In Situ Generation of Azonia-Containing Polyelectrolytes for Luminescent Photopatterning and Superbug Killing

Article abstract of DOI:10.1021/jacs.9b04757

Polyelectrolytes play an important role in both natural biological systems and human society, and their synthesis, functional exploration, and profound application are thus essential for biomimicry and creating new materials. In this study, we developed an efficient synthetic methodology for in situ generation of azonia-containing polyelectrolytes in a one-pot manner by using readily accessible nonionic reactant in the presence of commercially available cheap ionic species. The resulting polyelectrolytes are emissive in the solid state and can readily form luminescent photopatterns with different colors. The azonia-containing polyelectrolytes possess extraordinary potency of reactive oxygen species (ROS) generation, enabling them to impressively kill methicillin-resistant Staphylococcus aureus (MRSA), a drug resistant superbug, both in vitro and in vivo.

Full text of DOI:10.1021/jacs.9b04757

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Article
In-situ Generation of Azonia-containing Polyelectrolytes
for Luminescent Photopatterning and Superbug Killing
Xiaolin Liu, Mengge Li, Ting Han, Bing Cao, Zijie Qiu, Yuanyuan Li, Qiyao Li,
Yubing Hu, Zhiyang Liu, Jacky W. Y. Lam, Xianglong Hu, and Ben Zhong Tang
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.9b04757 • Publication Date (Web): 20 Jun 2019
Downloaded from http://pubs.acs.org on June 20, 2019
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In-situ Generation of Azonia-containing Polyelectrolytes for
Luminescent Photopatterning and Superbug Killing
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Xiaolin Liu,†,§, Mengge Li,‡, Ting Han,†,§ Bing Cao,‡ Zijie Qiu,†,§ Yuanyuan Li,†,§ Qiyao Li,†,§ Yubing
Hu,†,§ Zhiyang Liu,†,§ Jacky W. Y. Lam,†,§,* Xianglong Hu,‡,* Ben Zhong Tang†,§,‖,*
† Department of Chemistry, Hong Kong Branch of Chinese National Engineering Research Center for Tissue Restoration
and Reconstruction, Institute for Advanced Study, Department of Chemical and Biological Engineering, Institute of
Molecular Functional Materials, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong
Kong, China
‡ Ministry of Education Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics,
South China Normal University, Guangzhou 510631, China
§
HKUST-Shenzhen Research Institute, No. 9 Yuexing 1st RD, South Area, Hi-tech Park, Nanshan, Shenzhen 518057,
China
‖ Center for Aggregation-Induced Emission, SCUT-HKUST Joint Research Institute, State Key Laboratory of Luminescent
Materials and Devices, South China University of Technology, Guangzhou 510640, China
ABSTRACT: Polyelectrolytes play important role in both natural biological systems and human society, and their synthesis,
functional exploration, and profound application are thus essential for biomimicry and creating new materials. In this study,
we developed an efficient synthetic methodology for in-situ generation of azonia-containing polyelectrolytes in a one-pot
manner by using readily accessible nonionic reactant in the presence of commercially available cheap ionic species. The
resulting polyelectrolytes are emissive in the solid state, and can readily form luminescent photopatterns with different
colors. The azonia-containing polyelectrolytes possess extraordinary potency of reactive oxygen species (ROS) generation,
enabling them to impressively kill methicillin-resistant Staphylococcus aureus (MRSA), a drug resistant superbug, both in vitro
and in vivo.
INTRODUCTION
modifications are hard to be 100% completed, allowing
patches along the polymer chain, which are impossible to be
removed and purified. Some coupling reactions (Heck14 and
Sonogashira15) are also employed for the synthesis of
polyelectrolytes but they frequently require expensive and
limited types of ionic monomers.
Many important biological macromolecules are
polyelectrolytes, such as DNA, proteins, polypeptides and
polysaccharides.1-3 Polyelectrolytes are ionizable polymers
possessing the combined behaviors of polymers and
electrolytes, which can drastically change the fluid
properties of aqueous solutions, interact with oppositely
charged macromolecules, small ions, and even neutral
particles. Polyelectrolytes have demonstrated great
potency in many aspects, for example, thickening agents in
food industry, waste water treatment in environment
science, diagnostic and therapeutic agents in medicine.4-5
For biomimicry and creating new materials, it is attractive
to synthesize and study polyelectrolytes. However, the
progress is unsatisfactory because of their synthetic
difficulty.6 The main methodology for the synthesis of
polyelectrolytes is post-modification of nonionic
polymers.7-9 One archetype example is sodium polystyrene
sulfonate (NaPSS), which is synthesized by adding sulfonate
groups after polymerization.10-11 Another typical example is
polyacrylic acid (PAA), which is generally obtained by the
hydrolysis of polyacrylate.12-13 Theoretically, the post-
Most commercially available polyelectrolytes (such as
NaPSS and PAA) are commodity polymers, which are cheap
and useful in daily life but show no advanced functional
properties.16-17 Specialty polymers (such as conducting
polymers, liquid crystalline polymers, and biomedical
polymers) are attracting much interest because of their
novel functionalities.18-23 There are some progresses in
developing specialty polyelectrolytes, with water-soluble
conjugated polymers being a typical example. A plenty of
water-soluble conjugated polymers have been designed and
synthesized for bio-imaging, diagnosis and therapy,24-28
using their fluorescence and photodynamic properties.
However, traditional specialty polymers often suffer from
aggregation-caused quenching effect in the condensed
state, which significantly decreases
their emission
efficiency or intersystem crossing (ISC) efficiency because
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azonia-containing
of the high probability of the excited state to undergo
nonradiative relaxation.29 As it is hard to completely avoid
aggregation in diverse practical applications, new specialty
polyelectrolytes are in great demand to address these
problems.30
Scheme
polyelectrolytes
1.
Synthesis
of
1
2
3
4
5
6
7
8
In our previous work, some azonia aromatic compounds
have been found to show aggregation-induced emission
(AIE) characteristics with strong reactive oxygen species
(ROS) generation ability.31-34 The azonia rings are highly
electron-deficient, and they are thus easy to form donor-
acceptor (D-A) structures with tunable emission color by
combining with different electron donors.35 Many reported
antibiotics are also azonia-containing molecules but the
processability of these small molecules is quite limited.36
Thus, we intend to combine the excellent performance of
azonia aromatic compounds with processable polymers to
create new functional materials with expectable optical
properties and processability. The resulting azonia-
containing polyelectrolytes are expected to show good
processing ability that can be easily fabricated into
luminescent films for applications in surface modification,
patterning and large area display system. With high charge
density in the polymer chain, the azonia-containing
polyelectrolytes may show affinity to negative charge
species (such as bacteria membrane and DNA), which
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resistance issue. Systematic antibacterial explorations were
conducted, including bacteria staining and killing
methicillin-resistant Staphylococcus aureus (MRSA), a drug
resistant superbug in vitro and in vivo.
enable them to wrap the surface of bacteria and physically
37-38
kill them.4,
By introducing D-A structure into the
polyelectrolytes, the nonradiative decay channel is blocked
due to the rigid structure,29 which is beneficial for
bioimaging and ROS generation. As a result, the azonia-
containing polyelectrolytes are potential powerful weapons
to kill superbugs by photodynamic therapy besides
physically killing.39-40
RESULTS AND DISCUSSION
Polymerization. Monomers used in this work are easily
available. Allylamines 1ab, tetrafluoroboric acid (HBF4,
3a), sodium hexafluorophosphate (NaPF6, 3b), sodium
trifluoromethanesulfonate (NaCF3SO3, 3c), sodium
tetraphenylborate (NaBPh4, 3d), sodium tetrafluoroborate
(HBF4), and hexafluorophosphoric acid (HPF6) were
commercially available and used without further
purification. The internal diynes 2ah used in this work
were readily synthesized without column chromatography
purification. All the polymerizations were catalyzed by
[Cp*RhCl2]2 and Cu(OAc)2·H2O and conducted under air
atmosphere in a one-pot manner.
Owing to the attractive properties of azonia aromatic
compounds, many novel approaches have been developed
for the synthesis of azonia small molecules,41 including ring-
closing metathesis reactions,42-43 annulation reactions
based on C-H activation,44-46 and so on. But it is challenging
to develop these small molecule reactions for polymer
synthesis due to the limited organic reactions with mild
reaction condition, broad monomer scope and high
efficiency. In 2017, Jun et al. reported an efficient method
for the synthesis of benzoquinolizinium salts in a one-pot
manner from simple starting materials (Scheme 1A).47
Inspired by this work, we try to develop such efficient small
molecule reaction into useful tool for the synthesis of
azonia-containing polyelectrolyte.
To obtain soluble polyelectrolytes with high molecular
weights in high yields, we systematically investigated the
polymerization conditions using 1a, 2a and 3a as
monomers. The solvent, monomer ratio, catalyst loading,
concentration, and reaction time were carefully
investigated (Table 1). The effect of solvent on the
polymerization was first investigated (entries 15, Table 1).
Polar solvents such as MeOH, DCM, MeOH/DMSO, and
MeOH/DCM mixed solvents were investigated and the best
polymerization result was obtained in MeOH/DCM (v/v,
1/1), affording polymer with Mw of 19 200 Da in 72% yield
(entry 5, Table 1). It was found that monomer ratio (entries
56, Table 1) exerted little effect on the polymerization,
while the catalyst loading (entries 5, and 79, Table 1)
played a crucial role in the polymerization. Decreasing the
amount of [Cp*RhCl2]2 from 10 mol% to 5 mol% even
increased the Mw and yield (entry 7, Table 1), but further
reducing the loading of [Cp*RhCl2]2 or Cu(OAc)2·H2O led to
a sharp decrease in both the values of Mw and yield. With the
optimized catalyst loading, we further investigated the
In this study, we developed a synthetic methodology by
readily accessible nonionic reactant in the presence of
commercially available cheap ionic species to in-situ
generate azonia-containing polyelectrolytes in a one-pot
manner. The main-chain polyelectrolytes were generated in
excellent yields (up to 99%) with high molecular weights
(up to 28 700 Da). The azonia-containing polyelectrolytes
were luminescent in the solid state with good processing
ability, which enabled them to be excellent candidate
materials for fluorescent photopattern generation. With
extraordinary strong ROS generation ability, these
polyelectrolytes could impressively solve the bacterial
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Table 1. Optimization of the polyannulation reactiona
1
2
3
[1a]
[2a]
(M)
[Rh]
(%)
[Cu]
(equiv)
yield
(%)
b
b
b
entry
solvent
Mn
Mw
Mw/Mn
(M)
4
5
6
7
8
9
1
MeOH
0.20
0.20
0.20
0.20
0.20
0.20
0.20
0.20
0.20
0.25
0.15
0.20
0.20
0.20
0.20
0.20
0.20
0.20
0.20
0.25
0.20
0.20
0.20
0.25
0.15
0.20
0.20
0.20
10
10
10
10
10
10
5
5
5
trace
trace
trace
54
2c
3c
4
MeOH/DMSO
MeOH/DMSO
DCM
5
5
7 600
14 800
12 700
20 400
4 500
13 700
19 200
16 500
28 700
4 900
1.8
1.3
1.3
1.4
1.1
5
MeOH/DCM
MeOH/DCM
MeOH/DCM
MeOH/DCM
MeOH/DCM
MeOH/DCM
MeOH/DCM
MeOH/DCM
MeOH/DCM
MeOH/DCM
5
72
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
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6
5
87
7
5
93
8
2.5
5
5
4
9
2.5
5
trace
85
10
11
12d
13d
14e
5
15 800
6 400
12 400
6 700
3 500
20 500
9 600
16 100
8 700
7 900
1.3
1.5
1.3
1.3
2.3
5
5
72
5
5
70
5
5
21
5
5
47
aUnless otherwise noted, the polymerizations were carried out at 130 oC in air for 24 h, [3a] = 0.3M, in MeOH, DCM or their mixture
b
c
(1:1). Estimated by GPC in DMF on the basis of a linear polystyrene calibration. MeOH/DMSO = 8:2 (entry 2), and 6:4 (entry 3).
dReaction time was 18 h (entry 12) and 12 h (entry 13). eNaBF4 was used instead of HBF4.
effect of monomer concentration and reaction time on the
polymerization. When the monomer concentration of 1a
was decreased from 0.2 M to 0.15 M, both the Mw and yield
decreased sharply (entry 11, Table 1). When the monomer
concentration of 1a was improved from 0.2 M to 0.25 M, the
Mw and yield decreased slightly, with partial gelation
occurred (entry 10, Table 1). 24 h was adopted as the
optimal reaction time, as further decrease of the reaction
time led to unsatisfactory values of Mw and yield (entries
1213, Table 1).
With the optimized polymerization conditions in hand,
different monomer combinations were applied to test the
robustness and wide applicability of this polymerization
route (Table 2). Monomers 2ac were internal diynes with
flexible alkyl chain or oxyalkyl chain as spacer, while 2df
were rigid conjugated diynes with different electron
density. Monomers 3ad were abundant and cheap acid or
salt. Diyne 2af all reacted efficiently with 1a and 3a,
affording polyelectrolytes with high yield and molecular
weight (entries 16, Table 2). The diarylacetylene structure
was crucial for this polymerization, as only a trace amount
of product was obtained when tert-butyl-substituted diyne
2g (Scheme S1) was used as diyne monomer to react with
1a and 3a. The fluorene-substituted diyne 2h (Scheme S1)
also failed to be polymerized effectively, probably due to the
large steric hindrance of fluorene moiety. Regarding the
monomer scope of allylamines, both unsubstituted
allylamine 1a or methyl-substituted allylamine 1b could
react efficiently with diyne 2a or 2e in the presence of 3a
(entries 12, 78, Table 2). But 1b was less reactive
compared to 1a, which was probably due to the steric
hindrance of the methyl group. Finally, we further explored
the influence of ion source on the polymerization process.
Based on the mechanism of small molecules,47 we proposed
a mechanism of the polymerization route (Scheme S3). In
the proposed mechanism, the ion source could react with
the seven-membered rhodacycle complex D to form
benzoquinolizium salt, which was crucial to the
polymerization. We had demonstrated that HBF4 3a, NaPH6
3b and NaCF3SO3 3c could react efficiently with 1a and 2a
to generate polyelectrolytes with moderate Mw and yield
(entries 1, 910, Table 2), while the NaBPh4 3d was much
less reactive with 1a and 2a (entries 11, Table 2),
presumably resulting from the steric hindrance. HPF6 failed
to polymerize with 1a and 2a, probably due to the too
Table 2. Polyannulation results of different monomersa
yield
b
b
b
entry monomer
Mn
Mw
Mw/Mn
(%)
93
60
99
71
74
78
52
53
64
75
25
1
1a/2a/3a
1a/2b/3a
1a/2c/3a
1a/2d/3a
1a/2e/3a
1a/2f/3a
1b/2a/3a
1b/2e/3a
1a/2a/3b
1a/2a/3c
1a/2a/3d
20 400 28 700
11 900 14 900
17 900 24 000
14 000 20 000
18 900 22 700
1.4
1.3
1.3
1.4
1.2
1.4
1.5
1.3
1.6
1.5
1.3
2
3c
4
5
6 d
7d
8
5 700
8 100
17 700 26 000
18 800 23 700
13 100 21 500
16 800 25 100
9
10d
11
5 600
7 600
aUnless otherwise noted, the polymerizations were carried
out at 130 oC in air for 24 h, [1] = [2] = 0.2 M, [3] = 0.3 M, [Rh]
= 5 mol%, [Cu] = 5 equiv. Solvent: DCM/MeOH=1:1. bEstimated
by GPC in DMF on the basis of a linear polystyrene calibration.
cReaction time was 36 h. dPartially insoluble.
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Figure 1. 1H NMR spectra of (A) 1a in D2O and (B) 2a, (C) model compound 2 and (D) P1a/2a/3a in CD2Cl2. 13C NMR spectra of (E)
1a in D2O and (F) 2a, (G) model compound 2 and (H) P1a/2a/3a in CD2Cl2.
strong acidity or decomposition upon heating of HPF6.
These results indicated that we successfully developed an
efficient and powerful polymerization tool for the
construction of azonia-containing polyelectrolytes. The
only byproduct produced from this polymerization was
hydrogen ion, indicating its high atom economy.
(Figure S1), the N-H stretching vibration of 1a and the CC
stretching vibrations of 2a occurred at 3012 and 2220 cm-1,
respectively. These peaks could not be observed in the
spectra of P1a/2a/3a and 2. Meanwhile, a new peak
associated with B-F stretching vibrations appeared at 1083
cm-1, indicating the successful occurrence of the reaction.
Similar results were obtained in the FT-IR spectra of other
polymers (Figure S2-3).
Most of the obtained polyelectrolytes showed good
solubility in commonly used organic solvents, such as DCM,
chloroform, DMSO, and N,N-dimethylformamide (DMF),
whereas P1b/2a/3a and P1a/2a/3c were partially
insoluble in these solvents. The thermal properties of the
polyelectrolytes were evaluated by thermogravimetric
analysis (TGA), and the results indicated that the 5% weight
In addition, NMR spectra could provide more detailed
1
information about the polymer structures. In the H NMR
spectra, the protons at position “a”, “b” and “c” of 1a
resonate at δ 5.95 ppm, 5.43 ppm and 3.63 ppm,
respectively, disappeared in the 1H NMR spectra of
P1a/2a/3a and 2. Most importantly, new peaks emerged at
δ 8.84 ppm and 8.37 ppm in the spectra of P1a/2a/3a and
2, corresponding to the aromatic protons from the newly
formed benzoquinolizinium rings (Figure 1AD). The 13C
NMR spectra further verified the polymer structure (Figure
1EH). The characteristic peaks of CC in 2a was not
observed in the polymer spectrum. Instead, the aromatic
carbon on benzoquinolizinium rings resonated at δ
143120 ppm in the spectra of P1a/2a/3a and 2. For all the
10 polyelectrolytes, the characteristic peaks at δ 8.908.10
ppm all emerged in their 1H NMR spectra, and their
characteristic CC peaks at δ 90.088.0 ppm all disappeared
in their 13C NMR spectra, confirming successful fabrication
of their azonia-containing polyelectrolytes accordingly
(Figure S2248).
o
loss temperatures (Td) were in the range of 218323 C
(Figure S4), suggesting that they were thermally stable.
Additionally, P1a/2d/3a and P1a/2e/3a displayed 70% of
their weight even upon heating to 800 oC.
Structural Characterization. The structures of the
resulting polymers were characterized by FT-IR and NMR
spectra. To gain insight into the structures of these azonia-
containing polyelectrolytes, model compound 2 was
prepared by cascade double N-annulation reaction of
allylamine 1a, diphenylacetylene 1, and HBF4 under the
same synthetic conditions for the polyelectrolytes (Scheme
S2). Typical FT-IR analysis and 1H NMR and 13C NMR spectra
of polymer P1a/2a/3a, model compound 2, and their
corresponding monomers 1a and 2a were performed
accordingly for further illustration. In the FT-IR spectra
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Figure 2. (A) Photographs of P1a/2d/3a in DCM/hexane mixtures with different hexane fractions (fH) taken under 365 nm UV
irradiation from a handheld UV lamp. (B) Emission spectra of P1a/2d/3a in DCM/hexane mixtures with different hexane fractions.
Excitation wavelength: 380 nm. (C) Plot of relative emission intensity (I/I0) versus the composition of the DCM/hexane mixture of
P1a/2d/3a. Solution concentration: 10 μM. (D) Luminescent photographs of polymer P1/2/3 in the solid state. (E) Emission spectra
of thin films of P1/2/3. Excitation wavelength: 450 nm for P1a/2e/3a, and 380 nm for the other polymers. (F-I) Two-dimensional
fluorescent photopatterns generated by photolithography of films of (F) P1a/2a/3a, (G) P1a/2d/3a, (H) P1a/2e/3a, and (I)
P1a/2d/3a taken under UV irradiation. Excitation wavelength: 330−385 nm.
Photoluminescence
(PL)
Properties
and
than that in pure DCM solution (I0) (Figure 2C). Similar
phenomenon was observed for P1a/2e/3a (Figure S9).
Photopattern. The absorption and emission spectra of
dilute DCM solutions (10 μM) of the resulting azonia-
containing polyelectrolytes were shown in Figure S6-7. Due
to the strong electron-withdrawing azonia aromatic moiety,
the maximum emission wavelength of these polymers was
facilely tunable from 490 to 610 nm, arised from the
polymerization from diyne monomers with different
electron density.
After that, the solid fluorescence of these azonia-
containing polyelectrolytes were examined (Figure 2D), all
these polymers were emissive in solid state.
P1ab/2ac/3ab displayed yellow-green emission,
P1a/2d/3a and P1b/2e/3a emitted orange fluorescence,
and P1a/2e/3a exhibited red emission. PL spectra of these
polymers in solid state were further performed (Figure 2E).
Because of the excellent solubility and film-forming ability
of P1/2/3, their uniform films could be easily fabricated
without defect on silica wafers by a simple spin-coating
technique.
By incorporating TPE and TPA moiety into the
polyelectrolyte skeletons respectively, the resulting
polymer P1a/2d/3a and P1a/2e/3a showed typical AIE
features. Taking P1a/2d/3a as an example, its DCM
solution emitted weakly at 574 nm. With the addition of
hexane, a non-polar poor solvent for the polymer, the
emission intensity gradually increased, the photographs of
these dispersions taken in DCM/hexane mixtures with
different hexane fractions visually showed the trends in
fluorescence (Figure 2A), and the maximum emission
wavelengths slightly blue-shifted to 558 nm (Figure 2B).
The PL intensity of P1a/2d/3a aggregates in DCM/hexane
mixture with 99% hexane fraction (I99) was ~13-fold higher
Macroscopically processable polymers with high
refractive indices (RI) are promising candidate materials
for various photonic applications, including optical chips,
prisms, optical waveguides, memories and holographic
image recording systems.48 Since multi-fused heterocyclic
rings were incorporated in the polymer main-chain, the
azonia-containing polyelectrolytes are expected to show
high refractive index. The thin films of P1/2/3 were
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of ABDA absorption (Figure 3D). For comparison, a commercial
prepared by spin-coating and their refractive indexes were
measured accordingly. As summarized in Figure S8 and
Table S1, their thin films indeed showed high n values of
1.8171.600 in the spectral regin of 400900 nm. Their n
values at 632.8 nm (n632.8) were in the range of 1.6861.621,
which were much higher than common polymer such as
polystyrene, polycarbonate, poly(methyl methacrylate),
and polyacrylate with n632.8 in the region of 1.491.58.49
dye, Rose Bengal, which was widely used to generate 1O2 with
singlet oxygen quantum yield of 75%, was investigated under
the same condition (Figure S11-12). The decomposition rates
of ABDA in the presence of polyelectrolytes and Rose Bengal
were calculated quantificationally (Figure 3D) and the results
indicated that P1a/2e/3a was able to generate 1O2 much more
effectively than Rose Bengal. Such strong 1O2 generation ability
of P1a/2e/3a was probably due to the extended conjugation
length between donor and acceptor, which minimized the ΔEST
and enhanced the possibility of ISC process. Also, the strong D-
A conjugated structure of P1a/2e/3a rigidified its polymer
backbone, which could minimize its nonradiative decay and
thus promote the ISC process. The photostability study showed
that P1a/2e/3a indicated better photostability than organic
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The
generation
of
fluorescent
patterns
by
photolithography technique is of great significance in terms
of the photonic and electronic applications.50-52 As shown in
Figure 2FH, after irradiation by UV light in air for 20 min
through a copper photomask, the fluorescence of the
exposed regions (lines) was completely quenched due to
the photo-oxidation of the chromophores, while the
emissive squares were protected by copper and remained
intact. Thus, two-dimensional fluorescent patterns with
different emissive colors were generated with high
resolution and sharp edges. By changing the shape and scale
of the photomask, various patterns in different scales could
be generated, such as QR code, which could be used for
information storage (Figure 2I). Herein, these azonia-
containing polyelectrolytes were expected to be promising
materials for pattern fabrication, which would have
profound implications in constructing electronic and
photonic devices and various hybrid devices as excellent
luminescent photoresist materials in a cost-efficient
photolithography process. The photostability result
showed that these polyelectrolytes were stable under the
exposure of normal room light (Figure S13-14), and were
also able to undergo photo-oxidative bleaching process
with tunable refractive index under the exposure of strong
UV light source (Figure S16, Table S3).
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dyes
RB
and
5,10,15,20-tetrakis(4-sulfonatophenyl)-
porphyrin (TPPS), two traditional photosensitizers generally
employed for PDT (Figure S15).
ROS Generation. The unique azonia moiety in these
polymers encouraged us to explore their ROS generation ability
and application in bacteria killing.53-55 H2DCF-DA is a
commercial ROS indicator, which is non-fluorescent but emits
green fluorescence when oxidized by ROS.56 H2DCF-DA was
utilized to investigate the ROS generation ability of these
Figure 3. (A-C) UV-vis absorption spectra of ABDA in the
presence of (A) P1a/2e/3a, (B) P1a/2d/3a and (C)
P1a/2c/3a. (D) The decomposition rates of ABDA by P1/2/3
and rose Bengal where A0 and A are the absorbance of ABDA in
the presence of PSs at 378 nm before and after irradiation,
respectively.
azonia-containing
polyelectrolytes,
and
P1a/2e/3a,
P1a/2d/3a, and P1a/2c/3a were chosen for demonstration.
As shown in Figure S10, in the mixture of polyelectrolytes and
H2DCF-DA, the fluorescence intensity of H2DCF-DA at 525 nm
increased gradually with the extension of irradiation time. A
steeper slope of curves indicated much higher ROS generation
rate, suggesting that three polyelectrolytes exhibited different
ROS generation efficiency in the order of P1a/2e/3a >
P1a/2d/3a > P1a/2c/3a.
Superbug Killing. The strong 1O2 generation ability of these
polyelectrolytes motivated us to further explore its
performance as photosensitizer in bacteria inhibition.
P1a/2e/3a with most significant ROS generation was
chosen for further biological evaluation. The hydrodynamic
diameter of P1a/2e/3a micelles was determined to be
~106 nm by dynamic laser scattering (DLS) analysis, and
the transmission electron microscopy (TEM) analysis
confirmed the spherical morphology and size (Figure 4A).
Then, in vitro antimicrobial activities of P1a/2e/3a were
firstly evaluated towards representative Gram-positive S.
aureus and Gram-negative E. coli, respectively (Figure S18).
The polymer showed weak inhibition to E. coli even under
light irradiation, but strong inhibition to S. aureus under
white light irradiation with minimal inhibition
concentration (MIC) of 15 ug/mL. The different
antimicrobial ability was probably due to the membrane
difference between Gram-negative bacteria and Gram-
Among all the ROS species, such as superoxide (O2•-),
hydrogen peroxide (H2O2), hydroxyl radical (•OH), and singlet
1
oxygen (1O2), O2 is regarded as a primary cytotoxic agent.57
Herein, 9,10-anthracenediyl-bis-(methylene)-dimalonic acid
(ABDA), a specific probe to detect 1O2 was utilized to prove the
generation of 1O2 from azonia-containing polyelectrolytes.58 In
1
the presence of O2, ABDA is transformed into endoperoxide,
leading to a decrease of ABDA absorption at 378 nm. The
absorbance spectra of ABDA solution in the presence of
P1a/2c/3a, P1a/2d/3a, and P1a/2e/3a was recorded upon
white light irradiation (Figure 3AC). In the presence of these
polyelectrolytes, noticeable reduction of ABDA absorption was
observed, especially for P1a/2e/3a, which caused fastest drop
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Figure 4. (A) Hydrodynamic diameter distribution and TEM image of P1a/2e/3a aqueous suspension. (B) Fluorescent images, DIC
images and their merge images of MRSA upon treatment with P1a/2e/3a. (C) Quantitative antibacterial tests of P1a/2e/3a against
MRSA in the presence or absence of light irradiation. (D) Morphology change of MRSA upon diverse treatments observed by TEM.
(E) Morphology change of MRSA upon diverse treatments observed by SEM.
positive bacteria, it was difficult for polymer micelles to
access membrane of Gram-negative bacteria due to its extra
protective membrane components.39 Notably, undetectable
ROS generation of monomers 1a, 2e, and 3a was also
proved by the chemical trapping measurements with ABDA
as indicator (Figure S17).
After that, the quantitative MRSA inhibition of
P1a/2e/3a was performed in the presence of light
irradiation or not (Figure 4C). In dark state, P1a/2e/3a
exhibited moderate inhibition against MRSA, as the positive
charges on the polyelectrolyte main chain enabled the
micelles to adhere and fuse with the bacteria membrane,
thus physically damaged bacteria membrane to some
extent.62 Upon white light irradiation, P1a/2e/3a could
MRSA is one of the most notorious drug-resistant Gram-
positive bacteria in the hospital environment and
community settings, leading to a variety of clinical
syndromes such as endocarditis, pneumonia, and central
nervous system infections.59-61 As the polyelectrolyte
P1a/2e/3a showed good inhibition to Gram-positive S.
aureus, thus the inhibition potency against MRSA were
evaluated to further explore its antimicrobial ability against
drug-resistant bacteria. As shown in Figure 4B, the high
charge density in the polymer main chain enabled
P1a/2e/3a to possess high affinity to negatively charged
bacteria membrane, thus could stain MRSA quickly, as short
as 5 min. Furthermore, persistent fluorescence was found
for bacteria even upon incubation for 60 min, which was
favorable for extended light irradiation.
1
generate O2 efficiently apart from the physical damage
effect, leading to much stronger inhibition against MRSA
with an MIC value of ~30 ug/mL. In addition, the raw
monomers 1a, 2e, and 3a of P1a/2e/3a all exhibited
minimal bacteria inhibition even in the presence of light
irradiation, which further highlighted advantageous
P1a/2e/3a with remarkable PDT potency (Figure S19)
Furthermore, the morphology change of MRSA upon
diverse treatments was observed by TEM and SEM analysis
(Figure 4D-E). After incubation at 37 oC for 30 min, both the
control sample and single light-treating sample exhibited
smooth membrane surface and intact membrane structure,
while the cell surface of MRSA became rough and out of
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Figure 5. (A) Schematic illustration for the construction of MRSA-infected mouse burn model and the therapeutic profile. (B) Typical
photographs of MRSA-infected burn sites upon different treatments under dark or light irradiation during the therapeutic processes.
(C) Relative eschar size analysis after diverse treatments at the 14th day. (D) The number of MRSA in the infected tissues was
quantified at the 14th day. (E) Histologic analysis of the MRSA-infected burn injury tissue by hematoxylin and eosin staining for
different treatment groups. As a comparison, commercial vancomycin was evaluated in parallel. Blue dotted lines indicate the
epithelium border, green arrows show the adipose cells and black arrows present the hair follicles.
shape under the treatment of P1a/2e/3a in dark state,
many micelles were found to be around the bacteria,
demonstrating efficient binding, adhesion and further
fusion with MRSA membrane. Finally, as the yellow arrows
indicated, much more significant membrane shrinking and
deformation were observed upon micelles binding and
extra light irradiation.
sacrificed, and their wound tissues were harvested for
further evaluation. Although vancomycin could also
enhance the wound healing process, the quantitative
experiments showed that the inhibition effect of
P1a/2e/3a under white light irradiation was much better
than vancomycin, the golden standard for Gram-positive
bacteria treatment (Figure 5D, Figure S21). Histologic
analysis was conducted to further evaluate the treatment
effect (Figure 5E). Normal mouse skin was highly
heterogeneous tissue, containing epidermis, dermis with
hair follicle, and subcutaneous layer. At the 14th day, the
control group only showed partially re-epithelialized and
thickened epidermis, while tissue of the P1a/2e/3a under
light irradiation-treated group showed obvious re-
epithelialized, exhibiting intact skin microstructure
comparable with normal tissue. Thus, in vivo MRSA-infected
mouse burn model demonstrated that the photodynamic
effect of P1a/2e/3a could inhibit MRSA infection in the
burn injury mouse model and effectively accelerate the
healing process.
To
investigate
the
biocompatibility
of
the
polyelectrolytes, MTT assays were performed for
P1a/2e/3a upon incubation with primary skin fibroblast
cells for 24 h. P1a/2e/3a showed undetectable toxicity
toward the cells even up to 175 μg/mL under light
irradiation (Figure S20), exhibiting good biocompatibility
and antibacterial selectivity, which was favorable for in vivo
applications.
In vivo bacteria inhibition experiment was conducted on
a MRSA-infected mouse burn model.63 Different treatments
were applied to the MRSA-infected burn sites, and the
recovery process was evaluated in 14 days (Figure 5A).
Effectively accelerated would healing process was observed
when treated with vancomycin or P1a/2e/3a with light
irradiation, as compared to the control group (Figure 5B-C).
After the whole treating process in 14 days, the mice were
CONCLUSION
In summary, we have developed an efficient one-pot
polymerization route to in-situ generate functional azonia-
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Journal of the American Chemical Society
HKUST605/16), the Innovation and Technology Commission
(ITC-CNERC14SC01 and ITS/254/17), the National Key
Research and Development program of China
(2018YFE0190200), the Science and Technology Plan of Shen-
zhen (JCYJ20170818113530705 and
JCYJ20180306180231853), the Natural Science Foundation for
Distinguished Young Scholars of Guangdong Province
(2016A030306013), and the Pearl River Young Talents
Program of Science and Technology in Guangzhou
(201906010047).
containing polyelectrolytes using readily accessible
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nonionic reactants and commercially available cheap ionic
species. Compared with traditional synthetic strategies of
polyelectrolytes, this new strategy did not require post-
modification step or expensive ionic monomers. The
polymerization proceeded efficiently in air with high
tolerance to the monomer feed ratio, generating
polyelectrolytes in excellent yields (up to 99%) with high
molecular weights (up to 28 700) in high atom economy.
With electron-deficient azonia fused rings in the polymer
main-chain, the emission color of resulting polyelectrolytes
could be easily tuned by changing the electron donor. With
high luminescence in solid state, good processing ability,
and high refractive indices, these polymers were excellent
materials for fluorescent photopatterns and promising for
optical applications. Notably, the azonia-containing
polyelectrolytes had strong ROS generation ability and
could impressively kill the drug resistant superbug.
P1a/2e/3a was demonstrated to effectively kill MRSA both
in vitro and in the MRSA-infected mouse burn model. The
efficient one-pot synthetic methodology to azonia-
containing polyelectrolytes provided a new strategy for the
synthesis of polyelectrolytes, greatly enriching the family of
polyelectrolytes. Current charge-generating polymerization
provided these prominent functional positively charged
polyelectrolytes, which were promising candidates for
various biomedical applications, such as tissue engineering,
surface modification, and self-healing materials.
9
REFERENCES
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
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33
34
35
36
37
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(1) Fuoss, R. M., Polyelectrolytes. Science 1948, 108 (2812), 545-550.
(2) Regelson, W.; Kuhar, S.; Tunis, M.; Fields, J.; Johnson, J.;
Gluesenkamp, E., Synthetic Polyelectrolytes as Tumour Inhibitors.
Nature 1960, 186 (4727), 778-780.
(3) Rubinstein, M.; Papoian, G. A., Polyelectrolytes in Biology and Soft
Matter. Soft Matter 2012, 8 (36), 9265-9267.
(4) Li, X.; Bai, H.; Yang, Y.; Yoon, J.; Wang, S.; Zhang, X., Supramolecular
Antibacterial Materials for Combatting Antibiotic Resistance. Adv.
Mater. 2019, 31 (5), 1805092.
(5) Meka, V. S.; Sing, M. K.; Pichika, M. R.; Nali, S. R.; Kolapalli, V. R.;
Kesharwani, P.,
A Comprehensive Review on Polyelectrolyte
Complexes. Drug Discovery Today 2017, 22 (11), 1697-1706.
(6) Laschewsky, A., Recent Trends in the Synthesis of Polyelectrolytes.
Curr. Opin. Colloid Interface Sci. 2012, 17 (2), 56-63.
(7) Mortimer, D. A., Synthetic Polyelectrolytes—a Review. Polym. Int.
1991, 25 (1), 29-41.
(8) Laschewsky, A., Structures and Synthesis of Zwitterionic Polymers.
Polymers 2014, 6 (5), 1544-1601.
(9) Eftekhari, A.; Saito, T., Synthesis and Properties of Polymerized
Ionic Liquids. Eur. Polym. J. 2017, 90, 245-272.
(10) Sen, A. K.; Roy, S.; Juvekar, V. A., On the Importance of Purification
of Sodium Polystyrene Sulfonate. ISRN Anal. Chem. 2012, 2012.
(11) Tran, Y.; Auroy, P., Synthesis of Poly (Styrene Sulfonate) Brushes.
J. Am. Chem. Soc. 2001, 123 (16), 3644-3654.
(12) Hua, F.; Kita, R.; Wegner, G.; Meyer, W., Interactions between
Brushlike Polyacrylic Acid Side Chains on a Polyacrylate Backbone in
Dioxane–Water. ChemPhysChem 2005, 6 (2), 336-343.
(13) Mori, H.; Müller, A. H., New Polymeric Architectures with (Meth)
Acrylic Acid Segments. Prog. Polym. Sci. 2003, 28 (10), 1403-1439.
(14) Zhu, C.; Yang, Q.; Liu, L.; Wang, S., A Potent Fluorescent Probe for
the Detection of Cell Apoptosis. Chem. Commun. 2011, 47 (19), 5524-
5526.
(15) Moon, J. H.; McDaniel, W.; MacLean, P.; Hancock, L. F.,
Live-Cell-Permeable Poly (P-Phenylene Ethynylene). Angew. Chem.
2007, 119 (43), 8371-8373.
(16) Xiang, T.; Wang, L.-R.; Ma, L.; Han, Z.-Y.; Wang, R.; Cheng, C.; Xia,
Y.; Qin, H.; Zhao, C.-S., From Commodity Polymers to Functional
Polymers. Sci. Rep. 2014, 4, 4604.
ASSOCIATED CONTENT
Supporting Information.
This material is available free of charge via the Internet at
http://pubs.acs.org.
Details of the materials, methods, synthetic procedures, and
characterization data (IR, NMR, TGA, DSC, etc.); photophysical
properties, photo stability study, and light refraction data of the
polymers; ROS-generation detection, quantitative antibacterial
tests data, and MTT assays (PDF)
AUTHOR INFORMATION
Corresponding Author
* xlhu@scnu.edu.cn, huxlong@mail.ustc.edu.cn
* chjacky@ust.hk
* tangbenz@ust.hk
(17) Lemstra, P. J.; Kirschbaum, R., Speciality Products Based on
Commodity Polymers. Polymer 1985, 26 (9), 1372-1384.
(18) Fan, J.; Borguet, Y. P.; Su, L.; Nguyen, T. P.; Wang, H.; He, X.; Zou, J.;
Wooley, K. L., Two-Dimensional Controlled Syntheses of Polypeptide
ORCID
Molecular
Brushes
Via
N-Carboxyanhydride
Ring-Opening
Xiaolin Liu: 0000-0002-6909-117X
Xianglong Hu: 0000-0001-9202-1543
Ben Zhong Tang: 0000-0002-0293-964X
Polymerization and Ring-Opening Metathesis Polymerization. ACS
Macro Lett. 2017, 6 (9), 1031-1035.
(19) Nicholson, J. W., Polyelectrolyte Materials – Reflections on a
Highly Charged Topic. Chem. Soc. Rev. 1994, 23 (1), 53-58.
(20) Jiang, Y.; Freyer, J. L.; Cotanda, P.; Brucks, S. D.; Killops, K. L.;
Bandar, J. S.; Torsitano, C.; Balsara, N. P.; Lambert, T. H.; Campos, L. M.,
The Evolution of Cyclopropenium Ions into Functional Polyelectrolytes.
Nat. Commun. 2015, 6, 5950.
(21) Zhu, T.; Sha, Y.; Yan, J.; Pageni, P.; Rahman, M. A.; Yan, Y.; Tang, C.,
Metallo-Polyelectrolytes as a Class of Ionic Macromolecules for
Functional Materials. Nat. Commun. 2018, 9 (1), 4329.
(22) Zhu, T.; Xu, S.; Rahman, A.; Dogdibegovic, E.; Yang, P.; Pageni, P.;
Kabir, M. P.; Zhou, X.-d.; Tang, C., Cationic Metallo-Polyelectrolytes for
Robust Alkaline Anion-Exchange Membranes. Angew. Chem., Int. Ed.
2018, 57 (9), 2388-2392.
(23) Li, Y.; Du, W.; Sun, G.; Wooley, K. L., Ph-Responsive Shell Cross-
Linked Nanoparticles with Hydrolytically Labile Cross-Links.
Author Contributions
X.L. and M.L. contributed equally to this work.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENT
This work was financially supported by the National Science
Foundation of China (21788102, and 21674040), the Research
Grants Council of Hong Kong (16308116, C6009-17G and A-
9
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Journal of the American Chemical Society
Page 10 of 11
Macromolecules 2008, 41 (18), 6605-6607.
(45) Ge, Q.; Hu, Y.; Li, B.; Wang, B., Synthesis of Conjugated Polycyclic
(24) Jiang, H.; Taranekar, P.; Reynolds, J. R.; Schanze, K. S., Conjugated
Polyelectrolytes: Synthesis, Photophysics, and Applications. Angew.
Chem., Int. Ed. 2009, 48 (24), 4300-4316.
(25) Zhu, C.; Liu, L.; Yang, Q.; Lv, F.; Wang, S., Water-Soluble Conjugated
Polymers for Imaging, Diagnosis, and Therapy. Chem. Rev. 2012, 112
(8), 4687-4735.
(26) Elsabahy, M.; Heo, G. S.; Lim, S.-M.; Sun, G.; Wooley, K. L., Polymeric
Nanostructures for Imaging and Therapy. Chem. Rev. 2015, 115 (19),
10967-11011.
(27) Pu, K.-Y.; Liu, B., Fluorescent Conjugated Polyelectrolytes for
Bioimaging. Adv. Funct. Mater. 2011, 21 (18), 3408-3423.
(28) Yuan, H.; Liu, Z.; Liu, L.; Lv, F.; Wang, Y.; Wang, S., Cationic
Conjugated Polymers for Discrimination of Microbial Pathogens. Adv.
Mater. 2014, 26 (25), 4333-4338.
(29) Hu, F.; Xu, S.; Liu, B., Photosensitizers with Aggregation-Induced
Emission: Materials and Biomedical Applications. Adv. Mater. 2018, 30
(45), 1801350.
(30) Zhu, C.; Kwok, R. T. K.; Lam, J. W. Y.; Tang, B. Z., Aggregation-
Induced Emission: A Trailblazing Journey to the Field of Biomedicine.
ACS Appl. Bio Mater. 2018, 1 (6), 1768-1786.
(31) Jiang, M.; Kwok, R. T.; Li, X.; Gui, C.; Lam, J. W.; Qu, J.; Tang, B. Z., A
Simple Mitochondrial Targeting Aiegen for Image-Guided Two-Photon
Excited Photodynamic Therapy. J. Mater. Chem. B 2018, 6 (17), 2557-
2565.
(32) Jiang, M.; Gu, X.; Kwok, R. T.; Li, Y.; Sung, H. H.; Zheng, X.; Zhang, Y.;
Lam, J. W.; Williams, I. D.; Huang, X., Multifunctional Aiegens: Ready
Synthesis, Tunable Emission, Mechanochromism, Mitochondrial, and
Bacterial Imaging. Adv. Funct. Mater. 2018, 28 (1), 1704589.
(33) Wang, D.; Lee, M. M.; Shan, G.; Kwok, R. T.; Lam, J. W.; Su, H.; Cai,
Y.; Tang, B. Z., Highly Efficient Photosensitizers with
Far-Red/near-Infrared Aggregation-Induced Emission for in Vitro and
in Vivo Cancer Theranostics. Adv. Mater. 2018, 30 (39), 1802105.
(34) Zhang, T.; Li, Y.; Zheng, Z.; Ye, R.; Zhang, Y.; Kwok, R. T. K.; Lam, J.
W. Y.; Tang, B. Z., In Situ Monitoring Apoptosis Process by a Self-
Reporting Photosensitizer. J. Am. Chem. Soc. 2019, 141 (14), 5612-5616.
(35) Yin, J.; Tan, M.; Wu, D.; Jiang, R.; Li, C.; You, J., Synthesis of
Quinoliniums by Rhodium (Iii)-Catalyzed Multiple C–H Activation and
Annulation of Arylpyridiniums with Alkynes. Org. Lett. 2016, 18 (10),
2483-2486.
1
2
3
4
5
6
7
8
(46) Toriumi, N.; Asano, N.; Miyamoto, K.; Muranaka, A.; Uchiyama, M.,
N-Alkynylpyridinium Salts: Highly Electrophilic Alkyne–Pyridine
Conjugates as Precursors of Cationic Nitrogen-Embedded Polycyclic
Aromatic Hydrocarbons. J. Am. Chem. Soc. 2018, 140 (11), 3858-3862.
(47) Han, Y. R.; Shim, S.-H.; Kim, D.-S.; Jun, C.-H., Synthesis of
Benzoquinolizinium Salts by Rh (Iii)-Catalyzed Cascade Double N-
Annulation Reactions of Allylamines, Diarylacetylenes, and Hbf4. Org.
Lett. 2017, 19 (11), 2941-2944.
(48) Higashihara, T.; Ueda, M., Recent Progress in High Refractive
Index Polymers. Macromolecules 2015, 48 (7), 1915-1929.
(49) Hiorns, R., Polymer Handbook, 4th Edn, Edited by J Brandup, Eh
Immergut and Ea Grulke, Associate Editors a Abe and Dr Bloch, John
Wiley and Sons, New York, 1999, Pp 2250, Price £210 Isbn 0-471-
16628-6. Polym. Int. 2000, 49 (7), 807-807.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(50) Wang, Y.; Fedin, I.; Zhang, H.; Talapin, D. V., Direct Optical
Lithography of Functional Inorganic Nanomaterials. Science 2017, 357
(6349), 385-388.
(51) Perry, J. W., Two Beams Squeeze Feature Sizes in Optical
Lithography. Science 2009, 324 (5929), 892-893.
(52) Wang, Q. H.; Jin, Z.; Kim, K. K.; Hilmer, A. J.; Paulus, G. L. C.; Shih, C.-
J.; Ham, M.-H.; Sanchez-Yamagishi, J. D.; Watanabe, K.; Taniguchi, T.;
Kong, J.; Jarillo-Herrero, P.; Strano, M. S., Understanding and
Controlling the Substrate Effect on Graphene Electron-Transfer
Chemistry Via Reactivity Imprint Lithography. Nat. Chem. 2012, 4, 724.
(53) Yu, C. Y.; Xu, H.; Ji, S.; Kwok, R. T.; Lam, J. W.; Li, X.; Krishnan, S.;
Ding, D.; Tang, B. Z., Mitochondrion-Anchoring Photosensitizer with
Aggregation-Induced Emission Characteristics Synergistically Boosts
the Radiosensitivity of Cancer Cells to Ionizing Radiation. Adv. Mater.
2017, 29 (15), 1606167.
(54) You, X.; Ma, H.; Wang, Y.; Zhang, G.; Peng, Q.; Liu, L.; Wang, S.;
Zhang, D., Pyridinium-Substituted Tetraphenylethyleneentailing
Alkyne Moiety: Enhancement of Photosensitizing Efficiency and
Antimicrobial Activity. Chem. - Asian J. 2017, 12 (9), 1013-1019.
(55) Zhang, C.-J.; Hu, Q.; Feng, G.; Zhang, R.; Yuan, Y.; Lu, X.; Liu, B.,
Image-Guided Combination Chemotherapy and Photodynamic
Phenalenyl-Fused
Pyrylium
Cations:
Divergent
C−H
Activation/Annulation Reaction Sequence of Naphthalene Aldehydes
with Alkynes. Angew. Chem., Int. Ed. 2017, 56 (42), 13094-13098.
(36) Bica, K.; Rijksen, C.; Nieuwenhuyzen, M.; Rogers, R. D., In Search
of Pure Liquid Salt Forms of Aspirin: Ionic Liquid Approaches with
Acetylsalicylic Acid and Salicylic Acid. Phys. Chem. Chem. Phys. 2010, 12
(8), 2011-2017.
(37) Cao, B.; Xiao, F.; Xing, D.; Hu, X. L., Polyprodrug Antimicrobials:
Remarkable Membrane Damage and Concurrent Drug Release to
Combat Antibiotic Resistance of Methicillin-Resistant Staphylococcus
Aureus. Small 2018, 14 (41), 1802008.
(38) Wang, B.; Yuan, H.; Liu, Z.; Nie, C.; Liu, L.; Lv, F.; Wang, Y.; Wang, S.,
Cationic Oligo (P-Phenylene Vinylene) Materials for Combating Drug
Resistance of Cancer Cells by Light Manipulation. Adv. Mater. 2014, 26
(34), 5986-5990.
(39) Xiao, F.; Cao, B.; Wang, C.; Guo, X.; Li, M.; Xing, D.; Hu, X. L.,
Pathogen-Specific Polymeric Antimicrobials with Significant
Membrane Disruption and Enhanced Photodynamic Damage to Inhibit
Highly Opportunistic Bacteria. ACS Nano 2019, 13 (2), 1511-1525.
(40) Wang, B.; Wang, M.; Mikhailovsky, A.; Wang, S.; Bazan, G. C., A
Therapy Using
a Mitochondria-Targeted Molecular Probe with
Aggregation-Induced Emission Characteristics. Chem. Sci. 2015, 6 (8),
4580-4586.
(56) Zheng, Z.; Zhang, T.; Liu, H.; Chen, Y.; Kwok, R. T. K.; Ma, C.; Zhang,
P.; Sung, H. H. Y.; Williams, I. D.; Lam, J. W. Y.; Wong, K. S.; Tang, B. Z.,
Bright near-Infrared Aggregation-Induced Emission Luminogens with
Strong Two-Photon Absorption, Excellent Organelle Specificity, and
Efficient Photodynamic Therapy Potential. ACS Nano 2018, 12 (8),
8145-8159.
(57) Kearns, D. R., Physical and Chemical Properties of Singlet
Molecular Oxygen. Chem. Rev. 1971, 71 (4), 395-427.
(58) Zhu, C.; Yang, Q.; Liu, L.; Lv, F.; Li, S.; Yang, G.; Wang, S.,
Multifunctional Cationic Poly(P-Phenylene Vinylene) Polyelectrolytes
for Selective Recognition, Imaging, and Killing of Bacteria over
Mammalian Cells. Adv. Mater. 2011, 23 (41), 4805-4810.
(59) Courtney, C. M.; Goodman, S. M.; McDaniel, J. A.; Madinger, N. E.;
Chatterjee, A.; Nagpal, P., Photoexcited Quantum Dots for Killing
Multidrug-Resistant Bacteria. Nat. Mater. 2016, 15, 529.
(60) Chin, W.; Zhong, G.; Pu, Q.; Yang, C.; Lou, W.; De Sessions, P. F.;
Periaswamy, B.; Lee, A.; Liang, Z. C.; Ding, X.; Gao, S.; Chu, C. W.; Bianco,
S.; Bao, C.; Tong, Y. W.; Fan, W.; Wu, M.; Hedrick, J. L.; Yang, Y. Y., A
Macromolecular Approach to Eradicate Multidrug Resistant Bacterial
Infections While Mitigating Drug Resistance Onset. Nat. Commun. 2018,
9 (1), 917.
(61) Wu, C.; Shang, Z.; Lemetre, C.; Ternei, M. A.; Brady, S. F., Cadasides,
Calcium-Dependent Acidic Lipopeptides from the Soil Metagenome
That Are Active against Multidrug-Resistant Bacteria. J. Am. Chem. Soc.
2019, 141 (9), 3910-3919.
(62) Engler, A. C.; Wiradharma, N.; Ong, Z. Y.; Coady, D. J.; Hedrick, J. L.;
Yang, Y.-Y., Emerging Trends in Macromolecular Antimicrobials to
Fight Multi-Drug-Resistant Infections. Nano Today 2012, 7 (3), 201-
222.
Membrane-Intercalating
Conjugated
Oligoelectrolyte
with
High-Efficiency Photodynamic Antimicrobial Activity. Angew. Chem.,
Int. Ed. 2017, 56 (18), 5031-5034.
(41) Sucunza, D.; Cuadro, A. M.; Alvarez-Builla, J.; Vaquero, J. J., Recent
Advances in the Synthesis of Azonia Aromatic Heterocycles. J. Org.
Chem. 2016, 81 (21), 10126-10135.
(42) Fu, G. C.; Grubbs, R. H., The Application of Catalytic Ring-Closing
Olefin Metathesis to the Synthesis of Unsaturated Oxygen Heterocycles.
J. Am. Chem. Soc. 1992, 114 (13), 5426-5427.
(43) Abengozar, A.; Abarca, B.; Cuadro, A. M.; Sucunza, D.;
Alvarez-Builla, J.; Vaquero, J. J., Azonia Aromatic Cations by
Ring-Closing Metathesis: Synthesis of Azaquinolizinium Cations. Eur. J.
Org. Chem. 2015, 2015 (19), 4214-4223.
(44) Prakash, S.; Muralirajan, K.; Cheng, C. H., Cobalt-Catalyzed
Oxidative Annulation of Nitrogen-Containing Arenes with Alkynes: An
Atom-Economical Route to Heterocyclic Quaternary Ammonium Salts.
Angew. Chem., Int. Ed. 2016, 55 (5), 1844-1848.
(63) Li, Y.; Liu, G.; Wang, X.; Hu, J.; Liu, S., Enzyme-Responsive
Polymeric Vesicles for Bacterial-Strain-Selective Delivery of
Antimicrobial Agents. Angew. Chem., Int. Ed. 2016, 55 (5), 1760-1764.
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