Ferrocenyl amphiphilic Janus dendrimers as redox-responsive micellar carriers

Article abstract of DOI:10.1002/aoc.4908

Amphiphilic Janus dendrimers have attracted increasing attention due to their asymmetric structures and various functional properties compared to the conventional symmetric macromolecules. Herein, a novel ferrocenyl-terminated amphiphilic Janus dendrimer containing nine hydrophilic triethylene glycol branches was synthesized by two synthetic routes, namely the typical chemo selective coupling method and the mixed modular approach. Chemical redox triggers, namely Fe₂(SO₄)₃ as oxidant and ascorbic acid as reductant, could regulate the self-assembly behavior of the Janus dendrimer in water through the redox-switching between ferrocene and ferricinium cations, and the change of micelles formed were investigated and confirmed through scanning electron microscopy and dynamic light scattering. The cargo-loading property of the micelles self-assembled by the Janus dendrimer was further proved by the successful fabrication of Rhodamine B (RhB)-loaded micelles, and the oxidation-triggered release behavior of the encapsulated RhB could be mediated by changing the concentration of oxidants. This work provides an effective approach to prepare ferrocenyl-terminated amphiphilic Janus dendrimers and the self-assembled micelles might be used as a promising molecular carrier in areas such as drug delivery and catalysis.

Full text of DOI:10.1002/aoc.4908

Received: 29 January 2019
DOI: 10.1002/aoc.4908
Revised: 20 February 2019
Accepted: 21 February 2019
F U L L P A P E R
Ferrocenyl amphiphilic Janus dendrimers as
redox‐responsive micellar carriers
Shengdong Mu1,2 | Wentao Liu2 | Qiangjun Ling1 | Xiong Liu1,2 | Haibin Gu1
1 Key Laboratory of Leather Chemistry
Amphiphilic Janus dendrimers have attracted increasing attention due to their
and Engineering of Ministry of Education,
Sichuan University, Chengdu 610065,
China
2 National Engineering Laboratory for
Clean Technology of Leather
Manufacture, Sichuan University,
Chengdu 610065, China
asymmetric structures and various functional properties compared to the con-
ventional symmetric macromolecules. Herein, a novel ferrocenyl‐terminated
amphiphilic Janus dendrimer containing nine hydrophilic triethylene glycol
branches was synthesized by two synthetic routes, namely the typical chemo
selective coupling method and the mixed modular approach. Chemical redox
triggers, namely Fe2(SO4)3 as oxidant and ascorbic acid as reductant, could
regulate the self‐assembly behavior of the Janus dendrimer in water through
the redox‐switching between ferrocene and ferricinium cations, and the change
of micelles formed were investigated and confirmed through scanning electron
microscopy and dynamic light scattering. The cargo‐loading property of
the micelles self‐assembled by the Janus dendrimer was further proved by
the successful fabrication of Rhodamine B (RhB)‐loaded micelles, and the
oxidation‐triggered release behavior of the encapsulated RhB could be medi-
ated by changing the concentration of oxidants. This work provides an effective
approach to prepare ferrocenyl‐terminated amphiphilic Janus dendrimers and
the self‐assembled micelles might be used as a promising molecular carrier in
areas such as drug delivery and catalysis.
Correspondence
W. Liu, National Engineering Laboratory
for Clean Technology of Leather
Manufacture, Sichuan University,
Chengdu 610065, China.
Email: scu.collagen@gmail.com
H. Gu, Key Laboratory of Leather
Chemistry and Engineering of Ministry of
Education, Sichuan University, Chengdu
610065, China.
Email: guhaibinkong@126.com
Funding information
Science and Technology Department of
Sichuan Province, Grant/Award Number:
No. 2018HH0038; National Natural Sci-
ence Foundation of China, Grant/Award
Number: No. 21606165
KEYWORDS
ferrocene, Janus dendrimers, micelles, redox‐responsive, self‐assembly
1 | INTRODUCTION
The self‐assembly structure and functions of stimuli‐
responsive JDs based on specific non‐covalent interac-
The emerging amphiphilic Janus dendrimers (JDs) are a
class of asymmetric macromolecules that possess two
dendritic segments with diverse properties such as hydro-
philicity, size and functionality, etc.[1–3] and are attracting
wide attention owing to their combination of properties
of the constituting blocks in a unique way.[4,5] The inter-
est towards the JDs originates from their asymmetry
structures and applications in a variety of research fields
including catalysis,[2,6] light harvesting,[7] drug deliv-
ery,[8] bioimaging,[9] optoelectronics,[10] ionic liquid[11]
and thermal actuators.[12]
tions have been widely investigated in functional
materials by means of different external stimuli, such as
solvent polarity,[13,14] redox,[3,15–21] temperature,[22–25]
pH[26–31] and electrochemistry.[32–34] For the different
external stimuli, the redox‐responsive self‐assembly struc-
tures have attracted increasing attention in encapsulation
of drug and oxidation‐triggered release in biological
processes, which is attributed to the consecutive balance
exists between reactive oxygen species and antioxidants,
especially in cancer cells.[35,36] For example, Liu et al.
described a redox‐controlled drug delivery system based
Appl Organometal Chem. 2019;e4908.
wileyonlinelibrary.com/journal/aoc
© 2019 John Wiley & Sons, Ltd.
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https://doi.org/10.1002/aoc.4908

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MU ET AL.
on ferrocene (Fc)‐containing amphiphilic block copoly-
mers (PEG‐b‐PMAEFc) that were fabricated via atom
transfer radical polymerization (ATRP) using a PEG‐
based macro‐ATRP agent.[35]
Among the various redox function groups such as
sulfur,[20] selenium,[15,17] viologen[19] and Fc,[16,19,32,33]
the hydrophobic Fc with d6 Fe (II) 18‐electron is easily
oxidized into hydrophilic ferricinium (Fcium) cation
with d5 Fe (III) 17‐electron at a rather mild potential
of around +0.4 V vs. saturated calomel electrode (SCE),
and the Fcium then reversibly recovers into its original
neutral Fc form through chemical and electrochemical
means.[37–42] And notably, this redox process is attributed
to the gain and loss of one electron, and the molecular
structure of Fc group is not destroyed, which is a
great benefit for the reversible self‐assembly and disas-
sembly of Fc‐containing amphiphilic macromole-
cules.[16,32,43–46] For example, Eloi et al. reported the
micellization
and
reversible
disassembly
of
polystyrene‐b‐polyferrocenylsilane (PS‐b‐PFS) copolymers
by using the controllable chemical oxidation of the Fc
moieties in the PFS block to gradually change the
SCHEME 1 Synthesis routes of JD 9

MU ET AL.
3 of 14
solubility of the organometallic block.[44] However, there
are few reports on the redox‐responsive JDs systems.
Herein, as shown in Scheme 1, two synthetic routes
were adopted to synthesize a novel Fc‐terminated amphi-
philic JD 9. For the typical chemo selective coupling
method, two dendrons containing nine triethylene glycol
(TEG) and three Fc termini, respectively, were firstly
prepared and then linked by an esterification reaction in
the last step to get the targeted JD 9. For the alternative
mixed modular approach, a dendrimer carrying three
Fc termini and three alkynyl was firstly prepared by an
esterification reaction, and the TEG dendron then
grew by divergent method on a focal point of this
dendron through the copper(I)‐catalyzed azide alkyne
cycloaddition (CuAAC) click chemistry. The reversible
self‐assembly behavior of the obtained JD 9 in aqueous
solution was investigated and confirmed by manipulating
the addition of oxidant and reductant (Scheme 2), and the
morphology of the formed micelles was fully character-
ized by scanning electron microscope (SEM) and dynamic
light scattering (DLS). Finally, using the Rhodamine B
(RhB) as a model cargo, the loading ability of the self‐
assembled micelles of JD 9 was examined, and the
oxidation‐triggered release of RhB was confirmed in
response to external chemical stimuli.
2 | EXPERIMENTAL
2.1 | General
2‐Bromoethylamine hydrobromide, methyl gallate,
triethylene glycol mono methyl ether, oxalyl chloride,
2‐chlorobenzoyl chloride and 2‐propynylamine were
purchased from Energy Chemical and used directly.
The azido derivative 4[3] and azidomethylferrocene 6[2]
were synthesized according to the known procedures.
All the other chemicals were from commercial sources
and used as received. All the solvents used were dried
and freshly distilled.
A Bruker AC (400 MHz) spectrometer was employed
to determine the 1H NMR (400 MHz) and 13C NMR
(100 MHz) spectra of compounds. All the chemical shifts
were recorded in parts per million (δ, ppm) with
reference to tetramethylsilane (TMS). Mass spectra were
measured by using an Applied Biosystems Voyager‐DE
STR‐MALDI‐TOF spectrometer. The infrared spectra
were recorded by using an ATI Mattson Genesis
series FT‐IR spectrophotometer in the range of 400–
4000 cm−1. UV–visible absorption spectra were measured
by using a Perkin‐Elmer Lambda 19 UV–visible spec-
trometer. DLS measurements were conducted by using
SCHEME 2 Schematic diagram of redox‐responsive self‐assembly of JD 9 and its drug‐loading and oxidation‐triggered release

4 of 14
MU ET AL.
Malvern Zetasizer Nano‐ZS series equipment (Malvern
Instruments, UK) at 25 °C at an angle of 90°. SEM obser-
vations were carried out by using a SM‐7500F field emis-
sion SEM instrument (JEOL). Samples for SEM were
prepared by casting a drop of the solution on a silicon
grid, followed by drying at room temperature (r. t., 25 °C).
dissolved in 50 ml of THF. CuSO4·5H2O (3.05 g, 12.2
mmol, 3.3 equiv) dissolved in 20 ml distilled water was
added into the obtained reaction mixture, followed by
the dropwise injection of a freshly prepared sodium ascor-
bate (4.84 g, 24.4 mmol, 6.6 equiv) aqueous solution
(30 ml) to obtain a THF/water in a ratio of 1:1 (v/v). The
reaction mixture was agitated at r. t. for 72 hr under N2
atmosphere, and then vacuumed to wipe out the THF
solvent. The residue was dissolved in 100 ml of mixed
solvent of CH2Cl2 and aqueous ammonia (1:1, v/v), and
agitated for 30 min to remove the residual copper ions.
The organic layer was collected, dried by anhydrous
Na2SO4, and evaporated under reduced pressure. Purifica-
tion was conducted by column chromatography by using
CH2Cl2/methanol (100:1, v/v) as eluent to provide 7 as
2.2 | Synthesis of 5
Compounds 3 (0.25 g, 0.925 mmol, 1.0 equiv) and 4 (2.066
g, 3.05 mmol, 3.3 equiv) were dissolved in 50 ml of tetra-
hydrofuran (THF). CuSO4·5H2O (0.763 g, 3.05 mmol, 3.3
equiv) was dissolved in 20 ml of distilled water, and was
then injected into the above THF solution. After that,
sodium ascorbate (1.21 g, 6.1 mmol, 6.6 equiv) was dis-
solved in 30 ml of distilled water, and added slowly into
the THF solution, too. The prepared reaction mixture
was then agitated at r. t. for 72 hr under N2 atmosphere,
and then vacuumed to get rid of THF solvent. The residue
was dissolved in 100 ml of mixed solvent of dichloro-
methane (CH2Cl2) and aqueous ammonia (1:1, v/v), and
agitated for 30 min to eliminate the copper ions absorbed
inside the goal compound as [Cu (NH3)2(H2O)2]2+. The
organic layer was collected, dried by anhydrous Na2SO4,
and evaporated under reduced pressure. Purification
was conducted by column chromatography by using
CH2Cl2/methanol (1% → 10%) as eluent to get 5 as an
orange‐yellow solid. Yield: 45%. 1H NMR (400 MHz,
CDCl3, 25 °C, TMS), δppm: 8.40 (t, J = 10.6 Hz, 1H,
NHCO), 8.05 (s, 2H, 2 × NHCO), 7.72 (s, 2H, 2 ×
C=CH of triazole), 7.39 (s, 1H, C=CH of triazole), 7.20
(s, 4H, O=C‐ph), 7.16 (s, 2H, O=C‐ph), 6.42 (s, 2H, O‐
ph), 4.95 (s, 4H, 2 × OCH2), 4.82(s, 2H, OCH2), 4.65 (t,
J = 10.8 Hz, 4H, 2 × N‐N‐CH2), 4.50 (t, J = 9.6 Hz, 2H,
N‐N‐CH2), 4.45 (d, J = 4.8 Hz, 2H, CH2OH), 4.17–4.06
(m, 18H, 9 × OCH2), 3.95–3.91 (m, 4H, 2 × CH2NH),
3.85–3.81 (m, 2H, CH2NH), 3.71–3.49 (m, 90H, 9 ×
CH2OCH2CH2OCH2CH2O), 3.35, 3.34 and 3.33 (ts, 27H,
9 × OCH3). 13C NMR (100 MHz, CDCl3, 25 °C, TMS),
1
an orange‐yellow solid. Yield: 70.5%. H NMR (400 MHz,
CDCl3, 25 °C, TMS), δppm: 7.65 (s, 2H, 2 × C=CH of tri-
azole), 7.62 (s, 1H, C=CH of triazole), 7.33 (s, 2H, ph),
5.26 (s, 4H, 2 × ph‐OCH2), 5.19 (s, 2H, ph‐OCH2), 5.16
and 5.14 (ds, 6H, 3 × N=N‐N‐CH2), 4.29–4.08 (m, 23H, 4
× sub. Cp and 5 × free Cp, Cp = η5‐C5H5), 3.86 (s, 3H,
CH3). 13C NMR (100 MHz, CDCl3, 25 °C, TMS), δppm
:
151.9, 131.8, 122.7, 109.2 (ph), 143.3 (C of triazole), 123.4
(C of triazole), 81.5, 81.0 (Cp), 69.1, 68.9, 68.8 (Cp), 66.3,
63.2 (OCH2), 50.1, 49.9 (N‐N‐CH2). MS (ESI m/z), calcd.
For C50H47Fe3N9O5: 1021.52; found: 1044.2 (M + Na+).
2.4 | Synthesis of 8
NaOH (1.2 g, 29.0 mmol, 10 equiv) in water (10 ml) was
added dropwise into the solution of 7 (2.96 g, 2.9 mmol,
1 equiv) in dry THF (10 ml) at r. t. under N2 atmosphere.
The obtained mixture was stirred at 80 °C overnight,
poured into 1 M HCl (40 ml) below 5 °C, and then
extracted with CH2Cl2 (3 × 50 ml). The organic layers
were collected, combined, washed with brine, dried over
anhydrous Na2SO4 and concentrated to give the crude
product that was then purified via column chromatogra-
phy by using CH2Cl2/methanol (50:1, v/w) as eluent to
afford 8 as a yellow solid. Yield: 72%. 1H NMR (400
MHz, CDCl3, 25 °C, TMS), δppm: 7.67 (s, 2H, 2 × C=CH
of triazole), 7.61 (s, 1H, C=CH of triazole), 7.41 (s, 2H,
ph), 5.24 (s, 4H, 2 × ph‐OCH2), 5.17 (s, 2H, ph‐OCH2),
5.14 and 5.10 (ds, 6H, 3 × N=N‐N‐CH2), 4.28 (s, 4H, 2 ×
sub. Cp), 4.20 (t, J = 3.7 Hz, 2H, sub. Cp), 4.16–4.13 (m,
21H, 3 × sub. Cp and 3 × free Cp). 13C NMR (100 MHz,
CDCl3, 25 °C, TMS), δppm: 169.5(COOH), 151.7 (ph),
144.4, 143.9 (C of triazole), 139.9 (ph), 128.5 (ph), 123.5,
122.9 (C of triazole), 109.0 (ph), 81.6, 81.3 (Cp), 69.1,
69.0, 68.9 (Cp), 66.4 (Cp), 63.1, 60.5 (OCH2), 50.1, 49.9,
45.6 (N‐N‐CH2). MS (ESI m/z), calcd. For
C49H45Fe3N9O5: 1007.49; found: 1008.17 (M + H+).
δ
ppm: 166.9, 166.7(NHCO), 151.3, 150.8 (ph), 143.2, 142.5
(C of triazole), 140.3, 140.2, 139.9 (ph), 137.2, 135.5 (ph),
128.4, 128.1 (ph), 123.9, 123.3 (C of triazole), 106.2,
106.1, 105.9 (ph), 71.4, 70.9, 69.6, 69.5, 69.4, 69.3, 68.6,
67.8, 67.7 (OCH2), 65.0 (CH2OH), 63.2, 61.8 (ph‐OCH2),
57.9 (OCH3), 48.6, 48.2 (N‐N‐CH2), 39.4, 39.3 (CH2NH).
MS (ESI m/z), calcd. For C106H170N12O43: 2300.57; found:
2299.14 (M+).
2.3 | Synthesis of 7
Compound 2 (1.10 g, 3.7 mmol, 1.0 equiv) and
azidomethylferrocene 6 (2.94 g, 12.2 mmol, 3.3 equiv) were

MU ET AL.
5 of 14
at 0 °C. The obtained mixture was stirred at r. t. over-
night, poured into water (50 ml), and then extracted with
CH2Cl2 (3 × 50 ml). The combined organic layers were
washed with brine, dried over anhydrous Na2SO4 and
concentrated to give crude product that was then purified
by column chromatography with CH2Cl2/methanol (20:1,
2.5 | Synthesis of JD 9 by using 5 and 8
To a solution of 8 (2.42 g, 2.4 mmol, 1 equiv) in dry
CH2Cl2 (10 ml) was added oxalyl dichloride (3.0 g, 24
mmol, 10 equiv) dropwise at 0 °C under N2 atmosphere.
The obtained mixture was stirred at r. t. for 12 hr under
N2 atmosphere, and then concentrated under reduced
pressure to give the crude acyl chloride of 8 that was used
in the next step without further purification. To a mixture
of 5 (5.52 g, 2.4 mmol, 1 equiv) and trimethylamine
(Et3N, 607 mg, 6 mmol, 2.5 equiv) in dry CH2Cl2 (50
ml) was added the crude acyl chloride of 8 in dry CH2Cl2
(10 ml) dropwise at 0 °C. The obtained mixture was
stirred at r. t. overnight, poured into water (50 ml), and
then extracted with CH2Cl2 (3 × 50 ml). The combined
organic layer was washed with brine, dried over anhy-
drous Na2SO4 and concentrated to give a crude product
that was then purified by column chromatography with
CH2Cl2/methanol (20:1, v/v) as eluent to afford 9 as a yel-
1
v/v) as eluent to afford 10 as yellow oil. Yield: 52%. H
NMR (400 MHz, CDCl3, 25 °C, TMS), δppm: 7.65 (s, 2H,
2 × N‐C=CH), 7.62 (s, 1H, N‐C=CH), 7.39 (s, 2H, O=C‐
ph), 6.85 (s, 2H, CH2‐ph), 5.26 (s, 6H, 2 × N=N‐C‐CH2
and CH2‐O‐C=O), 5.20 (s, 2H, N=N‐C‐CH2), 5.17 (s, 2H,
N‐N‐CH2), 5.14 (s, 2 × N‐N‐CH2), 4.79 (d, J = 2.4 Hz,
4H, 2 × ≡C‐CH2), 4.74 (d, J = 2.4 Hz, 2H, ≡C‐CH2),
4.28 (t, J = 3.7 Hz, 4H, 2 × sub. Cp), 4.20–4.14 (m, 23H,
4 × sub. Cp and 3 × free Cp), 2.55 (t, J = 4.8 Hz, 2H, 2
× CH≡), 2.48 (t, J = 4.9 Hz, 1H, CH≡). 13C NMR (100
MHz, CDCl3, 25 °C, TMS), δppm: 165.6 (C=O), 152.0,
151.7 (ph), 143.9, 143.3 (N=N‐C), 141.7, 137.2, 132.1
(ph), 125.5 (N‐N‐C), 123.4, 122.8 (ph), 109.7, 108.6 (ph),
81.4, 81.0 (Cp), 79.2, 78.5, 76.2, 75.3 (CH ≡ C), 69.1,
68.9, 68.8 (Cp), 66.7, 66.2, 63.3, 60.4, 57.2, 53.5 (OCH2),
50.1, 49.9 (N‐N‐CH2). MS (ESI m/z), calcd. For
C65H57Fe3N9O8: 1259.76; found: 1260.50 (M + H+).
1
low solid. Yield: 46%. H NMR (400 MHz, CDCl3, 25 °C,
TMS), δppm: 8.17 (s, 1H, NHCO), 8.01 (s, 2H, 2 × NHCO),
7.77 (s, 2H, 2 × C=CH of triazole), 7.70 and 7.66 (ds, 4H,
4 × C=CH of triazole), 7.40 (s, 2H, ph), 7.15 and 7.13 (ds,
6H, ph), 6.74 (s, 2H, ph), 5.24–5.09 (m, 18H, 3 × N‐N‐CH2
and 6 × ph‐CH2‐O), 4.91 (s, 2H, O=C‐OCH2), 4.58–4.50
(m, 6H, 3 × NCH2CH2NHCO), 4.26–4.07 (m, 45H, 3 ×
sub. Cp, 3 × free Cp and 9 × ph‐OCH2), 3.85–3.82 (m,
6H, 3 × NCH2CH2NHCO), 3.76–3.48 (m, 90H, 9 ×
CH2OCH2CH2OCH2CH2O), 3.33, 3.32, 3.31 and 3.30
(tetra‐s, 27H, 9 × OCH3). 13C NMR (100 MHz, CDCl3,
25 °C, TMS), δppm: 166.5 (O=C‐O and NHC=O), 151.3,
151.0 (ph), 142.4, 142.3, 140.2, 128.1 (ph and C of tri-
azole), 123.2, 122.5 and 122.0 (ph and C of triazole),
106.2, 106.1 (ph), 80.5, 80.0 (Cp), 71.3, 70.9, 69.6, 69.5,
69.4, 68.6, 68.0, 67.9, 67.8 (Cp and OCH2), 62.2, 62.0
(OCH2), 58.0, 57.9 (OCH3), 52.5 (N‐N‐CH2), 49.1, 48.9,
48.5 (N‐N‐CH2), 39.3 (CH2‐NH), 32.1 (CH2‐NH). MS
2.7 | Synthesis of JD 9 by using 4 and 10
Compound 10 (2.2 g, 1.75 mmol, 1.0 equiv) and 4 (3.78 g,
5.59 mmol, 3.2 equiv) were dissolved in 100 ml of THF.
CuSO4·5H2O (1.57 g, 6.28 mmol, 3.6 equiv) aqueous solu-
tion (50 ml) was added slowly into the obtained reaction
mixture, followed by the dropwise addition of a freshly
prepared sodium ascorbate (2.5 g, 12.62 mmol, 7.2 equiv)
aqueous solution (50 ml) to obtain a THF/water in a ratio
of 1:1 (v/v). The reaction mixture was stirred at r. t. for 72
hr under N2 atmosphere, and then vacuumed to remove
THF. The residue was dissolved in 200 ml of mixed
solvent of CH2Cl2 and aqueous ammonia (1:1, v/v), and
agitated for 30 min to remove the remaining copper ions.
The organic layer was collected, dried by anhydrous
Na2SO4, and evaporated under reduced pressure. Purifi-
cation was conducted by column chromatography with
CH2Cl2/methanol (1% → 10%) as eluent to get 9 as an
orange‐yellow solid. Yield: 63%. 1H NMR (400 MHz,
CDCl3, 25 °C, TMS), δppm: 8.17 (s, 1H, NHCO), 8.01
(s, 2H, NHCO), 7.77 (s, 2H, 2 × C=CH‐N), 7.70 and
7.66 (ds, 4H, 4 × C=CH‐N), 7.40 (s, 2H, ph), 7.15–7.13
(m, 6H, ph), 6.74 (s, 2H, O=C‐ph), 5.24–5.09 (m, 18H, 3
× N‐N‐CH2, 6 × C‐CH2‐O), 4.91 (s, 2H, O=C‐OCH2),
4.58–4.50 (m, 6H, 3 × N‐N‐CH2), 4.26–4.07 (m, 45H, 3 ×
free and sub. Cp, 9 × OCH2), 3.85–3.82 (m, 6H, 3 × NH‐
CH2), 3.76–3.48 (m, 90H, 9 × CH2OCH2CH2OCH2CH2O),
3.33–3.30 (m, 27H, 9 × OCH3). 13C NMR (100 MHz,
(ESI m/z), calcd. For
C155H213Fe3N21O47: 3290.04;
found:1119.75 ((M + 3Na+)/3) and 1667.61(M/2 + Na+).
2.6 | Synthesis of 10
To a solution of 8 (3.8 g, 3.77 mmol, 1 equiv) in dry
CH2Cl2 (10 ml) was added oxalyl dichloride (4.79 g, 37.7
mmol, 10 equiv) dropwise at 0 °C under N2 atmosphere.
The obtained mixture was stirred at r. t. under N2 atmo-
sphere for 12 hr, and then concentrated under reduced
pressure to give the crude acyl chloride of 8 that was used
in the next step without further purification. To a mixture
of 3 (1.02 g, 3.77 mmol, 1 equiv) and Et3N (3.82 g, 37.7
mmol, 10 equiv) in dry CH2Cl2 (30 ml) was added the
crude acyl chloride of 8 in dry CH2Cl2 (10 ml) dropwise

6 of 14
MU ET AL.
CDCl3, 25 °C, TMS), δppm: 166.5(O=C‐O and NHC=O),
151.3, 151.0 (ph), 142.4, 142.3, 140.2 (ph and N=N‐C),
128.1 (ph and N‐N‐C), 123.2, 122.5, 122.0 (N=N‐C and
ph), 106.2, 106.1 (ph), 80.5,80.0 (Cp), 71.4,70.9, 69.6,
69.5, 69.4, 68.6, 68.0, 67.9, 67.8(Cp and CH2O), 62.2,
62.0 (CH2O), 58.0, 57.9(OCH3), 52.5 (N‐N‐CH2), 49.1,
48.9, 48.5 (N‐N‐CH2), 39.3(CH2‐NH), 32.1(CH2‐NH). MS
(ESI m/z), calcd. For C155H213Fe3N21O47: 3290.04; found:
1119.75 ((M + 3Na+)/3) and 1667.61(M/2 + Na+).
the unloaded excess RhB, the total volume of aggregate
was adjusted to 5 ml by the additon of deionized water,
and the concentration of 5.0 mg ml−1 was kept for JD 9.
The loading content (LCRhB) and encapsulation efficiency
(EERhB) were determined according to the following
formulas:
W1
LCRhBð%Þ ¼
EERhB ð%Þ ¼
× 100%
× 100%
W2
W1
W3
2.8 | Oxidation of 9 and back reduction
JD 9 (15 mg) was dissolved in 3 ml of distilled water in a
glass bottle, followed by the dropwise addition of
Fe2(SO4)3 whose molar equivalent was triple to that of
Fc units in 9. The obtained mixture was then agitated at
r. t. for 10 min until the original yellow color was con-
verted into pale green. After that, ascorbic acid, whose
molar equivalent was equal to that of Fe2(SO4)3, was
added as reductant into the glass bottle, and the obtained
mixture was further agitated for 10 min until the pale
green of oxidized 9 was completely converted into yellow.
where W1 is the loaded RhB (mg) by micelles of 9, and W2
is the added 9 (mg), whereas W3 is the used RhB (mg)
during loading process. The standard curve of RhB was
firstly drawn in distilled water, and then adopted to com-
pute the value of W1 by using UV–visible spectroscopy.
2.11 | In vitro oxidation‐triggered
substrate release from micelles of 9
The RhB‐loaded micelles of 9 (2 ml) was firstly injected
into a dialysis tube (MWCO = 3500 g mol−1) by using a
syringe, and the release experiment was then carried
out at r. t. by immersing the dialysis tube into a 10 ml
of Fe2(SO4)3 solution. The concentration of Fe2(SO4)3
were 0.1, 0.5 and 1.0 mg ml−1, respectively. UV–visible
spectroscopy was used to monitor the release of RhB. At
different intervals, the UV–visible spectrum of the aque-
ous solution outside the dialysis tube was recorded, and
the corresponding release amount of RhB was deter-
mined by using the standard curve of RhB in water.
2.9 | Self‐assembly of 9 in water
The micellar aggregate of JD 9 was prepared by using a
typical dialysis approach.[47,48] Concretely, 9 (20.0 mg)
was firstly dissolved in 4 ml of THF in a glass bottle con-
taining a stirring bar, and deionized water (1 ml) was
then added dropwise under vigorous stirring. After that,
the obtained mixture was agitated at r. t. for 12 hr, and
then transferred into a dialysis bag with molecular weight
cutoff (MWCO) of 3500 g mol−1. The dialysis treatment
was conducted against deionized water (1000 ml) for 72
hr at intervals of 4 hr, and the dialysate was replaced by
fresh deionized water. After the complete elimination of
THF solvent, the total volume of aggregate was adjusted
to 4 ml by injecting deionized water, and the concentra-
tion of 5.0 mg ml−1 was kept for JD 9.
3 | RESULTS AND DISCUSSION
3.1 | Synthesis and structure of JD 9
As shown in Scheme 1, two synthetic routes were
adopted to synthesize the targeted amphiphilic JD 9.
The first one is a typical chemo selective coupling method
in which two dendrons containing nine triethylene glycol
(TEG) and three Fc termini, respectively, were firstly pre-
pared by the convergent approach and then coupled
together in the last step of esterification reaction.[1,3]
The second one is the mixed modular approach that
involves a combination of convergent and divergent
methods in which one dendron is prepared by the conver-
gent approach and another dendron grows by divergent
method on a focal point of the first dendron.[1]
2.10 | Substrate‐loading of micelles of 9
25 mg of 9 and 5 mg of RhB were added in a glass bottle,
followed by the addition of 5 ml of deionized water to dis-
solve them, and the obtained mixture was agitated at r. t.
for 12 hr, and then transferred into a dialysis bag (MWCO
= 3500 g mol−1). The dialysis treatment was conducted
against deionized water (1000 ml) for 72 hr at intervals
of 4 hr, and the dialysate was replaced by fresh deionized
water until no RhB was detected in the aqueous solution
outside the dialysis bag. After the complete elimination of
In the chemo selective coupling route, the novel
amphiphilic JD 9 is synthesized by an esterification

MU ET AL.
7 of 14
reaction between the hydrophilic dendron 5 containing
nine TEG branches and the hydrophobic dendron 8 ter-
minated by three Fc groups. As shown in Scheme 1,
methyl 3,4,5‐trihydroxybenzoate is used as the starting
compound for the synthesis of the hydrophilic dendron
5. Its reaction with 3‐bromo‐1‐propyne leads to the for-
mation of methyl 3,4,5‐tri (prop‐2‐yn‐1‐yloxy) benzoate
2, and the methyl ester group of 2 is then reduced to a
hydroxymethyl group by LiAlH4 to yield the correspond-
ing 3,4,5‐tri (prop‐2‐yn‐1‐yloxy) benzyl alcohol 3. The
CuAAC “click” reaction of 3 with the key dendron 4 con-
taining three TEG branches and an azido focal point,
whose synthesis is detailed in supporting information
(SI), results in the formation of hydrophilic dendron 5
bearing a hydroxymethyl group. This “click” reaction is
conducted in THF/water (1:1) by using the classic
Sharpless−Fokin catalyst[3] (CuSO4 + NaAsc). Similarly,
the CuAAC “click” reaction is also used to prepare the
Fc‐terminated dendron 7 by using azidomethylferrocene
6 and methyl 3,4,5‐tri (prop‐2‐yn‐1‐yloxy) benzoate 2.
The methyl ester group is then hydrolyzed to provide
the hydrophobic dendron 8 containing carboxyl group.
The reaction of 8 with oxalyl chloride yields its benzoyl
chloride that then reacts with 5 containing a hydroxy-
methyl group with the aid of triethylamine (Et3N), pro-
viding the targeted JD 9.
1
The structure of 9 is confirmed by H, 13C NMR spec-
troscopy, mass spectrometry (MS), UV–visible and FT‐IR
spectra. Figure 1 shows the 1H NMR spectra of 9 and the
two starting dendrons 5 and 8, and their comparison con-
1
firms the structure of 9. In the H NMR of 5 (Figure 1A),
the signals for three triazole protons are observed at 7.72
and 7.39 ppm, which confirms the successful “click” reac-
tion between 3 and 4. The two triplet peaks at 8.40 and
8.05 ppm are assigned to the three acylamino NHCO pro-
tons, and the three peaks at 7.20, 7.16 and 6.42 ppm are
attributed to the phenyl protons in four benzene rings.
The characteristic signals of twenty‐seven methoxy
FIGURE 1 1H NMR spectra of 5 (A), 8 (B) and 9 (C) in CDCl3

8 of 14
MU ET AL.
protons in nine TEG branches are observed at 3.35–3.33
ppm, and the signals of its OCH2 protons are concen-
trated at 4.17–4.06 and 3.71–3.49 ppm. These results
prove the successful synthesis of the TEG‐containing
dendron 5 and its structure.
are observed at 142.4, 142.3, 123.2 and 122.5 ppm, and
the characteristic Cp carbons of Fc groups are found at
80.5, 80.0, 69.6, 69.5 and 69.4 ppm, respectively, while
the peaks at 58.0 and 57.9 ppm are attributed to the ter-
minal OCH3 carbons in the nine TEG structures. All the
Figure 1B provides the 1H NMR spectrum of the
dendron 8 in CDCl3. The two singlet peaks at 7.67 and
7.61 ppm arise from the three triazole protons, and the
peak at 7.41 ppm corresponds to the phenyl protons.
The peaks at 4.28, 4.20 and 4.16–4.13 ppm are attributed
to the characteristic signals of the twenty‐seven protons
of the substituted and free cyclopentadienyl (Cp) rings
in the three Fc units. These results fully confirm the suc-
cessful preparation of the Fc‐terminated dendron 8 and
its structure.
other peaks of the H and 13C NMR spectra are clearly
1
assigned and match well with the structure of 9. The mass
spectrum of 9 (Figure S23) provides fragment peaks at
1119.75 ((M + 3Na+)/3) and 1667.61(M/2 + Na+) Da,
but no molecular peak for theoretical C155H213Fe3N21O47
is found at 3290.04 Da or so, probably attributed to its
large molecular weight and the easy cleavage of C─O
bond. The UV–visible spectrum of 9 (Figure S25) exhibits
a maximum absorption (λmax) at 432 nm assigned to the
d‐d* transition of the iron center in the Fc units. The IR
spectrum (Figure S24) is in agreement with the formation
of 9 with bands at 3447 cm−1 (υNH), 2877 cm−1 (υCH2),
1714 cm−1 (υC=O), 1648 cm−1 (υC=O), 1584, 1541, 1496
and 1429 cm−1 (υC=C of benzene), 1332 and 1238 cm−1
(νC‐N), 1107 cm−1 (νC‐O‐C) and 848 cm−1 (υFeII).
1
In the H NMR spectrum of 9 (Figure 1C), no peak at
4.45 ppm assigned to the hydroxymethyl protons of 5 is
observed, and the peak at 4.91 ppm is attributed to the
methane protons adjacent to the ester bond (COO). These
results adequately demonstrate the successful synthesis of
the targeted JD 9 by the esterification reaction between
the two dendrons of 5 and 8. The three peaks at 7.77,
7.70 and 7.66 ppm is attributed to the six triazolyl pro-
tons, and the peaks at 8.17 and 8.01 ppm are assigned
to the three NHCO protons. The multiplet peaks at
4.26–4.07 ppm arise from the characteristic substituted
and free Cp protons in the three Fc moieties, and also
corresponds to nine methane protons close to the phenyl
ring. The peaks at 3.76–3.48 ppm originate from the
OCH2 protons of the nine TEG branches, and its charac-
teristic terminal OCH3 protons are observed at 3.33, 3.32,
3.31 and 3.30 ppm. All these data indicate the integrity of
the Fc and TEG structures and the successful synthesis of
9. In the 13C NMR spectrum of 9 in CDCl3 (Figure S22),
the peak at 166.5 ppm corresponds to the carbonyl car-
bons of the ester and acylamino groups, and the peak at
49.1 ppm originates from the carbon of CH2 close to the
ester group. The C=C carbons of the triazolyl moieties
In the mixed modular approach, the key intermediate
10 was firstly synthesized by an esterification reaction
between 3,4,5‐tri (prop‐2‐yn‐1‐yloxy) benzyl alcohol 3
and the hydrophobic dendron 8 containing three Fc ter-
1
mini. In the H NMR spectrum of 10 (Figure 2), no peak
at 4.64 ppm corresponding to the hydroxymethyl protons
of 3 is found, and the peak at 5.26 ppm is attributed to the
methane protons adjacent to the ester bond (COO),
which is mixed with the signal from the OCH2 protons
close to the triazole ring. These results fully confirm the
successful formation of the targeted intermediate 10 by
the esterification reaction between the two dendrons of
3 and 8. The two singlet peaks at 7.65 and 7.62 ppm orig-
inate from the three triazolyl protons, and the two peaks
at 7.39 and 6.85 ppm arise from the four phenyl protons
in two benzene rings. The signals of the characteristic
substituted and free Cp protons in three Fc structures
are observed at 4.28 and 4.20–4.14 ppm, and the two
FIGURE 2 1H NMR spectrum of 10 in CDCl3

MU ET AL.
9 of 14
triplet peaks at 2.55 and 2.48 ppm are attributed to the
three characteristic alkynyl protons. All these data indi-
cate the integrity of the triazolyl, Fc and alkynyl groups
and the formation of 10. In the 13C NMR of 10 (Figure
S26), the carbons of triazolyl rings are located at 143.9,
143.3, 123.4 and 122.8 ppm, and the Cp carbons of Fc
units are found at 81.5, 81.1, 69.1, 69.0 and 68.9 ppm,
while the four peaks at 79.3, 78.5, 76.3 and 75.4 originate
from the carbons of alkynyl groups. All the other peaks of
The JD 9 is obtained as an orange‐yellow solid, and
shows good solubility in common organic solvents such
as CH2Cl2, chloroform (CHCl3), THF, acetone, CH3CN,
methanol, N,N‐dimethylformamide (DMF) and dimethyl
sulfoxide (DMSO) and water. It is insoluble in diethyl
ether, petroleum ether and pentane, however.
3.2 | Redox reversibility of fc units in JD 9
1
the H and 13C NMR spectra are clearly assigned and
match well with the structure 10. The high‐resolution
mass spectrum of 10 (Figure S27) exhibits the molecular
peak at 1260.50 Da, in good agreement with the theoreti-
cal value of 1259.76 Da. The UV–visible spectrum of 10
(Figure S29) yields a λmax peak at 436 nm assigned to
the d‐d* transition of the iron center in the Fc units.
The IR spectrum (Figure S28) also provides complemen-
tary information for the formation and structure of 10.
Subsequently, the CuAAC “click” reaction of the inter-
mediate 10 with the dendron 4 containing three TEG
branches and an azido focal point leads to the formation
of the targeted JD 9. Similarly, this “click” reaction is
carried out in THF/water (1:1) by using the classic
Sharpless−Fokin catalyst[3] (CuSO4 + NaAsc). Compared
to the product by chemo selective coupling method,
the synthesized compound provides identical 1H
(Figure 1C), 13C NMR (Figure S31), MS (Figure S32), IR
(Figure S33) and UV–vis (Figure S34) spectra, indicating
the success of the mixed modular approach for the
preparation of JD 9.
A complete oxidation–reduction cycle experiment, in
which Fe2(SO4)3 was used as oxidizing agent and ascorbic
acid was selected as reducing agent, was carried out to
explore the redox reversibility of the Fc unit in JD 9.
The original color of aqueous solution of JD 9 is yellow
(Figure 3), and after the addition of Fe2(SO4)3 solution,
it was converted into pale green that is the typical color
of Fcium‐containing compound.[2,3] The UV–visible spec-
troscopy further provides powerful proof for the transfor-
mation of Fc groups into Fcium cations. As shown in
Figure 3, before oxidation, a strong absorption band at
431 nm is observed corresponding to the d‐d* transition
of the iron center in the Fc units. And after the addition
of Fe2(SO4)3, this characteristic peak disappears, and an
emerging absorption band at 630 nm is attributed to the
characteristic Fcium moieties.[2,3]
Subsequently, ascorbic acid was added stoichiometri-
cally to reduce the green Fcium‐containing JD. As
expected, with the addition of ascorbic acid solution, the
pale green of reaction mixture is gradually transferred
FIGURE 3 UV–visible spectral change of 9 during an oxidation–reduction cycle

10 of 14
MU ET AL.
into the original yellow of JD 9 (Figure 3). More impor-
tantly, no peak is observed at 630 nm, and the character-
istic peak for Fc units re‐appears at 431 nm. These results
undisputedly demonstrate the re‐formation of the neutral
Fc moieties. Furthermore, compared with the original
UV–visible curve of JD 9, the recovered compound
exhibits slightly decreased absorption strength at 431
nm, which is probably attributed to the dilution effect of
solvent used to dissolve Fe2(SO4)3 and ascorbic acid in
the cycle experiment. Overall, the Fc units in JD 9 are
confirmed to be chemically reversible.
region of aggregated 9. This leads to a remarkable change
of fluorescence intensity of pyrene (Figure 4a) and the
increase of intensity ratios (I3/I1) of the first peak (I1)
and third peak (I3) at 372 and 383 nm, respectively. As
shown in Figure 4b, the plot of I3/I1 intensity ratios versus
logarithmic concentrations of 9 enabled the CMC to be
determined at 0.316 mg ml−1 for JD 9. Similarly, the
CMC of oxidized JD 9 by Fe2(SO4)3 was also determined
by the pyrene fluorescence probe method, and the
obtained CMC value is 0.501 mg ml−1. The higher CMC
value of 9 in oxidation state is taken into account by
the hydrophilic property of Fcium groups. Based on the
above results, an aqueous solution of 5.0 mg ml−1 above
CMCs was applied to investigate the redox‐reduced self‐
assembly behavior of JD 9.
3.3 | Self‐assembly of JD 9 in aqueous
solution
The self‐assembly process of JD 9 was triggered by
dialysis treatment. The self‐assembled nanostructures
formed by the dropwise addition of distilled water into
the THF solution of 9 were characterized by SEM and
DLS. The nearly spherical morphology of self‐assembled
micelles in aqueous solution was observed by SEM
(Figure 5a), and the average diameter of these micelles
was estimated to be 43.3 nm or so (Figure 5b). The DLS
curve (Figure 5c) provides two hydrodynamic diameters
of 187 nm (76%) and 8.8 nm (24%) for these micelles. As
With both nine hydrophilic TEG chains and three hydro-
phobic Fc termini, the JD 9 is contemplated to self‐
assemble into interesting micelles in aqueous solution.
The spectrophotometry is applied to measure the critical
micelle concentration (CMC) of 9 and its self‐assembly
behavior using hydrophobic pyrene as a fluorescence
probe.[31,49] In pace with the gradual increase of concen-
tration, the JD 9 self‐assembles into micelles; meanwhile,
the pyrene substrate is located in the hydrophobic micro
FIGURE 4 Determination of the CMC for 9 and its oxidation product. Fluorescence spectra of 9 (a) and its oxidation product (c) in water
with pyrene. Plots of the I3/I1 ratios versus logarithmic concentrations of 9 (b) and its oxidation product (d)

MU ET AL.
11 of 14
FIGURE 5 SEM images, size distribution and DLS curves of 9 in water (5.0 mg ml−1) during an oxidation–reduction cycle. (a) SEM image
of the original 9 micelles; (b) size distribution (number %) of the original 9 micelles by SEM; (c) DLS curve of the original 9 micelles
(PDI = 0.450, average diameter = 187.1 nm, 76%; 8.8 nm, 24%). (d) SEM image of the oxidized 9 micelles; (e) size distribution (number %) of
the oxidized 9 micelles by SEM; (f) DLS curve of the oxidized 9 micelles (PDI = 0.308, average diameter = 257 nm); (g) SEM image of the
reduced 9 micelles; (h) size distribution (number %) of the reduced 9 micelles by SEM; (i) DLS curve of the reduced 9 micelles (PDI = 0.243,
average diameter = 132 nm, 82%; 9.0 nm, 18%)
expected, the diameter determined by SEM is typically
lower than that determined by DLS. The difference
between SEM and DLS may be caused by the fact that
SEM reflects directly the diameter of self‐assembled
micelles in the dry state, while the diameter provided by
DLS is the size of swollen micelles in solution.[50,51] In
brief, these results indicate that the micelles of 9 were
successfully formed in aqueous solution.
The redox‐responsive self‐assembly behavior of amphi-
philic JD 9 was further investigated by using Fe2(SO4)3 as
oxidant and ascorbic acid as reductant, respectively, in
aqueous water. In this way a thorough oxidation–
FIGURE 6 Standard curve of RhB (a) and oxidation‐triggered release profiles of RhB from 9 micelles using Fe2(SO4)3 as an oxidant (b)

12 of 14
MU ET AL.
reduction cycle was conducted. The change in morphol-
ogy and size of micelles was monitored by SEM and
DLS. Interestingly, when the self‐assembled micelles con-
verted into the oxidized ones by the addition of Fe2(SO4)3,
the near‐spherical morphology still was observed by SEM
(Figure 5d), nevertheless the average diameter of oxidized
micelles increased to 57 nm (Figure 5e) and the hydrody-
namic diameter by DLS is about 257 nm with PDI = 0.308
(Figure 5f). Obviously, the larger average diameter of oxi-
dized micelles should be attributed to the enhanced
hydrophily of Fcium cations. Furthermore, the oxidized
micelles were backtracked by the addition of ascorbic
acid to verify the reversibility of this conversion. As
expected, the reformed micelles possess spherical shape
by SEM (Figure 5g), and the micellar diameter of reduced
micelles lessened after the reduction with ascorbic acid
(Figure 5h). The determined diameter by SEM is 42.0
nm (Figure 5 h), which is perfectly matched with the
original diameter before oxidation (Figure 5a). The recov-
ery of micelles were further proved by the DLS (Figure 5i)
that provides two hydrodynamic diameters of 132 nm
(82%) and 9.0 nm (18%) for these micelles, in consistent
with the initial diameter. Based on the above results of
SEM and DLS, it is confirmed that the redox‐responsive
self‐assembly of JD 9 can be successfully carried out in
aqueous solution.
the cargo‐loading micelles, which confirms that the RhB
molecules were successfully encapsulated into the
micelles of 9. According to the standard curve of RhB
(Figure 6a), the amount of RhB loaded was then deter-
mined. And the measurement shows that the values of
LCRhB and EERhB were 1.98% and 2.6%, respectively.
The morphology and size of the RhB‐loaded micelles
of 9 in aqueous solution were then characterized by
SEM and DLS (Figure 7). The average diameter of the
nearly spherical micelles was determined to be 65.5 nm
by SEM (Figure 7b), which is slightly larger than that of
the empty micelles of 9 (Figure 5a). The DLS curve
(Figure 7c) shows also two hydrodynamic diameters of
349 nm (39%) and 8.0 nm (61%) for these micelles.
The oxidation‐triggered release of RhB from the
micelles of 9 was conducted by using Fe2(SO4)3 as an oxi-
dizing agent at the concentrations of 0.1, 0.5 and 1.0 mg
ml−1, respectively. In order to calculate the release
amount of RhB, we measured the absorbance of
Fe2(SO4)3 dialysate at 560 nm at different intervals by
using UV–visible spectroscopy. As shown in Figure 6b,
oxidation with Fe2(SO4)3 at all the concentrations can
trigger the release of RhB from micelles of 9. Obviously,
when the concentration of Fe2(SO4)3 was increased, the
release rate of RhB also became faster. At concentration
of 0.1 mg ml−1, the cumulative release of RhB reached
about 35% after 40 hr of treatment with Fe2(SO4)3, and
about 88% of encapsulated RhB escaped from the micelles
of 9 when the concentration of Fe2(SO4)3 was improved
to 0.5 mg ml−1. When the concentration was further
increased to 1.0 mg ml−1, the fast release speed was
observed in the first 8 hr, and the release amount reached
95%. The burst release is taken into account by the rapid
oxidation of Fc moieties in 9 into Fcium cations,
which results in the micellar swelling. Subsequently, in
comparison to the release speed of the first 8 hr, the
release rate was significantly slower after 8 hr, and
the cumulative release of RhB reached 100% after 40 hr
of treatment with Fe2(SO4)3. In short, the release rate of
RhB can be regulated by changing the concentration of
oxidizing agent.
3.4 | Substrate‐loading and release from
micelles of JD 9
The cargo‐loading ability of micelles self‐assembled by JD
9 was further investigated using RhB as a model sub-
strate. The deionized water was dropwise dispersed into
the mixed solution containing 9 and RhB in THF with
stirring. After further vigorous stirring for 12 h, the
obtained RhB‐loaded micelles were dialyzed against dis-
tilled water using a dialysis bag to remove the residual
THF and unloaded RhB molecules. As shown in Figure
S45, the characteristic absorption band of RhB at around
560 nm was found in the UV–vis absorption spectrum of
FIGURE 7 SEM image (a), size distribution (b), and DLS curve (PDI = 0.426, average diameter = 349 nm, 39%; 8.0 nm, 61%) (c) of RhB‐
loaded 9 micelles

MU ET AL.
13 of 14
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4 | CONCLUSIONS
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2012, 36, 380.
In summary, a novel ferrocenyl‐terminated amphiphilic
[7] T. Tuuttila, J. Lipsonen, M. Lahtinen, J. Huuskonen, K.
Janus dendrimer
9
containing nine hydrophilic
Rissanen, Tetrahedron 2008, 64, 10590.
triethylene glycol branches has been successfully synthe-
sized by two synthetic routes of the typical chemo selec-
tive coupling method and the mixed modular approach.
The redox‐controlled self‐assembly behavior of 9 in aque-
ous solution was also investigated and confirmed by SEM
and DLS. The self‐assembly of the Janus macromolecule
leads to nearly spherical nanoscale micelles in water. The
reversible swelling and shrinking of these micelles, as shown
by SEM and DLS, are triggered by the addition of Fe2(SO4)3
as oxidizing agent and ascorbic acid as reducing agent,
respectively, as a result of the redox‐controlled transition
between Fc groups and Fcium cations. Further, RhB‐loaded
micelles of JD 9 were successfully applied for the oxidation‐
triggered release and the cumulative release amount of RhB
can be mediated by changing the oxidant concentration.
This work provides a useful example for the redox‐
responsive self‐assembly of Fc‐terminated amphiphilic JD
systems and the present JD micelles could have diverse
applications, especially in oxidation‐triggered drug delivery.
[8] S. D. Mu, Q. J. Ling, X. Liu, J. Ruiz, D. Astruc, H. B. Gu,
J. Inorg. Biochem. 2019, 193, 31.
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[17] N. Ma, Y. Li, H. P. Xu, Z. Q. Wang, X. Zhang, J. Am. Chem. Soc.
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ACKNOWLEDGEMENT
[20] A. Napoli, M. J. Boerakker, N. Tirelli, R. J. M. Nolte, N. A. J. M.
This work was financially supported by the Science and
Technology Department of Sichuan Province (No.
2018HH0038) and the National Natural Science Founda-
tion of China (No. 21606165). The authors thank
Zhonghui Wang (College of Light Industry, Textile and
Food Engineering, Sichuan University) for her great help
in DLS observation and the ceshigo (www.ceshigo.com)
for help in SEM.
Sommerdijk, J. A. Hubbell, Langmuir 2004, 20, 3487.
[21] L. Zhang, G. R. Qiu, F. F. Liu, X. Liu, S. D. Mu, Y. R. Long, Q.
X. Zhao, Y. Liu, H. B. Gu, React. Funct. Polym. 2018, 132, 60.
[22] J. M. Hu, L. Dai, S. Y. Liu, Macromolecules 2011, 44, 4699.
[23] C. H. Luo, Y. Liu, Z. B. Li, Macromolecules 2010, 43, 8101.
[24] Z. S. Ge, S. Z. Luo, S. Y. Liu, J. Polym. Sci. A Polym. Chem. 2006,
44, 1357.
[25] P. R. Chiang, T. Y. Lin, H. C. Tsai, H. L. Chen, S. Y. Liu, F. R.
Chen, Y. S. Hwang, I. M. Chu, Langmuir 2013, 29, 15981.
[26] C. Wang, Q. S. Chen, H. P. Xu, Z. Q. Wang, X. Zhang, Adv.
Mater. 2010, 22, 2553.
CONFLICT OF INTEREST
The authors declare no conflict of interest.
[27] M. Rabnawaz, G. J. Liu, Macromolecules 2012, 45, 5586.
[28] G. Njikang, G. J. Liu, L. Z. Hong, Langmuir 2011, 27, 7176.
[29] P. Han, S. C. Li, W. Cao, Y. Li, Z. W. Sun, Z. Q. Wang, H. P. Xu,
ORCID
J. Mater. Chem. B 2013, 1, 740.
Haibin Gu https://orcid.org/0000-0003-0342-360X
[30] J. Del Barrio, L. Oriol, C. Sanchez, J. L. Serrano, A. Di Cicco, P.
Keller, M. H. Li, J. Am. Chem. Soc. 2010, 132, 3762.
[31] G. R. Qiu, L. Zhao, X. Liu, Q. X. Zhao, F. F. Liu, Y. Liu, Y. W.
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