Cyclodextrin-induced host-guest effects of classically prepared poly(NIPAM) bearing azo-dye end groups

Article abstract of DOI:10.3762/bjoc.8.224

A thermo-, pH- and cyclodextrin-(CD) responsive poly(N-isopropylacrylamide) (PNIPAM), with a N,N-dimethylaminoazobenzene end group was synthesized. Using 3-mercaptopropionic acid as a chain transfer agent, PNIPAM with a well-defined COOH end group was obtained. The acid end group was transferred to the corresponding acid chloride and then functionalized with N,Ndimethyl[4-(4'- aminophenylazo)phenyl]amine. This dye-end-group-labeled polymer showed acidochromic effects, depending on the pH and the presence of randomly methylated β-cyclodextrin (RAMEB-CD). Also higher cloud-point values for the lower critical solution temperature (LCST) in the presence of RAMEB-CD were observed. Additionally, this azo-dye-end-group-labeled polymer was complexed with hyperbranched polyglycerol (HPG) decorated with β-CD to generate hedgehog-like superstructures.

Full text of DOI:10.3762/bjoc.8.224

Cyclodextrin-induced host–guest effects of
classically prepared poly(NIPAM) bearing
azo-dye end groups
Gero Maatz, Arkadius Maciollek and Helmut Ritter*
Full Research Paper
Open Access
Address:
Beilstein J. Org. Chem. 2012, 8, 1929–1935.
Institute of Organic Chemistry and Macromolecular Chemistry,
Heinrich-Heine-University Duesseldorf, Universitaetsstraße 1,
D-40225 Duesseldorf, Germany
doi:10.3762/bjoc.8.224
Received: 01 August 2012
Accepted: 29 October 2012
Published: 14 November 2012
Email:
Helmut Ritter* - h.ritter@uni-duesseldorf.de
This article is part of the Thematic Series "Superstructures with
cyclodextrins: Chemistry and applications".
*
Corresponding author
Keywords:
Associate Editor: P. J. Skabara
azo-dye; cyclodextrins; end-group functionalization; host–guest
interaction; supramolecular aggregation
© 2012 Maatz et al; licensee Beilstein-Institut.
License and terms: see end of document.
Abstract
A thermo-, pH- and cyclodextrin- (CD) responsive poly(N-isopropylacrylamide) (PNIPAM), with a N,N-dimethylaminoazoben-
zene end group was synthesized. Using 3-mercaptopropionic acid as a chain transfer agent, PNIPAM with a well-defined COOH
end group was obtained. The acid end group was transferred to the corresponding acid chloride and then functionalized with N,N-
dimethyl[4-(4’-aminophenylazo)phenyl]amine. This dye-end-group-labeled polymer showed acidochromic effects, depending on
the pH and the presence of randomly methylated β-cyclodextrin (RAMEB-CD). Also higher cloud-point values for the lower crit-
ical solution temperature (LCST) in the presence of RAMEB-CD were observed. Additionally, this azo-dye-end-group-labeled
polymer was complexed with hyperbranched polyglycerol (HPG) decorated with β-CD to generate hedgehog-like superstructures.
Introduction
Polymers bearing dyes, such as azo, stilbene, anthraquinone or ation of dye-end-group-labeled polymers by using classical
fluorescence dyes, in the main or side chain have been widely free-radical polymerization techniques. Water-soluble poly-
described and investigated [1-15]. A few examples of dyes mers, which exhibit a lower critical solution temperature
located at the end group of polymers are prepared preferably (LCST), e.g., many poly(N-alkylacrylamides), have found
under anionic or controlled conditions such as reversible addi- numerous practical applications in waterborne smart materials
tion–fragmentation chain-transfer polymerization (RAFT) or such as bioactive surfaces, selective bioseparation, or hyper-
atom-transfer radical polymerization (ATRP) [14-16]. thermia-induced drug delivery [14]. Several reports are avail-
However, up to now, only a little is known about the prepar- able on the preparation and properties of thermally responsive
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Beilstein J. Org. Chem. 2012, 8, 1929–1935.
polyacrylamides containing azobenzene or stilbene dyes in the The final product 6 was obtained by condensation of 4 with the
side chain [3,14]. Furthermore, the interaction of dye-containing amino group of the dye N,N-dimethyl-[4-(4’-amino-
polymers with CD in water is of some interest, because of their phenylazo)phenyl]amine (5, Supporting Information File 1).
external, light-induced, reversible complexation [1-3,10,11]. In The molecular weight (Mn 3.4 kDa) and molecular weight
recent years, increasing attention has been given to supra- distribution (D 1.3) of 6 were determined by size-exclusion
molecular structures, the science of noncovalent assembly in chromatography (SEC). A Mn value of 5 was also calculated by
biological systems and chemical processes [12]. Hyper- end-group analysis based on 1H NMR measurements, showing
branched polymers such as polyglycerols (HPG), as a result of similar results (Supporting Information File 1).
their inherent dendritic topology, attract considerable interest
for a wide range of optical, medical or reagent-immobilization The UV–vis absorption spectrum of 6 in water showed the char-
applications [16].
acteristic broad band at λmax 460 nm, which corresponds to the
orange color at pH 7 [17]. However, upon decreasing of the pH
from 7 to 2, a large bathochromic (red) shift takes place, due to
Results and Discussion
Here, we describe the free-radical polymerization of the protonation of the azo dye of 6 [17]. As illustrated in
N-isopropylacrylamide (NIPAM, 1) in the presence of a Figure 1A this red shift corresponds to an increase of the
chain–transfer agent and its end-group functionalization by con- absorption up to 500–550 nm, whereas the band at 420 nm
densation with an azo dye. We also investigated the host–guest decreases. Thus, the protonated azonium tautomer is consid-
interaction of the azo-dye-labeled end group with randomly ered to be the predominant form in the red acidic aqueous solu-
methylated β-cyclodextrin (RAMEB-CD), and with HPG tion [17-19].
bearing β-CD on top. Thus, the focus of the present study was
directed towards the preparation and superstructure formation Due to our general interest in the use of CD in polymer chem-
of a thermo- and pH-responsive polymer bearing an azo dye at istry [3], the interaction of polymer 6 with RAMEB-CD was
the end group. In a first step, a chain-transfer polymerization investigated. The proposed formation of the host–guest struc-
(
CTP) of N-isopropylacrylamide (1) was carried out in the pres- ture between the azo-dye end group and the RAMEB-CD cavity
ence of 3-mercaptopropionic acid (2) and with 4,4’-azobis(4- was proved by use of 2D ROESY NMR spectroscopy
cyanovaleric acid) as initiator, to achieve a high degree of func- (Supporting Information File 1). The correlation signals
tionalization and yield of carboxy-terminated PNIPAM 3. Then, between the protons of the RAMEB-CD cavity and the aromatic
the free carboxy end group was transferred in to the corres- protons of the azo dye were observed. However, the correlation
ponding acid chloride by treatment with thionyl chloride, signals between the RAMEB-CD cavity and the methyl protons
yielding polymers with a propionyl chloride end group of the N,N-dimethylamine group of the azo dye were not
(
Scheme 1).
observed. This indicates a complete inclusion of the azo dye
Scheme 1: CTP of 1 and end-group functionalization with 5 yielding the azo-dye-end-group-labeled polymer 6.
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Beilstein J. Org. Chem. 2012, 8, 1929–1935.
Figure 1: Absorption spectra of 6 in water in a pH range from 7 to 2 (A). Absorption spectra of 6 in water depending on the pH in the presence of
RAMEB-CD (B).
inside the CD cavity with an orientation to the RAMEB-CD This is strong evidence for the interaction between the
axis [1]. In addition, UV–vis absorption spectra of 6 were hydrophobic azo-dye end group and the hydrophilic RAMEB-
recorded in aqueous solution at a pH range from 7 to 2 and in CD ring. Based on this experience, the complexation of the azo-
the presence of RAMEB-CD. Hereby, a strong blue shift in the dye end group of 6 with hyperbranched polyglycerol (HPG, 7)
absorption spectra was observed (Figure 1B). As mentioned decorated with β-CD was investigated. This kind of supra-
above, the absorption spectra of 6 after protonation indicate the molecular structure was generated to illustrate the broad appli-
formation of the azonium structure (Figure 1A). The subse- cability of 6 to generate, e.g., hedgehog-like nanoshapes. There-
quent complexation of this protonated azo dye with RAMEB- fore, 7 was prepared according to a procedure described in the
CD causes a hypsochromic shift. This strongly indicates that, literature recently [20-22]. The molecular weight of 7 (Mn
due to the presence of RAMEB-CD, a shift of the equilibrium 38 kDa) and the dispersity (D 1.7) were determined by SEC
from the azonium to the amonium form of the azo dye takes (Supporting Information File 1). To confirm the complexation
place. Consequently, the azo group in 6 is supramolecularly between the azo-dye-labeled polymers 6 and 7 and the forma-
protected from protonation by the surrounding CD ring, while tion of a hedgehog-like superstructure 8, DLS measurements in
the free dimethylamino group is easily protonated. These results water were carried out. As expected, the complexation of 6 by 7
correspond to the work of Toda et al. [19].
leads to an increase of the hydrodynamic diameters up to 18 nm
Figure 3).
(
Furthermore, the solution properties of polymer 6, depending on
the temperature in the presence of RAMEB-CD, were investi- The aggregation behavior of complex 8 in aqueous solution was
gated. As expected, 6 is soluble in cold water below the critical also investigated by DLS measurements. Figure 4 shows the
solution temperature (LCST). However, due to the hydrophobic temperature dependence of the z-average diameter (DZ) of the
azo-dye end group of 6, a slight reducing effect on the cloud hedgehog-like nanoshaped polymer 8. In the temperature range
point in comparison to pure PNIPAM, from 32 down to 29.5 °C from 25 to 32 °C no change of DZ was recorded.
is detected. As a result of complexation of the hydrophobic azo-
dye end group by RAMEB-CD, the cloud point increases from At 33 °C the DZ of 8 increased up to 21000 nm, but the values
2
9.5 back to 32 °C (Figure 2).
showed poor stability because of sedimentation. This means
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Beilstein J. Org. Chem. 2012, 8, 1929–1935.
Figure 2: LCST measurements of 6, the complex of 6 and RAMEB-CD, and in comparison to pure PNIPAM.
Figure 3: Hydrodynamic diameters of 6, 7 and 8 (1 mg/mL) at 20 °C.
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Beilstein J. Org. Chem. 2012, 8, 1929–1935.
Figure 4: z-Average diameter (DZ) of the complex 8 in water as a function of temperature (0.5 mg/mL, heating rate 0.5 °C/min).
that 8 is able to form larger particles above the LCST, even RAMEB-CD and β-CD were obtained from Wacker Chemie
resulting in precipitation [23]. However, the change of DZ GmbH, Burghausen, Germany and were used after being dried
showed a good reversibility upon cooling. The behavior can be overnight with a vacuum oil pump over P4O10. N,N-Dimethyl-
interpreted by the hydrophobic shell of 8 and the strong formamide (DMF) was purchased from Fluka, Germany.
hydrophobic interaction above the LCST, which causes the for- Dimethylsulfoxide-d6 (99.9 atom % D) and deuterium oxide,
mation of the large particles.
D2O were obtained from Deutero GmbH, Germany.
Conclusion
1H NMR spectra were recorded on a Bruker Avance DRX 300
In summary, we have presented the synthesis of an azo-dye- at 20 °C by using DMSO-d6 or deuteriumoxide (99.9%) as
end-group-labeled PNIPAM by free-radical polymerization. solvents. FTIR spectra were recorded on a Nicolet 6700 FTIR
The acidochromic and thermo-responsive behavior in aqueous spectrometer equipped with an ATR unit. The absorption
solution was analyzed by absorption and cloud-point measure- spectra were measured in 1 cm quartz cells on a Specord 210
ments. In addition, the influences of RAMEB-CD on both Plus UV–visible spectrophotometer (Analytik Jena AG,
effects were investigated. The intermolecular interaction Germany). SEC-MALS measurements were carried out on a
between the dye end group and RAMEB-CD was proven by combined system comprising the following elements: refrac-
absorption and 2D ROESY NMR experiments. Furthermore, we tive-index detector Optilabrex (Wyatt Technologies, laser
were able to show the formation of a hedgehog-like superstruc- wavelength 658 nm), three-angle light-scattering detector
ture, based on a hyperbranched polyglycerol, bearing CD miniDawn TREOS (Wyatt Technologies, laser wavelength
moieties, and the end-group-modified PNIPAM 6.
658 nm, detector angles at 43.5°, 90.0° and 136.5°), UV
detector Waters 486 (Waters), column set of HEMAbio 300 and
HEMAbio 100 (MZ-Analysentechnik), pump, degasser and
autosampler (Agilent 1200, Agilent technologies). The eluent
Experimental
General remarks
All reagents used were commercially available (Sigma-Aldrich, was ultrapure water at a flow rate 1 mL/min. The molecular
Acros Organics) and used without further purification. weight was calculated with Astra5 software from static-light-
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Beilstein J. Org. Chem. 2012, 8, 1929–1935.
scattering data, by using the Zimm model. As concentration ArH) 7.20 (br, NH), 3.84 (s, CH), 2.62 (br, CH2), 2.46 (br,
source, the refractive index was used. Calibration of the system CH2), 1.3–2.2 (backbone), 1.04 ppm (s, 6H, CH3); SEC
was performed with bovin serum albumin. Turbidity experi- measurements: Mn 3.4 kDa, PD 1.3; 1H NMR: 3.3 kDa.
ments were performed on a Tepper cloud-point photometer
TP1. The relative transmission of a laser beam with a wave-
Supporting Information
length of 670 nm was recorded for each experiment. The
measurements were performed in a temperature range between
The Supporting Information contains experimental
5
and 60 °C and at a heating rate of 1 °C min−1 by using Hellma
procedures for the preparation of 5, HPG,
propargyl-modified HPG, CD-monoazide, HPG bearing
β-CD (7), and spectroscopic data of 6 and the complex of 6
and RAMEB-CD.
Suprasil precision cells 110 Q-S. Critical solution temperatures
derived from these experiments were determined at 50% rela-
tive transmission. Dynamic light scattering (DLS) experiments
were carried out with a Malvern Zetasizer Nano; ZS ZEN 3600
at a temperature of 20 °C. The particle size distribution is
derived from a deconvolution of the measured intensity autocor-
relation function of the sample by a general purpose method,
i.e., the non-negative least squares algorithm, included in the
DTS software.
Supporting Information File 1
Experimental procedures and spectroscopic data.
[http://www.beilstein-journals.org/bjoc/content/
supplementary/1860-5397-8-224-S1.pdf]
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