Well-defined Star Polymers Research Articles

A synthetic optimization study on thermoresponsive core cross-linked starpolymers (CCSs)

The well-defined starpolymers can offer a precise stimuli-responsive drug delivery system (SDDS). For this, core cross-linked starpolymers (CCSs) using the poly(N-isopropylacrylamide)-b-poly(n-butyl acrylate) (PNB) linear arm chain and ethylene glycol diacrylate (EGDA) cross-linker were designed and synthesized by the reversible addition-fragmentation chain transfer (RAFT) system. The important synthetic parameters, including reaction time, radical concentration, and cross-linker concentration, were varied to optimize the reaction conditions for highly uniform PNiPAM-based amphiphilic starpolymers (PNBA). The reaction was monitored by GPC, resulting in the sharp monomodal PNBA GPC curve with an almost degraded original curve corresponding to the PNB linear chain. The PNBA revealed a dramatic size increase from 150 nm to 15,000 nm when the temperature increased up to 40 °C. Notably, the uniform CCS structure gives rise to a particular phase transformation system, which can be helpful in biomedical and catalytic applications with enhanced performance.

Organocatalytic Ring-Opening Polymerization of ϵ-Caprolactone with Phosphoramidimidates (PADIs) as a Bifunctional Brønsted Acid Catalyst.

In this study, an organocatalytic ring-opening polymerization (ROP) of ϵ-caprolactone (ϵ-CL) has been developed by employing PADIs as a novel and efficient acid/base bifunctional organocatalyst, which could afford metal-free poly(ϵ-caprolactone) with predictable molecular weight and narrow dispersity at a low catalyst loading under mild conditions. NMR and kinetic studies indicate that the ring-opening polymerizations of lactones catalyzed by PADIs proceed in a living and well controlled manner. Moreover, this organic Brønsted acid catalytic system could allow the synthesis of PCL with molecular weight above 60 kg/mol, as well as well-defined star polymers.

Highly Living Stars via Core-First Photo-RAFT Polymerization: Exploitation for Ultra-High Molecular Weight Star Synthesis.

Star polymers are highly functional materials that display unique properties in comparison to linear polymers, making them valuable in a wide range of applications. Currently, ultra-high molecular weight (UHMW) star polymers synthesized using controlled radical polymerization are prone to termination reactions that have undesirable effects, such as star-star coupling. Herein, we report the synthesis of the largest star polymers to date using controlled radical techniques via xanthate-mediated photo-reversible addition-fragmentation chain transfer (RAFT) polymerization using a core-first approach. Polymerization from xanthate-functionalized cores was highly living, enabling the synthesis of well-defined star polymers with molecular weights in excess of 20 MDa.

Comparative Analysis of Different Tube Models for Linear Rheology of Monodisperse Linear Entangled Polymers.

The aim of the present paper is to analyse the differences between tube-based models which are widely used for predicting the linear viscoelasticity of monodisperse linear polymers, in comparison to a large set of experimental data. The following models are examined: Milner–McLeish, Likhtman–McLeish, the Hierarchical model proposed by the group of Larson, the BoB model of Das and Read, and the TMA model proposed by the group of van Ruymbeke. This comparison allows us to highlight and discuss important questions related to the relaxation of entangled polymers, such as the importance of the contour-length fluctuations (CLF) process and how it affects the reptation mechanism, or the contribution of the constraint release (CR) process on the motion of the chains. In particular, it allows us to point out important approximations, inherent in some models, which result in an overestimation of the effect of CLF on the reptation time. On the contrary, by validating the TMA model against experimental data, we show that this effect is underestimated in TMA. Therefore, in order to obtain accurate predictions, a novel modification to the TMA model is proposed. Our current work is a continuation of earlier research (Shchetnikava et al., 2014), where a similar analysis is performed on well-defined star polymers.

Injectable, remoldable hydrogels with thermoresponsiveness, self-healing and cytocompatibility constructed via orthogonal assembly of well-defined star and linear polymers

Dual intelligent and multifunctional hydrogels constructed by host–guest orthogonal assembly of well-defined star and linear polymers.

Synthesis of well-defined star, star-block, and miktoarm star biodegradable polymers based on PLLA and PCL by one-pot azide-alkyne click reaction.

Based on the “arm-first” strategy, ring-opening polymerization (ROP) and one-pot azide–alkyne click reaction, well-defined star-shaped polymers with different architectures have been successfully synthesized, including the star homopolymers four-arm star-shaped polycaprolactone (4sPCL) and four-arm star-shaped poly(l-lactic acid) (4sPLLA), star-block copolymer 4sPCL-b-PLLA and miktoarm star-shaped copolymer PCL2PLLA2. The star homopolymers 4sPCL and 4sPLLA were synthesized by a click reaction of an azide small molecule initiator and HC Created by potrace 1.16, written by Peter Selinger 2001-2019 ]]> C-PCL or HCC-PLLA. The star-block copolymer 4sPCL-b-PLLA was synthesized by a click reaction of an azide small molecule initiator and the block copolymer HCC-PCL-b-PLLA. The miktoarm star polymer PCL2PLLA2 was synthesized by a one-pot azide–alkyne click reaction of simultaneous addition of equal proportions of HCC-PCL and HCC-PLLA. The structures of these star-shaped polymers have been confirmed by NMR, FT-IR and GPC. Furthermore, the melting and crystallization behaviors investigated using DSC and WXRD also confirm the formation of star-shaped polymers with different architectures.

Thiacalix[3]Triazine-centered regioregular poly(3-hexylthiophene) star: synthesis, structure and anion binding

The first synthesis of a well-defined star polymer consisting of three regioregular poly(3-hexylthiophene) (rr-P3HT) arms emanating from an electron acceptor thiacalix[3]wtriazine core via direct arylation polymerization is described. Its structural characteristics as well as optical and thermal properties were evaluated using Fourier transform infrared spectroscopy (FTIR), 1H and 13C nuclear magnetic resonance (NMR), X-ray diffraction (XRD), gel permeation chromatography (GPC), differential scanning calorimetry (DSC) and atomic force microscopy (AFM) methods. The UV-vis and photoluminescence spectroscopy results evidenced the impact of the electron-withdrawing feature of the thiacalix[3]triazine core and the star structure on the optical behavior of the star-shaped material, as compared to the rr-P3HT linear analogue. The anion-binding property of the star-shaped P3HT resulting in fluorescence quenching was also studied.

Copolymerization of Norbornene and Norbornadiene Using a cis-Selective Bimetallic W-Based Catalytic System.

The bimetallic cluster Na[W2(μ-Cl)3Cl4(THF)2]·(THF)3 ({W2}, {W 3 W}6+, a′2e′4), which features a triple metal-metal bond, is a highly efficient room-temperature initiator for ring opening metathesis polymerization (ROMP) of norbornene (NBE) and norbornadiene (NBD), providing high-cis polymers. In this work, {W2} was used for the copolymerization of the aforementioned monomers, yielding statistical poly(norbornene)/poly(norbornadiene) PNBE/PNBD copolymers of high molecular weight and high-cis content. The composition of the polymer chain was estimated by 13C CPMAS NMR data and it was found that the ratio of PNBE/PNBD segments in the polymer chain was relative to the monomer molar ratio in the reaction mixture. The thermal properties of all copolymers were similar, resembled the properties of PNBD homopolymer and indicated a high degree of cross-linking. The morphology of all materials in this study was smooth and non-porous; copolymers with higher PNBE content featured a corrugated morphology. Glass transition temperatures were lower for the copolymers than for the homopolymers, providing a strong indication that those materials featured a branched-shaped structure. This conclusion was further supported by viscosity measurements of copolymers solutions in THF. The molecular structure of those materials can be controlled, potentially leading to well-defined star polymers via the “core-first” synthesis method. Therefore, {W2} is not only a cost-efficient, practical, highly active, and cis-stereoselective ROMP-initiator, but it can also be used for the synthesis of more complex macromolecular structures.

Synthesis of star-branched poly(vinyl alcohol) and ice recrystallization inhibition activity

Antifreeze proteins are potent inhibitors of ice crystal growth (recrystallization), which is a highly desirable property for cryopreservation and other low temperature applications. It has emerged that relatively simple polymers based on poly(vinyl alcohol) can mimic this activity, but the link between architecture and activity is not known. Here, a trifunctional xanthate was designed and synthesized to prepare star-branched poly(vinyl alcohols) by RAFT/Xanthate mediated polymerization, and their ice growth inhibition activity probed for the first time. The trifunctional agent design affords the formation of well-defined star polymers, with no evidence of star-star linking, even at high conversions, and narrow molecular weight dispersity. It is observed that three-arm stars have identical activity to two-armed (i.e. linear) equivalents, suggesting that the total hydrodynamic size of the polymer (diameter three-arm∼two-arm) rather than total valence of the functional groups is the key descriptor of activity.

Well-defined star polymers for co-delivery of plasmid DNA and imiquimod to dendritic cells.

Co-delivery of antigen-encoding plasmid DNA (pDNA) and immune-modulatory molecules has importance in advancing gene-based immunotherapy and vaccines. Here novel star polymer nanocarriers were synthesized for co-delivery of pDNA and imiquimod (IMQ), a poorly soluble small-molecule adjuvant, to dendritic cells. Computational modeling and experimental results revealed that the polymers formed either multimolecular or unimolecular core-shell-type micelles in water, depending on the nature of the outer hydrophilic shell. Micelles loaded with both IMQ and pDNA were able to release IMQ in response to intracellular pH of the endo-lysosome and transfect mouse dendritic cells (DC2.4 line) in vitro. Importantly, IMQ-loaded micelle/pDNA complexes displayed much enhanced transfection efficiency than IMQ-free complexes. These results demonstrate the feasibility of co-delivery of pDNA and IMQ to antigen-presenting cells by multifunctional polymer nanocarriers with potential use in gene-based vaccine approaches.

Strategies for the Synthesis of Well-Defined Star Polymers by Anionic Polymerization with Chlorosilane Coupling and Preservation of the Star Architecture during Catalytic Hydrogenation

The synthesis of isoprene-based star polymers by anionic polymerization, chlorosilane coupling, and catalytic hydrogenation was studied in detail, with the goal of obtaining and preserving a well-defined star architecture. The coupling reaction between polyisoprenyllithium (PI-Li) and chlorosilanes, which can be intractably slow in apolar media, was dramatically accelerated by the concurrent addition of tetrahydrofuran (THF) with the coupling agent. In the presence of THF, PI-Li produces a yellow color allowing the living end concentration to be tracked visually, enabling near-stoichiometric coupling, as demonstrated by the synthesis of 6-arm star polymers and star block copolymers. Moreover, glassblowing techniques are not required. Star polymers coupled with chlorosilane terminating agents lost arms during catalytic hydrogenation. Several common hydrogenation catalysts were evaluated. The degree of degradation depended on the identity of the catalyst and the temperature of the reaction—more active catalysts and higher temperatures led to more scission—but not the reaction time. Degradation closely tracked the hydrogenation reaction indicating that scission is a catalytically activated process. This phenomenon is attributed to a decreasing affinity of the polymer for the catalyst with increasing saturation. Degradation of the star architecture depended strongly on the steric environment at the core. It was shown that the steric strain can be reduced by tuning the topology of the coupling agent to limit the number of arms per Si atom. The steric constraints at the core were further relaxed by adding a short run of butadiene units to the arms just prior to coupling, which nearly eliminated degradation during hydrogenation of a 6-arm star.

Controlled Formation of Star Polymer Nanoparticles via Visible Light Photopolymerization.

A recently developed visible light mediated photocontrolled radical polymerization technique using trithiocarbonates (i.e., conventional RAFT agents) as the sole control agent in the absence of additional photoinitiators or catalysts is utilized for the synthesis of core cross-linked star (CCS) polymer nanoparticles. The attractive features of this photopolymerization system, including high end-group fidelity at (near) complete monomer conversion, are exploited to facilitate a high-yielding, one-pot pathway toward well-defined star polymer products. Moreover, reinitiation of the photoactive trithiocarbonate moieties from within the star core is demonstrated to form (pseudo)miktoarm stars via an "in-out" approach, showing extremely high initiation efficiency (95%).

Star polymers by photoinduced copper-catalyzed azide-alkyne cycloaddition click chemistry

Well-defined star polymers consisting of tri-, tetra-, or octa-arms have been prepared via coupling-onto strategy using photoinduced copper(I)-catalyzed 1,3-dipolar cycloaddition click reaction. An azide end-functionalized polystyrene and poly(methyl methacrylate), and an alkyne end-functionalized poly(ε-caprolactone) as the integrating arms of the star polymers are prepared by the combination of controlled polymerization and nucleophilic substitution reactions; whereas, multifunctional cores containing either azide or alkyne functionalities were synthesized in quantitatively via etherification and ring-opening reactions. By using photoinduced copper-catalyzed azide–alkyne cycloaddition (CuAAC) click reaction, reactive linear polymers are simply attached onto multifunctional cores to form corresponding star polymers via coupling-onto methodology. The chromatographic, spectroscopic, and thermal analyses have clearly demonstrated that successful star formations can be obtained via photoinduced CuAAC click reaction. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015, 53, 1687–1695

Effective Delivery of siRNA into Cancer Cells and Tumors Using Well-Defined Biodegradable Cationic Star Polymers

Cancer is one of the most common causes of death worldwide. Two types of cancer that have high mortality rates are pancreatic and lung cancer. Despite improvements in treatment strategies, resistance to chemotherapy and the presence of metastases are common. Therefore, novel therapies which target and silence genes involved in regulating these processes are required. Short-interfering RNA (siRNA) holds great promise as a therapeutic to silence disease-causing genes. However, siRNA requires a delivery vehicle to enter the cell to allow it to silence its target gene. Herein, we report on the design and synthesis of cationic star polymers as novel delivery vehicles for siRNA to silence genes in pancreatic and lung cancer cells. Dimethylaminoethyl methacrylate (DMAEMA) was polymerized via reversible addition-fragmentation transfer polymerization (RAFT) and then chain extended in the presence of both cross-linkers N,N-bis(acryloyl)cistamine and DMAEMA, yielding biodegradable well-defined star polymers. The star polymers were characterized by transmission electron microscopy, dynamic light scattering, ζ potential, and gel permeation chromatography. Importantly, the star polymers were able to self-assemble with siRNA and form small uniform nanoparticle complexes. Moreover, the ratios of star polymer required to complex siRNA were nontoxic in both pancreatic and lung cancer cells. Treatment with star polymer-siRNA complexes resulted in uptake of siRNA into both cell lines and a significant decrease in target gene mRNA and protein levels. In addition, delivery of clinically relevant amounts of siRNA complexed to the star polymer were able to silence target gene expression by 50% in an in vivo tumor setting. Collectively, these results provide the first evidence of well-defined small cationic star polymers to deliver active siRNA to both pancreatic and lung cancer cells and may be a valuable tool to inhibit key genes involved in promoting chemotherapy drug resistance and metastases.

Z-RAFT star polymerization of styrene: Comprehensive characterization using size-exclusion chromatography

Reversible addition–fragmentation chain transfer (RAFT) polymerizations of styrene in bulk at 80°C using tri-, tetra-, and hexafunctional trithiocarbonates, in which the active RAFT groups are linked to the core via the stabilizing Z-group, were studied in detail. These Z-RAFT star polymerizations of styrene showed excellent molecular weight control up to very high monomer conversions and star sizes of more than 200kDa. The application of high pressure up to 2600bar was found to significantly increase the relative amount of living star polymer. Not even at very high monomer conversions and for large star molecules, a shielding effect of growing arms hampering the RAFT process could be identified. Absolute molecular weights of star polymers using a conventionally calibrated SEC setup were determined with high precision by using a mixture of linear and star-shaped RAFT agents. When using phenylethyl as the leaving R-group, well-defined star polymers that perfectly match the theoretical predictions were formed. However, when using benzyl as the leaving group, a pronounced impact of monomer conversion on the star polymer topology was observed and pure star polymers with the expected number of arms could not be obtained.

Well-Defined Star Polymers with Mixed-Arms by Sequential Polymerization of Atom Transfer Radical Polymerization and Reverse Addition−Fragmentation Chain Transfer on a Hyperbranched Polyglycerol Core

Mixed-arm star polymers were synthesized by atom transfer radical polymerization (ATRP) and reverse addition−fragmentation chain transfer (RAFT) sequential polymerization using the “core first” method. The synthesis consisted of three steps: (i) synthesis of a hyperbranched polyglycerol (HPG) core, (ii) ATRP with the first monomer (St, styrene), and (iii) then the polymerization with the second monomer (tert-butyl acrylate, tBA) from the core by the RAFT technique. After the hydrolysis of poly(tBA), poly(acrylic acid) (PAA) arms were obtained. In the whole process, the final products and intermediates were characterized by gel permeation chromatography (GPC), nuclear magnetic resonance spectroscopy (NMR), ultraviolet spectroscopy (UV), Fourier transform-infrared (FT-IR), and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) in detail. The arm number and arm length of polystyrene (PS) and poly(tBA) (PAA) in the star polymers were derived from GPC and MALDI-TOF MS ...

Synthesis of star polymers via nitroxide mediated free‐radical polymerization: A “core‐first” approach using resorcinarene‐based alkoxyamine initiators

AbstractThe synthesis of new octafunctional alkoxyamine initiators for nitroxide‐mediated radical polymerization (NMRP), by the derivatization of resorcinarene with nitroxide free radicals viz TEMPO and a freshly prepared phosphonylated nitroxide, is described. The efficiency of these initiators toward the controlled radical polymerization of styrene and tert‐butyl acrylate is investigated in detail. Linear analogues of these multifunctional initiators were also prepared to compare and evaluate their initiation efficiency. The favorable conditions for polymerization were optimized by varying the concentration of initiators and free nitroxides, reaction conditions, etc., to obtain well‐defined star polymers. Star polystyrene thus obtained were further used as macro‐initiator for the block copolymerization with tert‐butyl acrylate. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 5559–5572, 2007

Design and synthesis of star polymers with hetero-arms by the combination of controlled radical polymerizations and click chemistry

An alternative approach to the synthesis of well-defined star polymers with hetero-arms was described. An azide-functionalized dithioester chain transfer agent (CTA-N3) was designed and synthesized. Using CTA-N3 as the reversible addition–fragmentation chain transfer (RAFT) agent, styrene was polymerized in a controlled manner. The so-obtained polystyrene showed a high proportion of azide-functionalized chains (PS-N3, about 92%). The azide end-capped PS-N3 could be assembled, via click reaction with a bromide-containing trialkyne coupling agent, to form a 3-arm star polystyrene (PS3-Br) with a narrow molecular weight distribution. PS3-Br could further serve as a macro-initiator for the atom transfer radical polymerization (ATRP) of methyl methacrylate (MMA). Accordingly, well-defined star polymers containing three polystyrene and one poly(methyl methacrylate) (PMMA) arms, and with a narrow molecular weight distribution, were successfully prepared.

Z-RAFT Star Polymerizations of Acrylates: Star Coupling via Intermolecular Chain Transfer to Polymer

Six-arm star polymers of methyl acrylate (MA), butyl acrylate (BA), and dodecyl acrylate (DA) were generated in bulk at 60 °C via reversible addition−fragmentation chain transfer (RAFT) polymerization. A hexafunctional trithiocarbonate was employed as mediating compound, in which the active RAFT-agent moieties are interlinked to the central core molecule via the stabilizing Z-group. Well-defined star polymers with predictable number-average molecular weights of more than 1 × 106 g·mol-1 were obtained by this Z-RAFT star polymerization of acrylates. Narrow and monomodal molecular weight distributions were found up to intermediate monomer conversions. At higher monomer conversions, an unexpected high molecular weight component occurred with increasing extent when going from MA over BA to DA polymerization. This high molecular weight material was assigned to a star−star couple containing two living cores, which formation is not in accordance to the basic Z-RAFT star polymerization mechanism, but most likely arises from an intermolecular chain transfer to polymer reaction. The amount of star−star couples, which is an indication for the extent of long-chain branching, was quantified as a function of the monomer conversion and subsequently modeled via kinetic simulations. By this approach, the rate coefficient of intermolecular transfer to polymer at 60 °C was estimated to be ktrP,inter = 0.33 L·mol-1·s-1 in BA polymerization and ktrP,inter = 7.1 L·mol-1·s-1 in DA polymerization. The living process was found to be very effective up to high monomer conversions, indicating that steric congestion next to the star polymer core, where the actual RAFT process takes place, is not significantly hampering the Z-RAFT star polymerization of acrylates.

Preparation of Well-Defined Star Polymer from Hyperbranched Macroinitiator Based Attapulgite by Surface-Initiated Atom Transfer Radical Polymerization Technique

To prepare the well-defined star polymer grafted attapulgite nanofibrillar clay (WSP-ATP) with hydrophilic core and hydrophobic shell and higher percentage of grafting, the postgraft polymerization of vinyl polymer from hyperbranched macroinitiator based attapulgite (HMI-ATP) via the surface-initiated atom transfer radical polymerization (SI-ATRP) technique was investigated for the first time. The HMI-ATP, with bromoacetic ester surface groups, was prepared by the bromoacetylation of the surface hydroxyl groups of the hyperbranched aliphatic polyester grafted attapulgite (HAPE-ATP). The HAPE-ATP was prepared by the one-pot polycondensation of the AB2-type monomer 2,2-bis(hydroxymethyl)propionic acid (bis-MPA), from the surfaces of the amino group modified attapulgite nanofibrillar clay (A-ATP) with p-toluenesulfonic acid (p-TSA) as catalyst. Then the SI-ATRP of methyl methacrylate (MMA) was conducted from the HMI-ATP made in the presence of 1,10-phenanthroline and Cu(I)Br as catalyst in toluene. The postg...