UV light and temperature responsive supramolecular ABA triblock copolymers via reversible cyclodextrin complexation

Article abstract of DOI:10.1021/ma302386w

A novel triblock macromolecular architecture based on cyclodextrin (CD) complexation is presented. A CD-functionalized biocompatible poly(N-(2-hydroxypropyl)methacrylamide) (PHPMA) building block (3800 ≤ M _n ≤ 10 600 g mol^-1; 1.29 ≤ Crossed D sign _M ≤ 1.46) and doubly guest-containing poly(N,N-dimethylacrylamide) (PDMAAm) (6400 ≤ M_n ≤ 15 700 g mol^-1; 1.06 ≤ Crossed D sign_M ≤ 1.15) and poly(N,N-diethylacrylamide) (PDEAAm) (5400 ≤ M_n ≤ 12 100 g mol^-1; 1.11 ≤ Crossed D sign_M ≤ 1.33) segments were prepared via reversible addition-fragmentation chain transfer (RAFT) polymerization and subsequently utilized for the formation of a well-defined supramolecular ABA triblock copolymer. The block formation was evidenced via dynamic light scattering (DLS), nuclear Overhauser effect spectroscopy (NOESY), and turbidity measurements. Furthermore, the connection of the blocks was proven to be temperature responsive and - in the case of azobenzene guests - responsive to the irradiation with UV light. The application of these stimuli leads to the disassembly of the triblock copolymer, which was shown to be reversible. In the case of PDEAAm containing triblock copolymers, the temperature-induced aggregation was investigated as well.

Full text of DOI:10.1021/ma302386w

Article
pubs.acs.org/Macromolecules
UV Light and Temperature Responsive Supramolecular ABA Triblock
Copolymers via Reversible Cyclodextrin Complexation
Bernhard V. K. J. Schmidt,† Martin Hetzer,‡ Helmut Ritter,*,‡ and Christopher Barner-Kowollik*,†
†Preparative Macromolecular Chemistry, Institut fur Technische Chemie und Polymerchemie, Karlsruhe Institute of Technology
̈
(KIT), Engesserstr. 18, 76128 Karlsruhe, Germany
‡Lehrstuhl fur Praparative Polymerchemie, Institut fur Organische Chemie und Makromolekulare Chemie, Heinrich-Heine
̈
̈
̈
Universitat, Universitatsstrasse 1, Geb. 26.33.00, 40225 Dusseldorf, Germany
̈
̈
̈
S
* Supporting Information
ABSTRACT: A novel triblock macromolecular architecture
based on cyclodextrin (CD) complexation is presented. A CD-
functionalized biocompatible poly(N-(2-hydroxypropyl)-
methacrylamide) (PHPMA) building block (3800 ≤ Mn ≤
10 600 g mol−1; 1.29 ≤ ĐM ≤ 1.46) and doubly guest-
containing poly(N,N-dimethylacrylamide) (PDMAAm) (6400
≤ Mn ≤ 15 700 g mol−1; 1.06 ≤ ĐM ≤ 1.15) and poly(N,N-
diethylacrylamide) (PDEAAm) (5400 ≤ Mn ≤ 12 100 g mol−1;
1.11 ≤ ĐM ≤ 1.33) segments were prepared via reversible
addition−fragmentation chain transfer (RAFT) polymerization
and subsequently utilized for the formation of a well-defined
supramolecular ABA triblock copolymer. The block formation
was evidenced via dynamic light scattering (DLS), nuclear Overhauser effect spectroscopy (NOESY), and turbidity
measurements. Furthermore, the connection of the blocks was proven to be temperature responsive andin the case of
azobenzene guestsresponsive to the irradiation with UV light. The application of these stimuli leads to the disassembly of the
triblock copolymer, which was shown to be reversible. In the case of PDEAAm containing triblock copolymers, the temperature-
induced aggregation was investigated as well.
and chain transfer agents (CTAs)29 in aqueous polymer-
INTRODUCTION
■
izations. Recently, Harada and co-workers evidenced supra-
molecular interactions between host and guest containing gel
cubes on a macroscopic scale which proves the powerful
interactions between CDs and specific guest molecules.30
A further application of CDs in polymer chemistry is the
utilization as a linker molecule for the formation of supra-
molecular block copolymers. Hereby, controlled radical
polymerization techniques and click chemistry have proven to
be a very powerful tool set for the incorporation of CD end
groups into polymers. The most frequently applied click
reaction is CuAAc due to the convenient synthesis of
monoazido-functionalized β-CD (β-CD-N3). So far, mostly
AB diblock copolymers with different properties have been
described, e.g., with a light responsive linkage,31 with a redox
responsive linkage,32 with a thermoresponsive block33 and even
with schizophrenic behavior of the blocks.34,35 A further
example is a CD-centered star polymer, where two cores are
coupled using supramolecular interactions.36,37 The variety of
possible building blocks and guest moieties gives the
opportunity for several applications. For example, light-
Complex macromolecular architectures constitute an important
field in contemporary polymer chemistry. Block copolymers
belong to the most studied materials in this field and are
subjected to manifold applications.1,2 Apart from classical
anionic3 and cationic4 polymerization, living controlled radical
polymerizations, e.g., nitroxide-mediated radical polymeriza-
tion,5 atom transfer radical polymerization,6,7 and reversible
addition−fragmentation chain transfer (RAFT) polymeriza-
tion,8,9 have proven to be a very versatile tool for the generation
of new block copolymers with a large variety of different blocks
via convenient synthetic procedures. Furthermore, click
chemistry had a strong impact on the field of block copolymer
synthesis,10−12 e.g., via the copper(I)-catalyzed azide−alkyne
cycloaddition (CuAAc),13 the Diels−Alder,14 or the RAFT
hetero-Diels−Alder reaction,15 which provide numerous
opportunities to generate block copolymers as well as more
complex architectures.16,17
Cyclodextrins (CDs) gain more and more importance in
polymer chemistry due to their ability to form noncovalent
inclusion complexes with hydrophobic guest molecules,
opening the opportunity to generate new supramolecular
macromolecular architectures,18 e.g., stars,19,20 miktoarm
stars,21,22 hydrogels,23 or polymer brushes.24 Furthermore,
CDs can be utilized to solubilize hydrophobic monomers25−28
Received: November 19, 2012
Revised: January 19, 2013
Published: February 1, 2013
© 2013 American Chemical Society
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Scheme 1. Schematic Representation of the Formation of Supramolecular ABA Triblock Copolymers via CD Host/Guest
a
Complexation
a
β-CD is depicted orange; the guest groups are depicted blue; the outer PHPMA block is depicted black; the inner PDMAAm- and PDEAAm-blocks
are depicted red. (a) PDMAAm based supramolecular block copolymers with temperature- and light-responsive complexation and (b) PDEAAm-
based supramolecular block copolymers with cloud-point-triggered aggregate formation.
controlled supramolecular nanotubes have been described31 as
EXPERIMENTAL PART
■
well as vesicular nanocontainers with voltage-triggered release32
Materials. 1-Adamantylamine hydrochloride (ABCR, 99%), 2-
or the generation of dynamic core−shell nanoparticles.38
A
amino-1-propanol (TCI, 98%), 4,4′-azobis(4-cyanovaleric acid) (V-
501; Sigma-Aldrich, 98%), 1-chloro-6-hydroxyhexane (Acros, 95%), 2-
bromoisobutyric acid (Sigma-Aldrich, 98%), acetic acid (Roth, 99%),
aluminum chloride (ABCR, 99%), β-cyclodextrin (β-CD; Wacker,
pharmaceutical grade), carbon disulfide (Acros, 99.9%), copper
bromide (Sigma-Aldrich, 99%), diisopropylazodicarboxylate (DIAD;
ABCR, 94%), N,N′-dicyclohexylcarbodiimide (DCC; ABCR, 99%),
N,N-dimethylaminopyridine (DMAP; Sigma-Aldrich, 99%), N,N-
dimethylformamide (DMF; ABCR, 99%), ε-caprolactone (Alfa
Aesar, 99%), ethanethiol (Acros, 99%), ethylenediaminetetraacetic
acid disodium salt (EDTA; ABCR, 99%), iodine (Acros, 99.5%), 3-
mercaptopropionic acid (Acros, 99%), methacryloyl chloride (Sigma-
Aldrich, 97%), p-toluenesulfonyl chloride (ABCR, 98%),
N,N,N′,N″,N″-pentamethyldiethyltriamine (PMDETA; Merck,
99.9%), 4-phenylazophenol (ABCR, 98%), potassium carbonate
(VWR, rectapur), potassium iodide (Sigma-Aldrich, 99%), potassium
phosphate monohydrate (Sigma-Aldrich, puriss.), propargyl alcohol
(Alfa Aesar, 99%), silica gel (Merck, Geduran SI60. 0.063−0.200 mm),
sodium acetate (Roth, 99%), sodium azide (Acros, 99%), sodium
hydroxide (Roth, 99%), triethylamine (Acros, 99%), tetrabutylammo-
nium hydrogen sulfate (Sigma-Aldrich, 97%), and triphenylphosphine
(Merck, 99%) were used as received. Anhydrous dichloromethane
(DCM) and tetrahydrofuran (THF) were purchased from Acros
(extra dry over molecular sieves) and used as received. Diethyl ether
(VWR Analpur) was dried over CaH2 and distilled before use. Milli-Q
water was obtained from a Milli-Q Advantage A10 Ultrapure Water
Purification System (Millipore). All other solvents were of analytical
grade and used as received. 2,2′-Azobis(2-methylpropionitrile) (AIBN;
Fluka, 99%) was recrystallized twice from methanol. N,N-Diethylacryl-
amide (DEAAm; TCI, 98%) and N,N-dimethylacrylamide (DMAAm;
TCI, 99%) were passed over a short column of basic alumina prior to
use. N-(Adamantan-1-yl)-6-hydroxyhexanamide,19 2-((((2-
carboxyethyl)thio)carbonothioyl)thio)-2-methylpropanoic acid
(CEMP),43 2-(1-carboxy-1-methylethylsulfanylthiocarbonylsulfanyl)-
2-methylpropionic acid (CMP),44 4-cyano-4-(((ethylthio)-
carbonthioyl)thio)pentanoate,45 N-(2-hydroxypropyl)methacrylamide
(HPMA),46 mono-(6-azido-6-desoxy)-β-CD (β-CD-N3),47 and 6-(4-
(phenyldiazenyl)phenoxy)hexan-1-ol48 were prepared according to the
literature.
further example is a core−shell nanoassembly that shows
tumor-trigged release.39 One can imagine many applications
that can be derived from conventional covalently bound block
copolymers, e.g., self-assembly of supramolecular block
copolymers coupled via hydrogen bonding motifs in thin
films that mimick the behavior of their covalent role model.40
In our current approach, we connect two poly(N-(2-
hydroxypropyl)methacrylamide) (PHPMA) outer blocks with
a poly(N,N-dimethylacrylamide) (PDMAAm) or poly(N,N-
diethylacrylamide) (PDEAAm) inner block via a CD host/
guest complex to generate a novel supramolecular macro-
molecular architecture (see Scheme 1). We chose PHPMA due
to its potential application in drug delivery.41 PDMAAm was
selected to study the thermoresponsive behavior of the host/
guest complexation (refer to Scheme 1a), whereas PDEAAm
was chosen due to its cloud point of close to 30 °C42 and
therefore close to physiological temperatures. The cloud point
of PDEAAm can be utilized to form aggregates in aqueous
solution upon heating that are connected via supramolecular
interactions (see Scheme 1b).
Thus, we report the formation of a novel supramolecular
ABA triblock copolymer consisting of a PDMAAm or
PDEAAm inner block and a biocompatible PHPMA outer
block. The inner building block was synthesized via RAFT
polymerization employing novel doubly guest-functionalized
CTAs featuring adamantyl or photoresponsive azobenzene
guest groups. The outer building block was synthesized via
RAFT polymerization with an alkyne containing CTA and
subsequent CuAAc with β-CD-N3. The building blocks were
characterized via 1H NMR, electrospray ionization−mass
spectrometry (ESI-MS), and size exclusion chromatography
(SEC). The complex formation was investigated with dynamic
light scattering (DLS), cloud point measurements, and nuclear
Overhauser effect spectroscopy (NOESY).
Synthesis of 6-(Adamantan-1-ylamino)-6-oxohexyl-2-((((3-
((6-(-adamantan-1-ylamino)-6-oxohexyl)oxy)-3-oxopropyl)-
thio)carbonothioyl)thio)-2-methylpropanoate (CTA1). Accord-
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ing to a literature procedure,49 CEMP (0.61 g, 2.26 mmol, 1.0 equiv),
N-(adamantan-1-yl)-6-hydroxyhexanamide (1.50 g, 5.65 mmol, 2.5
equiv) and triphenylphosphine (1.48 g, 5.65 mmol, 2.5 equiv) were
dissolved in dry THF (15 mL). At 0 °C DIAD (1.3 mL, 5.65 mmol,
2.5 equiv) in dry THF (5 mL) was added dropwise. The reaction
mixture was stirred at ambient temperature overnight and
subsequently for 3 h at 40 °C. After cooling to ambient temperature,
DCM (50 mL) was added and the organic phase was washed twice
with saturated NaHCO3 solution (50 mL). The organic phase was
dried over Na2SO4 and filtered, and the solvent evaporated in vacuo.
The residue was subjected to column chromatography on silica gel
with n-hexane:ethyl acetate as eluent that was gradually changed from
1:1 to 1:2. The product was obtained as a yellow oil (0.88 g, 1.15
mmol, 51%). 1H NMR (400 MHz, CDCl3): [δ, ppm] = 1.15−1.28 (m,
4H, 2 × CH2−CH2−CH2−CO), 1.28−1.46 (m, 4H, 2 × CH2−
CH2−O), 1.48−1.75 (m, 28H, 4 × (CH3)2−C, 2 × CH2−CH2−C
O; 6 × CH2,adamantyl), 1.92−2.01 (m, 12H, 6 × CH2,adamantyl−C−NH),
2.04−2.10 (m, 10H, 6 × CHadamantyl; 2 × CH2−CO), 2.70 (t, 2H,
CH2−CH2−S), 3.52 (t, 2H, CH2−S), 4.08 (q, 4H, 2 × CH2−O−C
O), 5.19 (br m, 2H, 2 × NH). 13C NMR (100 MHz, CDCl3): [δ,
ppm] = 25.5, 25.7, and 25.8 (2 × CH2−CH2−CH2−CO; 2 × CH2−
CH2−CO, 2 × (CH3)2C), 28.3 and 28.5 (2 × CH2−CH2−O−C
O), 29.6 (6 × CHadamantyl), 31.4 (CH2−CH2−S), 33.2 (CH2−S), 36.5
CH, CH2−COO), 2.62−2.76 (m, 2H, C−CH2), 3.34 (q, 2H, J = 7.4
Hz, CH3−CH2), 4.71 (d, 2H, CH2−C−CH). 13C NMR (100 MHz,
CDCl3): [δ, ppm] = 12.9 (CH3), 25.0 (C−CH3), 29.7 (CH2−COO),
31.5 (C−CH2), 33.8 (CH3−CH2), 46.4 (C−CH2), 52.6 (CH2−C−
CH), 75.4 (CH2−C−CH), 77.4 (CH2−C−CH), 119.0 (C−N), 170.8
(CO), 216.8 (CS). ESI-MS: [M + Na+]exp = 324.08 m/z and [M
+ Na+]calc = 324.0163 m/z.
Exemplary Procedure for the RAFT Polymerization of
DEAAm. CTA1 (54.9 mg, 0.07 mmol, 1.0 equiv), DEAAm (500.0
mg, 3.94 mmol, 56.3 equiv), AIBN (4.2 mg, 0.03 mmol, 0.4 equiv),
DMF (3.3 mL), and a stirring bar were added into a Schlenk tube.
After three freeze−pump−thaw cycles the tube was backfilled with
argon, sealed, placed into an oil bath at 60 °C, and removed after 24 h.
The tube was subsequently cooled with liquid nitrogen to stop the
reaction. An NMR sample was withdrawn for the determination of
conversion, inhibited with a pinch of hydroquinone (∼5 mg), and
CDCl3 was added. Quantitative conversion was estimated based on the
NMR data (see the Characterization and Methods section for details
of the calculation). The residue was dialyzed against deionized water
with a SpectraPor3 membrane (MWCO = 1000 Da) for 3 days at
ambient temperature. The solvent was removed in vacuo to yield the
polymer as a yellow solid (422.0 mg, 76%, GPC (THF): MnGPC = 6500
g mol−1, ĐM = 1.11).
Exemplary Procedure for the RAFT Polymerization of
HPMA. CTA3 (60.5 mg, 0.20 mmol, 1.0 equiv), HPMA (2.00 g,
14.18 mmol, 35.5 equiv), V-501 (11.6 mg, 0.04 mmol, 0.2 equiv),
DMF (6.0 mL), acetic acid/sodium acetate buffer (pH 5.2, 0.27 M
acetic acid and 0.73 M sodium acetate; 6.0 mL), and a stirring bar were
added into a Schlenk tube. After three freeze−pump−thaw cycles the
tube was backfilled with argon, sealed, placed into an oil bath at 70 °C,
and removed after 2 h. The tube was subsequently cooled with liquid
nitrogen to stop the reaction. A NMR sample was withdrawn for the
determination of conversion, inhibited with a pinch of hydroquinone
(∼5 mg), and D2O was added. A conversion of 23% was estimated
based on the NMR data (see the Characterization and Methods
section for details of the calculation). The residue was dialyzed against
deionized water with a SpectraPor3 membrane (MWCO = 1000 Da)
for 3 days at ambient temperature. The solvent was removed in vacuo
to yield the polymer as a yellow solid (0.37 g, 80%, GPC (DMAc):
MnGPC = 6500 g mol−1, ĐM = 1.17).
Exemplary Click Reaction of Alkyne-Functionalized PHPMA
with β-CD-N3. Alkyne-functionalized PHPMA (MnGPC = 6500 g
mol−1; 150.0 mg, 0.023 mmol, 1.0 equiv), β-CD-N3 (133.8 mg, 0.115
mmol 5.0 equiv), PMDETA (34 μL, 0.163 mmol, 7.1 equiv), DMF
(5.3 mL), and a stirring bar were introduced into a Schlenk tube. After
three freeze−pump−thaw cycles the tube was filled with argon, and
CuBr (19.8 mg, 0.138 mmol, 6.0 equiv) was added under a stream of
argon. Subsequently, two freeze−pump−thaw cycles were performed,
the tube was backfilled with argon, and the mixture was stirred at
ambient temperature for 24 h. EDTA solution (5 wt %, 1 mL) was
added, and the residue was dialyzed against deionized water with a
SpectraPor3 membrane (MWCO = 2000 Da) for 3 days at ambient
temperature. The solvent was removed in vacuo to yield the CD-
functionalized polymer as a yellow solid (96.0 mg, 55%, GPC
(DMAc): MnGPC = 7300 g mol−1, ĐM = 1.29).
(6 × CH2,adamantyl), 37.7 (2 × CH2−CO), 41.9 (6 × CH2,adamantyl
−
C−NH), 51.9 (2 × C−NH), 56.4 (2x C(CH3)2), 65.0 and 66.1 (2 ×
CH2−O−CO), 171.5, 172.0, 172.1, and 172.9 (4 × CO), 220.9
(CS). ESI-MS: [M + Na+]exp = 785.58 m/z and [M + Na+]calc
785.3668 m/z.
=
Synthesis of Bis(6-(4-(phenyldiazenyl)phenoxy)hexyl)-2,2′-
(thiocarbonylbis(sulfanediyl))bis(2-methylpropanoate) (CTA2).
Based on a literature procedure,49 CMP (1.00 g, 3.54 mmol, 1.0
equiv), 6-(4-(phenyldiazenyl)phenoxy)hexan-1-ol (3.38 g, 11.33
mmol, 3.2 equiv), and triphenylphosphine (2.97 g, 11.32 mmol, 3.2
equiv) were dissolved in dry THF (20 mL). At 0 °C DIAD (2.2 mL,
11.21 mmol, 3.2 equiv) in dry THF (20 mL) was added dropwise. The
reaction mixture was stirred at ambient temperature overnight and
subsequently for 3 h at 40 °C. After cooling to ambient temperature,
DCM (100 mL) was added, and the organic phase was washed twice
with saturated NaHCO3 solution (100 mL). The organic phase was
dried over Na2SO4 and filtered, and the solvent evaporated in vacuo.
The residue was subjected to column chromatography on silica gel
with n-hexane:ethyl acetate as eluent that was gradually changed from
10:1 to 8:1. The product was obtained as an orange oil which solidified
1
on cooling (2.77 g, 3.30 mmol, 93%). H NMR (400 MHz, CDCl3):
[δ, ppm] = 1.37−1.57 (m, 4H, 2 × CH2−CH2−CH2−O), 1.58−1.72
(m, 16H, 4 × C−CH3; 2 × OC−O−CH2−CH2), 1.77−1.87 (m,
4H, 2 × O−CH2−CH2), 4.03 (t, 4H, 2 × CH2−O), 4.09 (t, 4H, 2 ×
CH2−O−CO), 7.00 (d, 4H, 4 × CHarom), 7.40−7.46 (m, 2H, 2 ×
CHarom), 7.47−7.56 (m, 4H, 4 × Carom), 7.82−7.97 (m, 8H, 8 ×
CHarom). 13C NMR (100 MHz, CDCl3): [δ, ppm] = 25.3 (4 × CH3−
C), 25.8 and 25.9 (4 × CH2−CH2−CH2−O), 28.4 (2 × O−CH2−
CH2), 29.2 (2 × OC−O−CH2−CH2), 56.3 (2 × C(CH3)2), 66.1 (2
× OC−O−CH2), 68.3 (2 × O−CH2), 114.8 (2 × O−Carom
−
CHarom), 122.7 (2x CHarom), 124.9 (4 × CHarom), 129.2 (4 × CHarom),
130.4 (2 × CHarom), 147.0 (2 × Carom−NN), 152.9 (2 × Carom−N
N), 161.8 (2 × O−Carom), 172.9 (2 × CO), 218.6 (CS). ESI-MS:
[M + H+]exp = 843.33 m/z and [M + H+]calc = 843.3284 m/z.
Synthesis of Prop-2-yn-1-yl-4-cyano-4-(((ethylthio)-
carbonothioyl)thio)pentanoate (CTA3). In a 100 mL Schlenk
flask, 4-cyano-4-(((ethylthio)carbonothioyl)thio)pentanoate (1.00 g,
3.80 mmol, 1.0 equiv), propargyl alcohol (0.5 mL, 8.65 mmol, 2.3
equiv), and DMAP (0.09 mg, 0.77 mmol, 0.2 equiv) were dissolved in
anhydrous DCM (20 mL). At 0 °C a solution of DCC (1.57 g, 7.61
mmol, 2.0 equiv) in anhydrous DCM (10 mL) was added. After 1 h
the solution was warmed to ambient temperature, stirred overnight,
filtered, and concentrated under reduced pressure. The residue was
purified via column chromatography on silica-gel with n-hexane:ethyl
acetate 10:1 as eluent. The product was obtained as a yellow oil (0.94
g, 3.13 mmol, 82%). 1H NMR (400 MHz, CDCl3): [δ, ppm] = 1.35 (t,
3H, J = 7.4 Hz, CH2−CH3), 1.87 (s, 3H, C−CH3), 2.27−2.59 (m, 3H,
Exemplary Supramolecular ABA Block Copolymer Forma-
tion via Cyclodextrin/Guest Interaction. CD-functionalized
PHPMA (MnGPC = 7300 g mol−1; 70.0 mg, 0.0096 mmol, 2.0 equiv)
was dissolved in DMF (4 mL) and added dropwise to a solution of
doubly adamantyl-functionalized PDMAAm (MnGPC = 6400 g mol−1;
30.0 mg, 0.0047 mmol, 1.0 equiv) in DMF (2 mL) under vigorous
stirring. The resulting solution was dialyzed against a deionized water/
DMF mixture with a SpectraPor3 (MWCO = 1000 Da) membrane at
4 °C. The water content was gradually changed from 70% to 100%
over 1 day, and the dialysis was continued for 3 days with deionized
water at 4 °C. The solvent was removed in vacuo to yield the
supramolecular complex in quantitative yield.
Characterization and Methods. NMR measurements were
carried out on a Bruker AM250 spectrometer at 250 MHz for
hydrogen nuclei for conversion determination and a Bruker AM400
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Scheme 2. Overview of the Synthetic Pathway Leading to the Doubly Guest-Functionalized Inner Building Block Featuring
Adamantyl or Azobenzene Guest Groups
spectrometer at 400 MHz for hydrogen nuclei and at 100 MHz for
carbon nuclei for structure verification. 2D NOESY (nuclear
Overhauser effect spectroscopy) spectra were measured on a Bruker
Avance III 600 spectrometer at 600 MHz with a mixing time of 0.3 s
and a concentration of 60 mg mL−1. For the determination of the
conversion of DMAAm the integrals of one vinylic proton (5.78−5.89
ppm) and the backbone protons (0.75−2.00 ppm) were employed.
The conversion of DEAAm was determined with the integral of one
vinylic proton (5.57−5.73 ppm) and with the integral of the side chain
methyl groups and backbone protons (0.81−1.97 ppm). The
conversion of HPMA was calculated with the integral of one vinylic
proton (5.48−5.58 ppm) and with the integral of one side-chain
proton (3.86−4.14).
Size exclusion chromatography (SEC) with N,N-dimethylacetamide
(DMAc) as eluent containing 0.03 wt % LiBr was performed for
PDMAAm and PHPMA on a Polymer Laboratories PL-GPC 50 Plus
Integrated System, comprising an autosampler, a PLgel 5 μm bead-size
guard column (50 × 7.5 mm) followed by three PLgel 5 μm MixedC
columns (300 × 7.5 mm), and a differential refractive index detector at
50 °C with a flow rate of 1.0 mL min−1. The SEC system was
calibrated against linear poly(styrene) standards standards with
molecular weights ranging from 160 to 6 × 106 g mol−1 or
poly(methyl methacrylate) standards with molecular weights ranging
from 700 to 2 × 106 g mol−1. All SEC calculations for PDMAAm were
carried out relative to a poly(styrene) calibration. The SEC
calculations for PHPMA were carried out relative to a poly(methyl
methacrylate) calibration. SEC with tetrahydrofuran (THF) as eluent
containing 200 ppm 2,6-di-tert-butyl-4-methylphenol for PDEAAm
was performed on a Polymer Laboratories PL-GPC 50 Plus Integrated
System, comprising an autosampler, a PLgel 5 μm bead-size guard
column (50 × 7.5 mm) followed by three PLgel 5 μm MixedC
columns (300 × 7.5 mm), a PLgel 5 μm MixedE column (300 × 7.5
mm), and a differential refractive index detector at 35 °C with a flow
rate of 1.0 mL min−1. The SEC system was calibrated against linear
poly(styrene) standards with molecular weights ranging from 160 to 6
× 106 g mol−1. All SEC calculations for PDEAAm were carried out
relative to poly(styrene) calibration. The molecular weight dispersity is
abbreviated as ĐM.
The capillary voltage, the tube lens offset voltage, and the capillary
temperature were set to 60 V, 110 V, and 275 °C, respectively.
Cloud points were measured on a Cary 300 Bio UV/vis
spectrophotometer (Varian) at 600 nm. The heating rate was set to
0.32 °C min−1 and the concentration at 1 mg mL−1. For the
determination of the cloud point the point of inflection of the
transmittance vs temperature plot was used.
Dynamic light scattering (DLS) was performed on a 380 DLS
spectrometer (Particle Sizing Systems, Santa Barbara, CA) with a 90
mW laser diode operating at 658 nm equipped with an avalanche
photodiode detector. Every measurement was performed four times at
10 °C for samples containing PDEAAm and at 25 °C for samples
containing PDMAAm. The data was evaluated with an inverse Laplace
algorithm. The scattered light was recorded at an angle of 90° to the
incident beam. For the temperature sequenced measurements the
sample was equilibrated at the specific temperature for 5 min, then the
DLS measurement was performed 3 times for 3 min, and the
temperature was changed again. The entire procedure was performed
three times, and the data points were finally averaged. All
hydrodynamic diameters (Dh) in the text are the averages of the
number-weighted distributions. The samples were prepared in Milli-Q
water and filtered with a 0.2 μm regenerated cellulose syringe filter
(Roth, Rotilabo).
UV/vis spectra were measured on a Cary 300 Bio UV/vis
spectrophotometer (Varian) at a temperature of 25 or 10 °C
depending on the sample.
UV irradiation for investigation of photoresponse was applied via a
BLB-8 UV lamp (8 W, Camag) with an emission maximum at 350 nm
(refer to Figure S36 for the emission spectrum) for the DLS samples
and via a UVASPOT 2000RF2 (2000 W, Honle technology) with its
̈
main irradiation between 315 and 420 nm for the NMR samples.
Theoretical molecular weights were calculated with the equation
[monomer]0
[CTA]0
Mntheo = conversion × M(monomer) ×
+ M(CTA)
RESULTS AND DISCUSSION
Synthesis of the Building Blocks. For the synthesis of the
■
Electrospray ionization−mass spectrometry (ESI-MS) was per-
formed on an LXQmass spectrometer (ThermoFisher Scientific, San
Jose, CA) equipped with an atmospheric pressure ionization source
operating in the nebulizer-assisted electrospray mode. The instrument
was calibrated in the m/z range 195−1822 Da using a standard
containing caffeine, Met-Arg-Phe-Ala acetate (MRFA), and a mixture
of fluorinated phosphazenes (Ultramark 1621) (all from Aldrich). A
constant spray voltage of 4.5 kV was used, and nitrogen at a
dimensionless sweep gas flow rate of 2 (∼3 L min−1) and a
dimensionless sheath gas flow rate of 12 (∼1 L min−1) were applied.
inner building blocks two doubly guest-functionalized CTAs
based on trithiocarbonates were designed. CTA1 contains two
adamantyl groups, and CTA2 contains two azobenzene groups.
The adamantyl group was chosen due to its high complexation
constant of up to 105 M−1 with β-CD.50 The azobenzene group
was chosen due its ability to change the conformation from
trans to cis in response to light irradiation. This change in
conformation leads to a significant change in the complexation
constant with β-CD; i.e., the guest is expelled from the host
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Figure 1. SEC traces for (a) PDMAAm polymerized with CTA1 (dashed line: PDMAAm151-Ad2; solid line: PDMAAm57-Ad2), (b) PDMAAm
polymerized with CTA2 (dashed line: PDMAAm103-Azo2; solid line: PDMAAm46-Azo2), (c) PDEAAm polymerized with CTA1 (dotted line:
PDEAAm89-Ad2; dashed line: PDEAAm78-Ad2; solid line: PDEAAm45-Ad2), and (d) PDEAAm polymerized with CTA2 (dotted line: PDEAAm80-
Azo2; dashed line: PDEAAm59-Azo2; solid line: PDEAAm36-Azo2).
Scheme 3. Overview of the Synthetic Pathway Leading to the β-CD-Functionalized Outer PHPMA Building Block
molecule upon irradiation with UV light. The guest molecules
were attached to the core CTA molecule via a short spacer
group to support its availability in the complex formation. As
shown in Scheme 2, both guest-functionalized CTAs were
synthesized via a Mitsunobu reaction from the corresponding
acids: CEMP in the case of CTA1 and CMP in the case of
CTA2.
Subsequently, the novel CTAs were employed in the RAFT
polymerization of DMAAm and DEAAm in DMF at 60 °C with
AIBN as initiator. DMAAm was selected to investigate the
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Figure 2. (a) SEC traces for PHPMA polymerized with CTA3 (solid line: PHPMA44-alkyne) and the product of the conjugation with β-CD-N3
1
(dashed line: PHPMA44-β-CD) and (b) comparison of the H NMR spectra of β-CD-N3 (top), the β-CD-functionalized PHPMA click product
(middle: PHPMA28-β-CD), and alkyne-functionalized PHPMA (bottom: PHPMA28-alkyne).
temperature response of the complex formation whereas
DEAAm was chosen due to its cloud point, providing the
opportunity to study the formation of block copolymer
aggregates in solution due to a coil-to-globule transition of
PDEAAm above the cloud point. In the case of PDMAAm,
molecular weights of 6400 and 15 700 g mol−1 with a ĐM
(molecular-weight dispersity) of 1.06 and 1.11, respectively,
were achieved with CTA1, while a molecular weight of 5400
and 11 000 g mol−1 with a ĐM of 1.08 and 1.11, respectively,
were reached with CTA2 (refer to Figure 1a,b, Figures S9 and
S10, and Table S1). The polymerization of DEAAm with
CTA1 afforded polymers with molecular weights ranging from
6500 to 12 100 g mol−1 and ĐM ranging from 1.11 to 1.27
(refer to Figure 1c, Figure S11, and Table S2). Furthermore,
PDEAAms with molecular weights ranging from 5400 to
11 000 g mol−1 and ĐM ranging from 1.16 to 1.33 (refer to
Figure 1d, Figure S12, and Table S3) were synthesized with
CTA2. The structure of the polymers was verified via 1H NMR
and ESI-MS (refer to Figures S13−S20).
For the outer building block the biocompatible monomer
HPMA was utilized.41 Therefore, a trithiocarbonate CTA with
an alkyne moiety was synthesized (refer to Scheme 3). A
dithiobenzoate CTA, the first choice for methacrylamide and
methacrylate monomers, was not further considered as the
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Figure 3. Comparison of the number-averaged particle size distributions of the building blocks (dashed line: PHPMA; dotted line: PDMAAM or
PDEAAM) and the supramolecular block copolymer (solid line) at a concentration of 1 mg mL−1: (a) PHPMA26-β-CD, PDMAAm151-Ad2 and
PDMAAm151-Ad2-b-(PHPMA26-β-CD)2 at 25 °C; (b) PHPMA26-β-CD, PDMAAm103-Azo2, and PDMAAm103Azo2-b-(PHPMA26-β-CD)2 at 25 °C;
(c) PHPMA28-β-CD, PDEAAm89-Ad2, and PDEAAm89-Ad2-b-(PHPMA28-β-CD)2 at 10 °C; (d) PHPMA28-β-CD and PDEAAm80-Azo2
PDEAAm80Azo2-b-(PHPMA28-β-CD)2 at 10 °C.
complex formation between the phenyl group and β-CD
cannot be ruled out. As the utilized CTA contains an
unprotected alkyne moiety, the conversion in the RAFT
polymerizations was kept at low values to suppress radical
transfer to the terminal alkyne.
Table S10), the Mn of the distribution remains close to
unchanged. Nevertheless, the peak maximum molecular weight
(Mp) increases as expected (Table S10), and a shift of the
distribution is visible.
1
Furthermore, H NMR shows the formation of the triazole
The polymerization of HPMA was conducted in a mixture of
DMF and acetic acid/sodium acetate buffer with V-501 as
initiator at 70 °C. The utilization of CTA3 afforded narrowly
distributed alkyne-functionalized PHPMA, e.g., a molecular
weight of 6500 g mol−1 and a ĐM of 1.17 (refer to Figure 2,
Figures S21 and S22, and Table S8). The structure of the
ring as the new signal at 8.1 ppm can be assigned to the triazole
proton (Figure 2b inset). Additionally, the H NMR spectrum
1
shows signals that can be assigned to both β-CD and PHPMA,
e.g., the anomeric CD protons between 4.3 and 4.6 ppm, the 2-
hydroxyl and the 3-hydroxyl protons between 5.5 and 6.0 ppm,
the hydroxyl protons of PHPMA between 4.6 and 4.8 ppm, or
the amide proton of PHPMA between 7.0 and 7.5 ppm (see
Figure 2b).
Self-Assembly of the Building Blocks to Form ABA
Triblock Copolymers. To ensure the availability of the
hydrophobic guest groups for the complex formation, the self-
assembly of the building blocks was accomplished via the
dialysis method. In brief, both polymer building blocks were
dissolved in an organic solvent, e.g., DMF, one solution was
added dropwise to the other under vigorous stirring, and the
organic solvent was removed via dialysis. The complexes were
finally lyophilized and subsequently characterized via DLS and
NOESY-NMR.
1
polymer was proven via ESI-MS and H NMR measurements
(refer to Figures S23 and S24). The subsequent functionaliza-
tion with β-CD was accomplished via a CuAAc reaction of the
alkyne-functionalized PHPMA and β-CD-N3. In the SEC trace
a shift of the RI signal to lower retention times is evident, thus
proving the increased hydrodynamic volume of the β-CD
conjugated PHPMA in comparison with the alkyne-function-
alized PHPMA (refer to Figure 2a and Figure S25).
Furthermore, the Mn of the molecular weight distribution
increases from 6500 to 7300 g mol−1. The distribution has a
small shoulder at higher molecular weights that could be due to
the conjugation of small amounts of difunctional azido β-CD.
In other cases with lower molecular weight PHPMA (refer to
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Figure 4. 2D NOESY NMR spectra of the supramolecular triblock copolymers in D2O at 25 °C: (a) PDMAAm151Ad2-b-(PHPMA26-β-CD)2; (b)
PDEAAm78Ad2-b-(PHPMA28-β-CD)2; (c) PDMAAm103Azo2-b-(PHPMA26-β-CD)2; (d) PDMAAm103Azo2-b-(PHPMA26-β-CD)2 after UV
irradiation for 7 min.
DLS is a versatile tool to investigate the complex formation
in solution. In our investigation we employed DLS to obtain
the hydrodynamic diameter (Dh) of the polymer coils in
solution. In principle, the Dh should increase upon complex
formation as three polymer chains are included in the complex.
The PDMAAm based complexes were measured at 25 °C, and
the complexes show larger Dh than the individual parts (refer to
Figure 3, Figure S26, and Table S11); e.g., PHPMA26-β-CD has
a Dh of 3.4 nm, PDMAAm151-Ad2 has a Dh of 4.7 nm, and the
supramolecular complex features a Dh of 7.8 nm. An exception
is the doubly adamantyl-functionalized PDMAAm with lower
molecular weight, which has a Dh of 175.0 nm for PDMAAm57-
Ad2, a Dh of 5.1 for PHPMA44-β-CD, and a Dh of 15.4 nm for
the supramolecular complex PDMAAm57-Ad2-b-(PHPMA44-β-
CD)2. In this case, the hydrophobic guest groups lead to
aggregation of or within the homopolymer. The complex shows
a smaller Dh, yet the value of 15.4 nm suggests further
aggregation probably due to more complicated structures in
solution. An example for doubly azobenzene-functionalized
PDMAAm is PDEAAm80Azo2-b-(PHPMA28-β-CD)2 with a Dh
of 8.9 nm. The individual building blocks PDEAAm80Azo2 and
PHPMA28-β-CD have a Dh of 4.9 and 3.4 nm, respectively.
Because of the cloud point of PDEAAm the DLS
measurements were performed at 10 °C in that case. A
significant increase in Dh was evident in most of the cases (refer
to Figure 3, Figure S26, and Table S11). An example for doubly
adamantyl-functionalized PDEAAm is PDEAAm89-Ad2-b-
(PHPMA28-β-CD)2 with a Dh of 7.4 nm consisting of
PDEAAm89-Ad2 with a Dh of 6.6 nm and PHPMA28-β-CD
with a Dh of 3.4 nm. Similar to PDMAAm lower molecular
weight, doubly adamantyl-functionalized PDEAAm shows very
large Dh (48.4 nm for PDEAAm45-Ad2) for the homopolymer
and a Dh of 6.1 nm after complexation with PHPMA28-β-CD.
For doubly azobenzene-functionalized PDEAAm an increase in
Dh from 4.9 nm for the middle-block PDEAAm80-Azo2 and 3.4
nm for the outer PHPMA28-β-CD blocks to 8.9 nm is observed
for the complex.
To evidence the molecular nature of the complex formation
NOESY NMR was utilized which is a well-suited tool to study
host/guest complex formation. The adamantyl-based systems
PDMAAm151Ad2-b-(PHPMA26-β-CD)2 and PDEAAm78Ad2-b-
(PHPMA28-β-CD)2 show cross-correlation peaks that corre-
spond to the signals of the adamantyl moiety at 1.72, 2.04, and
2.16 ppm and the inner protons of β-CD between 3.5 and 3.8
ppm (Figure 4a,b). This proves the close spatial proximity of
the adamantyl moiety and the inner CD protons which is the
case for inclusion complexes. NOESY spectra of the
azobenzene-based systems show weak cross-correlation peaks
originating from the azobenzene protons between 7.0 and 7.5
ppm and the inner CD protons (refer to Figure 4c and Figure
S27). The azobenzene moiety shows weaker cross-correlation
peaks in comparison with adamantyl systems which can be
explained with the weaker complexation and the larger distance
between the CD protons and the aromatic protons in the
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Figure 5. Number-averaged particle size distributions before applying the stimulus (solid line), during or directly after applying the stimulus (dashed
line) and after standing at ambient temperature/in daylight for the specified time (dotted line): (a) complex PDMAAm151Ad2-b-(PHPMA26-β-CD)2
before heating, during heating to 70 °C and after 3 days; (b) complex PDMAAm103Azo2-b-(PHPMA26-β-CD)2 before heating, during heating to 70
°C and after 1 day; (c) complex PDEAAm80Azo2-b-(PHPMA28-β-CD)2 before irradiation, directly after irradiation at 350 nm for 30 min and after 2
days; (d) complex PDMAAm103Azo2-b-(PHPMA26-β-CD)2 before irradiation, directly after irradiation at 350 nm for 30 min and after 1 day.
azobenzene. Nevertheless, the spectra are a strong hint for
inclusion complex formation. In general, the observed cross-
correlation peaks are weaker in the case of PDEAAm
containing samples as the concentration of the NMR samples
was lower due to less solubility of the block copolymer in D2O
compared to the PDMAAm-based copolymers.
In general, the described supramolecular ABA block
copolymer is in equilibrium with the building blocks due to
its noncovalent nature. Therefore, the existence of AB block
copolymers and nonconnected building blocks cannot be
excluded. However, the formation of the desired structure is
governed by the equilibrium constants that are rather high in
the described systems. Thus, the ABA block copolymer should
be present almost exclusively in solution.
Investigations of the Stimuli-Responsive Behavior of
the Supramolecular Assemblies. The prepared CD-based
host/guest complexes show thermoresponsivity due to the
usually negative enthalpy of complex formation.19,51,52 To
evidence the thermoresponsivity of the host/guest supra-
molecular triblock copolymers, guest-functionalized PDMAAm
was synthesized that features no cloud point. As shown in
Figure 5a,b, both the adamantyl- and azobenzene-based triblock
copolymers show a significant decrease in Dh from 7.8 to 4.2
nm for an adamantyl guest in the case of PDMAAm151Ad2-b-
(PHPMA26-β-CD)2 and from 11.2 to 5.4 nm in the case of
azobenzene in PDMAAm103Azo2-b-(PHPMA26-β-CD)2 upon
heating to 70 °C (additional examples are listed in the
Supporting Information, Figure S28 and Table S12).
Furthermore, the complexes form again after remaining at
ambient temperature which is proven by an increase in Dh close
to the original values. In the case of lower molecular weight
PDMAAm, the Dh increases with heating which is due to the
formation of aggregates in solution as the complex dissociates.
These aggregates could be formed due to the hydrophobic
guest groups that are unmasked which changes the solubility of
the PDMAAm. In analogy to the higher molecular weight
PDMAAms, the complexes reform again after remaining at
ambient temperature for 3−4 days and the Dh decreases. The
rate of the re-formation of the complexes can be followed by
DLS. It seems that azobenzene-based complexes form faster,
which may be attributed to the increased polarity of azobenzene
compared to adamantane which enhances the accessibility of
the guest moiety in aqueous solution. Moreover, the re-
formation of the complexes is faster with a higher degree of
polymerization of PDMAAm. An explanation for that effect is
the overall solubility of the polymer chain that changes
drastically after the complex dissociation for lower molecular
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Figure 6. (a) Temperature sequenced DLS measurement of PDEAAm78Ad2-b-(PHPMA28-β-CD)2 at a heating rate of 0.2 °C min−1 and a
concentration of 1 mg mL−1. (b) Temperature sequenced DLS measurement of PDEAAm59Azo2-b-(PHPMA28-β-CD)2 at a heating rate of 0.2 °C
min−1 and a concentration of 1 mg mL−1. (c) Turbidity measurements for PDEAAm78Ad2 (dashed line) and the supramolecular triblock copolymer
PDEAAm78Ad2-b-(PHPMA28-β-CD)2 (solid line) at a cooling rate of 0.32 °C min−1 and a concentration of 1 mg mL−1. (d) Turbidity measurements
for PDEAAm59Azo2 (dashed line) and the supramolecular triblock copolymer PDEAAm59Azo2-b-(PHPMA28-β-CD)2 (solid line) at a cooling rate of
0.32 °C min−1 and a concentration of 1 mg mL−1.
weight polymers and the earlier mentioned aggregates disturb
the complex re-formation.
(PHPMA26-β-CD)2. In almost all cases the Dh after standing in
daylight is close to the initial value. As shown in Figure 5b,d,
the azobenzene-based PDMAAm block copolymers are dual
responsively bound as their supramolecular connection is
sensitive to heat and light. The light triggered complex
dissociation could be observed furthermore via 2D NOESY
NMR (see Figure 4d and an overlay in Figure S30). The
intensity of the corresponding cross-correlation peaks decreases
significantly after irradiation of UV light for 7 min. Never-
theless, the peaks do not vanish completely. This can be
attributed to the fact that the complexes could re-form during
the NOESY measurement with a measuring time of around 9 h.
Furthermore, an equilibrium between cis- and trans-azoben-
zenes is formed where small amounts of trans-azobenzenes with
higher complexation constant remain in the solution and the
irradiation time is limited as RAFT polymers are sensitive to
UV irradiation. The formation of cis-azobenzenes can be
monitored via UV spectroscopy as well. The UV spectra of all
samples show a significant increase of the absorption at 440 nm
after irradiation at 350 nm for 30 min (see Figures S31−33).
Concomitantly, the absorption of trans-azobenzene moieties at
340 nm decreases drastically. As the absorption of trans-
azobenzene is overlapping with the absorption of the
trithiocarbonate, a quantitative statement with respect to the
trans- and cis-azobenzene content in solution is difficult.
Nevertheless, judging from the shape of the absorption band
after irradiation, only minor amounts of trans-azobenzene
remain.
In addition to the thermoresponsivity of the employed host/
guest complexes, azobenzenes provide the opportunity to
generate structures that are sensitive to light irradiation as
azobenzenes show a transition from the thermodynamically
more stable trans- to the cis-conformation at wavelengths close
to 360 nm. This photoisomerization is reversible and the
reisomerization can be induced by heat or light with
wavelengths of close to 430 nm. Furthermore, the complex-
ation constants are higher for the trans-conformation compared
to the cis-conformation (460 M−1 for a trans-azobenzene test
compound and 2.5 M−1 for a cis-azobenzene test compound).53
In general, higher complexation constants (up to 104 M−1)54
and differences between cis- and trans-conformations could be
achieved via the utilization of α-CD instead of β-CD. In here,
azobenzene-based β-CD complexes were irradiated with UV
light at 350 nm for 30 min, and the change in Dh was
monitored via DLS. A significant decrease was evident, e.g.,
from 8.9 to 4.8 nm after irradiation in the case of
PDEAAm80Azo2-b-(PHPMA28-β-CD)2 (see Figure 5c,d, Table
S13, and Figure S29), evidencing that the block copolymers are
debonded in a photoresponsive fashion. After keeping the
samples at ambient temperature and daylight, the block
copolymers formed again as proven by an increased Dh value,
e.g., 8.2 nm compared to the original value of 8.9 nm in the case
of PDEAAm80Azo2-b-(PHPMA28-β-CD)2 and 10.1 nm com-
pared to 11.2 nm before in the case of PDMAAm103Azo2-b-
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The utilization of PDEAAm as inner block provides the
opportunity for temperature-induced aggregation.21,34,35,37 As
shown in Figure 6, the block copolymers are present as random
coils at lower temperatures, e.g., a Dh of around 7 nm for
PDEAAm78Ad2-b-(PHPMA28-β-CD)2 up to 30 °C or a Dh
around 8 nm for PDEAAm59Azo2-b-(PHPMA28-β-CD)2 up to
20 °C (Figure 6a,b). The situation changes upon heating over
the cloud point where aggregates are formed. In the case of
PDEAAm78Ad2-b-(PHPMA28-β-CD)2 aggregates with Dh be-
tween 24 and 90 nm are formed between 31 and 36 °C. A
broader temperature range from 21 to 34 °C is covered with
PDEAAm59Azo2-b-(PHPMA28-β-CD)2, where Dh between 54
and 222 nm are observed (refer to Figure S34 and Table S14
for further examples and information). With further heating
these aggregates agglomerate leading to particles with sizes over
1000 nm in all cases except of PDEAAm36Azo2-b-(PHPMA28-β-
CD)2 where particles between 500 and 1000 nm are found. The
behavior of these triblock copolymers resembles the behavior of
literature known systems where a plateau as well as further
agglomeration is described.21,35,37 One possible explanation for
agglomeration at higher temperatures is the decreased complex
stability, making a dynamic exchange of the building blocks
possible. Thus, the stabilization effect of the PHPMA corona on
the PDEAAm cores is decreasing and finally the aggregates
begin to agglomerate. The DLS data are in agreement with the
plots of turbidimetry as evident via the direct comparison in
Figures 6a,c and 6b,d.
tigated after heating above the cloud point of the PDEAAm
block.
ASSOCIATED CONTENT
* Supporting Information
■
S
Analytical data of the chain transfer agents and other
synthesized molecules, additional experimental data on the
obtained polymers and the supramolecular complexes; addi-
tional experimental procedures on the synthesis of HPMA and
the chain transfer agent precursors. This material is available
free of charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
■
*Tel (+49) 721 608-45642, Fax (+49) 721 608-45740, e-mail
christopher.barner-kowollik@kit.edu (C.B.-K.); Tel (+49) 211
81-14760, Fax (+49) 211 81-15840, e-mail h.ritter@uni-
duesseldorf.de (H.R.).
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
The authors acknowledge financial support for the current
project from the German Research Council (DFG). C.B.-K.
acknowledges additional financial support from the Karlsruhe
Institute of Technology (KIT) in the context of the Excellence
Initiative for leading German universities and the Ministry for
Turbidity measurements show in almost all cases an
increased cloud point of the complexes compared to the
uncomplexed PDEAAm blocks (refer to Figure 6, Figure S35,
and Table S15), which is an expected behavior of supra-
molecular block copolymers with a thermoresponsive
block.19,21,35,37 A possible explanation for such a behavior is
the shielding of the hydrophobic end groups by the CD moiety.
In the case of doubly adamantyl-functionalized polymers the
difference in the cloud points lies between 4 and 2 °C, whereas
the difference with azobenzene-functionalized polymers is
rather small and the cloud points are almost the same. A
reason for the different behavior of the guest groups may be the
enhanced polarity of the azobenzene moiety and the weaker
association with β-CD. Furthermore, an increase of the cloud
point with molecular weight is evident as well.
Science and Arts of the state of Baden-Wurttemberg. The
authors acknowledge Prof. Dr. Luy (KIT) for helpful
discussions.
̈
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CONCLUSIONS
■
We present the synthesis of a novel macromolecular
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