropionate as chain transfer agent; a telom-
erization system which is similar to the one used in this
In systems with CT . 1, “telomerization” will result
in a complex mixture of telomers and polymers.19 For
the production of compounds with a controlled molecular
mass and well-defined end groups such systems are

3636 Costioli et al.
Macromolecules, Vol. 38, No. 9, 2005
unsuitable. In the case considered here, DMF (CT
)
increase its reactivity as well as stabilize the growing
radical.36,39 This effect was demonstrated by Saini et
al.,39 who observed that the solvent effect on the
copolymerization of styrene or methyl methacrylate with
acrylamide disappeared once the acrylamide was re-
placed by N,N-dimethylacrylamide, i.e., a monomer that
cannot exist in the enolform.
10.3) hence constitutes an unsuitable solvent, while a
6:4 mixture of methanol and water (CT ) 1.7) could most
likely be used. A similar effect was observed by Loubat
et al.14 for the telomerization of acrylic acid in the
presence of thioglycolic acid as transfer agent. They
found that the CT value for any telomerization can be
lowered by increasing the molar fraction of water in the
mixture. In fact, they could reach a CT ) 1 by increasing
the fraction of water in THF to 80%. In our study a
similar investigation of the effect of increasing amounts
of water was not possible, since we produced PNIPAAm,
which, other than acrylic acid, precipitates from hydro-
organic mixtures when the proportion of water reaches
Among the solvents used in this study, the 1:1
mixture of dioxane and water presents a special case.
When the telomerization was carried out in this mixture
compared to pure dioxane, the rate of monomer con-
sumption was increased as expected, and full monomer
conversion was reached in a few minutes, Figure 3. Only
in this case among all investigated, however, did we also
observe a change (increase) of the telogen consumption
rate, Figure 4. As a consequence, the CT value calculated
for this system was still comparatively high (3.2).
Gromov et al.28,34,40 have observed an abrupt increase
of the rate of polymerization of acrylamide in aqueous
solvents when the molar fraction of water surpassed a
certain value. They explained this phenomenon by a
hydrophobic effect. Even below the phase transition
temperature PNIPAAm is known to form associates/
microaggregates in water.41 These microaggregates may
solubilize residual monomer molecules thereby altering
their local concentration, but may also exert a favorable
influence on the spatial arrangement of groups involved
in the chain propagation reaction.34,40 The influence of
a similar phenomenon can perhaps explain the increase
of the transfer reaction rate observed for the dioxane/
water system compared to all other investigated sol-
vents and solvent mixtures, especially if we assume that
the PNIPAAm microaggregates would preferentially
solubilize the chain transfer agent, which after all
contains a large hydrophobic group. The increase of the
local telogen concentration would conceivably increase
the transfer rate by a kind of “micellar catalysis” .
a certain critical value (cononsolvency effect).37,38
A
study of the PNIPAAm solubility in different mixtures
of methanol and water (data not shown) showed that
the maximum content of water in such a solution was
40%, at higher contents the PNIPAAm precipitated.
However, such a mixture gave the above-mentioned CT
value of 1.7, which allows the construction of a satisfac-
tory telomer carrying a reactive hydrazide moiety in
good proportion.
Several approaches to explain the solvent effect in
polymerizations can be found in the pertinent literature.
Gromov et al.34,35 also reported that changing the
solvent in a polymerization reaction may cause a change
in the overall rate of polymerization by several orders
of magnitude. This effect was most pronounced when
changing from an organic solvent to an aqueous solu-
tion. This solvent dependence was explained by a
decrease in the activation energy of the chain propaga-
tion reaction, which determines the rate constant,
kp.24,25,28 Acrylamide monomers can exist in a self-
associated form (dimers, trimers) due to their ability to
form intermolecular hydrogen bonds.35,36 Gromov et al.35
proposed that only the individual monomer is able to
participate in the chain propagation reaction. Solvents,
which destabilize the monomer associates by interaction
with the monomer via hydrogen bridges or by a dipole-
dipole interaction, will therefore increase the propagat-
ing rate of the polymerization. Chapiro et al.,36 on the
other hand, proposed that the growing radical chains
react preferentially with the monomer aggregates rather
than with a free monomer. However, according to their
theory solvents, which form hydrogen bridges or dipole-
dipole interactions stabilize rather than break the
associates. In both cases we can thus expect a faster
polymerization reaction in solvents that are able to
interact with the monomer/monomer associate struc-
tures.
Such an effect can serve as a basis for the explanation
of some of our results. The highest CT value (10.3) is
found for DMF, i.e., a solvent that is unable to form
strong hydrogen bonds or dipole-dipole interactions
with the monomer. Similar and intermediate CT values
are found for dioxane (CT ) 6.0, dipole-dipole interac-
tion) and methanol (CT ) 5.5, hydrogen bonds). The
value dropped to 3.2 when the reaction was carried out
in a 1:1 mixture of dioxane/water andsas already
statedsto a value as low as 1.7 when a 6:4 methanol/
water mixture was used. The strong decrease in the CT
value observed upon the addition of water may in
addition be due to the influence water has on certain
acrylamide monomers. It has been claimed28,35 that the
ability of water to form strong hydrogen bonds can favor
the enol form of the acrylamide monomer and therefore
Conclusions
The telomerization kinetics of NIPAAm show the
expected general behavior. The solvent is crucial for
creating a well-behaved system and exerts its effect via
the monomer consumption rate. Solvents, such as hydro-
organic mixtures, that interact well with the monomer
(hydrogen bridge formation) result in chain transfer
constants close to 1 (e.g., CT ) 1.7 for a 6:4 mixture of
methanol/water) and hence should be suitable for the
intended telomerization. Organic solvents and in par-
ticular solvents lacking the ability to interact with the
monomer, e.g., DMF, resulted in much higher CT values
(CT ) 10.7 for DMF). In such systems the desired chain
transfer effect on the polymer size (distribution) is much
less pronounced. A further decrease of the CT value by
adding more water to the reaction mixture is not
feasible in the case of NIPAAm due to the possible
manifestation of cononsolvency effects. Even in the case
of a comparatively predictable monomer like NIPAAm,
the characterization of the reaction kinetics is advised
for any new reaction system, as we observed at least
one case in our study, where not only the monomer
consumption rate, but also that of the telomer and
consequently the polymerization rate changed (dioxane/
water, 1:1), presumably due to a hydrophobic effect.
Ansin view of the high water contentssurprisingly high
chain transfer constant of CT ) 3.2 was observed in this
case.

Macromolecules, Vol. 38, No. 9, 2005
Investigation of Telomerization Kinetics 3637
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Acknowledgment. This work was financed by the
Swiss National Science Foundation (SNF, Grant No.
2100-049276.96 to R.F.), by the Commission for Tech-
nology and Innovation (CTI, Grant No 4731.2 to R.F.),
and by polyTag Technology SA, Ma¨nnedorf, Switzer-
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