Synthesis and Micellization of Star‐Shaped Poly(ethylene glycol)‐block‐Poly(ε‐caprolactone)

Summary: The relationship between the architecture of block copolymers and their micellar properties was investigated. Diblock, 3‐arm star‐shaped and 4‐arm star‐shaped block copolymers based on poly(ethylene glycol) and poly(ε‐caprolactone) were synthesized. Micelles of star‐shaped block copolymer in an aqueous solution were then prepared by a solvent evaporation method. The critical micelle concentration and the size of the micelles were measured by the steady‐state pyrene fluorescence method and dynamic light scattering, respectively. The CMC decreased in the order di‐, 3‐arm star‐shaped and 4‐arm star‐shaped block copolymer. The size of the micelles increased in the same order as the CMC. Theory also predicts that the formation of micelles becomes easier for 4‐arm star‐shaped block copolymers than for di‐ and 3‐arm star‐shaped block copolymers, which qualitatively agrees with the experiments.

     

Nanoporous Gold Film Prepared by the Epoxidation of Poly(styrene‐b‐butadiene) Diblock Copolymer Templated Micelles

A new approach is developed for the preparation of nanoporous gold (Au) films using diblock copolymer micelles as templates. Stable Au nanoparticles (NPs) with a narrow distribution are prepared by modifying NPs functionalized with 4‐(dimethylamino)pyridine ligands (DMAP Au NPs) and a spherical micelle formed through the epoxidation of poly(styrene‐b‐butadiene) diblock copolymer to produce poly(styrene‐b‐vinyl oxirane) (PS‐b‐PBO) in tetrahydrofuran–acetonitrile solution. The exchange reaction of 4‐aminothiophenol of PS‐b‐PBO diblock copolymer micelles with DMAP Au NPs can produce block copolymer–Au NPs composite films. After the pyrolysis of the diblock copolymer templates at a specific temperature to avoid the collapse of the Au NPs, a nanoporous Au film is prepared.     

Effect of pH on the Micellar Morphology of Semicrystalline PCL‐b‐PEO Block Copolymers in Aqueous Solution

The effect of pH on the micellar morphology of a semicrystalline poly(?‐caprolactone)‐block‐poly(ethylene oxide) block copolymer (PCL₆₆‐b‐PEO₄₄) in aqueous solution is investigated. Spherical micelles are formed in neutral and acidic solutions. However, addition of alkali to the neutral micellar solution triggers a sphere‐to‐cylinder transformation of the micellar morphology. The micelles are stable in both neutral and acidic solutions, but the size of the micelles becomes gradually larger in the alkali solution. This phenomenon is interpreted in terms of the effect of pH value on the reduced tethering density of the corona in the semicrystalline micelles.     

Folate‐Conjugated Poly(N‐(2‐hydroxypropyl) methacrylamide)‐block‐Poly(benzyl methacrylate): Synthesis,Self‐Assembly,and Drug Release

Well‐defined amphiphilic diblock copolymers of poly(N‐(2‐hydroxypropyl)methacrylamide)‐block‐poly(benzyl methacrylate) (PHPMA‐b‐PBnMA) are synthesized using reversible addition–fragmentation chain transfer polymerization. The terminal dithiobenzoate groups are converted into carboxylic acids. The copolymers self‐assemble into micelles with a PBnMA core and PHPMA shell. Their mean size is <30 nm, and can be regulated by the length of the hydrophilic chain. The compatibility between the hydrophobic segment and the drug doxorubicin (DOX) affords more interaction of the cores with DOX. Fluorescence spectra are used to determine the critical micelle concentration of the folate‐conjugated amphiphilic block copolymer. Dynamic light scattering measurements reveal the stability of the micelles with or without DOX. Drug release experiments show that the DOX‐loaded micelles are stable under simulated circulation conditions and the DOX can be quickly released under acidic endosome pH.     

Synthesis of Three Types of Amphiphilic Poly(ethylene glycol)‐block‐Poly(sebacic anhydride) Copolymers and Studies of their Micellar Solutions

Summary: Linear, three‐ and four‐armed block copolymers based on PEG and PSA were synthesized by melt polycondensation reactions. The CMC of the copolymer was measured using the dye solubilization method. The copolymers were found to self‐aggregate in water to form micelles above the CMC. The micellar solutions were prepared with different methods and investigated by DLS and AFM. The DLS method was used to measure the mean hydrodynamic diameters of the micelles. It was found that preparation method and condition of the micellar solution, as well as the structure and composition of the copolymer had effects on the hydrodynamic diameter of the copolymer micelles. AFM studies showed that the morphology of the micelle was spherical.

Synthesis of 3‐armed stars based on poly(ethylene glycol) and poly(sebacic anhydride).     

pH‐Sensitive Micelles Formed by Interchain Hydrogen Bonding of Poly(methacrylic acid)‐block‐Poly(ethylene oxide) Copolymers

pH‐sensitive micelles formed by interchain hydrogen bonding of poly(methacrylic acid)‐block‐poly(ethylene oxide) copolymers were prepared and investigated at pH < 5. Both and R_h of the micelles increase with decreasing pH of the solution, displaying an asymptotic tendency at low pH values. The observed micelles are well‐defined nanoparticles with narrow size distributions (polydispersity ΔR_h/R_h ≤ 0.05) comparable with regular diblock copolymer micelles. The CMCs occur slightly below c = 1 × 10^?4 g · mL^?1. The micelles are negatively charged and their time stability is lower than that of regular copolymer micelles based purely on hydrophobic interactions.

     

Effect of Sonication on Polymeric Aggregates Formed by Poly(ethylene oxide)‐Based Amphiphilic Block Copolymers

The effect of sonication on the size and structure of polymeric aggregates formed by amphiphilic block copolymers was studied by the combination of dynamic and static light scattering. Poly(ethylene oxide)‐block‐polyisoprene, poly(ethylene oxide)‐block‐polystyrene diblock copolymers, and poly(ethylene oxide)‐block‐polyisoprene‐block‐poly(ethylene oxide) triblock copolymer were used as typical polymeric amphiphiles. Sonication was found to be an effective method to break up inter‐micellar associations and split large polymeric aggregates, present initially in the aqueous solutions, into monodisperse micelles. The content and type of hydrophobic block, copolymer solution‐preparation protocol, and copolymer concentration were also investigated as co‐factors in conjunction to the effect of sonication time.

     

Mesh‐Like Vesicles Formed From Blends of Poly(4‐vinyl pyridine)‐b‐polystyrene‐b‐poly(4‐vinyl pyridine) Block Copolymers via Gradual Blending Method

In this study, we developed a novel blending strategy, namely, the gradual blending method, to tune the micellar structure. Different from the most commonly used premixing blending method, which different block copolymers are premixed in a common solvent before their individual self‐assembly, the gradual blending method involves gradually adding one type of block copolymer into the pre‐generated micellar solution formed from another type of block copolymer. Moreover, we obtained a novel mesh‐like vesicle from the self‐assembly of the mixtures of P4VP₄₃‐b‐PS₂₆₀‐b‐P4VP₄₃ and P4VP₄₃‐b‐PS₃₆₆‐b‐P4VP₄₃ in 1,4‐dioxane/water solution using the gradual blending method.     

Optically Active Poly[{methyl(1‐naphthyl)silylene}(o‐phenylene)methylene]‐Poly(ethylene glycol) Block Copolymer Micelles

Summary: Optically pure (+) and isotactic poly[{methyl(1‐naphthyl)silylene}(o‐phenylene)methylene] terminated with methylphenylchlorosilyl was obtained by the Pt‐catalyzed ring‐opening polymerization of optically pure 1‐methyl‐1‐(1‐naphthyl)‐2,3‐benzosilacyclobut‐2‐ene in the presence of methylphenylchlorosilane as a chain transfer agent. The polymer formed was transformed into a block copolymer by reacting the terminal chlorosilyl group with a commercial poly(ethylene glycol) monomethyl ether. The formation of micelles by the block copolymer in THF‐water mixtures was investigated by fluorescence and UV. More detailed information about the aggregation of the polymer in the micelles was obtained by circular dichroism spectroscopy. It was found that dense aggregates were formed at a concentration higher than the critical micelle concentration. This concentration was higher for lower molecular weight polymer, at higher temperatures, and in more hydrophobic solvent systems. The highly aggregated structure was altered by changing the solvent system.

     

Aggregation and Crosslinking of Poly(N,N‐dimethylacrylamide)‐b‐pullulan Double Hydrophilic Block Copolymers

The self‐assembly of polymers is a major topic in current polymer chemistry. In here, the self‐assembly of a pullulan based double hydrophilic block copolymer, namely pullulan‐b‐poly(N,N‐dimethylacrylamide)‐co‐poly(diacetone acrylamide) (Pull‐b‐(PDMA‐co‐PDAAM)) is described. The hydrophilic block copolymer induces phase separation at high concentration in aqueous solution. Additionally, the block copolymer displays aggregates at lower concentration, which show a size dependence on concentration. In order to stabilize the aggregates, crosslinking via oxime formation is described, which enables preservation of aggregates at high dilution, in dialysis and in organic solvents. With adequate stability by crosslinking, double hydrophilic block copolymer (DHBC) aggregates open pathways for potential biomedical applications in the future.     

The Aggregation Behavior of Poly(ethylene oxide)‐Poly(methyl methacrylate) Diblock Copolymers in Organic Solvents

Poly(ethylene oxide)‐poly(methyl methacrylate) and poly(ethylene oxide)‐poly(deuteromethyl methacrylate) block copolymers have been prepared by group transfer polymerization of methyl methacrylate (MMA) and deuteromethyl methacrylate (MMA‐d₈), respectively, using macroinitiators containing poly(ethylene oxide) (PEO). Static and dynamic light scattering and surface tension measurements were used to study the aggregation behavior of PEO‐PMMA diblock copolymers in the solvents tetrahydrofuran (THF), acetone, chloroform, N,N‐dimethylformamide (DMF), 1,4‐dioxane and 2,2,2‐trifluoroethanol. The polymer chains are monomolecularly dissolved in 1,4‐dioxane, but in the other solvents, they form large aggregates. Solutions of partially deuterated and undeuterated PEO‐PMMA block copolymers in THF have been studied by small‐angle neutron scattering (SANS). Generally, large structures were found, which cannot be considered as micelles, but rather fluctuating structures. However, ¹H NMR measurements have shown that the block copolymers form polymolecular micelles in THF solution, but only when large amounts of water are present. The micelles consist of a PMMA core and a PEO shell.     

Thermoresponsive Properties of Poly(N‐vinylcaprolactam)‐Poly(ethylene oxide) Aqueous Systems: Solutions and Block Copolymer Networks

Two‐ and three‐dimensional phase diagrams have been constructed for thermosensitive poly(N‐vinylcaprolactam)‐poly(ethylene oxide) (PVCL‐PEO) aqueous systems. Both solutions and swollen block copolymer networks have been investigated to elucidate the effect of the copolymer content and crosslinking density on their temperatures of phase separation (T_ph.s.). The introduction of hydrophilic PEO into an aqueous solution of PVCL decreases its T_ph.s.. This suggests that the strength of the hydrogen bonds within the thermoresponsive PVCL‐water system is weakened by the introduction of PEO that also interacts with water. Based on the DSC investigation of the swollen networks, it was found that the influence of PEO on the phase behavior of weakly crosslinked networks is comparable with that of PVCL‐PEO‐H₂O solutions. For networks with a higher degree of crosslinking, the presence of the crosslinks is of major importance for the explanation of the T_ph.s. location. This detailed phase analysis led to the proposal of an irregular water distribution in these swollen networks.     

Size Tunable Core Crosslinked Micelles from HPMA‐Based Amphiphilic Block Copolymers

A variety of core crosslinkable hydroxypropylmethacrylamide‐based block copolymers are synthesized by reversible addition‐fragmentation chain transfer (RAFT) polymerization, which are composed of hydroxypropyl‐methacrylate as hydrophilic block combined with a statistical hydrophobic block from laurylmethacrylate and the photo crosslinkable monomer. It is discovered that the self‐assembled micellar aggregates from these systems vary strongly in size depending not only on the velocity of the polarity switch (nanoprecipitation or slow dialysis) but also on the solvent from which they were dialyzed. In this way micellar aggregates with an R _h varying between 15 and 80 nm can be prepared from the same block copolymer. In addition, a new hydrophobic crosslinkable hymecromone moiety is introduced. In this way the differently sized nanoparticles can be effectively stabilized by photo‐crosslinking, leading to a high stability of the photo crosslinkable polymeric micelles against disintegration by detergents.     

Double Hydrophilic Poly(ethylene oxide)‐block‐Poly(dehydroalanine) Block Copolymers: Comparison of Two Different Synthetic Routes

Two different synthetic pathways give access to the amphiphilic block copolymer poly(ethylene oxide)‐block‐poly(tert‐butoxycarbonylaminomethylacrylate). In the first approach, two end‐functionalized segments are linked via click chemistry; and in the second approach, a poly(ethylene oxide) (PEO) based macroinitiator is chain extended via atom transfer radical polymerization (ATRP). In both cases the linking unit consists of an amide group, which is necessary to effectively deprotect the corresponding polymer precursor without cleavage of both segments. For this, amide‐containing ATRP initiators are employed and successful synthesis by nuclear magnetic resonance (NMR) and size exclusion chromatography (SEC) analyses before comparing both pathways is demonstrated. After deprotection, a novel double hydrophilic block copolymer, poly(ethylene oxide)‐block‐poly(dehydroalanine), is obtained, which is investigated using SEC (aqueous and DMSO) and ¹H‐NMR spectroscopy. Containing a potentially zwitterionic PDha segment and a high density of both amino and carboxylic groups, pH‐dependent aggregation of the block copolymer is expected and is studied using dynamic light scattering, revealing interesting solution properties. The corresponding polymers are applied in various areas including drug delivery systems or in biomineralization.     

Poly(ethylene oxide)‐ and Poly(perfluorohexylethyl methacrylate)‐Containing Amphiphilic Block Copolymers: Association Properties in Aqueous Solution

Amphiphilic di‐ and triblock copolymers containing poly(ethylene oxide) (PEO) as the hydrophilic block and poly(perfluorohexylethyl methacrylate) (PFMA) as the hydrophobic block were synthesized by atom‐transfer radical polymerization using hydroxy‐terminated PEO as the macroinitiator. The copolymers were characterized by size exclusion chromatography and ¹H NMR spectroscopy. Self‐association in aqueous solution has been investigated using surface tension measurements, dynamic light scattering (DLS), and transmission electron microscopy (TEM). From surface tension measurements in water, a characteristic concentration (c*) can be detected, which is interpreted as the critical micelle concentration (cmc). The cmc decreases with an increase in fluoro content in the triblock copolymer up to 11 wt.‐% PFMA (solubility limit). DLS studies have been carried out for different samples above the cmc, showing small aggregates (micelles) and single chains for diblock copolymer solutions. In the case of triblock copolymers large clusters were the dominant aggregates in addition to the micelles and single chains. The effect of temperature and concentration on the micelle and cluster formation has been investigated by DLS. Micelle size was found to be resistant to any change by temperature, however, a slight but significant increase in apparent hydrodynamic radius was observed with an increase in concentration, while both temperature and concentration affected the formation of large clusters, especially in concentrated solutions. TEM has been carried out to visualize the morphology of the aggregates after transferring the solution to carbon film. The initial concentration for the preparation of TEM samples was found to have a strong influence on the morphology of the aggregates. By adding colloidal gold particles to the solutions, the typical covering by the polymer was observed by TEM.

Decay‐rate distributions for PEO₁₀F5 (4.0 g · L^?1); obtained from the time correlation functions.     

Emulsion Self‐Assembly Synthesis of Chitosan/Poly(lactic‐co‐glycolic acid) Stimuli‐Responsive Amphiphiles

An amphiphilic graft copolymer using chitosan (CS) as a hydrophilic main chain and poly(lactic‐co‐glycolic acid) (PLGA) as a hydrophobic side chain is prepared through an emulsion self‐assembly synthesis. CS aqueous solution is used as a water phase and PLGA in chloroform is served as an oil phase. A water‐in‐oil (W/O) emulsion is fabricated in the presence of the surfactant span‐80. The self‐assembly reaction is performed between PLGA and CS under the condensation of EDC. Fourier transform IR (FTIR) spectroscopy reveals that PLGA is grafted onto the backbone of CS through the interactions between end carboxyl and amino groups of the two components. ¹H NMR spectroscopy directly indicates the grafting content of PLGA in the CS‐graft‐PLGA (CS‐g‐PLGA) copolymer is close to 25%. X‐ray diffraction (XRD) confirms that the copolymer exhibits an amorphous structure. The CS‐g‐PLGA amphiphile can self‐assemble to form micelles with size in the range of ≈100–300 nm, which makes it easy to apply in various targeted‐drug‐release and biomaterial fields.     

Synthesis and Solution Self‐Assembly of Polyisoprene‐block‐poly(ferrocenylmethylsilane): A Diblock Copolymer with an Atactic but Semicrystalline Core‐Forming Metalloblock

Polyisoprene‐block‐poly(ferrocenylmethylsilane) (PI‐b‐PFMS) copolymers, containing the atactic but semicrystalline PFMS block, have been prepared by sequential anionic polymerization of isoprene and methyl[1]silaferrocenophane. The reaction to form the metalloblock is not living in nature, but still enabled three block copolymers to be prepared (PI₃₅‐b‐PFMS₅, PI₂₀₀‐b‐PFMS₁₀, and PI₂₄₇‐b‐PFMS₂₃) with relative narrow molar mass distributions (polydispersity < 1.3). The self‐assembly of all three materials was studied in PI selective n‐alkanes and found to afford lenticular platelets, tapered cylindrical micelles, and regular cylinders, as the length of the PFMS block increased. PI₂₀₀‐b‐PFMS₁₀ micelles could be increased in length by self‐seeding a sample of short micelles at temperatures of 90 °C and above; however, this process also resulted in an increase in width. Addition of a solution of PI₂₄₇‐b‐PFMS₂₃ copolymer to preformed seed micelles also resulted in an increase in length, although growth is not linearly related to the amount of copolymer added beyond ≈600 nm.

     

Effects of Poly(N‐isopropylacrylamide) (PNIPAAm) on the Conformational Change of Poly(N 5‐hydroxyalkyl glutamine) (PHAG) in PHAG‐PNIPAAm Block Copolymer with Temperature

Diblock copolymers consisting of poly(N ⁵‐hydroxyalkylglutamine) (PHAG) and poly(N‐isopropylacrylamide) (PNIPAAm) were prepared by aminolysis with aminoalkanols of the side‐chain ester of poly(γ‐benzyl L ‐glutamate) (PBLG) as a part of PBLG‐PNIPAAm block copolymers. The molecular weight ratio of the initial PBLG to the resulting PHAG was nearly 0.35. The effect of PNIPAAm on the conformational change of PHAG in PHAG‐PNIPAAm block copolymers with temperature was investigated by circular dichroism. Poly[N ⁵‐(2‐hydroxyethyl)‐L ‐glutamine] (PHEG) and the PHEG‐PNIPAAm copolymer (GNE) stayed in a randomly coiled conformation whereas poly[N ⁵‐(3‐hydroxypropyl)‐L ‐glutamine] (PHPG), poly(N ⁵‐(4‐hydroxybutyl)‐L ‐glutamine) (PHBG), PHPG‐PNIPAAm copolymer (GNP), and PHBG‐PNIPAAm copolymer (GNB) underwent conformational transitions with temperature. The conformational change of the PHPG block in GNP copolymer occurred from an α‐helix to a random coil after the incorporation of PNIPAAm into the copolymer. The thermodynamic parameters of the thermally induced helix‐coil transition for PHBG and PHBG‐PNIPAAm in aqueous solution were calculated.     

Contrast Inversion in TEM Studies of Poly(ferrocenylsilane)‐block‐Poly(dimethylsiloxane) Diblock Copolymers

This paper describes an unusual contrast inversion phenomenon in TEM imaging of PFS‐b‐PDMS block copolymer bulk samples. It is clearly observed especially in samples that show a lamellar morphology that the contrast inversion is accompanied by a contraction of the PDMS domains and an expansion of the Fe‐rich domains. The location of the iron‐ and silicon‐rich domains was monitored by EDX analysis. We infer that the contrast inversion was caused by electron beam radiation‐induced damage to, and possible cross‐linking of, PDMS chains. A simple way to selectively deposit metal on electron beam patterned polymer film was demonstrated.

     

One‐Step Method for Synthesis of PDMS‐Based Macroazoinitiators and Block Copolymers from the Initiators

Summary: This paper presents a facile one‐step method for the synthesis of macroazoinitiator (MAI) by direct polycondensation of hydroxyalkyl‐terminated polydimethylsiloxane (PDMS) with 4,4′‐azobis‐4‐cyanopentanoic acid (ACPA) under mild conditions. The PDMS‐based MAI was characterized by FTIR, ¹H NMR, GPC, and UV spectroscopy, and further used as an initiator for polymerization of methyl methacrylate (MMA) to obtain PMMA‐co‐PDMS block copolymer. TEM observation and DSC analysis demonstrated that the PMMA‐co‐PDMS block copolymer had a microphase‐separated structure.

Schematic representation for syntheses of macroazoinitiators (MAI) by the direct polycondensation and corresponding block copolymers.