4. AIE polymers via
ATRP
The ATRP technique was coincidentally invented and discovered separately
by three different groups of researchers around the world in 1995: by
(1) Sawamoto and co-workers,[38] (2) Matyjaszewski
and co-worker,[39] and (3) Percec and
co-worker.[40] After ATRP was patented in 1998 by
Matyjaszewski and Wang as one of the most successful RDRP
process,[41] numerous other U.S. patents,
applications and publications worldwide also featured this
polymerization technique.[43] ATRP is based on a
process termed Atom Transfer Radical Addition (ATRA) developed in
1945,[131] involving the anti-Markonikov addition
of alkyl halide radicals to alkenes in the Kharasch addition
reactions.[132] Sawamoto and co-workers in 1995,
discovered that by combining ruthenium-based catalyst
RuCl2(PPh3), CCl4, and
methylaluminum bis-(2,6-di-tert-butylphenoxide)
[MeAl(ODBP)2] to form a ternary initiating system,
it is able to polymerize methyl methacrylate (MMA) via a radical
pathway, thus behaving similarly to the ATRA
process.[38] On the other hand, Matyjaszewski and
co-workers discovered that polymerising styrene using an alkyl chloride
initiator and a CuCl/2,2’-bipyridine (Cu(bpy)Cl) catalyst complex
yielded well-defined high molecular weight homopolymers with lowÐ values.[39] Later on the same year,
Percec and co-worker discovered that styrene polymerisation can also be
carried out using arenesulfonyl chlorides initiators catalysed by
CuCl/bpy catalyst complex, producing homopolymers with good conversions
but with relatively high Ð values (Ð >
1.50).[40]
In general, for a typical ATRP mechanism, a redox reaction between an
initiator bearing at least one transferable atom(s) or group(s) and a
transition metal complex bearing a transition metal salt at a lower
oxidation state and ligands attached to it. The metal catalyst cleaves
the initiator homolytically and itself is oxidized in the process,
enabling monomer addition to take place. The homolytic atom or group
then transfers between the growing polymer chain end and the metal
catalysts, causing the metal centre to cycle between lower and higher
oxidation states, thus establishing a dynamic equilibrium.
ATRP has over 19,000 papers till date covering many areas ranging from
synthesis to real-life applications of polymers synthesized from ATRP.
ATRP shares the same advantages with RAFT and NMP as it provides a
simple route to synthesize polymers with good control of molecular
weight, low dispersity (Ð ) values, good tolerance against many
functional groups, and the ability to produce well-defined polymer
architectures. The main drawback of this technique is the presence of
trace amounts of metal ions such as Cu in the end polymer product which
is difficult to remove and can pose problems for certain applications.
However, this problem can be circumvented by using UV-mediated
metal-free catalysts such as the use of
phenothiazine[133] and
perylene[134].[135]Nevertheless, the versatility of ATRP enabled it to be used as a
technique to synthesize AIE polymers with a slightly different design to
the monomers and initiators involved compared to RAFT.
4.1 Core-functionalized polymers AIE polymers via
ATRP
A good example of AIE core-functionalized polymer produced via ATRP is
by Guan, Lei and co-workers in 2016, where they synthesized a novel
polyelectrolyte
tetraphenylethene-graft-poly[2-(methacryloyloxy)-ethyltrimethylammonium
chloride] (TPE–PMETAC) using ATRP from a TPE-derived four arm
macro-initiator, tetraphenylethylene-2-bromo-2-methylpropionate
(TPE-BMP). This polymer is capable of self-assembly into a core-shell
microsphere structure in an aqueous solution where the TPE block forms
the core and PMETAC forms the shell (Figure
7A ).[45] The AIE feature comes from polymer chain
aggregation at high concentrations, and is induced by simple exchange of
counterions. It was discovered that TPE-PMETAC fluorescence intensity
increase nonlinearly with increasing THF volume fraction similar to a
phenomenon termed aggregation-induced enhanced emission
(AIEE),[136] giving a bright blue emission at
~465 nm in 2/98 v/v water/THF solvent system. In
addition, it was observed that the fluorescence intensity of cationic
microspheres containing quaternary ammonium groups increases according
to the series Cl- < (perchlorate)
ClO4- <
(hexafluorophosphate) PF6- <
(bis-(trifluoromethylsulfonyl)imide) TFSI-, through
ion-pairing interactions leading to “hydrophobic-induced collapse” of
PMETAC block.[45] Reducing the size of
microspheres, reduces the electrostatic repulsion forces between each
microsphere and induces aggregation, evident in the size of the
microspheres ranked from largest to smallest; TFSI-,
PF6-,
ClO4-.
About two years later in 2018, the same group developed persistent
fluorescent bioprobes for cell-tracking and identification by
synthesizing a novel multi-stimuli-responsive star polymer
tetraphenylethene-graft -tetra-poly[N -[2-(diethylamino)-ethyl]acrylamide]
(TPE-tetraPDEAEAM) possessing inherent AIE properties using ATRP
technique and TPE-BMP as the macro-ATRP initiator containing AIE-active
TPE.[137] The main difference lies in the
stimuli-responsiveness of the side group where the former is
electrically charged, while the latter is electrically neutral. These
polymers respond to changes in temperature, pH levels and
CO2 levels, with obvious soluble-to-insoluble phase
transition at the lower critical solution temperature (LCST). The
reversible temperature-responsiveness behavior of TPE-tetraPDEAEAM can
be determined by heating it to temperatures above the LCST (turns
cloudy) and allowing it to cool down to temperatures below the LCST
(reverts back to transparent aqueous solution). In aqueous solution, the
LCST decreases from 41.5 to 34.5 °C upon increase of polymer
concentration from 0.5 to 2.0 g L-1, along with
aggregation of TPE moieties at the LCST of 37.5 °C, resulting in
enhanced fluorescence. TPE-tetraPDEAEAM were incubated with HeLa cells
for 48 h at a concentration range of 50 – 400 µg mL-1with cell viability of greater than 95%. The polymers are not cytotoxic
to the cells at a concentration of 200 µg mL-1 for 48
h, which allowed for tracking of the cells for as long as nine passages.
Incorporating AIE moieties to functionalize polymer cores were also
exemplified by other groups,[44, 138-144] where
they have been used as stimuli-responsive materials, cellular tracking
agents, and advanced drug delivery systems.
4.2 End-functionalized AIE polymers via
ATRP
End-functionalized polymers with AIE-active moieties can also exhibit
fluorescence properties, and was explored by Hadjichristidis and
co-worker in 2019.[145] In this example, the
authors synthesized a TPE-terminated linear polyethylene (PE) using
Tris(3-(4-(1,2,2-triphenylvinyl)phenoxy)propyl)borane, synthesized from
hydroboration of (2-(4(allyloxy)phenyl)ethene-1,1,2-triyl)tribenzene
with BH3, as an initiator for the polyhomologation of
dimethylsulfoxonium methylide to afford well-definedα -TPE-ω -OH linear polyethylenes (PE). All polymeric
products showed AIE fluorescence either in the bulk phase or the
solution phase, due to self-assembly behavior of the PE-based block
copolymers in DMF solvent. The fluorescence intensity of the solutions
can be determined from the block copolymer compositions and micelle
size. At 90% v/v n -hexane fraction in a 0.1 g
L-1 toluene/n -hexane solvent system, the
highest PL intensity was observed which is 4.5-fold higher than pure
toluene solvent system. For TPE-PE-b -Pt BuA polymers, the
critical micelle concentration (CMC) values are in the range of\(0.5\ \ 1.5\times 10^{-2}\) mg mL-1, with the
highest CMC value recorded to be \(1.47\times 10^{-2}\) mg
mL-1 for the polymer with the highest Pt BA
content. The authors then extended their work to synthesize amphiphilic
block copolymers TPE-PE-b -PAA by treating
TPE-PE-b -Pt BA with TFA to hydrolyze the t Bu group
to COOH group.[146] The synthesized polymer is
responsive to pH changes and it can emit fluorescence when exposed to
certain ions. Changes in fluorescence intensity was attributed to pH
responsivity of the PAA block, causing different degree of aggregation
of the TPE block. In addition, the influence of different cations at
different pH levels on the fluorescence of TPE-PE-b -PAA was also
investigated. The authors found that for the cations;
Li+, Na+, K+,
Cs+, electron cloud polarizability was the dominant
factor in determining fluorescence intensity, and therefore ranked them
in increasing fluorescence order Li+ <
Na+ < K+.
Cs+ has the largest polarisable electron cloud,
however due to the secondary factor electron repulsion, it was not
ranked after K+.
PhotoATRP can also be a viable option to synthesize polymers, which was
exploited by Yang, Xiao and co-workers in 2021, to produce poly(methyl
methacrylate)s (TPE-PMMA) with AIE properties by combining methyl
methacrylate monomers with 4-(1,2,2-triphenylvinyl)benzyl
2-bromo-2-phenylacetate (TPE-BPA) AIE-functionalized initiator, and
catalyzed by air-stable copper(II) bromide/tris(2-pyridylmethyl)amine
(CuIIBr2/TPMA) photocatalyst under
benign conditions.[147] Polymerization reaction
was conducted using LED light of wavelength 405 nm, and the introduction
of the TPE moiety did not affect the polymerization kinetics and
temporal control. AIEE effect was observed for TPE-PMMA solutions with
higher molecular weights and with increased viscosity.
In 2016, Hong and co-workers prepared AIE-active amphiphilic
tetraphenylthiophene (TP)-terminated poly(acrylic acid) (TP-PAA) using
ATRP technique.[148] The resulting polymer
self-assembled, primarily through hydrogen bond among carboxylic acid
moieties at concentrations above the critical aggregation concentration
(CAC) to form aggregates. The t BA pendant groups can be
hydrolyzed by acids to the final AA pendant groups. In water, when
TP-PAA concentration exceeds the CAC value
(\(5.25\times 10^{-6}\text{\ M}\)), the polymers aggregate into small
micelles and fluoresces. At pH 2 to 9, there is almost negligible
fluorescence as the fraction of aggregate emission is less than monomer
emission. In contrast, at pH 9 to 12, the polymer fluoresces strongly.
The authors tested TP-PAA as a potential bovine serum albumin (BSA)
detector, where aggregate emission was more pronounce when mixed with
BSA than the monomer emission.
Expanding on the application aspect of AIE-active polymers, in 2018,
Liu, Li and co-workers prepared polymeric micelles based on
tetraphenylethene (TPE) conjugated
poly(N- 6-carbobenzyloxy-L-lysine)-b -poly(2-methacryloyloxyethyl
phosphorylcholine) (TPE-PLys-b -PMPC) copolymer, which contains
AIE-active TPE block in the micelle core (Figure
7B ).[149] The polymers were then loaded with an
anti-cancer drug, DOX, for triggered intracellular drug release traced
by fluorescent imaging of the micelles, which was made possible through
hydrophobic interaction between DOX and PLys blocks in the polymer.
Blank TPE-PLys-b-PMPC showed insignificant toxicity while DOX-loaded
micelles showed excellent growth inhibition against HeLa cells and 4T1
cells, making such polymers a good candidate for antitumor and
anticancer treatments.
Variations in the chemical structure of the AIE moiety, besides the
commonly known TPE functional group, can also be employed to expand the
range of choice of AIE molecules. Ouyang, Zhang, Wei and co-workers in
2020, prepared AIE-active FPNs 10-phenylphenothiazine-poly(benzyl
methacrylate-co -2-methacryloyloxyethyl phosphorylcholine)
(PTH-P(BzMA-MPC)-20(40)) capable of self-assembly into spherical
micelles (Figure 7C ).[150]PTH-P(BzMA-MPC)-20 with ratio of PTH-Br/MPC/BzMA as 1/40/20 and
PTH-P(BzMA-MPC)-40 with ratio of PTH-Br/MPC/BzMA as 1/40/40 FPNs emit
fluorescence intensely with high quantum yield of 34.3% and 41.2%
respectively measured against Rhodamine B (1 mg/mL) in ethanol as the
standard, good water dispersibility and low CMC values.
PTH-P(BzMA-MPC)-20 and PTH-P(BzMA-MPC)-40 FPNs were evaluated for cell
viability with L02 cells, with both polymers bearing greater than 90%
cell viability even after 24 h incubation at a concentration of 320
µg/mL.
In 2012, Xu, Lu and co-workers synthesized a pyrazoline-based TPP-NI
possessing a electron donor group (dimethyl-amino) and an electron
acceptor group (1,8-napthalimide) capable of intramolecular charge
transfer (ICT) and AIE effects. TPP-NI was then used as the intiator to
polymerize styrene (St), methyl methacrylate (MMA), and 2-hydroxyethyl
methacrylate (HEMA) separately.[151] With
reference to the PL intensity of pure DMF solution, PS showed 155-fold
increase in PL intensity when dissolved in DMF-ethanol solvent system,
while PMMA showed 65-fold increase when dissolved in DMF-water system,
and PHEMA showed 10-fold increase when dissolved in DMF-water system
with 70-fold increase when the solvent was acidified. PHEMA amplifies
the pH value effect as it causes more dimethylamino groups of TPP-NI to
be exposed, which made it possible for PHEMA to serve as an optical
sensor and drug-delievery agent via effective encasement of hydrophobic
drug molecules. In a few other similar examples, AIE end-functionalized
polymers were also synthesized,[152-156] where
they have been used to study the ATRP process mechanism and certain
stimuli-responsive polymers for material fabrications.
4.3 AIE monomer/component-functionalized polymers via
ATRP
Xu, Lu and co-workers have explored the possibility of transforming the
ICT, AIE dual property molecule into a polymerizable monomer in 2013,
and successfully synthesized
poly(2-butyl-6-(5-(4-(diethylamino)phenyl)-3-(4-(4-vinylbenzyloxy)phenyl)-4,5-dihydro-1H -pyrazol-yl)-1H -benzo-[de ]isoquinoline-1,3(2H )-dione)
(PStTPP-NI) using ATRP technique.[157] The
fluorophore displays AIEE effect and increased quantum yields in strong
polar solvents. StTPP-NI shows almost negligible QY in DMF solution
(0.16%), while bearing a high QY of 27% in cyclohexane solution. In
another example where Luo, Li and co-workers in 2020, synthesized
P(t BA-r -TPEA)-b -PCholMA) (BCP-1) from
acrylate-functionalized TPE units (TPEA), where these AIE-active units
are found in the corona forming part of the block
copolymer.[158] Quantum yield after micellization
of BCP-1 was found to greatly increase from 0.38% (before
micellization) to 9.36%, which can be used to monitor the micellization
process and to study the effects of solvents on the process.
Furthermore, some variations of AIE-functionalized components include
AIE moieties as pendent groups,[159] as
monomers,[160, 161] and as part of hyperbranched
polymers,[162] were exemplified by other groups
using ATRP.
4.4 AIE polymers via Surface-initiated
ATRP
Surface-initiation methods imparts different unique properties onto the
solid surface and enables good customization of these surfaces. In 2017,
Wen, Zhang, Wei and co-workers incorporated AIE functionalities onto
silica nanoparticles (SNPs) via the Stöber method to prepare luminescent
silica nanoparticles (LSNPs), which was then converted into a
macro-initiator where zwitterionic 2-(methacryloyloxy)ethyl
phosphorylcholine (MPC) monomers were polymerized via surface-initiated
ATRP (SI-ATRP) to form SNPs-AIE-pMPC (Figure
8A ).[163] Similar to the work by Ouyang, Zhang,
Wei and co-workers in 2020,[150] Xu, Zhang, Wei
and co-workers had extended their work from randomly dispersed
PTH-P(BzMA-MPC)-20(40) FPNs to PTH-functionalized mesoporous silica
nanoparticles (MSNs) with surface grafted block copolymer
PTH@MSNs-poly(PEGMA-co -IA) from poly(ethylene glycol)methyl
acrylate (PEGMA) and itaconic acid (IA) as monomers using light
irradiation.[164] Some interesting properties of
this polymer includes the ability to conjugate with the anticancer drugcis -diammineplatinum dichloride (CDDP) with pH-responsive
behaviors for sophisticated controlled drug delivery systems with high
water dispersibility, low cytotoxicity and excellent candidate as a cell
imaging agent.
The scope of AIE molecules can also be expanded to include molecules
with no perceivable aromatic rings or AIE-like features. An unusual case
of AIE fluorescence was reported by Kopeć and co-workers in 2020, when
ATRP was used to synthesize and graft well-defined low molecular weight
(M n < 10,000 g mol-1)
polyacrylonitrile (PAN) from silicon (Si) wafers (Figure
8B ).[165] PAN is a non-conjugated polymer that
does not contain any phenyl ring structures, yet it is still capable of
AIE fluorescence behavior. The reason can be explained by the clustering
of the nitrile groups in PAN, causing an overlap of π and lone pair
electron clouds, resulting in similar RIM effects as TPE
groups.[166] These PAN brushes were prepared via
photoinduced ATRP, allowing for significant reduction in catalyst
amounts. A review put together by Yuan and Zhang in
2016,[167] elaborates in more detail the beauty of
nonconventional macromolecular luminogens with AIE characteristics which
can be attributed to the similar clustering behavior as PAN, resulting
to fluorescence of the polymeric product.