Well-defined Block Copolymers Research Articles

Amphiphilic polymer Co-networks based on cross-linked tetra-PEG-b-PCL star block copolymers

A new class of AB4-type amphiphilic polymer co-networks (ACN) was prepared by hetero-complementary 2-(4-nitrophenyl)-benzoxazinone/amine end group cross-linking chemistry in dimethyl sulfoxide (DMSO). For this purpose, a well-defined star block copolymer (tetra-PEG-b-PCL) consisting of a hydrophilic tetra-arm PEG core (Mn ∼ 5 kg mol−1) and hydrophobic PCL wings with a total molar mass of Mn ∼ 10 kg mol−1 was synthesized by ring-opening polymerization (ROP). This tetra-PEG-b-PCL star block copolymer was functionalized either with 2-(4-nitrophenyl)-benzoxazinone or with amino terminal groups. The ACN synthesis was carried out by conversion of these two star block copolymers. The overlap concentration of c* ∼76 g L−1 determined by viscosity measurements of both stars showed no significant temperature dependence. The network syntheses carried out at different concentrations (0.5 c* to 2.5 c*) resulted in conversion degrees in the range of p ≈ 95 % or higher as detected by HR MAS NMR spectroscopy. As in previous work on the synthesis of A4B4 networks using the same cross-linking chemistry, deviations from the expected network structure (increased proportion of double links between two stars) were detected also here by multi quantum NMR spectroscopy. The expected environmentally sensitive behavior of the ACNs was confirmed in terms of their equilibrium swelling in solvents of different quality to PEG and PCL. The scaling of the swelling and viscoelasticity data as a function of preparation concentration showed deviations from the expectations of a perfectly cross-linked star polymer network. Finally, a two-step gelation process was observed by rheology at 30 °C in DMSO, which is related to associations between the 2-(4-nitrophenyl)-benzoxazinone groups surrounded by PCL blocks that become apparent on the time scale of rheology when the molar mass is increased as a result of cross-linking.

Design of functional soft interfaces with precise control of the polymer architecture

AbstractSoft interfaces formed by polymer materials are important interfaces for biological systems (biointerfaces), and controlling their chemical and physical structures at the nanoscale plays an important role in understanding the mechanism and development of interface functionalities. Controlled radical polymerization (CRP) is highly suited for designing biointerfaces composed of polymer chains because it enables the formation of well-defined polymer brushes, block copolymers, and comb-type copolymers. This focus review describes the design of functional soft interfaces based on investigations of the structure-property relationships of CRPs. In particular, polymer brush surfaces showing autonomous property changes, 2D/3D transformations of lipid bilayers, and molecular interactions in bactericidal cationic polymer brushes are depicted.

The Effect of Block Ratio and Structure on the Thermosensitivity of Double and Triple Betaine Block Copolymers.

AB-type and BAB-type betaine block copolymers composed of a carboxybetaine methacrylate and a sulfobetaine methacrylate, PGLBT-b-PSPE and PSPE-b-PGLBT-b-PSPE, respectively, were synthesized by one-pot RAFT polymerization. By optimizing the concentration of the monomer, initiator, and chain transfer agent, block extension with precise ratio control was enabled and a full conversion (~99%) of betaine monomers was achieved at each step. Two sets (total degree of polymerization: ~300 and ~600) of diblock copolymers having four different PGLBT:PSPE ratios were prepared to compare the influence of block ratio and molecular weight on the temperature-responsive behavior in aqueous solution. A turbidimetry and dynamic light scattering study revealed a shift to higher temperatures of the cloud point and micelle formation by increasing the ratio of PSPE, which exhibit upper critical solution temperature (UCST) behavior. PSPE-dominant diblocks created spherical micelles stabilized by PGLBT motifs, and the transition behavior diminished by decreasing the PSPE ratio. No particular change was found in the diblocks that had an identical AB ratio. This trend reappeared in the other set whose entire molecular weight approximately doubled, and each transition point was not recognizably impacted by the total molecular weight. For triblocks, the PSPE double ends provided a higher probability of interchain attractions and resulted in a more turbid solution at higher temperatures, compared to the diblocks which had similar block ratios and molecular weights. The intermediates assumed as network-like soft aggregates eventually rearranged to monodisperse flowerlike micelles. It is expected that the method for obtaining well-defined betaine block copolymers, as well as the relationship of the block ratio and the chain conformation to the temperature-responsive behavior, will be helpful for designing betaine-based polymeric applications.

One-pot asymmetric living copolymerization-induced chiral self-assemblies and circularly polarized luminescence.

Controlled synthesis of conjugated block polymers enables the optimization of their self-assembly and may lead to distinct optical properties and functionalities. Herein, we report a direct chain extension of one-handed helical poly(acyl methane) with 1-ethynyl-4-iodo-2,5-bis(octyloxy)benzene, affording well-defined π-conjugated poly(acyl methane)-b-poly(phenylene ethynylene) copolymers. Although the distinct monomers are polymerized via different mechanisms, the one-pot copolymerization follows a living polymerization manner, giving the desired optically active block copolymers with controllable molar mass and low distribution. The block copolymerization induced chiral self-assembly simultaneously due to the one-handed helicity of the poly(acyl methane) block, giving spherical nanoparticles, one-handed helices, and chiral micelles with controlled dimensions regarding the composition of the generated copolymers. Interestingly, the chiral assemblies exhibit clear circularly polarized luminescence with tunable handedness and a high dissymmetric factor.

Controlled ring-opening (co)polymerization of macrolactones: a pursuit for efficient aluminum-based catalysts

This work reports on the search for highly efficient aluminum-based complexes for the synthesis of high molar mass polymacrolactones and their well-defined block copolymers with small ring lactones, ε-caprolactone and l-lactide.

Switchable copolymerization of mixed monomers catalyzed by imidazolium ionic liquids

A metal-free and switchable route to synthesize block polyesters from monomer mixtures was developed using imidazolium ionic liquids.

Helix-Induced Asymmetric Self-Assembly of π-Conjugated Block Copolymers: From Controlled Syntheses to Distinct Properties.

Conspectusπ-Conjugated polymers have gained significant interest because of their potential applications in optoelectronics, bioelectronics, and other domains. The controlled synthesis of π-conjugated block polymers optimizes their performance and enables novel properties and functions. However, precise control of the self-assembled architectures of π-conjugated polymers remains a formidable challenge. Inspired by the precise helical architectures of biomacromolecules, the helical polymers and the supramolecular helical assemblies have gained significant attention. Helical polymers with an excess of one-handed helicity can be optically active with a strong tendency toward self-assembly. Incorporating a helical polymer into a π-conjugated polymer can induce asymmetric helical assemblies, leading to novel chiral materials with unique functionalities.To control the self-assembly of architectures, π-conjugated polymers are usually synthesized into block copolymers by incorporating a polymer with self-assembling characteristics. Although various π-conjugated block copolymers have been produced, precise and asymmetric self-assembly is still challenging and has rarely been addressed. Incorporating helical polymers into the π-conjugated polymers can induce a precise and asymmetric self-assembly, which transfers the chirality of the helical polymer block to the π-conjugated polymer, resulting in chiral supramolecular architectures with unique chiroptical properties and functionalities. However, synthesizing hybrid block copolymers containing two distinct polymer blocks is complicated. Some general strategies such as connecting the chain ends of two preformed homopolymers and extending the chain of a prefabricated π-conjugated polymer with a second monomer are time-consuming and require complex synthetic protocols. Therefore, developing novel strategies for the facile synthesis of π-conjugated block copolymers with a predictable molar mass, low dispersity, and tunable composition is of practical importance.Recently, we investigated a controlled synthesis of helical polyisocyanides, helical polyallenes, and helical polycarbenes by developing advanced Pd(II) and Ni(II) catalysts. These helical polymers were successfully incorporated into π-conjugated polymers, including polythiophene, polyfluorene, and poly(phenyleneethynylene), via a one-pot sequential living block polymerization of the two distinct monomers using Pd(II)- or Ni(II)-complexes as catalysts. As a result, a variety of well-defined π-conjugated block copolymers containing helical polymeric blocks were readily synthesized. Although the copolymerized monomers possess different structures and polymerization mechanisms, the one-pot block copolymerization followed a living polymerization mechanism and provided the desired π-conjugated block copolymers in high yields with controlled molar mass, narrow size distribution, and tunable composition.Remarkably, the helical polymeric block induces the π-conjugated block copolymer asymmetric self-assembly into a supramolecular, one-handed helical architecture resulting in distinct optical properties. More interestingly, by utilizing the crystallization of conjugated blocks and one-handed helical blocks, the crystallization-driven and helix-induced precise asymmetric living self-assembly yielded a family of uniform and single-handed helical architectures with controlled dimensions, narrow distribution, and well-defined helicity. The transfer of helical chirality to the supramolecular architectures rendered the achiral π-conjugated blocks with unique chiroptical properties such as the emission of white light over a broad optical spectrum and the circularly polarized luminescence.

Exploiting the Monomer-Feeding Mechanism of RAFT Emulsion Polymerization for Polymerization-Induced Self-Assembly of Asymmetric Divinyl Monomers.

We exploited the monomer-feeding mechanism of reversible addition-fragmentation chain transfer (RAFT) emulsion polymerization to achieve the successful polymerization-induced self-assembly (PISA) of asymmetric divinyl monomers. Colloidally stable cross-linked block copolymer nanoparticles with various morphologies, such as vesicles, were directly prepared at high solids. Morphologies of the cross-linked block copolymer nanoparticles could be controlled by varying the monomer concentration, degree of polymerization (DP) of the core-forming block, and length of the macro-RAFT agent. X-ray photoelectron spectroscopy (XPS) characterization confirmed the presence of unreacted vinyl groups within the obtained block copolymer nanoparticles, providing a landscape for further functionalization via thiol-ene chemistry. Finally, the obtained block copolymer nanoparticles were employed as additives to tune the mechanical properties of hydrogels. We expect that this study not only offers considerable opportunities for the preparation of well-defined cross-linked block copolymer nanoparticles, but also provides important insights into the controlled polymerization of multivinyl monomers.

Interfacial Supra-Assembly of Copolymer Nanoparticles Enables the Formation of Nanocomposite Crystals with a Tunable Internal Structure.

It is highly desirable but technically challenging to precisely control the spatial composition and internal structure of crystalline nanocomposite materials, especially in a one-pot synthetic route. Herein, we demonstrate a versatile pathway to tune the spatial distribution of guest species within a host inorganic crystal via an incorporation strategy. Specifically, well-defined block copolymer nanoparticles, poly(methacrylic acid)x-block-poly(styrene-alt-N-phenylmaleimide)y [PMAAx-P(St-alt-NMI)y], are synthesized by polymerization-induced self-assembly. Such anionic nanoparticles can supra-assemble onto the surface of larger cationic nanoparticles via an electrostatic interaction, forming colloidal nanocomposite particles (CNPs). Remarkably, such CNPs can be incorporated into calcite single crystals in a spatially controlled manner: the depth of CNPs incorporation into calcite is tunable. Systematic investigation indicates that this interesting phenomenon is governed by the colloidal stability of CNPs, which in turn is dictated by the PMAAx-P(St-alt-NMI)y adsorption density and calcium ion concentration. This study opens up a general and efficient route for the preparation of a wide range of crystalline nanocomposite materials with a controlled internal composition and structure.

Cinnamyl-Modified Polyglycidol/Poly(ε-Caprolactone) Block Copolymer Nanocarriers for Enhanced Encapsulation and Prolonged Release of Cannabidiol.

The present study describes the development of novel block copolymer nanocarriers of the phytocannabinoid cannabidiol (CBD), designed to enhance the solubility of the drug in water while achieving high encapsulation efficiency and prolonged drug release. Firstly, a well-defined amphiphilic block copolymer consisting of two outer hydrophilic polyglycidol (PG) blocks and a middle hydrophobic block of poly(ε-caprolactone) bearing pendant cinnamyl moieties (P(CyCL-co-CL)) were synthesized by the click coupling reaction of PG-monoalkyne and P(CyCL-co-CL)-diazide functional macroreagents. A non-modified polyglycidol/poly(ε-caprolactone) amphiphilic block copolymer was obtained as a referent system. Micellar carriers based on the two block copolymers were formed via the solvent evaporation method and loaded with CBD following two different protocols-loading during micelle formation and loading into preformed micelles. The key parameters/characteristics of blank and CBD-loaded micelles such as size, size distribution, zeta potential, molar mass, critical micelle concentration, morphology, and encapsulation efficiency were determined by using dynamic and static multiangle and electrophoretic light scattering, transmission electron microscopy, and atomic force microscopy. Embedding CBD into the micellar carriers affected their hydrodynamic radii to some extent, while the spherical morphology of particles was not changed. The nanoformulation based on the copolymer bearing cinnamyl moieties possessed significantly higher encapsulation efficiency and a slower rate of drug release than the non-modified copolymer. The comparative assessment of the antiproliferative effect of micellar CBD vs. the free drug against the acute myeloid leukemia-derived HL-60 cell line and Sezary Syndrome HUT-78 demonstrated that the newly developed systems have pronounced antitumor activity.

Novel Fluorescent Benzimidazole-Hydrazone-Loaded Micellar Carriers for Controlled Release: Impact on Cell Toxicity, Nuclear and Microtubule Alterations in Breast Cancer Cells.

Fluorescent micellar carriers with controlled release of a novel anticancer drug were developed to enable intracellular imaging and cancer treatment simultaneously. The nanosized fluorescent micellar systems were embedded with a novel anticancer drug via the self-assembling behavior of well-defined block copolymers based on amphiphilic poly(acrylic acid)-block-poly(n-butyl acrylate) (PAA-b-PnBA) copolymer obtained by Atom Transfer Radical Polymerization (ATRP) and hydrophobic anticancer benzimidazole-hydrazone drug (BzH). Through this method, well-defined nanosized fluorescent micelles were obtained consisting of a hydrophilic PAA shell and a hydrophobic PnBA core embedded with the BzH drug due to the hydrophobic interactions, thus reaching very high encapsulation efficiency. The size, morphology, and fluorescent properties of blank and drug-loaded micelles were investigated using dynamic light scattering (DLS), transmission electron microscopy (TEM), and fluorescent spectroscopy, respectively. Additionally, after 72 h of incubation, drug-loaded micelles released 3.25 μM of BzH, which was spectrophotometrically determined. The BzH drug-loaded micelles were found to exhibit enhanced antiproliferative and cytotoxic effects on MDA-MB-231 cells, with long-lasting effects on microtubule organization, with apoptotic alterations and preferential localization in the perinuclear space of cancer cells. In contrast, the antitumor effect of BzH alone or incorporated in micelles on non-cancerous cells MCF-10A was relatively weak.

Synthesis of Hydrophobic Block Copolymer Nanoparticles in Alcohol/Water Stabilized by Poly(methyl methacrylate) via RAFT Dispersion Polymerization-Induced Self-Assembly

Poly(methyl methacrylate) (PMMA) is an important common polymer widely used in industry. While PMMA has been used as a core-forming block for polymerization-induced self-assembly (PISA), a powerful approach for the synthesis of block copolymer nanoparticles, it has not been utilized as a corona block due to PMMA being insoluble in common solvents for PISA formulations (e.g., water and alcohols). Exploiting the solubility of PMMA-dithiobenzoate (DTB) in ethanol/water mixtures, such macroRAFT agents have in the present work been successfully employed for reversible addition–fragmentation chain transfer (RAFT) PISA in ethanol/water (80/20 by volume). RAFT dispersion polymerization of benzyl methacrylate mediated by PMMA-DTB macroRAFT agents with various degrees of polymerization has been investigated. Transmission electron microscopy analyses revealed well-defined block copolymer nano-objects, including spheres, worms, as well as vesicles. Nanoparticles comprising a PMMA outer layer would have superior compatibility with various hydrophobic polymer matrices, thereby enabling various new applications such as, e.g., use as nanofillers.

Regulating copolymer architecture using photoiniferter polymerization to direct composite morphology

Due to mild conditions and straightforward synthetic routes, photoiniferter polymerization has received increasing use as a facile method for preparation of polymers with highly controlled structure. However, low quantum yields inherent to thiocarbonylthio species result in polymerization speeds that are considerably slower than traditional controlled radical polymerization techniques. To improve polymerization speed while maintaining high level control, it is critical to understand relationships between reaction parameters and ultimate polymer structure. In this work, initiating light intensity, reactant concentration, and monomer pendant groups were manipulated in the photoiniferter polymerization of acrylate monomers to explore the effect of these conditions on reaction kinetics and molecular weight control. Polymerization rate of n-butyl acrylate was significantly enhanced by increasing light intensity rivaling speeds of conventional thermally initiated RAFT polymerization while enabling more precise control over molecular weight. Interestingly, photoiniferter rate asymptotically approached saturation at relatively high light intensities. Moreover, degradation of trithiocarbonate species occurred at greater intensities, ultimately resulting in moderate increases in molecular weight. Increased reactant concentration enabled faster rates with bulk polymerization, possibly due to reduced macro radical mobility and termination. Additionally, comparing photoiniferter polymerization of methyl acrylate and hydroxyethyl acrylate showed that greater polarity considerably enhanced polymerization speeds. Finally, the utility of precisely controlling polymer structure was demonstrated by synthesizing and incorporating a series of amphiphilic block copolymers with increasing molecular weight into a photocurable epoxy resin. The well-defined block copolymer structures enabled controllable phase separation and thermomechanical properties in epoxy composites. This work showed that photoiniferter polymerization speeds could be significantly enhanced using elementary reaction conditions, and that these conditions enable facile production of well-defined copolymers allowing tailored composite morphology and properties.

In Situ Formation of Silica Nanoparticles Decorated with Well-Defined Homopolymers and Block Copolymers

In Situ Formation of Silica Nanoparticles Decorated with Well-Defined Homopolymers and Block Copolymers

Controlled “one-pot” block copolymerization of β-butyrolactone and oxiranes via quantitative active centers transformation

The synthesis of block copolymers of oxiranes and β-butyrolactone based on a method of sequential monomer addition was developed. The anionic controlled polymerization of protected glycidol - ethoxyethyl glycidyl ether (EEGE) and β-butyrolactone (BBL) was used. By quantitatively transforming the hydroxyl groups at the ends of the polyoxirane chains to the carboxylate centers, a one-pot synthesis was possible without further purification of the intermediates. The main part of the study was directed toward verifying the degree of precision of the transformation step and copolymer synthesis and clarifying the role of hydroxyl groups potentially present during the polymerization of BBL. It was also found that the presence of a small excess of anhydride during the transformation reaction did not affect the subsequent synthesis steps. The use of a macroinitiator in the form of poly(ethylene glycol) allowed us to obtain well-defined block copolymers of oxiranes and BBL of di-, tri- and pentablock structures.

All-Polyhydroxyalkanoate Triblock Copolymers via a Stereoselective-Chemocatalytic Route

Biodegradable polyhydroxyalkanoate (PHA) homopolymers and statistical copolymers are ubiquitous in microbially produced PHAs, but the step-growth polycondensation mechanism the biosynthesis operates on presents a challenge to access well-defined block copolymers (BCPs), especially higher-order tri-BCP PHAs. Here we report a stereoselective-chemocatalytic route to produce discrete hard-soft-hard ABA all-PHA tri-BCPs based on the living chain-growth ring-opening polymerization of racemic (rac) 8-membered diolides (rac-8DLR; R denotes the two substituents on the ring). Depending on the composition of the soft B block, originated from rac-8DLR (R = Et, nBu), and its ratio to the semicrystalline, high-melting hard A block, derived from rac-8DLMe, the resulting all-PHA tri-BCPs with high molar mass (Mn up to 238 kg mol-1) and low dispersity (Đ = 1.07) exhibit tunable mechanical properties characteristic of a strong and tough thermoplastic, elastomer, or a semicrystalline thermoplastic elastomer.

RAFT-Mediated Emulsion Polymerization-Induced Self-Assembly for the Synthesis of Core-Degradable Waterborne Particles.

Poly(N-acryloylmorpholine) (PNAM)-decorated waterborne nanoparticles comprising a core of either degradable polystyrene (PS) or poly(n-butyl acrylate) (PBA) were synthesized by polymerization-induced self-assembly (PISA) in water. A PNAM bearing a trithiocarbonate chain end (PNAM-TTC) was extended via reversible addition-fragmentation chain transfer (RAFT)-mediated emulsion copolymerization of either styrene (S) or n-butyl acrylate (BA) with dibenzo[c,e]oxepane-5-thione (DOT). Well-defined amphiphilic block copolymers were obtained. The in situ self-assembly of these polymers resulted in the formation of stable nanoparticles. The insertion of thioester units in the vinylic blocks enabled their degradation under basic conditions. The same strategy was then applied to the emulsion copolymerization of BA with DOT using a poly(ethylene glycol) (PEG) equipped with a trithiocarbonate end group, resulting in PEG-decorated nanoparticles with degradable PBA-based cores.

Nanoparticle forming polyelectrolyte complexes derived from well-defined block copolymers

Polymers can be used in nanoparticle associated formulations to encapsulate cytotoxic drugs (e.g., paclitaxel). Polyelectrolyte complexes (PECs) that form drug associated colloids also have potential to form particulate associated formulations. We used RAFT polymerisation to prepare small families of narrow molecular weight distributed (i) methacrylate block co-polymers comprised of oligomeric ethylene glycol, poly(ethylene glycol) methyl ether methacrylate (PEGMA), and dimethyl amino pendent chains, 2-(dimethylamino) ethyl methacrylate (DMAEMA), and (ii) poly(methacrylic acid), PMAA. These polymers were examined for their ability to form PECs capable of drug encapsulation. Optimal control in RAFT polymerisation was confirmed by the linear increase of molecular weight and the narrow dispersity of the polymers (<1.2) as determined by 1H nuclear magnetic resonance and gel permeation chromatography. Dynamic light scattering and transmission electron microscopy showed formation of well-defined monodispersed nanoparticles with a hydrodynamic diameter of 25 ± 3 nm upon self-assembly of poly(PEGMA0.23-b-DMAEMA0.77)99 and PMAA75. These PECs are highly haemocompatible. Thin film hydration was used to encapsulate two hydrophobic drugs, paclitaxel and carmofur, into spherical nanoparticles. The results show that carmofur was encapsulated markedly more effectively than paclitaxel (72 vs 1.5%).

Amphiphilic tetra-PCL-b-PEG star block copolymers using benzoxazinone-based linking groups

Two well-defined amphiphilic tetra-arm star block copolymers with a poly(ε-caprolactone) core and poly(ethylene glycol) arms were prepared by a hetero-complementary linkage reaction and studied with respect to their solution behavior in water.

Novel degradable amphiphilic 4-arm star PLA-b-POEOA and PLGA-b-POEOA block copolymers: synthesis, characterization and self-assembly

Well-defined amphiphilic biodegradable block copolymers (BCPs) are promising materials as drug/gene carriers because they can self-assemble in aqueous medium and form various nanostructures.