Self‐Assembled Acrylic ABA Triblock Copolymer Hydrogels with Various Block Compositions: Water Absorbency,Rheology, and SAXS

A series of well‐defined symmetric poly(methyl methacrylate)‐b‐poly(sodium methacrylate)‐b‐poly(methyl methacrylate) (PMMA‐b‐PSMA‐b‐PMMA) triblock copolymers with various block compositions is synthesized. The amphiphilic ABA triblock copolymers form polyelectrolyte hydrogels in water by self‐assembly. The hydrophobic PMMA endblocks act as physical cross‐links in the form of frozen micelles, while the hydrophilic PSMA midblocks span the 3D network. The influence of various synthetic parameters on the self‐assembly and the macroscopic properties of these hydrogels is systematically investigated by water absorbency, oscillatory shear rheology, and small‐angle X‐ray scattering. The polymer concentration during the hydrogel formation affects the ratio between looping and bridging chains. The number of MMA units per endblock (n_A) determines the size and the relaxation rates of the physical cross‐links and thus, the mechanical stability of the hydrogels. More SMA units in the midblock (n_B) increase the water absorbency, while the mechanical moduli decrease. Even lower G‐moduli are achieved by partly exchanging the symmetric ABA triblock with AB diblock copolymers, which can only form non‐elastic dangling ends.     

Morphology Transition of Dual‐Responsive ABC Terpolymer in Water: Effect of Hydrophobic Block

To reveal the importance of hydrophobic block in morphology transition of responsive copolymers, four well‐defined ABC terpolymers with the same poly(dimethylamino ethyl methacrylate) (PDMAEMA) and PEG segments are synthesized by sequential RAFT polymerization. Poly (n‐hexyl methacrylate) (PnHMA), poly(n‐butyl methacrylate) (PnBMA), poly(ethyl methacrylate) (PEMA), and poly(methyl methacrylate) (PMMA), with glass transition temperatures of ?5, 20, 65, and 100 °C, respectively, are selected as hydrophobic segments. The structures and compositions of four terpolymers, that is, mPEG₄₅‐b‐PnHMA₂₉‐b‐PDMAEMA₂₈(EHD), mPEG₄₅‐b‐PnBMA₂₈‐b‐PDMAEMA₃₂ (EBD), mPEG₄₅‐b‐PEMA₃₁‐b‐PDMAEMA₃₀ (EED), and mPEG₄₅‐b‐PMMA₃₀‐b‐PDMAEMA₂₉ (EMD), are confirmed by gel permeation chromatography and ¹H NMR. Their morphology transitions in water are investigated via a combination of UV‐vis spectroscopy, light scattering, zeta potential measurements, and cryogenic transmission electron microscopy. All terpolymers can form spherical micelle by direct dissolution in acidic water. However, the spherical micelles of EBD and EHD progressively switch to cylinders and vesicles upon variations of external pH and temperature. In contrast, the spherical micelles of EMD and EED reversibly form larger aggregates when the temperature is above the cloud point of PDMAEMA in basic water. This study demonstrates the importance of hydrophobic block on the morphology transition of responsive copolymers.     

Block copolymers by transformation of living anionic polymerization into controlled/“living” atom transfer radical polymerization

A method for the transformation of living anionic polymerization (LAP) to controlled/“living” atom transfer radical polymerization (ATRP) is reported and utilized for the preparation of block copolymers. The macroinitiators, polystyrene and polystyrene-block-polyisoprene containing the 2-bromoisobutyryl end group (PS-Br, M_n = 12 200, M_w/M_n = 1.04; PS-b-PIP-Br, M_n = 16 800, M_w/M_n = 1.03), were prepared by LAP of styrene and styrene/isoprene, correspondingly, and suitable termination agents. These compounds were used as macroinitiators for controlled/“living” ATRP to prepare block copolymers with methyl acrylate (PS-b-PMA), butyl acrylate (PS-b-PBA), methyl methacrylate (PS-b-PMMA), a mixture of styrene and acrylonitrile (PS-b-P(S-r-AN)) and also chain extension with styrene (PS-b-PS and PS-b-PIP-b-PS). The block copolymers were characterized by means of size exclusion chromatography, ¹H NMR and FT-IR spectroscopy.     

PLLA-Based Block Copolymers via Raft Polymerization—Impact of the Synthetic Route and Activation Mechanism

Designing supramolecular structures with well-defined dimensions and diverse morphologies via the self-assembly of block copolymers is renowned. Specifically, the design of 1D fiber nanostructures is extensively emphasized, due to their unique properties in many areas, such as microelectronics, photonics, and particularly in the biomedical field. Herein, amphiphilic diblock copolymers of P(l -lactide)-b-P(N-t-butoxy-carbonyl-N´-acryloyl-1,2-diaminoethane)-co-P(N-isopropylacrylamide) PLLA_n-b-P(BocAEAm)_m-co- P(NiPAAm)_Ɩ are developed. Two synthetic strategies are investigated to equip PLLA with a chain transfer agent (CTA), either by Steglich esterification of PLLA-OH or via the ring-opening polymerization of l -lactide using a CTA containing a hydroxyl functional group. The second strategy proves to be superior in terms of degree of functionalization. The corona-forming blocks, with degrees of polymerization of 200 and above are achieved in good definition by photo-iniferter RAFT polymerization (Đ ≤ 1.25), while a Đ of 1.75 is obtained by conventional RAFT polymerization. The self-assembly of the developed system leads to the formation of nanofibers with a height of 11 nm and a length of ≈300 nm, which is determined by atomic force microscopy (AFM). These fibers are the basis for new antimicrobial nanomaterials after deprotection, as the subject of upcoming work.     

Block copolymers by sequential group transfer polymerization: poly(methyl methacrylate)-block-poly(2-ethylhexyl acrylate) and poly(methyl methacrylate)-block-poly(tert-butyl acrylate)

Poly(methyl methacrylate)-block-poly(2-ethylhexyl acrylate) (PMMA-block-PEHA) and poly(methyl methacrylate)-block-poly(tert-butyl acrylate) with a methacrylate/acrylate unit ratio of 1:1 and 1:3, 16000 < M _n < 44000 and 1,9 < M _w/M _n < 2,5, were prepared by sequential group transfer polymerization using (1-methoxy-2-methyl-1-propenyloxy)trimethylsilane as initiator and tetrabutylammonium fluoride monohydrate as a catalyst in tetrahydrofuran at ?30°C, PMMA being the first block. The increase in M _n during the successive addition of monomers is linearly dependent on the (co)polymer yield and size-exclusion chromatography (SEC) curves are shifted towards higher molecular weights in comparison with PMMA macroinitiators. The block structure of the copolymers was also proven by extraction experiments. The presence of homopolymers in the copolymers was not detected. When the former copolymer is prepared in a reverse way (PEHA segment being the first), the MMA polymerization ceases at ≈ 43–45% conversion.     

Nitroxide-controlled free radical polymerization of a sugar-carrying acryloyl monomer

Controlled free radical polymerization of a sugar-carrying acrylate, 3-O-acryloyl-1,2 : 5,6-di-O-isopropylidene-α-D -glucofuranoside (AIpGlc), was achieved in p-xylene at 100°C by using a di-tert-butyl nitroxide (DBN)-based alkoxyamine as an initiator and dicumyl peroxide (DCP) as an accelerator. The polymerization gave low-polydispersity (1.2 < M_w/M_n < 1.6) polymers with predicted molecular weights. The same approach with a DBN-capped polystyrene (PS-DBN) as an initiator afforded block copolymers of the type PS-b-PAIpGlc. The acidolysis of the homopolymers and block copolymers gave well-defined glucose-carrying polymers PAGlc and PS-b-PAGlc, respectively. These amphiphilic PS-b-PAGlc block copolymers were observed to exhibit microdomain surface morphologies that differ for different copolymer compositions. This success opens up a new, simple route to the synthesis of well-defined sugar-carrying polymers of various architectures.     

Polymer Containing Multiple Secondary Structures—A Competition between Helical Induction and C-T Complexation

Though “foldamers” have greatly developed, molecules that fold beyond 2° structures are less common. The design and synthesis of triblock copolymers of the “A-B-A” type containing two types of helix formation blocks are presented. Two blocks (A and B) are chosen, with one comprised of L-polyproline as block “A” and the other block (B) comprised with three naphthalene diimide-derivatives separated by two proline residues. Block (B) is carefully designed to serve as a bifunctional initiator for the ring-opening polymerization of proline-N-carboxy anhydride as well as to encapsulate an electron-rich aromatic species by charge transfer complexation (C-T). As a result of (C-T) complexation with dialkoxy pyrene, the native helical structure of the middle block is transformed into a 1D columnar structure without affecting the 2° structure of the polyproline block. In this way, the initial helix₁-b-helix₂-b-helix₁ structure of the block copolymers is transformed into a helix₁-b-columnar-b-helix₁ structure. The C-T complexation and related structural changes of the block copolymers are characterized using UV-vis, fluorescence, and circular dichroism spectroscopy.     

Phase morphologies in block copolymers of polystyrene and columnar liquid crystalline polydiethylsiloxane

Well-defined diblock copolymers of polystyrene (PS) and polydiethylsiloxane (PDES) were synthesized by sequential anionic polymerization. By means of differential scanning calorimetry (DSC), the PDES blocks were shown to exist in the columnar mesophase at ambient temperatures. PS-b-PDES block copolymers with a PS content > 21 wt.-% build lamellar structures, below this percentage PS cylinders were found that are arranged in sheets, forming a (somewhat irregular) overall lamellar structure. Both the low PS content at which the transition from lamellar to cylindrical structures takes place, as well as the peculiar organization of the PS cylinders in the latter were ascribed to the mesomorphic nature of the PDES block in combination with the fact that the glass transition temperature of PS (T_g ≈ 100°C) is much higher than the isotropization temperature of the PDES block (T_i 〈ca. 50°C).     

Influence of poly(ethylene oxide)‐poly(propylene oxide)‐poly(ethylene oxide) triblock copolymers on stereoselective catalysis in water

The first application of (EO)_n‐(PO)_m‐(EO)_n triblock copolymers as surfactants in asymmetric hydrogenation is described. We observed a dependence of the activity and enantioselectivity on the asymmetric hydrogenation of methyl (Z)‐α‐acetamidocinnamate on the length of the (PO)_m domain of the copolymer. The activity and enantioselectivity were observed to be independent of the hydrophilic‐lipophilic‐balance (HLB) or the critical micelle concentration (cmc) of the copolymer. The size of the (EO)_n unit does not play an important role, however the addition of a small amount of SDS enhances the enantioselectivities significantly. The triblock copolymers were also successfully used as phase transfer reagent in two‐phase Suzuki carbon‐carbon coupling reactions. The use of polymeric reagents in micellar and phase‐transfer systems has the advantage that these reagents can be easily separated from the reaction mixture by means of a membrane.     

Poly(hydroxyl propyl methacrylate)‐b‐Poly(oligo ethylene glycol methacrylate) Thermoresponsive Block Copolymers by RAFT Polymerization

Thermoresponsive amphiphilic poly(hydroxyl propyl methacrylate)‐b‐poly(oligo ethylene glycol methacrylate) block copolymers (PHPMA‐b‐POEGMA) are synthesized by RAFT polymerization, with different compositions and molecular weights. The copolymers are molecularly characterized by size‐exclusion chromophotography, and ¹H NMR spectroscopy. Dynamic light scattering (DLS) and static light scattering (SLS) experiments in aqueous solutions show that the copolymers respond to temperature variations via formation of self‐organized nanoscale aggregates. Aggregate structural characteristics depend on copolymer composition, molecular weight, and ionic strength of the solution. Fluorescence spectroscopy experiments confirm the presence of less hydrophilic domains within the aggregates at higher temperatures. The thermoresponsive behavior of the PHPMA‐b‐POEGMA block copolymers is attributed to the particular solubility characteristics of the hydrophilic, water insoluble PHPMA block that are modulated by the presence of the water soluble POEGMA block.     

A New Associative Diblock Copolymer of Poly(ethylene glycol) and Dense 1,2,3‐Triazole Blocks: Self‐Association Behavior and Thermoresponsiveness in Water

In this work, new diblock copolymers of poly(ethylene glycol) (PEG) and dense 1,2,3‐triazole blocks (EGm‐b‐APn and EGm‐b‐ABn, where m and n denote the degrees of polymerization), are synthesized by copper(I)‐catalyzed azide–alkyne cycloaddition polymerization of 3‐azido‐1‐propyne (AP) and 3‐azido‐1‐butyne (AB), respectively, in the presence of PEG possessing a propargyl group. Their self‐association behavior and thermoresponsive property in water are investigated. The characterization data indicate that EG45‐b‐AP6 and EG45‐b‐AP14 form dominantly spherical micelles, EG18‐b‐AP4 and EG18‐b‐AP10 form vesicles, and EG18‐b‐AB7 forms rodlike micelles. Aqueous solutions of EG18‐b‐AP10, EG45‐b‐AP14, and EG18‐b‐AB7 undergo lower critical solution temperature (LCST)‐type phase separation. The thermoresponsive association behavior can be controlled by adjusting the ratio of block lengths and by attaching methyl substituents.     

Thermosensitive AB4 four-armed star PNIPAM-b-HTPB multiblock copolymer micelles for camptothecin drug release

Thermo-sensitive poly(N-isoproplacrylamide)_m-block-hydroxyl-terminated polybutadiene-block-poly(N-isoproplacrylamide)_m (PNIPAM_m-b-HTPB-b-PNIPAM_m, m = 1 or 2) block copolymers, AB₄ four-armed star multiblock and linear triblock copolymers, were synthesized by ATRP with HTPB as central blocks, and characterization was performed by ¹H NMR, Fourier transform infrared, and size exclusion chromatography. The multiblock copolymers could spontaneously assemble into more regular spherical core–shell nanoscale micelles than the linear triblock copolymer. The physicochemical properties were detected by a surface tension, nanoparticle analyzer, transmission electron microscope (TEM), dynamic light scattering, and UV–vis measurements. The multiblock copolymer micelles had lower critical micelle concentration than the linear counterpart, TEM size from 100 to 120 nm, and the hydrodynamic diameters below 150 nm. The micelles exhibited thermo-dependent size change, with low critical solution temperature of about 33–35 °C. The characteristic parameters were affected by the composition ratios, length of PNIPAM blocks, and molecular architectures. The camptothecin release demonstrated that the drug release was thermo-responsive, accompanied by the temperature-induced structural changes of the micelles. MTT assays were performed to evaluate the biocompatibility or cytotoxicity of the prepared copolymer micelles.     

Synthesis of (styrene-p-chlorostyrene) tri-block copolymers and their properties in dilute solutions

Two series of well-characterized (styrene-p-chlorostyrene) tri-block copolymers of B_mA_nB_m- and A_mB_nA_m-types (A: styrene monomeric unit, B: p-chlorostyrene monomeric unit. n = 2m denotes the number of units) were synthesized by anionic polymerization technique. Their intrinsic viscosities in toluene, 2-butanone, and cumene were studied over a wide range of molecular weights. The data were analyzed on the basis of two-parameter theories. The unperturbed dimensions of the block copolymers are expressed by those of the parent homopolymers and the composition. The conformational behaviours of the B_mA_nB_m and A_mB_nA_m copolymers are similar in the non-selective solvents, toluene and 2-butanone, whereas in the selective solvent, cumene, which is a Θ solvent for poly-p-chlorostyrene and a good solvent for polystyrene, a molecule of the A_mB_nA_m copolymers takes a more extended chain conformation and a greater value of the longrange interaction parameter than the B_mA_nB_m copolymers of the same composition. However, an anomaly which suggests “Intrachain phase separation” was not observed in the viscosity behaviours of the block copolymers in cumene as well as in toluene and 2-butanone.     

Temporally Controlled Ultrasonication‐Mediated Atom Transfer Radical Polymerization in Miniemulsion

Due to the increasing requirement for more environmentally and industrially relevant approaches in macromolecules synthesis, ultrasonication‐mediated atom transfer radical polymerization (sono‐ATRP) in miniemulsion media is applied for the first time to obtain precisely defined poly(n‐butyl acrylate) (PBA) and poly(methyl methacrylate) (PMMA) homopolymers, and poly(n‐butyl acrylate)‐block‐poly(tert‐butyl acrylate) (PBA‐b‐PtBA) and poly(n‐butyl acrylate)‐block‐poly(butyl acrylate) (PBA‐b‐PBA) copolymers. It is demonstrated in the reaction setup with strongly hydrophilic catalyst copper(II) bromide/tris(2‐pyridylmethyl)amine (Cu^IIBr₂/TPMA) responsible for two principal mechanisms – interfacial and ion‐pair catalysis reflecting single‐catalyst approach. This solution turns out to be an excellent tool in controlled preparation of well‐defined polymers with narrow molecular weight distribution (up to Ð = 1.28) and preserves chain‐end functionality (DCF = 0.02% to 0.32%). Temporal control over the polymer chain growth is successfully conducted by turning the ultrasonication on/off. Taking into consideration long OFF stage (92.5 h) during ultrasonication‐induced polymerization in miniemulsion, synthesis is efficiently reinitiated without any influence on controlled characteristics maintaining the precise structure of received PBA homopolymers, confirmed by narrow molecular weight distribution (Ð = 1.26) and high retention of chain‐end functionality (DCF = 0.01%). This procedure constitutes an excellent simple and eco‐friendly approach in preparation of functional polymeric materials.     

Oxidative crosslinking polymerization of poly[(methyl methacrylate)-co-(2-(n-pyrrolyl)ethyl methacrylate)] with iron chloride in nitromethane

Poly[(methyl methacrylate)-co-(2-(N-pyrrolyl)ethyl methacrylate)] (PMMA-co-PEMA, 1) containing 0,7 to 7 mol-% pyrrolylethyl methacrylate (PEMA) units was crosslinked via oxidative polymerization with FeCl₃ in inert atmosphere. The properties of the products 2 depended on the amount of electroactive side groups and on the molecular weight of the precursor copolymers 1 as well as on the reaction conditions. Crosslinking between pendant pyrrole groups and an increase in the glass transition temperature in the oxidative coupling could be avoided using precursor copolymers 1 with low PEMA content (<1 mol-%).     

Synthesis and properties of well-defined multiblock copolymers: poly(4,4′-isopropylidenediphenyl carbonate)-block-polystyrene

Well-defined poly(4,4′-isopropylidenediphenyl carbonate)-block-polystyrene multiblock copolymers, PC-b-PS, were prepared by condensation of PC prepolymers having chloroformyl end-groups with PS prepolymers having hydroxyl end-groups. Both prepolymers had narrow molecular weight distribution (PC prepolymer: M?_w/M?_n ≤ 1,31, PS prepolymer: M?_w/M?_n ≤ 1,03). The course of the polycondensation reaction depends on the molecular weight of the prepolymers used as substrates. After fractionation, the obtained multiblock copolymers are homogeneous in chemical composition and have a narrow molecular weight distribution. The mechanical properties of the copolymers depend on the weight fraction of the PS blocks. All copolymers exhibit two glass transition temperatures, close to those of the parent homopolymers.     

pH‐Switchable Complexation between Double Hydrophilic Heteroarm Star Copolymers and a Cationic Block Polyelectrolyte

Double hydrophilic heteroarm star copolymers of poly(methacrylic acid) (PMAA) and poly(ethylene oxide) (PEO) were synthesized via atom‐transfer radical polymerization (ATRP) using the “in‐out” method. The synthesis consisted of three steps. Namely, ATRP was applied to the preparation of a star macroinitiator with PEO arms and a cross‐linked core resulting from the polymerization of divinylbenzene (DVB) in the first step, chain extension with tert‐butyl methacrylate (tBMA) under ATRP conditions, and subsequent hydrolysis of the tert‐butyl groups afforded (PEO)_n‐PDVB‐(PMAA)_n heteroarm star copolymers with a cross‐linked microgel core. This novel type of double hydrophilic heteroarm star copolymer can be considered as unimolecular micelles with hybrid coronas. The star copolymers exhibited pH‐dependent solubility in water, being soluble at high pH and insoluble at low pH, due to the formation of hydrogen‐bonded complexes between the PEO and PMAA arms. A mixed solution of the heteroarm star copolymer and a PEO‐b‐PQDMA diblock copolymer, where PQDMA is poly(2‐(dimethylamino)ethyl methacrylate) fully quaternized with methyl iodide, remained stable in the whole pH range, and exhibited an intriguing pH‐switchable complexation behavior accompanied with structural rearrangement.

     

Stabilization of polystyrene/poly(methyl methacrylate) blends by in situ compatibilization with graft copolymers

Copolymers of styrene and ortho-vinylbenzaldehyde (o-VBA) are useful precursors to multicomponent polymer systems. Graft copolymers of poly(styrene-stat-o-VBA) can be produced by free-radical chain transfer to methyl methacrylate monomer to yield materials that display some potential as interfacial agents with binary blends of polystyrene and poly(methyl methacrylate). Significant improvements in ultimate tensile strengths and energy to rupture values have been witnessed for polystyrene/poly(methyl methacrylate) mixtures that contain various levels of the graft component. Scanning electron microscopy of representative fracture surfaces demonstrate a decrease in the particle size of the dispersed phase; it is suggested that this morphological factor contributes to the superior mechanical properties of these composites. In this regard, both the isolated and the crude graft copolymers are able to compatibilize, and thereby enhance, the material properties of polystyrene/poly(methyl methacrylate) blends.     

Spherical Compound Micelles with Lamellar Stripes Self‐Assembled from Star Liquid Crystalline Diblock Copolymers in Solution

Detailed investigations on the self‐assembly of amphiphilic star block copolymers composed of three‐arm poly(ethylene oxide) (PEO) and poly(methacrylate) (PMAAz) with an azobenzene side chain (denoted as 3PEO‐b‐PMAAz) into stable spherical aggregates with clear lamellar stripes in solution are demonstrated. Four block copolymers, 3PEO₁₂‐b‐PMA(Az)₃₃, 3PEO₂₂‐b‐PMA(Az)₃₁, 3PEO₂₂‐b‐PMA(Az)₆₂, and linear PEO₆₈‐b‐PMA(Az)₃₁, are synthesized. The liquid crystalline properties of the block copolymers are studied by differential scanning calorimetry, polarized optical microscopy techniques, and wide‐angle X‐ray diffraction. The morphologies of the compound micelles self‐assembled in tetrahydrofuran (THF)/water mixtures are observed by means of transmission electron microscopy and scanning electron microscopy. The size of the spherical micelles is influenced by the self‐assembly conditions and the lengths of two blocks. The well‐defined three‐arm architecture of the hydrophilic blocks is a key structural element to the formation of stable spherical compound micelles. The micelle surface integrity is affected by the lengths of PEO blocks. The lamellar stripes are clearly observed on these micelles. This work provides a promising strategy to prepare functional stable spherical compound micelles self‐assembled by amphiphilic block copolymers in solution.     

Amphiphilic Zwitterionic Bioderived Block Copolymers from Glutamic Acid and Cholesterol – Ability to Form Nanoparticles and Serve as Vectors for the Delivery of 6-Mercaptopurine

In this work, the straightforward synthesis of amphiphilic zwitterionic bioderived block copolymers (BCPs) using glutamic acid (Glu) and cholesterol (Chol) as building blocks are reported. The previously established Glu-derivative NBoc-Glu-OtBu-methacrylate (NBoc-Glu-OtBu-MA) serves as hydrophobic precursor for the zwitterionic block, while a mostly unexplored cholesteryl-derived methacrylate monomer (Chol-MA) with increased side chain flexibility functions as the hydrophobic block. In the first step, NBoc-Glu-OtBu-MA is polymerized via reversible addition-fragmentation chain-transfer (RAFT) polymerization. Afterward, the linear polymer is chain-extended with Chol-MA, yielding P(NBoc-Glu-OtBu-MA)_n-b-(Chol-MA)_m BCPs with varying block ratios. After deprotection under acidic conditions, polymers with a block weight ratio of 87:13 (Glu-OH-MA:Chol-MA) readily assemble into polymeric nanoparticles (NPs) of a desirable size below 100 nm diameter, making them good candidates for biomedical applications. The experimental results are supported using computations of the partition coefficients and machine learning models for the prediction of the polymer densities of the different BCPs. In addition, high (up to 20 wt.%) loading of the hydrophobic anti-cancer drug 6-mercaptopurine (6-MP) is achieved in these NPs during the assembly process. The cytostatic activity of 6-MP NPs is demonstrated in vitro on MDA-MB-231 breast cancer cells. These results emphasize the potential of amphiphilic zwitterionic bioderived NPs for the delivery of hydrophobic drugs.