End-group-functionalized poly(N,N-diethylacrylamide) via free-radical chain transfer polymerization: Influence of sulfur oxidation and cyclodextrin on self-organization and cloud points in water

Article abstract of DOI:10.3762/bjoc.10.61

In this work we report the synthesis of thermo-, oxidation- and cyclodextrin- (CD) responsive end-group-functionalized polymers, based on N,N-diethylacrylamide (DEAAm). In a classical free-radical chain transfer polymerization, using thiol-functionalized

Full text of DOI:10.3762/bjoc.10.61

End-group-functionalized poly(N,N-diethylacryl-
amide) via free-radical chain transfer polymerization:
Influence of sulfur oxidation and cyclodextrin on
self-organization and cloud points in water
Sebastian Reinelt, Daniel Steinke and Helmut Ritter*
Full Research Paper
Open Access
Address:
Beilstein J. Org. Chem. 2014, 10, 680–691.
Heinrich-Heine-University of Düsseldorf, Institute of Organic
Chemistry and Macromolecular Chemistry, Department of Preparative
Polymer Chemistry, Universitätsstraße 1, 40225 Düsseldorf, Germany
doi:10.3762/bjoc.10.61
Received: 02 December 2013
Accepted: 26 February 2014
Published: 19 March 2014
Email:
Helmut Ritter* - H.Ritter@uni-duesseldorf.de
This article is part of the Thematic Series "Superstructures with
cyclodextrins: Chemistry and applications II".
* Corresponding author
Keywords:
Guest Editor: G. Wenz
chain-transfer polymerization; cyclodextrins; end-group
functionalization; host–guest interaction; lower critical solution
temperature (LCST); poly(N,N-diethylacrylamide)
© 2014 Reinelt et al; licensee Beilstein-Institut.
License and terms: see end of document.
Abstract
In this work we report the synthesis of thermo-, oxidation- and cyclodextrin- (CD) responsive end-group-functionalized polymers,
based on N,N-diethylacrylamide (DEAAm). In a classical free-radical chain transfer polymerization, using thiol-functionalized
4-alkylphenols, namely 3-(4-(1,1-dimethylethan-1-yl)phenoxy)propane-1-thiol and 3-(4-(2,4,4-trimethylpentan-2-
yl)phenoxy)propane-1-thiol, poly(N,N-diethylacrylamide) (PDEAAm) with well-defined hydrophobic end-groups is obtained.
These end-group-functionalized polymers show different cloud point values, depending on the degree of polymerization and the
presence of randomly methylated β-cyclodextrin (RAMEB-CD). Additionally, the influence of the oxidation of the incorporated
thioether linkages on the cloud point is investigated. The resulting hydrophilic sulfoxides show higher cloud point values for the
lower critical solution temperature (LCST). A high degree of functionalization is supported by 1H NMR-, SEC-, FTIR- and
MALDI–TOF measurements.
Introduction
Supramolecular chemistry was first defined by J. M. Lehn in the H-bonds in DNA double helical structures. Both examples
1970`s as “chemistry of the intermolecular bond” [1,2]. represent the importance of non-covalent interactions in living
However, its origin goes back to Fisher`s “lock and key” model systems [3,4]. Since then, the field of self-assembly through
and also to Watson and Cricks description of the role of molecular recognition has attracted much attention also in the
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design of smart materials. In this context, cyclodextrins (CD) The scope of our investigation was the preparation of multiple-
are of interest as ring shaped host molecules, e.g., for the design stimuli-responsive PDEAAm polymers possessing hydrophobic
of stimuli-responsive hydrogels [5] or of optical sensors [6]. end-groups suitable for host–guest interactions with β-cyclodex-
Certain stimuli-responsive materials are characterized by the trin derivatives. Since 4-alkylphenyl moieties are good guests
presence of thioethers in the main chain. Tirelli et al. investi- for ß-cyclodextrin [37,38], we were encouraged to use 4-tert-
gated the oxidation-responsive behavior of thioethers for butylphenol as well as 4-tert-octylphenol and modify them with
biomedical applications [7-10]. The stimulus of these mostly mercapto groups. By doing so, well-defined PDEAAm end-
poly(propylene sulfide) containing copolymers is based on the group labeled polymers can be obtained by using classical free-
oxidation of thioethers to more hydrophilic sulfoxides or radical chain transfer polymerization techniques. These poly-
sulfones [11,12]. The specific sulfoxidation of a polymer bound mers contain oxidation-sensitive thioether linkages. Up to now,
end-group, which is in the focus of our present work, has not to the best of our knowledge, the simultaneous influence of oxi-
yet been investigated.
dation and cyclodextrin-sensitive end-groups on the solution
properties of poly(N,N-diethylacrylamide) has not been investi-
Polymeric materials exhibiting sensitivity to temperature are gated.
widely investigated [13]. Within this group of materials, ther-
mosensitive water-soluble polymers, possessing a lower critical Results and Discussion
solution temperature (LCST), have attracted much attention in Synthesis of thiol functionalized 4-alkylphenols. As depicted
several studies within the last decades [13-17].
in Scheme 1, the synthesis of the thiol-functionalized phenol
derivatives was accomplished in a three step synthesis. Etherifi-
The nature of the end-group of a short chain polymer may have cation of the phenolic hydroxy groups of 1a and 1b with allyl
a certain impact on the temperature dependence solubility in bromide (2) and subsequent radical addition of ethanethioic
aqueous media [18-24]. There are two prevalent approaches to S-acid (4) yielded the corresponding thioesters S-(3-(4-(1,1-
introduce well-defined end-groups in the polymer backbone: (a) dimethylethan-1-yl)phenoxy)propyl) ethanthioate (5a) and S-(3-
direct introduction by the use of suitable initiators respectively (4-(2,4,4-trimethylpentan-2-yl)phenoxy)propyl) ethanthioate
chain-transfer agents [23-25] or (b) indirect by polymer analo- (5b). The thioester functions were hydrolyzed to obtain the
gous modification of existing end-groups. For the post-modifi- thiols 3-(4-(1,1-dimethylethan-1-yl)phenoxy)propane-1-thiol
cation highly efficient reactions are needed to ensure a high (6a) and 3-(4-(2,4,4-trimethylpentan-2-yl)phenoxy)propane-1-
degree of functionalization. For this reason, often “click reac- thiol (6b) in good yields after purification. The successful syn-
tions” [26] such as esterifications [27], azide–alkyne [22], thesis was furthermore confirmed by 1H NMR, 13C NMR and
thiol–ene [28], thiol–isocyanate [29] and others are used. FTIR spectroscopy as well as mass spectrometry (see
Thereby most studies have in common that synthesis of the Supporting Information File 1, Figures S1 to S4 for the 1H and
polymer with thermo-responsive properties is preferably accom- 13C NMR data).
plished by either living anionic polymerization, or controlled
radical polymerization [18,21,22,24,29-34]. Some publications Synthesis of the end-group functionalized polymers. The
make use of free-radical chain transfer polymerization and thiol functionalized 4-alkylphenols (6a and 6b) were used as
subsequent polymer post-modification [25,27,35,36].
chain transfer agents (CTA) for the free-radical polymerization
Scheme 1: Synthetic route for the synthesis of thiol functionalized 4-alkylphenols.
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Beilstein J. Org. Chem. 2014, 10, 680–691.
of N,N-diethylacrylamide (DEAAm) (7) (see Scheme 2). First influence of the chain length on the solubility in water. The
the chain-transfer constant of 6a and 6b for the polymerization molar ratio of [CTA] to [2,2’-azobis(2-methylpropionnitrile)
of DEAAm in N,N-dimethylformamide (DMF) at 70 °C was (AIBN)] was kept thereby constant at a ratio of 20 to 1. The
calculated from experimental results by using the Mayo method final polymers (8a–d and 9a–d) were obtained as colorless
[39]. Chain-transfer constants of CTr,6a = 0.84 and CTr,6b = 0.87 solids after dialysis for 7 days. The analytical data of 8a–d and
were found (see Supporting Information File 1, Figure S5), 9a–d are listed in Table 1.
which are close to the ideal value of 1.0 where the concentra-
tion of the transfer agent relative to the monomer concentration Exemplarily, Figure 1 shows a section of the MALDI–TOF
remains constant [40].
spectrum of polymer 8b confirming a high degree of 4-tert-
butylphenol end-group functionalization. Just single series of
For our investigation the molar ratio of [DEAAm] to [CTA] peaks with a peak separation of 127.1 which corresponds to the
was varied from 20 to 1 up to 50 to 1 in order to investigate the mass of DEAAm plus the proposed end-group (224.1) and
Scheme 2: Synthetic route for the chain transfer polymerization of N,N-diethylacrylamide (7) with CTA 6a and 6b and subsequent oxidation of the
resulting polymers to the corresponding polymers containing sulfoxides.
Table 1: Number average molecular weights ( ), dispersity (D), glass transition temperatures (Tg) and cloud points of the end-group-functionalized
polymers (8a–d and 9a–d).
Polymer
CTA
Ratio
[DEAAm]/[CTA]
Tg
[°C]
Cloud point
[°C]c
[kDa]a
[kDa] (D)b
8a
8b
8c
8d
6a
6a
6a
6a
20
30
40
50
2.5
4.8
6.1
7.8
3.3 (4.0)
5.6 (3.0)
5.7 (3.2)
7.2 (2.8)
49.1
62.3
65.9
75.3
15.1
21.2
24.3
25.8
9a
9b
9c
9d
6b
6b
6b
6b
20
30
40
50
2.9
4.4
5.9
7.2
3.4 (3.7)
5.4 (3.1)
5.2 (3.4)
6.9 (3.0)
50.4
63.9
73.2
75.4
21.3
25.2
27.6
28.7
aDetermined by 1H NMR spectroscopy through end-group analysis; bdetermined by size exclusion chromatography with DMF as eluent and a lower
cut off of the column of 1.0 kDa; cdetermined by turbidimetry measurements at a heating rate of 1 K/min. The concentration was 10 mg/mL in Milli-
pore water. The cloud point values were derived from the heating curve.
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Figure 1: Section of the MALDI –TOF spectrum of polymer 8b, indicating the high degree of end-group functionalization by the use of free-radical
chain transfer polymerization.
sodium (23) can be found. Additionally, the
values deter- (see Table 1). The NMR based
values were obtained by
mined from SEC data were in agreement with the values calcu- comparing the integral of aromatic signals at 6.7–6.8 ppm and
lated by end-group analysis based on 1H NMR measurements 7.1–7.3 ppm with the signals of the backbone between
Figure 2: 1H NMR spectrum of polymer 9b in CDCl3 (300 MHz, rt).
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Beilstein J. Org. Chem. 2014, 10, 680–691.
2.0–3.9 ppm and 0.7–2.0 ppm, respectively (see Figure 2 for trum clearly indicated an upfield shift of the OCH2-group
polymer 9b and Supporting Information File 1, Figure S6 for supporting also a successful oxidation. Thus the analytical data
8b).
reveals no indication for further oxidation of the polymer chain
or additional oxidized structures, e.g. of the methine groups in
Oxidation of the end-group-functionalized polymers. The the main chain.
selective oxidation of the thioether groups to the corresponding
sulfoxides was accomplished by oxidation with hydrogen Impact of the degree of polymerization and structure of the
peroxide in analogy to literature [11].
end-group on the cloud point values. Aqueous solutions of
poly(N,N-diethylacrylamide) (PDEAAm) exhibtit a coil to
As expected, the MALDI–TOF mass spectrum for 8bOx globule transition at the lower critical solution temperature
showed only one series of peaks, which was shifted by (LCST) of approximately 33 °C in water for low molecular
16 Dalton in comparison to the origin series of peaks (see weight polymers as stated in previous studies [41,42]. In the
Figure 3). The FTIR spectrum showed a decrease of transmis- present study, the cloud points of PDEAAm were measured on
sion at a wave length of 1024 cm−1 corresponding to the S=O 1 wt % aqueous solution in water. A concentration of 1 wt %
stretching vibration of the sulfoxide [11] and no shift of the seemed to be a reasonable concentration since Idziak et al. [42]
C=O vibration at 1625 cm–1. Additionally, the 1H NMR spec- showed that a variation of the polymer concentration of
Figure 3: Top left: Section of the FTIR-spectrum of polymer 8b (black line) in comparison to 8bOx (red line); top right: 1H NMR spectrum of polymer
8b (black line) and polymer 8bOx (red line) in CDCl3 (300 MHz, rt); bottom left: Section of the MALDI–TOF spectrum of polymer 8bOx, supporting the
high efficiency of the oxidation of the thioether linkage to the corresponding sulfoxides; bottom right: Comparison of the MALDI–TOF spectrum of
polymer 8b (black line) with polymer 8bOx (red line).
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Beilstein J. Org. Chem. 2014, 10, 680–691.
PDEAAm (obtained in a free-radical polymerization with AIBN
as initiator) in the range of 0.5 wt % up to 20 wt % does not
considerably affect the LCST.
All obtained polymers (8a–d, 9a–d) were completely soluble in
cold water below their LCST. Since the molecular weights of
the presented polymers (8a–d, 9a–d) were relatively low, the
hydrophobic end-groups shifted the cloud point significantly to
lower temperatures in comparison to the cloud point of unmodi-
fied PDEAAm. Accordingly, the impact of the hydrophobic
end-group on the cloud point of the polymer increased with
decreasing molecular weight and thus showing an inverse
dependency (Figure 4 and Table 2). This is in agreement with
the findings of previous studies. As stated by Chung et al. the
dehydration of the polymer chain during the phase transition is
initiated at the chain ends, where the mobility is highest [36].
For poly(N-isopropylacrylamide) (PNIPAM) previous studies
demonstrated a broadened phase transition for polydisperse and
low molecular weight samples [18,32,43]. Although the poly-
mers (8a–d, 9a–d) investigated in the present study were
Figure 4: Dependency of the cloud point values on the degree of poly-
merization (calculated by end-group analysis based on 1H NMR
measurements).
(
= 2.5 kDa) as the molecular weight decreased by 5.3 kDa.
prepared via a free-radical instead of a living polymerization In contrast, with regard to cloud points of the 4-tert-octylphenol
technique and had a relative low molecular weight, the optical end-group functionalized polymers (9a–d) only a drop from
transmission diagrams indicate a relatively sharp transition in a 28.7 °C (9d,
= 7.2 kDa) to 21.3 °C (9a,
= 2.9 kDa) was
temperature range of 1 °C up to 2 °C as well as a good revers- found whereas the molecular weight decreased by 4.3 kDa. Our
ibility upon cooling (see Supporting Information File 1, Figures findings regarding the cloud point depression of thermorespon-
S7 and S8).
sive polymers containing hydrophobic end-groups with
decreasing molecular weight [20,24,30,44] or the effect of an
As it can be seen in Table 2 and Figure 4 the hydrophobic char- increasing hydrophobic environment in amphiphilic conet-
acter caused by the chain-end was considerable for both types works [45] are in accordance with previous studies. Theoretic-
of end-groups. For instance, the cloud point of 8d ally a stronger remarkable effect on the cloud point of the poly-
(
= 7.8 kDa) dropped from 25.8 °C to 15.1 °C for 8a mers bearing a 4-tert-octylphenol end-group compared to the
Table 2: Cloud points of the different polymers (8a–d and 9a–d): Influence of RAMEB-CD and oxidation with H2O2.
Cloud Point
[°C]b
Cloud Point after addition of RAMEB-CD
[°C]b
(Pn)
[kDa]a
Polymer
Before oxidation After oxidationc
1 equiv
2 equiv
4 equiv
RAMEB-CDd
RAMEB-CDd
RAMEB-CDd
8a
8b
8c
8d
2.5 (18)
15.1
21.2
24.3
25.8
21.0
28.8
30.0
30.7
27.9
24.5
26.2
27.0
34.2
33.6
33.4
33.2
34.2
33.8
33.4
33.5
4.8 (36)
6.1 (46)
7.8 (59)
9a
9b
9c
9d
2.9 (21)
4.4 (32)
5.9 (44)
7.2 (54)
21.3
25.2
27.6
28.7
24.3
27.4
28.2
28.8
–e
–e
21.1
20.7
22.4
27.2
33.7
33.3
33.2
33.3
19.6
26.3
aDetermined by 1H NMR spectroscopy through end-group analysis; bdetermined by turbidimetry measurements at a heating rate of 1 K/min. The
concentration was 10 mg/mL in Millipore water. The cloud point values were derived from the heating curve; coxidation was performed in aqueous
hydrogen peroxide solution as stated in the experimental section; dthe stoichiometry was calculated on the basis of the data obtained from end-group
analysis based on 1H NMR measurements; ethe polymer is insoluble in water, no optical clear solution down to 5 °C.
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4-tert-butylphenol end-group could be expected. Consequently
hydrophobic interactions must play an important role for this
effect. Regarding Figure 4 and Table 2 the hydrophobic interac-
tions seem to be stronger for the 4-tert-octylphenol-modified
polymers and thus leading to higher cloud points since aggrega-
tion leads to a suppression of the hydrophobicity of a polymer
[25,35,36].
Impact of oxidation of the thioether-linkages on the solu-
tion properties. Since the polymers bear thioether groups, the
influence of their oxidation to sulfoxides on the cloud point was
investigated. The more hydrophilic polar sulfoxide group in
comparison to the thioether group should lead to an increase of
solubility in water. Thus higher cloud point values for all poly-
mers were found (see Table 2). The cloud point shifts are shown
in Figure 5 for polymer 8 as well as 9. The illustration indicates
that the strength of response to oxidation of the aqueous solu-
tions of polymers 8 and 9 is a function of the degree of poly-
Figure 5: Shifts of the cloud points after the oxidation of the polymers
(8a–d, 9a–d) to its corresponding sulfoxides (8aOx–8dOx,
9aOx–9dOx) as a function of degree of polymerization.
merization. Thus the oxidation showed a more remarkable Complexation of the polymer end-groups with randomly-
cloud point shift of the short chain polymers. Furthermore, it methylated-β-cyclodextrin (RAMEB-CD) – Impact on the
turned out, that the cloud points of the 4-tert-butylphenol end- cloud points. In addition the solution properties of polymers
group functionalized polymers (8a–d) were tunable to a larger 8a–d and 9a–d as a function of temperature were also evalu-
extent via oxidation compared to the polymers bearing the ated in the presence of different amounts of RAMEB-CD. In
4-tert-octylphenol group. For instance polymer 8b showed a general, the 4-tert-butylphenyl as well as the 4-tert-octylphenyl
threefold higher cloud point shift (7.6 °C) than the corres- end-group are able to build host-guest inclusion complexes with
ponding 4-tert-octylphenol-bearing polymer 9b (2.2 °C). As an the RAMEB-CD cavity [38,46]. This interaction was verified
example, the cloud point curve of polymer 8b before and after by 2D NOESY NMR spectroscopy clearly showing correlation
oxidation is illustrated in Figure 6.
signals between the protons of the RAMEB-CD cavity and the
Figure 6: Turbidimetry measurements of polymer 8b (straight black line – heating curve; dotted black line – cooling curve), 8bOx (straight red line –
heating curve; dotted red line – cooling curve) and the complex of 8b and RAMEB-CD (2 equiv) (straight blue line – heating curve; dotted blue line –
cooling curve) in aqueous solution at a concentration of 10 mg/mL.
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Beilstein J. Org. Chem. 2014, 10, 680–691.
aromatic protons as well as the aliphatic protons in case of the end-group is difficult, a slight excess of RAMEB-CD is neces-
4-tert-octyl end-group. Exemplarily, in Figure 7 the 2D NOESY sary for the complete covering of each 4-tert-butylphenol end-
spectrum of polymer 8b in the presence of RAMEB-CD is group. These findings are in accordance with the literature
shown.
[24,44].
The formation of host–guest complexes of the polymer bound The addition of equimolar amounts of RAMEB-CD to solu-
end-group with the RAMEB-CD cavity should reduce the tions of polymers 9a–d containing 4-tert-octylphenol end-
hydrophobic character of the end-group and thus increase the groups led to an unexpected decrease of the cloud point. This
cloud points of the polymers to a value close to the value of effect was most remarkable for the low molecular weight poly-
pure PDEAAm as already shown by our group [24,47]. Taking mers 9a and 9b. For instance, a polymer 9a was fully insoluble
a fourfold excess of RAMEB-CD in relation to the polymer in water in the presence of one equivalent RAMEB-CD even at
end-group this assumption was fulfilled for all polymers (8a–d temperatures down to 5 °C. In case of polymer 9c the cloud
and 9a–d). The values of the cloud point were increased after point dropped from 27.6 to 19.6 °C. Increasing the amount of
complexation up to the range of 33.2 °C and 34.2 °C, respect- RAMEB-CD led to an increase of the cloud points again.
ively (Table 2). However the addition of a twofold excess of
RAMEB-CD to 8a–d increased the cloud points also to values Dynamic light scattering measurements: Influence of
above 33 °C. Exemplarily, the shift of the cloud point curve of RAMEB-CD on self-organization behavior. Dynamic light
polymer 8b after addition of two equivalents RAMEB-CD is scattering (DLS) measurements were conducted in order to
illustrated in Figure 6. The addition of only an equimolar understand the surprising phenomena that the cloud point of
amount of RAMEB-CD caused an increase of the cloud points 4-tert-octylphenol end-group bearing polymers first decreased
of 8a–d up to values between 24.5 °C (8b) and 27.9 °C (8a) by adding small amounts of RAMEB-CD (one equivalent) to
(Table 2). Due to the fact that the host–guest interactions are the aqueous polymer solution and subsequent increased again
equilibria and the sterical accessibility of the polymer bound by rising the amount of RAMEB-CD up to four equivalents.
Figure 7: 2D NMR NOESY spectrum of polymer 8b with two equivalents RAMEB-CD in D2O (600 MHz, rt).
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The number averaged hydrodynamic diameters (dh) of the poly- These results indicated that the 4-tert-alkylphenol end-groups
mers 8a–d and 9a–d in aqueous solution (concentration: tend to aggregate strongly leading to the formation of intermol-
10 mg/mL; temperature: 10 °C) were determined to 4.6 nm up ecular core-shell micellar-like structures as stated in Figure 8.
to 6.8 nm. The addition of one equivalent RAMEB-CD to the However, it should be mentioned that especially after the addi-
aqueous polymer solutions of 8a–d and 9c–d led to a decrease tion of RAMEB-CD the intensity-weighted distributions
of the number averaged hydrodynamic diameter (see Table 3). showed also the formation of larger aggregates, but since the
Exemplarily Figure 8 shows the hydrodynamic diameter of scattering intensity is dependent on the sixth power of the radius
aqueous solutions of polymer 9c, RAMEB-CD and polymer 9c of the particle the percentage of these particles is exaggerated
in the presence of one equivalent RAMEB-CD.
[48].
The formation of thermo-responsive micelles of end-group
functionalized respectively block copolymers in aqueous solu-
tion have been investigated in previous studies [35,48,49].
Studies on hydrophobically PNIPAM have also demonstrated
the formation of core-shell structures exhibiting a corona of
PNIPAM chains [25,35,36]. The formation of micellar-like
structures lead to an isolation of the hydrophobic end-groups
from water and thus to a dramatically supression of the
hydrophobicity of the polymer. Due to the interaction of the
polymeric end-group with RAMEB-CD the formation of these
core-shell structures is inhibited. The 4-tert-octylphenol end-
group has a stronger hydrophobic character compared to the
4-tert-butylphenol group. Furthermore, it is well know that
RAMEB-CD is able to build 2:1 complexes with 4-tert-
octylphenol derivatives [46]. Thus it seems likely that one
equivalent RAMEB-CD is not sufficient to depress the
hydrophobic character of the 4-tert-octylphenol end-group
Table 3: Number averaged hydrodynamic diameters of the polymers
and the supramolecular complexes with RAMEB-CD in water at 10 °C.
Polymer
Hydrodynamic diameter [nm]
10 mg/mL
10 mg/mL + 1 equiv
RAMEB-CD
8a
8b
8c
8d
9a
9b
9c
9d
6.3 ± 1.6
5.2 ± 1.5
5.4 ± 1.5
4.6 ± 1.5
6.8 ± 1.8
6.5 ± 1.7
6.5 ± 1.8
6.5 ± 1.7
2.4 ± 0.8
3.6 ± 1.2
3.4 ± 1.2
3.4 ± 1.2
Insolublea
Insolublea
2.9 ± 1.0
3.1 ± 1.1
aAt a temperature of 10 °C the solution was not optical clear, the
sample is already aggregating.
Figure 8: Left: Schematic illustration of the micellar-like structures and reversibility by addition of RAMEB-CD; Right: DLS measurements size distrib-
utions for RAMEB-CD (orange line), 9c (black line) and 9c plus 1 equiv RAMEB-CD (blue line).
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Beilstein J. Org. Chem. 2014, 10, 680–691.
completely, so that the micellar-like structures of 9a–d in tures hence an increase of the cloud points were observed by
aqueous solution are more hydrophilic than the supramolecular addition of one equivalent RAMEB-CD. This phenomenon is
complexes of 9a–d with one equivalent RAMEB-CD. Conse- illustrated in Figure 9.
quently, as described above, a decrease of the cloud points of
aqueous solutions of polymers 9a–d were observed when Conclusion
adding only one equivalent RAMEB-CD. In case of the 4-tert- In summary, we have evidenced the synthesis and characteriza-
butylphenol modified polymers 8a–d the supramolecular tion of ω-(4-alyklphenyl)-functionalized PDEAAm via free-
complexes are more hydrophilic than the micellar-like struc- radical chain transfer polymerization in N,N-dimethylfor-
Figure 9: Schematic illustration of the micellar-like structures, its deformation upon addition of one equivalent RAMEB-CD and the influence on the
cloud point values determined by turbitidy measurements on aqueous solutions (concentration: 10 mg/mL).
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9. Lallana, E.; Tirelli, N. Macromol. Chem. Phys. 2013, 214, 143–158.
doi:10.1002/macp.201200502
mamide as solvent. By changing the feed ratio of [CTA] to
[DEAAm] the solution properties were tunable. A linear
decrease of the cloud point with a decreasing degree of poly-
merization was observed. Aqueous polymer solutions showed
multiple-stimuli-responsive behavior.
10.Li, M.-H.; Keller, P. Soft Matter 2009, 5, 927–937.
doi:10.1039/b815725a
11.Carampin, P.; Lallana, E.; Laliturai, J.; Carroccio, S. C.; Puglisi, C.;
Tirelli, N. Macromol. Chem. Phys. 2012, 213, 2052–2061.
doi:10.1002/macp.201200264
12.Napoli, A.; Boerakker, M. J.; Tirelli, N.; Nolte, R. J. M.;
Sommerdijk, N. A. J. M.; Hubbell, J. A. Langmuir 2004, 20, 3487–3491.
doi:10.1021/la0357054
The cloud points of the aqueous polymer solutions were tunable
by two different stimuli. The incorporated thioether linkages
were addressable by oxidation. The corresponding more
hydrophilic sulfoxides showed an increase of the cloud point
values up to almost 8 °C depending on the end-group and the
molecular weight of the polymer. Thus we were able to show
for the first time the influence of sulfur oxidation of polymer
bound end-groups on the solution properties in water. Simulta-
neously the cloud points were tunable by the addition of
RAMEB-CD. The cloud points of all polymers (8a–d, 9a–d)
could shift to a value of 33–34 °C in case of RAMEB-CD in
excess.
13.Schmaljohann, D. Adv. Drug Delivery Rev. 2006, 58, 1655–1670.
doi:10.1016/j.addr.2006.09.020
14.Liu, H. Y.; Zhu, X. X. Polymer 1999, 40, 6985–6990.
doi:10.1016/S0032-3861(98)00858-1
15.Dimitrov, I.; Trzebicka, B.; Müller, A. H. E.; Dworak, A.;
Tsvetanov, C. B. Prog. Polym. Sci. 2007, 32, 1275–1343.
doi:10.1016/j.progpolymsci.2007.07.001
16.Roy, D.; Brooks, W. L. A.; Sumerlin, B. S. Chem. Soc. Rev. 2013, 42,
7214–7243. doi:10.1039/c3cs35499g
17.de las Heras Alarcón, C.; Pennadam, S.; Alexander, C.
Chem. Soc. Rev. 2005, 34, 276–285. doi:10.1039/b406727d
18.Plummer, R.; Hill, D. J. T.; Whittaker, A. K. Macromolecules 2006, 39,
8379–8388. doi:10.1021/ma0614545
19.Pietsch, C.; Schubert, U. S.; Hoogenboom, R. Chem. Commun. 2011,
47, 8750–8765. doi:10.1039/c1cc11940k
Supporting Information
20.Jochum, F. D.; zur Borg, L.; Roth, P. J.; Theato, P. Macromolecules
2009, 42, 7854–7862. doi:10.1021/ma901295f
A full experimental section can be found in the Supporting
Information. Description of the materials, characterization
methods and syntheses of the obtained compounds;
spectroscopic data (1H, 13C and 2D NMR); curves of the
turbidity measurements, Mayo-Plot for the determination of
the chain transfer constant.
21.Akiyama, H.; Tamaoki, N. Macromolecules 2007, 40, 5129–5132.
doi:10.1021/ma070628v
22.Narumi, A.; Fuchise, K.; Kakuchi, R.; Toda, A.; Satoh, T.;
Kawaguchi, S.; Sugiyama, K.; Hirao, A.; Kakuchi, T.
Macromol. Rapid Commun. 2008, 29, 1126–1133.
doi:10.1002/marc.200800055
23.Kujawa, P.; Segui, F.; Shaban, S.; Diab, C.; Okada, Y.; Tanaka, F.;
Winnik, F. M. Macromolecules 2006, 39, 341–348.
doi:10.1021/ma051876z
Supporting Information File 1
Title Experimental part.
[http://www.beilstein-journals.org/bjoc/content/
supplementary/1860-5397-10-61-S1.pdf]
24.Schmidt, B. V. K. J.; Hetzer, M.; Ritter, H.; Barner-Kowollik, C.
Macromol. Rapid Commun. 2013, 34, 1306–1311.
doi:10.1002/marc.201300478
25.Winnik, F. M.; Davidson, A. R.; Hamer, G. K.; Kitano, H.
Macromolecules 1992, 25, 1876–1880. doi:10.1021/ma00033a006
26.Kolb, H. C.; Finn, M. G.; Sharpless, K. B. Angew. Chem., Int. Ed. 2001,
40, 2004–2021.
References
1. Lehn, J. M. Pure Appl. Chem. 1978, 50, 871–892.
doi:10.1351/pac197850090871
doi:10.1002/1521-3773(20010601)40:11<2004::AID-ANIE2004>3.3.CO
;2-X
2. Lehn, J.-M. Angew. Chem., Int. Ed. Engl. 1990, 29, 1304–1319.
doi:10.1002/anie.199013041
27.Maatz, G.; Maciollek, A.; Ritter, H. Beilstein J. Org. Chem. 2012, 8,
1929–1935. doi:10.3762/bjoc.8.224
3. Fischer, E. Ber. Dtsch. Chem. Ges. 1894, 27, 2985–2993.
doi:10.1002/cber.18940270364
28.Yu, B.; Chan, J. W.; Hoyle, C. E.; Lowe, A. B.
J. Polym. Sci., Part A: Polym. Chem. 2009, 47, 3544–3557.
doi:10.1002/pola.23436
4. Watson, J. D.; Crick, F. H. C. Nature 1953, 171, 737–738.
doi:10.1038/171737a0
5. Yamaguchi, H.; Kobayashi, Y.; Kobayashi, R.; Takashima, Y.;
Hashidzume, A.; Harada, A. Nat. Commun. 2012, 3, No. 603.
doi:10.1038/ncomms1617
29.Li, H.; Yu, B.; Matsushima, H.; Hoyle, C. E.; Lowe, A. B.
Macromolecules 2009, 42, 6537–6542. doi:10.1021/ma9010878
30.Xia, Y.; Burke, N. A. D.; Stöver, H. D. H. Macromolecules 2006, 39,
2275–2283. doi:10.1021/ma0519617
6. Fleischmann, C.; Ritter, H. Macromol. Rapid Commun. 2013, 34,
1085–1089. doi:10.1002/marc.201300292
31.Matyjaszewski, K.; Xia, J. Chem. Rev. 2001, 101, 2921–2990.
doi:10.1021/cr940534g
7. Hu, P.; Tirelli, N. Bioconjugate Chem. 2012, 23, 438–449.
doi:10.1021/bc200449k
32.Xia, Y.; Yin, X.; Burke, N. A. D.; Stöver, H. D. H. Macromolecules 2005,
38, 5937–5943. doi:10.1021/ma050261z
8. Napoli, A.; Valentini, M.; Tirelli, N.; Müller, M.; Hubbell, J. A. Nat. Mater.
2004, 3, 183–189. doi:10.1038/nmat1081
33.Hales, M.; Barner-Kowollik, C.; Davis, T. P.; Stenzel, M. H. Langmuir
2004, 20, 10809–10817. doi:10.1021/la0484016
690

Beilstein J. Org. Chem. 2014, 10, 680–691.
34.Freitag, R.; Baltes, T.; Eggert, M. J. Polym. Sci., Part A: Polym. Chem.
1994, 32, 3019–3030. doi:10.1002/pola.1994.080321603
35.Chung, J. E.; Yokoyama, M.; Aoyagi, T.; Sakurai, Y.; Okano, T.
J. Controlled Release 1998, 53, 119–130.
doi:10.1016/S0168-3659(97)00244-7
36.Chung, J. E.; Yokoyama, M.; Suzuki, K.; Aoyagi, T.; Sakurai, Y.;
Okano, T. Colloids Surf., B 1997, 9, 37–48.
doi:10.1016/S0927-7765(97)00015-5
37.Rekharsky, M. V.; Inoue, Y. Chem. Rev. 1998, 98, 1875–1918.
doi:10.1021/cr970015o
38.Müller, B.-K.; Ritter, H. J. Inclusion Phenom. Macrocyclic Chem. 2012,
72, 157–164. doi:10.1007/s10847-011-9955-0
39.Mayo, F. R. J. Am. Chem. Soc. 1943, 65, 2324–2329.
doi:10.1021/ja01252a021
40.Matyjaszewski, K.; Davis, T. P., Eds. Handbook of radical
polymerization; John Wiley and Sons: Hoboken, 2002.
doi:10.1002/0471220450
41.Lessard, D. G.; Ousalem, M.; Zhu, X. X.; Eisenberg, A.; Carreau, P. J.
J. Polym. Sci., Part B: Polym. Phys. 2003, 41, 1627–1637.
doi:10.1002/polb.10517
42.Idziak, I.; Avoce, D.; Lessard, D.; Gravel, D.; Zhu, X. X.
Macromolecules 1999, 32, 1260–1263. doi:10.1021/ma981171f
43.Schild, H. G.; Tirrell, D. A. J. Phys. Chem. 1990, 94, 4352–4356.
doi:10.1021/j100373a088
44.Duan, Q.; Miura, Y.; Narumi, A.; Shen, X.; Sato, S.-I.; Satoh, T.;
Kakuchi, T. J. Polym. Sci., Part A: Polym. Chem. 2006, 44, 1117–1124.
doi:10.1002/pola.21208
45.Kali, G.; Vavra, S.; László, K.; Iván, B. I. Macromolecules 2013, 46,
5337–5344. doi:10.1021/ma400535r
46.Kemnitz, M.; Ritter, H. Beilstein J. Org. Chem. 2012, 8, 2176–2183.
doi:10.3762/bjoc.8.245
47.Ritter, H.; Sadowski, O.; Tepper, E. Angew. Chem., Int. Ed. 2003, 42,
3171–3173. doi:10.1002/anie.200250814
48.André, X.; Zhang, M.; Müller, A. H. E. Macromol. Rapid Commun.
2005, 26, 558–563. doi:10.1002/marc.200400510
49.Yan, J.; Ji, W.; Chen, E.; Li, Z.; Liang, D. Macromolecules 2008, 41,
4908–4913. doi:10.1021/ma7026726
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