Sequential Reversible Addition-fragmentation Chain Transfer Research Articles

One stone two birds: from one azlactone-functionalized monomer to a heterofunctional diblock copolymer

An innovative combination of RAFT polymerization using easy-to-implement conditions and post-polymerization modification by click aminolysis for efficient preparation of heterofunctional diblock copolymers derived from vinyl azlactone.

Morphologically Tunable Rectangular Platelets Self-Assembled from Diblock Molecular Brushes Containing Azopyridine Pendants.

Two-dimensional (2D) platelet structures are of growing importance as building blocks for the preparation of optical and electrical devices. However, the creation of morphologically tunable rectangular platelets through polymer self-assembly still remains a challenge. Herein, we describe a rational strategy for the fabrication of 2D rectangular platelets by stacking azopyridine-containing diblock molecular brushes in two dimensions in a selective solvent. Amphiphilic PEG-co-(PtBA-g-PAzoPy) DMBs with poly(ethylene glycol) (PEG) block, poly(t-butyl acrylate) (PtBA) backbone, and poly(6-(4-(4-pyridyazo)phenoxy)-hexyl methacrylate) (PAzoPy) brush were synthesized by sequential reversible addition-fragmentation chain transfer polymerization and atom transfer radical polymerization. Various rectangular platelets were obtained via the solution self-assembly of PEG-co-(PtBA-g-PAzoPy) through a heating-cooling-aging process in which the morphology and size of platelets could be controlled by adjusting the composition of DMBs as well as the solvent polarity. In addition, we investigated the metal chelation ability and H-bonding-assisted co-assembly capability of PEG-co-(PtBA-g-PAzoPy). The results displayed that 2D hybrids and flower-like platelets were formed, respectively. Our study presents an efficient method to fabricate rectangular platelets with tunable morphologies.

Design of thermo-responsive cell culture dishes using poly(N-isopropylacrylamide)-block-polystyrene copolymers for cell sheet technology

The main objective of this work was to assess the cell sheet fabrication of a newly designed thermo-responsive polymer. Thermo-responsive diblock copolymers of poly(N-isopropylacrylamide)-block-polystyrene (PNIPAM-b-PS) with different block ratios were synthesized via sequential reversible addition-fragmentation chain transfer (RAFT) polymerization. The prepared copolymers were characterized by Fourier transform infrared (FTIR) spectroscopy, nuclear magnetic resonance and gel permeation chromatography techniques in terms of molecular weight and composition. Physical adsorption was employed to prepare thermo-responsive films. Employing atomic force microscopy (AFM) and water contact angle (WCA) measurements, we found that the PNIPAM-b-PS diblock copolymer coatings showed a temperature-triggered phase transition in water through the reversible hydration of PNIPAM segments. Thermo-responsive PNIPAM-b-PS coatings were utilized as functional substrates for human dermal fibroblasts (HDFs) adhesion and detachment. By adjusting PNIPAM to PS segments ratio, HDFs successfully detached from the PNIPAM-b-PS spin-coated tissue culture polystyrene (TCPS) substrates in a temperature-induced manner.

Glycopolymer Decorated pH-Dependent Ratiometric Fluorescent Probe Based on Förster Resonance Energy Transfer for the Detection of Cancer Cells.

Development of fluorescent imaging probes is an important topic of research for the early diagnosis of cancer. Based on the difference between the cellular environment of tumor cells and normal cells, several "smart" fluorescent probes have been developed. In this work, a glycopolymer functionalized Förster resonance energy transfer (FRET) based fluorescent sensor is developed, which can monitor the pH change in cellular system. One-pot sequential reversible addition-fragmentation chain transfer (RAFT)polymerization technique is employed to synthesize fluorescent active triblock glycopolymer that can undergo FRET change on the variation of pH. A FRET pair, fluorescein o-acrylate (FA) and 7-amino-4-methylcoumarin (AMC) is linked via a pH-responsive polymer poly [2-(diisopropylamino)ethyl methacrylate] (PDPAEMA), which can undergo reversible swelling/deswelling under acidic/neutral condition. The presence of glycopolymer segment provides stability, water solubility, and specificity toward cancer cells. The cellular FRET experiments on cancer cells (MDA MB 231) and normal cells (3T3 fibroblast cells) demonstrate that the material is capable of distinguishing cells as a function of pH change.

Biocompatible Nanoparticles Based on Amphiphilic Random Polypeptides and Glycopolymers as Drug Delivery Systems.

In this research, the development and investigation of novel nanoobjects based on biodegradable random polypeptides and synthetic non-degradable glycopolymer poly(2-deoxy-2-methacrylamido-d-glucose) were proposed as drug delivery systems. Two different approaches have been applied for preparation of such nanomaterials. The first one includes the synthesis of block-random copolymers consisting of polypeptide and glycopolymer and capable of self-assembly into polymer particles. The synthesis of copolymers was performed using sequential reversible addition-fragmentation chain transfer (RAFT) and ring-opening polymerization (ROP) techniques. Amphiphilic poly(2-deoxy-2-methacrylamido-d-glucose)-b-poly(l-lysine-co-l-phenylalanine) (PMAG-b-P(Lys-co-Phe)) copolymers were then used for preparation of self-assembled nanoparticles. Another approach for the formation of polypeptide-glycopolymer particles was based on the post-modification of preformed polypeptide particles with an oxidized glycopolymer. The conjugation of the polysaccharide on the surface of the particles was achieved by the interaction of the aldehyde groups of the oxidized glycopolymer with the amino groups of the polymer on particle surface, followed by the reduction of the formed Schiff base with sodium borohydride. A comparative study of polymer nanoparticles developed with its cationic analogues based on random P(Lys-co-d-Phe), as well as an anionic one—P(Lys-co-d-Phe) covered with heparin––was carried out. In vitro antitumor activity of novel paclitaxel-loaded PMAG-b-P(Lys-co-Phe)-based particles towards A549 (human lung carcinoma) and MCF-7 (human breast adenocarcinoma) cells was comparable to the commercially available Paclitaxel-LANS.

Side-Chain Density Driven Morphology Transition in Brush–Linear Diblock Copolymers

We report the synthesis and self-assembly of brush-linear diblock copolymers with variable side-chain length and density. Poly(pentafluorophenyl acrylate-g-ethylene glycol)-b-polystyrene ((PPFPA-g-PEG)-b-PS) brush-linear diblock copolymers are prepared by sequential reversible addition-fragmentation chain transfer (RAFT) polymerization of PPFPA and PS, followed by postpolymerization reaction between the precursor PPFPA-b-PS diblock copolymer and amine-functionalized PEG. By controlling the PEG chain length and the degree of substitution, we obtained brush-linear diblock copolymers with different side-chain lengths and densities. The solid-state morphologies of the diblocks are then examined by small-angle X-ray scattering (SAXS). At low PEG side-chain density, the segregation of PEG and PS away from PPFPA leads to the formation of PEG and PS lamellar domains with PPFPA in the interface. At high PEG side-chain density, the segregation is between the PPFPA-g-PEG brush block and the PS linear block, and the domain morphology is determined by the composition of the brush block. A partial experimental phase diagram is presented, and it illustrates the importance of both side-chain length and density on the microdomain morphology of brush-linear diblock copolymers.

Self-healable and reprocessable networks involving diblock copolymer and hindered urea bonds

In this contribution, we reported a novel design of the self-healable (and/or reprocessable) networks involving diblock copolymers and hindered urea bonds (HUBs). The diblock copolymers were crosslinked with a crosslinker bearing hindered urea bonds (HUBs). Toward this end, a novel crosslinker (denoted HUDA) was synthesized via the reaction of 2-isocyanatoethylacrylate with N,N′-di-tert-butylethylenediamine, a hindered diamine. The diblock copolymers were composed of polystyrene (PS) and poly(n-butyl acrylate-stat-HUDA) [denoted P(BA-stat-HUDA)] blocks, which were synthesized via a two-step sequential reversible addition-fragmentation chain transfer (RAFT) polymerization approach. In the P(BA-stat-HUDA) blocks, HUDA acted as not only one of the copolymerization monomers but also the crosslinker bearing HUBs. In the networks, the PS microdomains behaved as the nanoreinforcement of P(BA-stat-HUDA) matrix. It was found that the PS-b-P(BA-stat-HUDA) networks displayed the self-healing properties or/and reprocessing properties. The self-healing properties were quite dependent on the concentration of hindered urea bonds. The self-healing behavior is attributable to the intense metathesis of HUBs in the crosslinked networks.

Synthesis, aqueous solution behavior and self-assembly of a dual pH/thermo-responsive fluorinated diblock terpolymer

The synthesis of fluorinated dual-responsive block terpolymers via sequential reversible addition–fragmentation chain transfer (RAFT) polymerization is presented.

PNIPAM-b-PDMAEA double stimuli responsive copolymers: Effects of composition, end groups and chemical modification on solution self-assembly

Doubly temperature- and pH-responsive HOOC-poly(N-isopropylacrylamide)-b-poly(2-(dimethylamino)ethyl acrylate)-C12H25 (HOOC-PNIPAM-b-PDMAEA-C12H25) and HOOC-poly(2-dimethylamino)ethyl acrylate)-b-poly(N-isopropylacrylamide)-C12H25 (HOOC-PDMAEA-b-PNIPAM-C12H25) diblock copolymers were successfully synthesized via sequential reversible addition-fragmentation chain transfer (RAFT) polymerization. Hydrophilic COOH groups and hydrophobic C12H25 groups were selectively placed at the chain end of either the thermoresponsive or the pH-responsive block. The amine precursor diblocks were converted to strong, cationic block polyelectrolytes by quaternizing the tertiary amine groups of PDMAEA block with methyl iodide. The self-assembly behavior of amine-based and quaternized diblock copolymers was investigated in aqueous media of varying pH and temperature by utilizing light scattering techniques and fluorescence spectroscopy. The novel diblock copolymers formed nanoassembled structures at temperatures above the nominal lower critical solution temperature (LCST) of the PNIPAM block. However, the amine-based and quaternized block copolymers form loose aggregate structures even at room temperature, due to the existence of the hydrophobic C12H25 terminal groups. Moreover, the solution pH was found to affect the self-assembly behavior of the amine-based diblock copolymers because of the presence of the PDMAEA block.

Triblock Copolymers Based on Sucrose Methacrylate and Methyl Methacrylate: RAFT Polymerization and Self‐Assembly

AbstractABA and BAB triblock amphiphilic copolymers based on sucrose methacrylate and methyl methacrylate are synthesized by sequential reversible addition–fragmentation chain transfer polymerization using S,S′‐bis(R,R′‐dimethyl‐R′′‐acetic acid)‐trithiocarbonate as a chain transfer agent. The copolymers present narrow molar mass dispersity, controlled molar mass and architecture as determined by gel permeation chromatography and 1H and 13C nuclear magnetic resonance. The copolymers with molar and mass fractions of poly(sucrose methacrylate) block ranging from 1 to 22 mol% and 3 to 52 wt%, respectively, and different molar masses present characteristics of a surfactant such as self‐assembly. The self‐assembly of the triblock copolymers in water, N,N‐dimethylformamide (DMF), dichloromethane, tetrahydrofuran, or benzene results mostly in vesicles as confirmed by scanning electron microscopy images and small‐angle X‐ray of the dispersions. Moreover, the copolymers present the capability to stabilize aromatic molecules (Nile Red dye) and nonpolar solvents in an aqueous phase and polar ionic molecules (methylene blue) and water in a nonpolar medium, suggesting the potential for application in drug encapsulation, environmental remediation systems, and molecular extraction in liquid–liquid immiscible systems, for example. Films prepared by casting from copolymer solutions in DMF present a lamellar structure with the lamellar thickness varying according to the copolymer molar mass.

Core-Cross-Linked Micelles Made by RAFT Polymerization with a Polycationic Outer Shell Based on Poly(1-methyl-4-vinylpyridinium)

A convergent synthesis of amphiphilic polymers with a polystyrene (PS) core and a polyelectrolytic poly(1-methyl-4-vinylpyridinium iodide) (P4VPMe+I–) shell is reported. The polymers were obtained by reversible addition–fragmentation chain transfer (RAFT) polymerization in water using a trithiocarbonate chain transfer agent [R0-SC(S)SPr, R0 = −C(Me)(CN)CH2CH2COOH]. Two types of particle structure, both having a spherical morphology and diameters in the 85–150 nm range, have been obtained as stable latexes with polymer content up to 10% in weight. The first structure consists of core-cross-linked micelles (CCMs), where amphiphilic P4VPMe+I–-b-PS arms are cross-linked at the hydrophobic end by the use of diethylene glycol dimethacrylate. The Coulombic repulsion between the outer shells of the precursor micelles ensures the absence of macrogelation during the cross-linking step. The second structure consists of nanogels (NGs), where the entire hydrophobic core is cross-linked during the last step of simultaneous chain extension and cross-linking of a P4VPMe+I–-b-PS intermediate with a short PS block. The lack of radical polymerization for the 4VPMe+I– monomer and the lack of chain extension with styrene for a R0-P4VPMe+I–-SC(S)SPr intermediate were circumvented by the synthesis of R0-P4VP-b-PS-SC(S)SPr containing a short PS block by sequential RAFT polymerization of 4-vinylpyridine (4VP) and styrene, followed by quantitative cationization of the P4VP block by MeI and subsequent sequential (for the CCMs) or simultaneous (for the NGs) chain extension and cross-linking.

Exploitation of the Nanoreactor Concept for Efficient Synthesis of Multiblock Copolymers via MacroRAFT-Mediated Emulsion Polymerization.

Multiblock copolymers are a class of polymeric materials with a range of potential applications. We report here a strategy for the synthesis of multiblock copolymers based on methacrylates. Reversible addition-fragmentation chain transfer (RAFT) polymerization is implemented as an emulsion polymerization to generate seed particles as nanoreactors, which can subsequently be employed in sequential RAFT emulsion polymerizations. The segregation effect allowed the synthesis of a high molar mass (>100,000 g·mol-1) decablock homopolymer at a high polymerization rate to an extent not previously achieved. A heptablock copolymer containing seven different 100 unit blocks was also successfully prepared, demonstrating how the strategy can be employed to precisely control the polymer composition at a level hitherto not accessible in environmentally friendly aqueous emulsion polymerization. Importantly, the methodology is a batch process without any intermediate purification steps, thus, rendering industrial scale up more feasible.

Nonmigratory Poly(vinyl chloride)-block-polycaprolactone Plasticizers and Compatibilizers Prepared by Sequential RAFT and Ring-Opening Polymerization (RAFT-T̵-ROP)

Well-defined nonmigrating polymeric plasticizers, poly(vinyl chloride)-block-polycaprolactone (PVC-b-PCL), were synthesized by sequential reversible addition–fragmentation chain transfer (RAFT) polymerization and ring-opening polymerization (ROP) with 2-hydroxyethyl 2-(ethoxycarbonothioylthio)propanoate (HECP) as RAFT agent and incipient initiator for ROP of e-caprolactone (CL, oxepan-2-one). Kinetic experiments demonstrated that HECP provided good control in RAFT polymerization of vinyl chloride (VC) with dispersity (Đ) ∼ 1.2 for 3400 < Mn < 11000. Chain extension experiments with VC and vinyl acetate proved the high end-group fidelity of the macroRAFT agent formed. The hydroxy end-group of the PVC macroRAFT agent allowed its use as a ROP initiator in forming a series of PVC-b-PCL with different PCL block lengths by RAFT-T-ROP. Characterization by wide-angle X-ray diffraction (WAXD), polarized light microscopy (PLM), and differential scanning calorimetry (DSC) indicates that there is enhanced chain enta...

What will happen when thermoresponsive poly(N-isopropylacrylamide) is tethered on poly(ionic liquid)s?

The thermoresponsive ionic liquid diblock copolymer of poly[1-(4-vinylbenzyl)-3-methylimidazolium tetrafluoroborate]-block-poly(N-isopropylacrylamide) (P[VBMI][BF4]-b-PNIPAM) containing a hydrophilic poly(ionic liquid) block of P[VBMI][BF4] is prepared by sequential reversible addition–fragmentation chain transfer (RAFT) polymerization. This P[VBMI][BF4]-b-PNIPAM exhibits an abnormal thermoresponsive phase transition at a temperature above the phase transition temperature (PTT) of the PNIPAM block. For P[VBMI][BF4]-b-PNIPAM including a short P[VBMI][BF4] block, its aqueous solution becomes turbid at a temperature above the PTT of the thermoresponsive PNIPAM block, whereas for P[VBMI][BF4]-b-PNIPAM containing a relatively long P[VBMI][BF4] block even in the case of a relatively long PNIPAM block, the aqueous solution remains transparent at a temperature far above the PTT of the PNIPAM block, although a soluble-to-insoluble phase transition of the PINIPAM block is confirmed by dynamic light scattering (DLS) analysis and variable temperature 1H NMR analysis. The reason that P[VBMI][BF4]-b-PNIPAM exhibits an abnormal thermoresponse is discussed and ascribed to the highly hydrophilic and charged poly(ionic liquid) block of P[VBMI][BF4] leading to the formation of small-sized micelles at a temperature above the PTT.

Synthesis, self-assembly and self-healing properties of organic–inorganic ABA triblock copolymers with poly(POSS acrylate) endblocks

A novel organic–inorganic ABA triblock copolymer with a poly(acrylate amide) (PAA) midblock and poly(POSS acrylate) [P(POSS)] endblocks was synthesized via sequential reversible addition–fragmentation chain transfer (RAFT) polymerization.

Antifouling Surfaces Based on Fluorine-Containing Asymmetric Polymer Brushes: Effect of Chain Length of Fluorinated Side Chain.

The influence of chain length of a fluorinated side chain of an asymmetric polymer brush with poly(ethylene glycol) (PEG) side chains on the antifouling property was systematically investigated so as to obtain more knowledge for deepening our understanding of the structure-(antifouling)-property relationship of asymmetric polymer brush. A series of asymmetric polymer brushes, consisting of hydrophobic poly(pentafluoropropyl methacrylate) (PPTFMA) side chains with the number of repeat units of pentafluoropropyl methacrylate (PTFMA) ranging from 8 to 42 and hydrophilic PEG side chains, was first synthesized by sequential reversible addition-fragmentation chain transfer (RAFT) polymerization and atom transfer radical polymerization (ATRP). Subsequently, thin films were prepared by spin-casting the solution of these brushes onto indium tin oxide (ITO) and SiO2 substrates. Water contact angle analysis showed that the hydrophobicity of the film surface increased with the length of PPTFMA side chain. The atomic force microscopy (AFM) measurement demonstrated that these films had a roughness of <3 and <10 nm onto ITO glass and SiO2 substrates, respectively. The antifouling behaviors of these films in bovine serum albumin (BSA) solution were evaluated by quartz crystal microbalance (QCM), which showed that the asymmetric brush surfaces had considerable antifouling performance with less protein adsorption in comparison with the bare surface. In addition, the films made from polymer brushes with shorter PPTFMA side chains exhibited better antifouling and fouling-release behaviors.

Precisely Tunable Sol-Gel Transition Temperature by Blending Thermoresponsive ABC Triblock Terpolymers.

Here, we report a facile methodology to control the sol-gel transition temperature (Tgel) of a physically cross-linked hydrogel by blending two kinds of ABC triblock terpolymers. Well-defined triblock terpolymers including thermosensitive N-isopropylacrylamide (NIPAAm), ABC1, and ABC2, were prepared by sequential reversible addition-fragmentation chain transfer polymerization. The chemical structure as well as the molecular weight of the A and B blocks for both polymers are identical, whereas the C blocks are different. The C block of ABC1 (C1) is a statistical copolymer of NIPAAm with hydrophobic n-butyl acrylate (BA), while that of ABC2 (C2) is a PNIPAAm homopolymer. Independently prepared ABC triblock terpolymer solutions exhibit well-defined sol-gel transitions. The Tgel of ABC1 is lower than that of ABC2 since hydrophobic BA is copolymerized into block C1. Remarkably, the Tgel varies linearly within this temperature range by simply blending the two polymers, while the resultant gel strength (∼G') remains almost unchanged. Therefore, the Tgel can be precisely adjusted by the mixing ratio of the two polymers. This method for straightforward manipulation of Tgel has great potential for various soft material applications such as biomaterials for tissue engineering, drug delivery systems, and injectable gels.

Poly(vinylidene fluoride)-block-poly(N-vinylpyrrolidone) diblock copolymers: Synthesis via sequential RAFT/MADIX polymerization and self-assembly behavior

In this contribution, we reported the synthesis of poly(vinylidene fluoride)-block-poly(N-vinylpyrrolidone) (PVDF-b-PVPy) diblock copolymers via a sequential reversible addition-fragmentation chain transfer / macromolecular design via the interchange of xanthate (RAFT/MADIX) approach. First, the radical polymerization of vinylidene fluoride (VDF) was carried out with O-ethyl-S-(1-methoxycarbonyl)ethyldithiocarbonate as the starting chain transfer agent and a xanthate-terminated PVDF was obtained. The xanthate-terminated PVDF was then used as the macromolecular chain transfer agent further to mediate the radical polymerization of N-vinylpyrrolidone (NVP) and the PVDF-b-PVPy diblock copolymers were successfully synthesized. The kinetics of NVP polymerization was investigated by means of gel permeation chromatography (GPC). By controlling the molar ratios of the macromolecular chain transfer agent to NVP, a series of PVDF-b-PVPy diblock copolymers with variable lengths of PVPy were obtained. The PVDF-b-PVPy diblock copolymers displayed the interesting self-assembly behavior. It was found that for the PVDF-b-PVPy diblock copolymers no self-assembly behavior was exhibited in bulks. Nonetheless, the diblock copolymers were capable of self-assembling into the nanoobjects in aqueous solutions. In addition, the diblock copolymers displayed composition-dependent microphase-separated morphologies in their blends with poly(hydroxyether of bisphenol A). The different self-assembly behaviors have been interpreted in terms of differential scanning calorimetry (DSC), transmission electron microscopy (TEM) and atomic force microscopy (AFM).

Morphology-Variable Aggregates Prepared from Cholesterol-Containing Amphiphilic Glycopolymers: Their Protein Recognition/Adsorption and Drug Delivery Applications.

In this study, a series of diblock glycopolymers, poly(6-O-methacryloyl-d-galactopyranose)-b-poly(6-cholesteryloxyhexyl methacrylate) (PMAgala-b-PMAChols), with cholesterol/galactose grafts were prepared through a sequential reversible addition-fragmentation chain transfer (RAFT) polymerization and deprotection process. The glycopolymers could self-assemble into aggregates with various morphologies depending on cholesterol/galactose-containing block weight ratios, as determined by transmission electronic microscopy (TEM) and dynamic laser light scattering (DLS). In addition, the lectin (Ricinus communis agglutinin II, RCA120) recognition and bovine serum albumin (BSA) adsorption of the PMAgala-b-PMAChol aggregates were evaluated. The SK-Hep-1 tumor cell inhibition properties of the PMAgala-b-PMAChol/doxorubicin (DOX) complex aggregates were further examined in vitro. Results indicate that the PMAgala-b-PMAChol aggregates with various morphologies showed different interaction/recognition features with RCA120 and BSA. Spherical aggregates (d ≈ 92 nm) possessed the highest RCA120 recognition ability and lowest BSA protein adsorption. In addition, the DOX-loaded spherical complex aggregates exhibited a better tumor cell inhibition property than those of nanofibrous complex aggregates. The morphology-variable aggregates derived from the amphiphilic glycopolymers may serve as multifunctional biomaterials with biomolecular recognition and drug delivery features.

Macroscopic Adhesion of Thermoreversible ABC Triblock Copolymer-Based Hydrogels Via Boronic Acid-Sugar Complexation.

Two complementary thermoreversible ABC triblock copolymers containing either phenylboronic acids with low pKa values or galactosyl groups in the hydrophilic B blocks are synthesized by sequential reversible addition-fragmentation chain transfer polymerization and subsequent modification of the functional groups. Both ABC triblock copolymers undergo reversible sol-to-gel transitions upon temperature change and form physically cross-linked hydrogels under physiological conditions. Furthermore, the spontaneous adhesion of these thermoreversible hydrogels via the formation of boronic esters between the phenylboronic acid and galactosyl groups under physiological conditions is realized for the first time.