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.