The Temperature‐Responsive Nanoassemblies of Amphiphilic Random Copolymers Carrying Poly(siloxane) and Poly(oxyethylene) Pendant Chains

Novel amphiphilic random copolymers carrying poly(oxyethylene) and poly(siloxane) pendant chains are synthesized by atom transfer radical polymerization starting from either a fluorescent, julolidine‐based initiator, or a nonfluorescent initiator. For both copolymer systems, dynamic light scattering measurements carried out on aqueous solutions as a function of temperature reveal the occurrence of a sharp and fully reversible transition between two different self‐associative states of individual, single‐chain self‐folded nanoassemblies, so‐called unimer micelles, (D_h = 8–10 nm) and collapsed multichain aggregates (D_h = 700–1400 nm) at a critical temperature T_c. Covalently linked julolidine terminal and added ethidium bromide are separately used as fluorescent probes and both prove the temperature‐dependence of the different self‐association of the copolymers in water.     

The glass transition temperatures of homogeneous blends of polystyrene,poly(methyl methacrylate), and copolymers of styrene and methyl methacrylate

The glass transition temperatures T_g of homogeneous binary blends of the homo- and the statistical copolymers of the system poly(styrene-co-methyl methacrylate) were studied. Some of the blends, which are in the equilibrium phase separated, were forced into homogeneity. T_g (?) of the homopolymer blends (PS/PMMA)? follows the Fox equation, while T_g (x) of the pure copolymers P(S_xMMA_{1 ? x}) exhibits a minimum. This minimum can be effectively removed by blending the copolymers with small fractions (? ≈ 0,2) of one of the two homopolymers or a differently composed copolymer P(S_yMMA_{1 ? y}).     

The use of cholesterol-containing biodegradable block copolymers to exploit hydrophobic interactions for the delivery of anticancer drugs

A series of biodegradable amphiphilic block copolymers with controlled composition and relatively low polydispersity index were synthesized from monomethoxy polyethylene glycol (mPEG-OH, 5 kDa) via organocatalytic ring opening polymerization of aliphatic cyclic carbonate monomers - trimethylene carbonate (TMC) or cholesteryl 2-(5-methyl-2-oxo-1,3-dioxane-5-carboxyloyloxy)ethyl carbamate (MTC-Chol) or a copolymer of both the monomers (TMC and MTC-Chol): mPEG₁₁₃-b-PTMC₆₇, mPEG₁₁₃-b-P(MTC-Chol₁₁) and mPEG₁₁₃-b-P(MTC-Chol_x-co-TMC_y)_x+y. These well-defined polymers were employed to study the role of molecular weight and composition of the hydrophobic block of the polymers in loading paclitaxel (PTX), an extremely hydrophobic anticancer drug with rigid structure and strong tendency of self-association to form long fibers. The PTX-loaded micelles were fabricated by simple self-assembly without sonication or homogenization procedures. The results demonstrated that the presence of both MTC-Chol and TMC in the hydrophobic block significantly increased PTX loading levels, and the micelles formed from the polymer with the optimized composition (i.e. mPEG₁₁₃-b-P(MTC-Chol₁₁-co-TMC₃₀)) were in nanosize (36 nm) with narrow size distribution (PDI: 0.07) and high PTX loading capacity (15 wt.%). In vitro treatment of human liver hepatocellular carcinoma HepG2 cells with blank micelles showed that these polymeric carriers were non-cytotoxic with cell viability greater than 90% at ∼2400 mg/L. Importantly, PTX-loaded micelles were able to kill cancer cells much more effectively compared to free PTX. In addition, these nanocarriers also possessed exceptional kinetic stability. The results from non-invasive near-infrared fluorescence (NIRF) imaging studies showed that these micelles allowed effective passive targeting, and were preferably accumulated in tumor tissue with limited distribution to healthy organs.     

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.     

Structure and hydrodynamic properties of poly[styrene-b-(ethene-co-butene)-b-styrene] micelles in 1,4-dioxane

Three-block copolymers poly[styrene-b-(ethene-co-butene)-b-styrene], where the middle aliphatic block amounts to about 70 wt.-%, form micelles in 1,4-dioxane with an aliphatic core and a polystyrene shell. The basic characteristics concerning the ratio unimer/micelles, the micellar molar mass, the radius of gyration, and the hydrodynamic radius were determined by combining the results of light scattering, small-angle X-ray scattering, photon correlation spectroscopy, osmometry, and viscometry. The characteristics of the micelles, approximated by the model of concentric spheres, were calculated from the data of light scattering and small-angle X-ray scattering. From a comparison of the geometric and hydrodynamic dimensions of the micelles it follows that in dilute solutions they behave like rigid spheres.     

Molecular Dynamics of Amphiphilic Random Copolymers in the Bulk: A 1H and 19F NMR Relaxometry Study

A set of amphiphilic random copolymers of poly(ethylene glycol) methacrylate (PEGMA) and perfluorohexylethyl acrylate (FA) with different compositions synthesized by atom transfer radical polymerization (ATRP) is investigated by ¹H and ¹⁹F NMR relaxometry. In particular, a thorough investigation of T₁ and T₂ relaxation times at variable temperature and copolymer composition provides the first complete and detailed characterization of the dynamics of both the main chain backbone and the side chains of the PEGMA‐co‐FA copolymers. The results highlight an intramolecular segregation of rigid main chain and mobile side chains, and an additional self‐assembling of the PEGMA and FA side chains into distinct nanodomains, driven by the hydrophobic interactions between FA side chains. The obtainment and observation of nanoscale phase separation in random copolymers is a promising achievement to the aim of controlling self‐assembly in the bulk by suitably modulating copolymers composition, which can open novel avenues to easier fabrications and applications in nanotechnologies.     

Effects of A‐B Block Copolymer Additives on Interfacial Tension of A/B Polymer Blends Near the Critical Temperature: Comparison of Mean‐Field Calculations with Experiments

A simple square‐gradient theory (SGT) for the interfacial tension of homopolymer‐A/homopolymer‐B blends with A‐B diblock copolymer additives near the critical solution temperature, T_c, has been proposed to describe the experimental finding that, as the temperature changes away from T_c, the interfacial tension γ increases, and then decreases, exhibiting a maximum. Dynamic mean‐field calculations (DMF) of a self‐consistent field treatment are also performed to describe it and are compared with those of the proposed SGT. Both of SGT and DMF reasonably describe the γ‐maximum behavior and the additive‐concentration dependence of the location of γ‐maximum in γ‐T relation. Agreements of SGT with DMF results are quite satisfactory, although SGT, in general, gives thinner adsorbed layers of block copolymers than those evaluated by DMF.     

Structure of polystyrene-block-poly(ethylene oxide) diblock copolymer micelles in water

Micellization in water of two homologous series of AB-type diblock copolymers, composed of polystyrene (PS) as the A block and poly(ethylene oxide) (PEO) as the B block, were investigated by small-angle X-ray scattering (SAXS) and dynamic light scattering (DLS). The copolymers have molecular weights M _n in the range 2 000—34 800, and have in a given series, the same number of repeating units of the PS block, (N_PS = 10 and 38), and a variable number of repeating units of the PEO block (N_PEO values in the range 23–704). In order to avoid secondary association of micelles, a dialysis technique was used to prepare the micellar systems, in the case of copolymers having high M _n values of the PS block. The experimental micelle properties such as the core radius R_c and the aggregation number N of non-equilibrium structures, so called “frozen micelles”, obtained by dialysis, were found to be independent of the copolymer characteristics. However, for equilibrium structures, obtained by direct solubilization of the copolymers (N_PS = 10) in water, R_c and N were found to decrease with increasing N_PEO for the homologous series.     

Effect of Aromatic Co‐Solvents on the Efficiency of Atom Transfer Radical Coupling Reactions of Fluorinated and Non‐Fluorinated Vinyl Aromatic Polymers

Monobrominated versions of poly(pentafluorostyrene) (PPFSBr), polystyrene (PSBr), and poly(methyl acrylate) (PMABr) are prepared by atom transfer radical polymerization (ATRP) and employed in a variety of atom transfer radical coupling (ATRC)‐type reactions to observe the impact of external aromatic faces on the extent of coupling (X_c). In ATRC reactions assisted with the radical trap 2‐methyl‐2‐nitrosopropane (MNP), X_c is nearly unchanged when the electron‐rich benzene co‐solvent (50% v/v with THF) is replaced with the electron‐poor hexafluorobenzene (HFB) for PSBr and PMABr. In the case of PPFSBr, the addition of benzene to the reaction mixture results in far lower extents of coupling (X_c < 0.2). ¹H NMR spectra of the radical trap MNP in HFB show greater aggregation to the inactive form, compared to the spectra obtained in benzene. To remove the effect of the radical trap interacting with the aromatic co‐solvent and altering the rate of coupling, traditional ATRC reactions are performed with the same co‐solvent systems and, in this case, HFB results in higher X_c values across all polymer types. This is consistent with HFB pushing the position of the K_ATRP further toward the active radical, while benzene increases the reactivity of the MNP radical trap.     

High Refractive Index Copolymers from Aromatic Heterocycle-Based Vinyl Sulfides and Phthalimide/Maleimide Derivatives

Herein, the rational design and facile synthesis of high-refractive-index copolymers with good optical transparency and tunable thermal stability using aromatic heterocycle-based vinyl sulfides via conventional radical copolymerization is presented. 2-Thiazolylvinylsulfide (2TVS), 1,3,4-thiadiazolylvinylsulfide (1,3,4-TVS), 3-methylimidazolylvinylsulfide (3MIVS), and 5-methlthio-1,3,4-thiadiazolylvinylsulfide (MeSTVS) are selected to enhance the refractive index, and N-vinylphthalimide (NVPI) and N-phenylmaleimide (NPMI) are chosen as comonomers to achieve improved transparency and thermal stability while maintaining the refractive index. The sulfur, ─C═N─, and imide contents in the copolymers are varied by adjusting the monomer structures and their compositions, and their effects on the refractive index, Abbe number, and optical and thermal properties are investigated. The MeTVS monomer in poly(MeSTVS) and poly(MeSTVS-co-NVPI) contained three sulfur atoms and two ─C═N─ units; consequently, these polymers exhibit excellent refractive indices in the 1.7139–1.6567 range at 589 nm, Abbe numbers between 19.1–29.1, good transparency (>90% at 400 nm), and tunable thermal properties (T_g = 49–138 °C, T_d10 = 244–268 °C). Optically transparent poly(1,3,4-TVS-co-NVPI) films (>95% at 400 nm) with improved thermal stability (T_g = 89–175 °C, T_d10 = 251–301 °C) are obtained while maintaining a relatively high refractive index (1.6662–1.6752).     

Prolate and Temperature‐Responsive Self‐Assemblies of Amphiphilic Random Copolymers with Perfluoroalkyl and Polyoxyethylene Side Chains in Solution

Two amphiphilic random copolymers, PEGMAx‐co‐FAy (x = 90 and 70 mol%), are synthesized by ATRP and their solutions are investigated as a function of solvent, concentration, and temperature by DLS and SANS analyses. Both copolymers self‐assemble in nanostructures by single‐chain folding in water solutions over a wide range of temperatures. The values of the DLS hydrodynamic radius and the SANS radius of gyration are found to be ≈4 nm and ≈3.4–3.7 nm, respectively. Moreover, SANS shows the self‐folded nanoassemblies to be prolated spheroids with a ratio of polar/equatorial axes of ≈5:1 for PEGMA90‐co‐FA10 and ≈2:1 for PEGMA70‐co‐FA30. On heating above a critical temperature T_c, multichain microassemblies are formed that revert back to nanoassemblies on cooling below T_c. This temperature‐responsive transition is fully and sharply reversible.     

pH‐Responsive Double‐Hydrophilic Block Copolymers: Synthesis and Drug Delivery Application

A novel double‐hydrophilic block copolymer P(MEO₂MA‐co‐OEGMA)‐b‐PAMA has been successfully synthesized by two‐step RAFT polymerization. Then, the amino groups of PAMA blocks in the copolymers react with 1‐pyrenecarboxaldehyde via a “Schiff‐base” reaction, and the resulting copolymers are self‐assembled to form spherical micelles in aqueous solution. Because the “Schiff‐base” linkage is pH sensitive, the release rate of pyrene depends upon the pH of solution. Complete release is achieved at pH 1, and the control release is much faster at pH 5.5 than that at pH 7.4. With progress of pyrene release, the micelles are disassembled gradually and disappeared completely at last. This double‐hydrophilic copolymer is a promising candidate of drug carrier for the aldehyde‐ containing hydrophobic drugs.     

Solution behavior of a graft copolymer in selective solvents for its backbone or grafts

Association of a graft copolymer polyisoprene-graft-polystyrene in solvent mixtures selective either for polyisoprene backbone (THF/heptane) or for polystyrene grafts (THF/ethanol; 1,4-dioxane/ethanol) was studied by static and dynamic light scattering and sedimentation velocity. Values of molar mass and dimensions of graft copolymer micelles were determined, and qualitative information on the dynamics of the unimer ? micelles equilibrium was obtained.     

Fluorination of polymers containing COOH/COOR-groups with SF4/HF, 2

Carboxyl- and ester groups of low molecular-weight compounds are selectively and quantitatively converted into trifluoromethyl moieties by reaction with SF₄/HF as shown in a previous paper. This reaction is now applied to the polymers poly(acrylic acid), poly(acrylic esters) and poly[(acrylic acid)-co-(acrylic ester)]. Poly(acrylic acid) yields gelled products whereas poly(acrylic ester) and the copolymers yield highly fluorinated soluble polymers upon reaction with SF₄/HF. Under mild reaction conditions the carbonyl groups in acrylic acid/acrylic ester copolymers are selectively fluorinated. Unter vigorous reaction conditions, acid as well as ester moieties of the copolymers are completely fluorinated. Macroscopic gelation during fluorination is most probably associated with intermolecular ether formation. Molecular weights, NMR spectra and glass transition temperatures of the reaction products are given.     

Reactive poly(2-vinyl-4,4-dimethyl-5-oxazoione) and poly[(2-vinyl-4,4-dimethyl-5-oxazolone)-co-(methyl methacrylate)]s. Synthesis,characterization and chemical modification with 4-methoxy-4′-(β-aminoethoxy)biphenyl

Poly(2-vinyl-4,4-dimethyl-5-oxazolone) ( P₀ ) and poly[(2-vinyl-4,4-dimethyl-5-oxazolone)-co-(methyl methacrylate)]s with increasing content of methyl methacrylate units ( P₁–P₄ ) were synthesized and characterized. NMR spectra were discussed in terms of monomer sequence distribution and tacticity effects. The reaction of 4-methoxy-4′-hydroxybiphenyl ( 1 ) with 2-ethyl-2-oxazoline was utilized to prepare 4-methoxy-4′-(β-aminoethoxy)biphenyl ( 3 ) through the intermediate 4-methoxy-4′-[(N-propanoyl)-β-aminoethoxy]biphenyl ( 2 ). The homopolymer P ₀ and two copolymers P ₂ and P ₃ were functionalized with 4-methoxybiphenyl side groups by reaction with 3 via a ring-opening process in N,N-dimethylformamide (DMF) or 1,2-dichloroethane. The resulting copolymers P₅–P₈ were characterized by ¹H and ¹³C NMR. The highest degree of functionalized units was obtained in DMF at 80°C.     

Synthesis of Amphiphilic Comb‐Shape Copolymers Via Ring‐Opening Polymerization of a Macromonomer

Amphiphilic comb‐shape copolymers PCL‐co‐P(MTC‐mPEG₁₆) (where PCL, MTC, and mPEG refer to poly(ε‐caprolactone), 2‐methyltrimethylene carbonate, and methoxy poly(ethylene glycol), respectively) are synthesized by ring‐opening polymerization of ε‐caprolactone and cyclic carbonate‐terminated PEG macromonomer (MTC‐mPEG₁₆) with benzyl alcohol as an initiator and Sn(Oct)₂ as a catalyst. Amphiphilic copolymers PCL‐co‐P(MTC‐mPEG₁₆) can form micelles in aqueous solution by self‐assembly. The diameters of PCL‐co‐P(MTC‐mPEG₁₆) micelles characterized by dynamic light scattering area few dozens of nanometers with a narrow size distribution and the morphology of the micelles observed through transmission electron microscopy are nanosized spheres. The in vitro drug release of comb‐shape copolymer PCL‐co‐P(MTC‐mPEG₁₆) micelles is more stable and sustained than that of linear block copolymers mPEG‐b‐PCL.

     

Thermo‐responsive Poly(methyl methacrylate)‐block‐poly(N‐isopropylacrylamide) Block Copolymers Synthesized by RAFT Polymerization: Micellization and Gelation

Summary: RAFT polymerization was used to prepare PMMA‐b‐PNIPAM copolymers. Two different chain transfer agents, tBDB and MCPDB, were used to mediate the sequential polymerizations. Micellar solutions and gels were prepared from the resulting copolymers in aqueous solution. When heated above T_c of PNIPAM (about 31 °C), DLS revealed that PNIPAM coronas collapsed, resulting in aggregation of the original micelles. The micellar gels underwent syneresis above T_c as water was expelled from the ordered gel structure, the lattice periodicity of which was determined by SANS. A large decrease in lattice spacing was observed above T_c. The gel became more viscoelastic at high temperature, as revealed by shear rheometry which showed a large increase in G″.

     

Investigations of the crystallization of polyethylene by means of simultaneous small-angle and wide-angle X-ray scattering

The isothermal crystallization of linear polyethylene fractions was studied by means of simultaneous measurements of wide-angle X-ray scattering (WAXS) and small-angle X-ray scattering (SAXS) employing synchrotron radiation. From WAXS the overall degree of crystallinity x_c was determined. From SAXS, the scattering power Q was evaluated and compared with several different models for the crystallizing system. When the scattering arises solely from the supermolecular structures, such as spherulites, Q is proportional to x_s·x_cL·(1 ? x_cL), where x_s is the fraction of material transformed into such structures and x_cL is the degree of crystallinity within these structures. By comparing x_c with Q it was possible to separate the primary and secondary crystallization and to show that secondary crystallization takes place within the lamellar stacks where the crystals become thicker and the amorphous layers become thinner. The process of recrystallization during annealing of crystalline samples was studied in the same way. Other models were treated in a similar manner.     

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.     

Study of the compatibility of poly[styrene-co-(cinnamic acid)]/poly[(ethyl methacrylate)-co-(2-dimethylaminoethyl methacrylate)] blends

Compatibilization of an immiscible polymer pair, polystyrene and poly(ethyl methacrylate), is achieved by introducing along the polymer chains cinnamic acid and 2-dimethylaminoethyl methacrylate groups, respectively. The miscibility behavior of a series of poly[styrene-co-(cinnamic acid)] (PSCA) copolymers containing 5, 8, and 23 mol-% of acidic units, with poly[(ethyl methacrylate)-co-(2-dimethylaminoethyl methacrylate)] (PEMADAE) was investigated by DSC and FTIR. Based on the single composition-dependent glass transition criterion, each PSCA copolymer is miscible with PEMADAE over the three blend compositions studied. The glass transition temperatures are higher than predicted according to the additivity principle. This indicates the occurrence of strong intermolecular interactions between the polymeric chains of the two components. The T_g-composition curves of the investigated systems are interpreted according to the Kwei and the Schneider approaches. The results of the FTIR study reveal that the changes detected in the carbonyl stretching frequency region are the consequence of hydrogen bonding between the carboxylic acid groups in PSCA and the carbonyl groups in PEMADAE.