Triblock Copolymers Based on Sucrose Methacrylate and Methyl Methacrylate: RAFT Polymerization and Self‐Assembly

ABA and BAB triblock amphiphilic copolymers based on sucrose methacrylate and methyl methacrylate are synthesized by sequential reversible addition–fragmentation chain transfer polymerization using S,S′‐bis(R,R′‐dimethyl‐R′′‐acetic acid)‐trithiocarbonate as a chain transfer agent. The copolymers present narrow molar mass dispersity, controlled molar mass and architecture as determined by gel permeation chromatography and ¹H and ¹³C nuclear magnetic resonance. The copolymers with molar and mass fractions of poly(sucrose methacrylate) block ranging from 1 to 22 mol% and 3 to 52 wt%, respectively, and different molar masses present characteristics of a surfactant such as self‐assembly. The self‐assembly of the triblock copolymers in water, N,N‐dimethylformamide (DMF), dichloromethane, tetrahydrofuran, or benzene results mostly in vesicles as confirmed by scanning electron microscopy images and small‐angle X‐ray of the dispersions. Moreover, the copolymers present the capability to stabilize aromatic molecules (Nile Red dye) and nonpolar solvents in an aqueous phase and polar ionic molecules (methylene blue) and water in a nonpolar medium, suggesting the potential for application in drug encapsulation, environmental remediation systems, and molecular extraction in liquid–liquid immiscible systems, for example. Films prepared by casting from copolymer solutions in DMF present a lamellar structure with the lamellar thickness varying according to the copolymer molar mass.     

Amphiphilic PEG‐b‐PMCL‐b‐PDMAEMA Triblock Copolymers: From Synthesis to Physico‐Chemistry of Self‐Assembled Structures

A synthetic route toward a new family of amphiphilic mPEG‐b‐PMCL‐b‐PDMAEMA triblock copolymers is reported. Chemical structures and compositions are confirmed by ¹H NMR and SEC. Polydispersity indices are typically <1.4, indicating good control of the reactions. The physicochemical parameters associated with mPEG‐b‐PMCL‐b‐PDMAEMA self‐assembled structures are investigated. Nanoparticles are prepared via a co‐solvent method, and parameters such as nanoparticle $\overline {M} _{{\rm w}} $ , N_agg, A₂, and R_h are calculated based on static and dynamic light scattering data. Critical aggregation concentrations for the polymers are determined by measuring surface tensions of polymer solutions. TEM is employed to visualize the morphology of the assemblies.

     

Tunable Morphologies From Bulk Self‐Assemblies of Poly(acryloxypropyl triethoxysilane)‐b‐poly(styrene)‐b‐poly(acryloxypropyl triethoxysilane) Triblock Copolymers

Reactive poly(acryloxypropyl triethoxysilane)‐b‐poly(styrene)‐b‐poly(acryloxypropyl triethoxysilane) (PAPTES‐b‐PS‐b‐PAPTES) triblock copolymers are prepared through nitroxide‐mediated polymerization (NMP). The bulk morphologies formed by this class of copolymers cast into films are examined by small‐angle X‐ray scattering (SAXS) and transmission electron microscopy (TEM). The films morphology can be tuned from spherical structures to lamellar structures by increasing the volume fraction of PS in the copolymer. Thermal annealing at temperatures above 100 °C provides sufficient PS mobility to improve ordering.     

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.     

Self‐Assembly of Globular‐Protein‐Containing Block Copolymers

Self‐assembly has emerged as a powerful approach to control nanostructure in materials containing globular proteins, both through templated self‐assembly and direct self‐assembly of globular protein‐polymer conjugates or fusion proteins. The folded structures of globular proteins that are critical to their function introduce complex shapes and interactions into block copolymers that significantly alter the physics of self‐assembly. This article discusses the different methods for controlling the nanostructure of globular proteins using block copolymers, highlighting efforts at understanding the physics of self‐assembly in concentrated solution and solid‐state bioconjugate copolymers.

     

Synthesis and Self‐Assembly of Novel Amphiphilic Six‐Armed Star Copolymers TP[PDMAEMA‐b‐PSt]6

A triphenylene (TP)‐based hexafunctional initiator was prepared and used in successive ATRP of DMAEMA and St. Well‐defined six‐armed star block copolymers TP[PDMAEMA‐b‐PSt]₆ bearing hydrophilic backbones inside and hydrophobic blocks outside were successfully synthesized. The self‐assembly behaviors of the novel amphiphilic copolymer were further investigated. Co‐existing spherical and bowl‐shaped aggregates were observed from their neutral aqueous solution, while large spherical structures with different dimensions were obtained from their diluted HCl and CF₃COOH aqueous solution, respectively. Dynamic light scattering in different aqueous solutions were conducted to give further confirmation. The possible mechanism of the morphology formation was proposed.

     

Spontaneous Self‐Assembly and Micellization of Random Copolymers in Organic Solvents

Spontaneous self‐assembly of random and statistical copolymers in solution, especially in organic solvents, is unusual due to the structural irregularity of the copolymer chain and close proximity of short incompatible segments. This study describes the first observation of supramolecular structures such as micelles and vesicles formed by a random copolymer in organic solvents. Upon dissolution in methanol or tetrahydrofuran, the random copolymer poly(trifluoroethyl methacrylate‐random‐methacrylic acid) forms small spherical micelles, worm‐like assemblies, and large vesicles spontaneously. Self‐assembly is driven by the high incompatibility between the fluorinated and acidic repeat units. Micelle size can also be altered by the addition of metal ions, which interact with the carboxylic acid groups of methacrylic acid through complexation or Coulombic forces. These findings demonstrate an easy, single‐step approach to creating nanoscale structures with tunable size and morphologies in organic solvents from easily synthesized random copolymers, with potential applications in coatings, selective membranes, catalysis, and drug delivery.     

Solution Self‐Assembly of Core‐Labeled Block Random‐Copolymers Prepared by Ring Opening Metathesis Polymerization

Herein, the synthesis of block random‐copolymers via ring opening metathesis polymerization (ROMP) is presented. A random‐copolymer of norbornene dimethyl ester with different xanthen‐functionalized norbornene derivatives was used as a hydrophobic block while, the hydrophilic part was built from an ethylene glycol‐substituted monomer. The self‐association of these block random‐copolymers in MeOH was strongly influenced by the ionization state of the dye molecules, as shown by a combination of UV–Vis absorption and dynamic light scattering measurements. Aggregate sizes were significantly smaller for samples with charged dye molecules in the core of the aggregate. These findings were attributed to ion pair formation of the charged dye molecules and the according counter ions, thus, inducing strongly attractive dipole–dipole interactions. The optical properties of the dyes under investigation, however, were preserved within the polymer aggregates.

     

Tertiary Amine Methacrylate‐Based ABC Triblock Copolymers: Synthesis,Characterization, and Self‐Assembly in both Aqueous and Nonaqueous Media

Water soluble poly[2‐(diisopropylamino)ethyl methacrylate]‐block‐poly[2‐(dimethylamino) ethyl methacrylate]‐block‐poly[2‐(N‐morpholino)ethyl methacrylate] triblock copolymers are synthesized via group transfer polymerization. They are molecularly soluble in acidic solution but give PDPA‐core three‐layer “onion‐like” micelles in alkaline solution. They also give two types of micelles in hexane depending on whether a cosolvent is used: i) PMEMA‐core “onion‐like” reverse micelles are formed with a cosolvent, or, ii) [PDMA‐b‐PMEMA]‐core core–shell micelles without. In addition, novel shell cross‐linked micelles and reverse SCL micelles are also synthesized by cross‐linking the inner PDMA shell of both PDPA‐core micelles in water and PMEMA‐core reverse micelles in hexane.

     

Self‐Assembly and Photoresponsivity Property of Amphiphilic ABA Triblock Copolymers Containing Azobenzene Moieties in Dilute Solution

The self‐assembly and photoresponsivity of amphiphilic azobenzene‐containing ABA triblock copolymers PA6C_m‐b‐PEG_n‐b‐PA6C_m synthesized by atom transfer radical polymerization (ATRP) were reported. Different self‐assembly morphologies formed by the gradual addition of water to the copolymer solutions in THF. The formation process and aggregate morphology were characterized by UV–Visible spectroscopy and transmission electron microscope (TEM). The triblock copolymers start to form aggregates at the critical water content (CWC). With the addition of water, the aggregates show different morphologies, such as spherical micelles, vesicles, network‐like aggregates, and colloidal spheres, which involves the transformation between primary and secondary aggregates and the association/disassociation of aggregates. Photoresponsive property and aggregation behavior of these copolymers in solution under UV–Visible light irradiation were also investigated.

     

Synthesis and Self‐Assembly of Functionalized Cyclooctene Block Copolymers via ROMP

A novel block copolymer consisted of MACIT and HCO segments was synthesized via ROMP in the ionic liquid [bmim][PF₆] with good control over the polymerization process. The molecular weight of the block copolymer was estimated by ¹H NMR, and the molar composition ratio of repeating units in the MACIT block to those in the HCO block was 100:120 (120:120 in feed). The micellar characterization was carried out by DLS, AFM, and TEM. The hydrodynamic diameter of the micelles, measured by DLS, was 129 ± 0.09 nm with a narrow distribution (PDI = 0.034). The TEM image showed spherical micelles.

     

Self‐Assembled Structures in Block Copolymer Blends: SAXS,SANS and TEM Study

Phenomena associated with the order‐disorder transition, microdomain morphology and phase behavior of a deuterated block copolymer (BCP) blend I / II (where I is dPS‐block‐dPMMA and II is dPS‐block‐PI) were studied by SAXS, SANS and TEM. The studied, almost symmetric, copolymers differ essentially in microdomain morphology. One of them ( I ) is in disordered microdomain state, while the other ( II ) displays lamellar morphology at ordinary temperatures. Self‐assembled structures in blends were investigated as a function of concentration of the added microphase‐separated copolymer and temperature. The ODT positions were located in all the blends, the position of ODT depending only slightly on the concentration of the ordered copolymer. A systematic increase in long period D of the lamellar phase is observed with the growing content of the disordered copolymer. The evaluation of TEM shows the gradual diminishing of macrophase separated regions of disordered copolymer I with growing content of the lamellar copolymer II .

     

Synthesis and Self‐Assembly Behavior of Organic–Inorganic Poly(ethylene oxide)‐block‐Poly(MA POSS)‐block‐Poly(N‐isopropylacrylamide) Triblock Copolymers

In this work, the synthesis of 3‐methacryloxypropylheptaphenyl POSS, a new POSS macromer (denoted MA‐POSS) is reported. The POSS macromer is used to synthesize PEO‐b‐P(MA‐POSS)‐b‐PNIPAAm triblock copolymers via sequential atom transfer radical polymerization (ATRP). The organic‐inorganic, amphiphilic and thermoresponsive ABC triblock copolymers are characterized by means of nuclear magnetic resonance spectroscopy (NMR) and gel permeation chromatography (GPC). Differential scanning calorimetry (DSC) and atomic force microscopy (AFM) show that the hybrid ABC triblock copolymers are microphase‐separated in bulk. Cloud point measurements show that the effect of the hydrophiphilic block (i.e. PEO) on the LCSTs is more pronounced than the hydrophobic block (i.e. P(MA‐POSS)). Both transmission electron microscopy (TEM) and dynamic light scattering (DLS) show that all the triblock copolymers can be self‐organized into micellar aggregates in aqueous solutions. The sizes of the micellar aggregates can be modulated by changing the temperature. The temperature‐tunable self‐assembly behavior is interpreted using a combination of the highly hydrophobicity of P(MA‐POSS), the water‐solubility of PEO and the thermoresponsive property of PNIPAAm in the triblock copolymers.     

Novel Synthesis of HPMA Copolymers Containing Peptide Grafts and Their Self‐Assembly Into Hybrid Hydrogels

A new pathway for the synthesis of HPMA graft copolymers was developed and their self‐assembly into hybrid hydrogels was investigated. Linear water‐soluble polyHPMA was chosen as the polymer backbone, whereas coiled‐coil forming peptides, covalently attached to the backbone, formed the grafts. Peptides of different chain lengths were chosen for evaluation. The results revealed that graft length greatly affected gelation ability. At least four heptads were needed to facilitate the hybrid system to form hydrogels under the experimental conditions used. The major factors affecting the kinetics of hydrogel self‐assembly were concentration and temperature.

     

Physical Properties of PBMA‐b‐PBA‐b‐PBMA Triblock Copolymers Synthesized by Atom Transfer Radical Polymerization

The physical properties of well‐defined poly(butyl methacrylate)‐block‐poly(butyl acrylate)‐block‐poly(butyl methacrylate) (PBMA‐b‐PBA‐b‐PBMA) triblock copolymers synthesized by atom transfer radical polymerization (ATRP) are reported. The glass transition and the degradation temperature of copolymers were determined by differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). DSC measurements showed phase separation for all of the copolymers with the exception of the one with the shortest length of either inner or outer blocks. TGA demonstrated that the thermal stability of triblock copolymers increased with decreasing BMA content. Dynamic mechanical analysis was used for a preceding evaluation of adhesive properties. In these block copolymers, the deformation process under tension can take place either homogeneously or by a neck formation depending on the molecular weight of the outer BMA blocks and on the length of the inner soft BA segments. Microindentation measurements were also performed for determining the superficial mechanical response and its correlation with the bulk behavior.

Stress‐strain curves for the different PBMA‐b‐PBA‐b‐PBMA specimens at room temperature and at 10 mm/min.     

Poly(4‐vinyl imidazole): A pH‐Responsive Trigger for Hierarchical Self‐Assembly of Multicompartment Micelles Based upon Triblock Terpolymers

Poly(vinyl pyridine) has widely been used as a pH‐responsive polymer to trigger changes in self‐assembly of block copolymer micelles. However, the polymer is known to display toxic features, which limits its ultimate applicability for biological applications. Here, poly(4‐vinyl imidazole) (P4VIm), a much more biocompatible polymer, is used as a pH‐responsive block to modulate the self‐assembly of ABC triblock terpolymers. In this article, the synthesis of the poly(1‐acryloyl fructopyranose)‐block‐ poly(n‐butyl acrylate)‐block‐ poly(4‐vinyl imidazole) (PFruA₅₂‐b‐PBuA₃₀₀‐b‐P4VIm₂₅₀) triblock terpolymers is first discussed by sequential reversible addition fragmentation chain transfer (RAFT) polymerization. Subsequently, the structure formation of the triblock terpolymer is elucidated by step‐wise solvent exchange. The polymer readily dissolves in methanol, but self‐assembles into micelles with PBuA cores and mixed shell in methanol–water mixtures. Solvent exchange against buffer solutions of pH 6–6.5 leads to collapse of P4VIm due to deprotonation and induces self‐assembly into caterpillar‐like non‐spherical nanoparticles, most likely via the formation of intermediate Janus particles. The rearrangement into larger hierarchical structure, as seen by small angle X‐ray scattering (SAXS), is found to process within several hours. The article is concluded by demonstrating lower cytotoxicity values for the present polymer in comparison to a structurally analogous triblock terpolymer based on poly(vinyl pyridine).     

Microstructure Induced Rigidity of Polysiloxane Yielding Hierarchical Self‐Assembly of Alkyl Side Chains

The influence of a backbone microstructure on the side chain crystallization of a comb‐like polymer is analyzed systematically using a tailor‐made random versus block siloxane copolymer system. While the side alkyl chains of the random siloxane undergo a stepwise order–disorder (OD) transition to form well‐ordered orthorhombic structure at low temperature, the packing structure of the alkyl chains pertaining to the block siloxane maintains their original hexagonal lattice up to a temperature of as low as 173 K. The unit lattice ordering of side alkyl chains in the random siloxane polymer is also accompanied by a major restructuring of the backbone conformation ultimately losing out long range ordered structure in the solid state. The OD transitions of side alkyl chains and their dynamic relationship with the backbone conformation are established unambiguously by a combination of temperature dependent small‐angle X‐ray and wide‐angle X‐ray scattering techniques. The observed conformational variations in random versus block polymers are explicitly discussed in terms of molecular chain mobility and theory of macromolecular chain conformation.     

Preparation of PEGylated Iodine‐Loaded Nanoparticles via Polymer‐Directed Self‐Assembly

The preparation of size‐tunable PEGylated, iodine‐loaded nanoparticles is investigated for biomedical applications. Di‐iodination of polyvinyl phenol and encapsulation of the iodinated polymer via directed self‐assembly with an amphiphilic polyethylene glycol‐based diblock copolymer are reported. Nanoparticles with iodine loadings up to 45 wt% are achieved using a rapid, scalable process. The size of the nanoparticles can be readily tuned between 35 and 130 nm by increasing the ionic strength of the antisolvent used during nanoparticle self‐assembly. The resulting PEGylated iodine‐loaded nanoparticles have potential applications in nanomedicine for 1) quantitative biodistribution analysis via inductively coupled plasma mass spectrometry (ICP‐MS) or 2) X‐ray contrast in biomedical imaging. For quantitative biodistribution studies using ICP‐MS, a limit of detection of 2 µg mL^?1 in mouse serum is achieved. For biomedical imaging, the X‐ray attenuation rates are comparable to currently commercially available iodine‐based contrast agents. Therefore, encapsulation of the iodinated polymer enables formulation of trackable, size tunable nanoparticles as a versatile platform for developing nanomedicines.     

Dramatic Solvent Effect on Interaction Kinetics and Self‐Organization of Phenyl‐C61 Butyric Acid Methyl Ester in a Triblock Copolymer

The interactions of a triblock copolymer containing a PEO central and two 4VP end blocks with PCBM were studied in different solvents. The interaction is too slow to be detected in toluene, but in THF a well‐defined charge transfer complex is formed, allowing the interaction kinetics to be studied. Rate constants along with other kinetic and thermodynamic parameters were determined. The 4VP units in the copolymer interact with the fullerene derivative more than two orders of magnitude faster than a small model compound. There is interplay between charge complextaion kinetics and self‐assembled supramolecular micellar structures of the copolymer/PCBM system. The findings should provide useful insight in design and formation of nanoscale domains of fullerene and derivatives in polymer blend systems.

     

Self‐Assembly and Responsive Behavior of Poly(peptide)‐Based Copolymers

Well‐defined copolymers synthesized by combining poly(ethylene glycol) (PEG) and amino acid based building blocks are investigated with regard to their helical rigidity and self‐assembly. Optical active block copolymers reported here are designed to have a pendant amino acid and polymerizable group, that is, isonitrile in order to induce helix formation and reduce the mobility of polymer chains by forming a hydrogen bond network so that a helix with reasonable rigidity can be obtained. Due to the amphiphilicity and a relatively shorter PEG as a coil, these polymers form micelles as observed under transmission electron microscopy in which copolymers PEG₁₀₈‐b‐PPIC₇₆₄ and PEG₁₀₈‐b‐PPIC₁₀₂₀ appear to be evolving into nanoparticles with a size distribution of 100–200 nm. Circular dichroism spectroscopy is employed to study the nature of the helix and its rigidity. The folding and unfolding of polymer helix as a result of the ability of a selective solvent to form/disrupt hydrogen bonds with the peptide linkage is also discussed to highlight the responsive nature of the polymer.