Aqueous Reversible Addition-fragmentation Chain Transfer Research Articles

Efficient Synthesis of μ-A(BC)C Miktoarm Star Polymer Assemblies via Aqueous Photoinitiated Polymerization-Induced Self-Assembly.

In this study, green light-activated photoiniferter reversible addition-fragmentation chain transfer (RAFT) polymerization of glycerol methacrylate was performed using an ω,ω-heterodifunctional macro-RAFT agent. Because of the different RAFT controllability of two RAFT groups toward methacrylic monomers, only one RAFT group was activated under green light irradiation, leading to the formation of a diblock copolymer macro-RAFT agent with one RAFT group located at the chain end and the other RAFT group located between two blocks. The obtained diblock copolymer macro-RAFT agent was then used to mediate aqueous photoinitiated RAFT dispersion polymerization of diacetone acrylamide (DAAM), which formed μ-A(BC)C miktoarm star polymer assemblies with a diverse set of morphologies. Comparing with the ABC triblock copolymer, it was found that the architecture of the μ-A(BC)C miktoarm star polymer facilitated the formation of higher-order morphologies. Kinetic studies indicated that the aqueous photoinitiated RAFT dispersion polymerization exhibited ultrafast polymerization behavior, with quantitative monomer conversion being achieved within 5 min. Size exclusion chromatography analysis confirmed that good RAFT control was maintained during the polymerization. A morphological phase diagram for μ-A(BC)C miktoarm star polymer assemblies was constructed by varying the monomer concentration and the [DAAM]/[Macro-RAFT] ratio. We expect that this study not only develops an approach for the preparation of miktoarm star polymer assemblies but also provides mechanistic insights into the polymerization-induced self-assembly of nonlinear polymers.

Crystallization-Driven Controlled 2D Self-Assemblies via Aqueous RAFT Emulsion Polymerization.

Aqueous emulsion polymerization is a robust technique for preparing nanoparticles of block copolymers; however, it typically yields spherical nanoassemblies. The scale preparation of nanoassemblies with nonspherical high-order morphologies is a challenge, particularly 2D core-shell nanosheets. In this study, the polymerization-induced self-assembly (PISA) and crystallization-driven self-assembly (CDSA) are combined to demonstrate the preparation of 2D nanosheets and their aggregates via aqueous reversible addition-fragmentation chain transfer (RAFT) emulsion polymerization. First, the crucial crystallizable component for CDSA, hydroxyethyl methacrylate polycaprolactone (HPCL) macromonomer is synthesized by ring opening polymerization (ROP). Subsequently, the RAFT emulsion polymerization of HPCL is conducted to generate crystallizable nanomicelles by a grafting-through approach. This PISA process simultaneously prepared spherical latices and bottlebrush block copolymers comprising poly(N',N'-dimethylacrylamide)-block-poly(hydroxyethyl methacrylate polycaprolactone) (PDMA-b-PHPCL). The latexes are now served as seeds for inducing the formation of 2D hexagonal nanosheets, bundle-shaped and flower-like aggregation via the CDSA of PHPCL segments and unreacted HPCL during cooling. Electron microscope analysis trace the morphology evolution of these 2D nanoparticles and reveal that an appropriate crystallized component of PHPCL blocks play a pivotal role in forming a hierarchical structure. This work demonstrates significant potential for large-scale production of 2D nanoassemblies through RAFT emulsion polymerization.

Aqueous RAFT Dispersion Polymerization Mediated by an ω,ω-Macromolecular Chain Transfer Monomer: An Efficient Approach for Amphiphilic Branched Block Copolymers and the Assemblies.

Herein, an ω,ω-macromolecular chain transfer monomer (macro-CTM) containing a RAFT (reversible addition-fragmentation chain transfer) group and a methacryloyl group was synthesized and used to mediate photoinitiated RAFT dispersion polymerization of hydroxypropyl methacrylate (HPMA) in water. The macro-CTM undergoes a self-condensing vinyl polymerization (SCVP) mechanism under RAFT dispersion polymerization conditions, leading to the formation of amphiphilic branched block copolymers and the assemblies. Compared with RAFT solution polymerization, it was found that the SCVP process was promoted under RAFT dispersion polymerization conditions. Morphologies of branched block copolymer assemblies could be controlled by varying the monomer concentration and the [HPMA]/[macro-CTM] ratio. The branched block copolymer vesicles could be used as seeds for seeded RAFT emulsion polymerization, and framboidal vesicles were successfully obtained. Finally, degrees of branching of branched block copolymers could be further controlled by using a binary mixture of the macro-CTM and a linear macro-RAFT agent or a small molecule CTM. We believe that this study not only provides a versatile strategy for the preparation of branched block copolymer assemblies but also offers important insights into polymer synthesis via heterogeneous RAFT polymerization.

Harnessing Cytosine for Tunable Nanoparticle Self-Assembly Behavior Using Orthogonal Stimuli.

Nucleobases control the assembly of DNA, RNA, etc. due to hydrogen bond complementarity. By combining these unique molecules with state-of-the-art synthetic polymers, it is possible to form nanoparticles whose self-assembly behavior could be altered under orthogonal stimuli (pH and temperature). Herein, we report the synthesis of cytosine-containing nanoparticles via aqueous reversible addition-fragmentation chain transfer polymerization-induced self-assembly. A poly(N-acryloylmorpholine) macromolecular chain transfer agent (mCTA) was chain-extended with cytosine acrylamide, and a morphological phase diagram was constructed. By exploiting the ability of cytosine to form dimers via hydrogen bonding, the self-assembly behavior of cytosine-containing polymers was altered when performed under acidic conditions. Under these conditions, stable nanoparticles could be formed at longer polymer chain lengths. Furthermore, the resulting nanoparticles displayed different morphologies compared to those at pH 7. Additionally, particle stability post-assembly could be controlled by varying pH and temperature. Finally, small-angle X-ray scattering was performed to probe their dynamic behavior under thermal cycling.

Enhancing Aqueous Reversible Addition–Fragmentation Chain Transfer Photopolymerization in Continuous Flow Reactors with Hairy Hollow Conjugated Microporous Polymer Nanocomposites

Enhancing Aqueous Reversible Addition–Fragmentation Chain Transfer Photopolymerization in Continuous Flow Reactors with Hairy Hollow Conjugated Microporous Polymer Nanocomposites

NIR-Photocontrolled Aqueous RAFT Polymerization with Polymerizable Water-Soluble Zinc Phthalocyanine as Photocatalyst

In order to give an answer for the challenges of long wavelength-photocontrolled radical polymerization in aqueous solutions and to address the shortcomings of conventional near-infrared (NIR) photocatalysts (PCs) that are difficult to subject to post-treatment, we designed and synthesized a series of β-tetra-substituted water-soluble zinc phthalocyanines (β-TS-Zns) as the NIR PCs for reversible addition-fragmentation chain transfer (RAFT) polymerization successfully under irradiation with NIR (λmax = 730 nm) light at room temperature. Importantly, the NIR PCs can also be designed as polymerizable monomers and covalently loaded on the polymer chains, which are endowed with permanent NIR photocatalysis of the resultant polymers. Moreover, the polymerization can not only be carried out in water but also in phosphate buffer saline (PBS) solution, yielding polymers with controlled molar mass and narrow dispersities (Đ = 1.03-1.25). Therefore, this NIR-photocontrolled aqueous RAFT polymerization system may provide a charming strategy for possible applications in tissue engineering biomaterial in situ benefiting from the high penetration ability of NIR light.

A Perspective on the History and Current Opportunities of Aqueous RAFT Polymerization.

Reversible addition-fragmentation chain transfer (RAFT) polymerization has proven itself as a powerful polymerization technique affording facile control of molecular weight, molecular weight distribution, architecture, and chain end groups - while maintaining a high level of tolerance for solvent and monomer functional groups. RAFT is highly suited to water as a polymerization solvent, with aqueous RAFT now utilized for applications such as controlled synthesis of ultra-high molecular weight polymers, polymerization induced self-assembly, and biocompatible polymerizations, among others. Water as a solvent represents a non-toxic, cheap, and environmentally friendly alternative to organic solvents traditionally utilized for polymerizations. This, coupled with the benefits of RAFT polymerization, makes for a powerful combination in polymer science. This perspective provides a historical account of the initial developments of aqueous RAFT polymerization at the University of Southern Mississippi from the McCormick Research Group, details practical considerations for conducting aqueous RAFT polymerizations, and highlights some of the recent advances aqueous RAFT polymerization can provide. Finally, some of the future opportunities that this versatile polymerization technique in an aqueous environment can offer are discussed, and it is anticipated that the aqueous RAFT polymerization field will continue to realize these, and other exciting opportunities into the future.

Aqueous Reversible Addition-Fragmentation Chain Transfer (RAFT) Polymerization: Synthesis, Properties, and Application of an Amphoteric Superplasticizer

Aqueous Reversible Addition-Fragmentation Chain Transfer (RAFT) Polymerization: Synthesis, Properties, and Application of an Amphoteric Superplasticizer

Synthesis of a hydrosoluble reversible addition‐fragmentation chain transfer agent and application in the preparation of micro/nano‐polyacrylamide gel dispersions

AbstractA hydrosoluble reversible addition‐fragmentation chain transfer (RAFT) agent named S‐(2‐propionic acid)‐S′‐(2‐methylpropionic acid) trithiocarbonate (PAMPATTC) is successfully synthesized. Then the micro/nano‐polyacrylamide gel dispersions are prepared via one‐pot RAFT polymerization in water to solve the problems of complicated preparation process and particle size control of common profile‐controlling and flooding agents. The structure of the RAFT agent is characterized and confirmed by fourier transform infrared spectroscopy (FTIR) and proton nuclear magnetic resonance (1H‐NMR). The effects of different reaction conditions on the properties of polyacrylamide gel dispersions are studied. The polymer dispersity index (PDI) of the polyacrylamide gel dispersions is tested by aqueous gel permeation chromatography, confirming the activity characteristics of RAFT polymerization. The rheological characteristics of the polyacrylamide gel dispersions and liner polyacrylamide are characterized. Compared with the liner polyacrylamide at similar viscosities, it is confirmed that the polyacrylamide gel dispersions were closer to Newtonian fluid, especially at high shear rates and the increasing amount of RAFT agent. The viscoelasticity tests under frequency scanning further confirm that the polyacrylamide gel dispersions are successfully synthesized via aqueous RAFT polymerization. The particle sizes are measured to show that the particle size of the polyacrylamide gel dispersions is micro/nano‐scale. The micromorphology of polyacrylamide gel dispersions is determined to indicate the irregular spherical structure, confirming that the micro‐particles are indeed formed by the aggregation of nano‐particles.

Type I Photoinitiator-Functionalized Block Copolymer Nanoparticles Prepared by RAFT-Mediated Polymerization-Induced Self-Assembly.

Type I photoinitiators have been widely used in UV-vis curing technology for the fabrication of functional polymer materials such as coatings, inks, and adhesives. To overcome the drawbacks of using small molecular type I photoinitiators and expand the potential applications of UV-vis curing technology, attaching type I photoinitiators onto the surface of polymer colloids is an attractive strategy. Here we report a robust strategy for the efficient preparation of type I photoinitiator-functionalized block copolymer nanoparticles with various morphologies via aqueous reversible addition-fragmentation chain transfer (RAFT)-mediated polymerization-induced self-assembly (PISA), in which the photoinitiating ability of the type I photoinitiator end group provides a landscape for further functionalization. These block copolymer nanoparticles could also be used as heterogeneous photoinitiators to generate hydrogels with nanoparticles embedded inside. Significantly, the properties and functionalities of these hydrogels could be further controlled by using different block copolymer nanoparticles. This study provides a robust strategy toward the preparation of type I photoinitiator-functionalized block copolymer nanoparticles with the capacity to be modified with varying functionalities.

Indole, Phenyl, and Phenol Groups: The Role of the Comonomer on Gene Delivery in Guanidinium Containing Methacrylamide Terpolymers

This report highlights the importance of hydrophobic groups mimicking the side chains of aromatic amino acids, which are tryptophan, phenylalanine, and tyrosine, in guanidinium bearing poly(methacrylamide)s for the design of non-viral gene delivery agents. Guanidinium containing methacrylamide terpolymers are prepared by aqueous reversible addition-fragmentation chain transfer (aRAFT) polymerization with different hydrophobic monomers, N-(2-indolethyl)methacrylamide (IEMA), N-phenethylmethacrylamide (PhEMA), or N-(4-hydroxyphenethyl)methacrylamide (PhOHEMA) by aiming similar contents. The well-defined polymers are obtained with a molar mass of ≈15 000gmol-1 and ≈1.1 dispersity. All terpolymers demonstrate almost comparable in vitro cell viability and hemocompatibility profiles independent of the type of side chain. Although they all form positively charged, enzymatically stable polyplexes with plasmid DNA smaller than 200nm, the incorporation of the IEMA monomer improve these parameters by demonstrating a higher DNA binding affinity and forming nanoassemblies of about 100nm. These physicochemical characteristics are correlated with increased transfection rates in CHO-K1cells dependent on the type of the monomer and the nitrogen to phosphate (N/P) ratio of the polyplexes, as determined by luciferase reporter gene assays.

Comparing Zwitterionic and PEG Exteriors of Polyelectrolyte Complex Micelles.

A series of model polyelectrolyte complex micelles (PCMs) was prepared to investigate the consequences of neutral and zwitterionic chemistries and distinct charged cores on the size and stability of nanocarriers. Using aqueous reversible addition-fragmentation chain transfer (RAFT) polymerization, we synthesized a well-defined diblock polyelectrolyte system, poly(2-methacryloyloxyethyl phosphorylcholine methacrylate)-block-poly((vinylbenzyl) trimethylammonium) (PMPC-PVBTMA), at various neutral and charged block lengths to compare directly against PCM structure–property relationships centered on poly(ethylene glycol)-block-poly((vinylbenzyl) trimethylammonium) (PEG-PVBTMA) and poly(ethylene glycol)-block-poly(l-lysine) (PEG-PLK). After complexation with a common polyanion, poly(sodium acrylate), the resulting PCMs were characterized by dynamic light scattering (DLS) and small angle X-ray scattering (SAXS). We observed uniform assemblies of spherical micelles with a diameter ~1.5–2× larger when PMPC-PVBTMA was used compared to PEG-PLK and PEG-PVBTMA via SAXS and DLS. In addition, PEG-PLK PCMs proved most resistant to dissolution by both monovalent and divalent salt, followed by PEG-PVBTMA then PMPC-PVBTMA. All micelle systems were serum stable in 100% fetal bovine serum over the course of 8 h by time-resolved DLS, demonstrating minimal interactions with serum proteins and potential as in vivo drug delivery vehicles. This thorough study of the synthesis, assembly, and characterization of zwitterionic polymers in PCMs advances the design space for charge-driven micelle assemblies.

Scalable Aqueous Reversible Addition–Fragmentation Chain Transfer Photopolymerization-Induced Self-Assembly of Acrylamides for Direct Synthesis of Polymer Nanoparticles for Potential Drug Delivery Applications

The synthesis of polymer nanoparticles for potential drug delivery applications via photoinduced electron transfer–reversible addition–fragmentation chain transfer aqueous dispersion polymerizations employing Eosin Y/triethanol amine as catalytic system is described. A scalable synthesis procedure for the polymerization of poly(dimethyl acrylamide)-b-(poly(diaceteone-stat-dimethyl acrylamide)) is reported under visible light (λmax = 530 nm). A variety of solid contents and block lengths for the solvophilic and solvophobic blocks are investigated, expanding the compositional space of worms, jellyfish, and vesicles using flow chemistry. A simple two-step process using a coupled flow reactor setup is used without the need for intermediate purification.

Quantitative preparation of multiblock glycopolymers bearing glycounits at the terminal segments by aqueous reversible addition–fragmentation chain transfer polymerization of acrylamide monomers

Quantitative preparation of multiblock glycopolymers bearing glycounits at the terminal segments by aqueous reversible addition–fragmentation chain transfer polymerization of acrylamide monomers

The influence of gradient and statistical arrangements of guanidinium or primary amine groups in poly(methacrylate) copolymers on their DNA binding affinity.

Herein, we report the first gradient guanidinium containing cationic copolymers and investigate their binding ability to plasmid DNA (pDNA). To understand the effect of different charge distributions and cationic charge sources (primary amines vs. guanidinium group) on (pDNA) binding affinity, we synthesized a library of well-defined statistical cationic copolymers comprising N-(2-hydroxy-propyl)methacrylamide (HPMA) and N-(3-aminopropyl)methacrylamide (APMA) or N-(3-guanidinopropyl)methacrylamide (GPMA) and compared them with gradient polymers containing the same monomers of similar composition. All copolymers were synthesized through aqueous reversible addition-fragmentation chain transfer (aRAFT) polymerization at various monomer ratios by aiming at similar molar masses with low dispersity indices. For the molar mass characterization, in addition to size exclusion chromatography with two different systems, hydrodynamic characterization utilizing analytical ultracentrifugation, viscometry, and accompanied density measurements was conducted. pDNA was used as a model drug to demonstrate the impact of copolymer architecture on binding efficiency. For both HPMA-APMA and HPMA-GPMA copolymers, the gradient distribution demonstrated superior binding and denser packing of pDNA than their statistical counterparts at 20% and lower cationic charge contents. With respect to charge origin, the guanidinium group represented a higher binding efficiency than primary amines with the same nitrogen to phosphate ratio (N/P ratio). Our study demonstrates the profound effect of gradient monomer arrangement on the ability of polyplex formation and reveals the potential for further investigation in gene delivery applications. Gradient guanidinium containing copolymers have great promise for gene delivery applications due to their high affinity toward pDNA even at very low degrees (<20%) of charged monomer content.

Visible light induced aqueous RAFT polymerization using a supramolecular perylene diimide/cucurbit[7]uril complex

A water-soluble perylene diimide (PDI), in the presence of triethanolamine (TEOA), is used as a metal-free photocatalyst for aqueous reversible addition–fragmentation chain transfer (RAFT) polymerization under green light.

Poly(sarcosine)-Based Nano-Objects with Multi-Protease Resistance by Aqueous Photoinitiated Polymerization-Induced Self-Assembly (Photo-PISA).

Poly(sarcosine) (PSar) is a non-ionic hydrophilic polypeptoid with numerous biologically relevant properties, making it an appealing candidate for the development of amphiphilic block copolymer nanostructures. In this work, the fabrication of poly(sarcosine)-based diblock copolymer nano-objects with various morphologies via aqueous reversible addition-fragmentation chain-transfer (RAFT)-mediated photoinitiated polymerization-induced self-assembly (photo-PISA) is reported. Poly(sarcosine) was first synthesized via ring-opening polymerization (ROP) of sarcosine N-carboxyanhydride, using high-vacuum techniques. A small molecule chain transfer agent (CTA) was then coupled to the active ω-amino chain end of the telechelic polymer for the synthesis of a poly(sarcosine)-based macro-CTA. Controlled chain-extensions of a commercially available water-miscible methacrylate monomer (2-hydroxypropyl methacrylate) were achieved via photo-PISA under mild reaction conditions, using PSar macro-CTA. Upon varying the degree of polymerization and concentration of the core-forming monomer, morphologies evolving from spherical micelles to worm-like micelles and vesicles were accessed, as determined by dynamic light scattering and transmission electron microscopy, resulting in the construction of a detailed phase diagram. The resistance of both colloidally stable empty vesicles and enzyme-loaded nanoreactors against degradation by a series of proteases was finally assessed. Overall, our findings underline the potential of poly(sarcosine) as an alternative corona-forming polymer to poly(ethylene glycol)-based analogues of PISA assemblies for use in various pharmaceutical and biomedical applications.

“pH-triggered” drug release using shell cross-linked micelles from aqueous RAFT-synthesized PAPMA-b-PNIPAM copolymers

A new polymer namely poly (N-(3-aminopropyl) methacrylamide)-b-poly(N-isopropylacrylamide) (PAPMA-b-PNIPAM) was made for pH-triggered drug delivery by means of aqueous reversible addition-fragmentation chain transfer (RAFT) polymerization. PAPMA-b-PNIPAM was hydrophilic at 25 °C, and micelles were formed at 39 °C. The PAPMA chain was crosslinked with terephthaldicarboxaldehyde at pH = 9.0 and shell cross-linking (SCL) micelles were prepared. The sizes of the SCL micelles were 45~65 nm which can be reversible dissociated under acidic conditions. The formation of temperature-responsive SCL micelles and their cleavage behaviours were characterized.

Synthesis and Assembly of Designer Styrenic Diblock Polyelectrolytes.

Harnessing molecular design principles toward functional applications of ion-containing macromolecules relies on diversifying experimental data sets of well-understood materials. Here, we report a simple, tunable framework for preparing styrenic polyelectrolytes, using aqueous reversible addition-fragmentation chain transfer (RAFT) polymerization in a parallel synthesis approach. A series of diblock polycations and polyanions were RAFT chain-extended from poly(ethylene oxide) (PEO) using (vinylbenzyl)trimethylammonium chloride (PEO-b-PVBTMA) and sodium 4-styrenesulfonate (PEO-b-PSS), with varying neutral PEO block lengths, charged styrenic block lengths, and RAFT end-group identity. The materials characterization and kinetics study of chain growth exhibited control of the molar mass distribution for both systems. These block polyelectrolytes were also demonstrated to form polyelectrolyte complex (PEC) driven self-assemblies. We present two simple outcomes of micellization to show the importance of polymer selection from a broadened pool of polyelectrolyte candidates: (i) uniform PEC-core micelles comprising PEO-b-PVBTMA and poly(acrylic acid) and (ii) PEC nanoaggregates comprising PEO-b-PVBTMA and PEO-b-PSS. The materials characteristics of these charged assemblies were investigated with dynamic light scattering, small-angle X-ray scattering, and cryogenic-transmission electron microscopy imaging. This model synthetic platform offers a straightforward path to expand the design space of conventional polyelectrolytes into gram-scale block polymer structures, which can ultimately enable the development of more sophisticated ionic materials into technology.

Sodium Bis(acyl)phosphane oxide (SBAPO): An efficient photoinitiator for blue light initiated aqueous RAFT dispersion polymerization

We report a novel blue light initiated aqueous reversible addition–fragmentation chain transfer (RAFT) dispersion polymerization of 2-hydroxypropyl methacrylate (HPMA) with a poly (glycerol monomethacrylate) homopolymer as the macro-RAFT agent and sodium bis(acyl)phosphane oxide (SBAPO) as the photoinitiator. High monomer conversions were achieved within 1 h of blue light irradiation. Taking advantage of the temperature-insensitive feature of photoinitiator, the effect of reaction temperature on the blue light initiated aqueous RAFT dispersion polymerization was studied in detail. A new morphological phase diagram was constructed for the first time by changing the degree of polymerization (DP) of the core-forming block and the reaction temperature. Moreover, a typical morphological phase diagram for the blue light initiated aqueous RAFT dispersion polymerization at 70 °C was also built and various morphologies have been prepared. Effect of wavelength of light (405 and 465 nm) on copolymer compositions and morphologies was studied. Finally, a fully one-pot blue light initiated aqueous RAFT polymerization was developed for the synthesis of various diblock copolymer nano-objects.