Characterization of New Amphiphilic Block Copolymers of N‐Vinyl Pyrrolidone and Vinyl Acetate, 1 – Analysis of Copolymer Composition,End Groups,Molar Masses and Molar Mass Distributions

New amphiphilic block copolymers consisting of N‐vinyl pyrrolidone and vinyl acetate were synthesized via controlled radical polymerization using a reversible addition/fragmentation chain transfer (RAFT)/macromolecular design via the interchange of xanthates (MADIX) system. The synthesis was carried out in 1,4‐dioxane as process solvent. In order to get conclusions on the mechanism of the polymerization the molecular structure of formed copolymers was analysed by means of different analytical techniques. ¹³C NMR spectroscopy was used for the determination of the monomer ratios. End groups were analysed by means of matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry. This technique was also used to determine possible fragmentations of the RAFT end groups. By means of a combination of size exclusion chromatography, ¹³C NMR and static light scattering molar mass distributions and absolute molar masses could be analysed. The results clearly show a non‐ideal RAFT mechanism.

     

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.     

Assembled Structures and Chiroptical Properties of Amphiphilic Block Copolymers Synthesized by RAFT Polymerization of N‐Acryloyl‐L‐alanine

Amino acid‐based amphiphilic block copolymers involving poly(N‐acryloyl‐L ‐alanine), poly(A‐Ala‐OH), which exhibits a characteristic chiroptical property and pH‐dependent solubility, have been synthesized by reversible addition‐fragmentation chain transfer (RAFT) polymerization. The direct polymerization of A‐Ala‐OH without any protecting chemistry using the dithiocarbamate‐terminated polystyrene or poly(N‐acryloyl‐L ‐phenylalanine methyl ester) as a macrochain transfer agent produced well‐defined amphiphilic block copolymers. The self‐assembly behaviors and chiroptical properties of these amphiphilic block copolymers in selective solvents were investigated by dynamic light scattering, circular dichroism, and UV–Vis spectroscopic methods.

     

Stabilizing the Microphase Separation of Block Copolymers by Controlled Photo‐crosslinking

Photo‐crosslinkable material is produced via self‐assembly of poly(methyl methacrylate)‐block‐poly(n‐butyl acrylate) (PMMA‐b‐PBA) block copolymers, in which the MMA block is decorated with coumarin moieties. The block copolymer is synthesized by reversible addition‐fragmentation chain transfer (RAFT) polymerization. Atomic force microscopy (AFM) reveals microphase separation into nanodomains of controlled and regular morphology. The local elastic modulus of different nanodomains is determined using the PeakForce Quantitative Nano‐Mechanics (PFQNM) mode of AFM. The global modulus, as determined by mechanical spectroscopy, agrees well with the local values. The crosslinking of the block copolymer, via photodimerization of the incorporated coumarin moieties using UV light, is traced by UV–vis absorption measurements and resulted in an increase of the global elastic modulus. The crosslinking reaction proceeding in the solid state is surprisingly effective and stabilizes the morphology to such an extent that equilibrium phase separation, as targeted by annealing, is effectively suppressed.

     

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.     

A Simple Route to Rod‐Coil Block Copolymers of Oligo‐ and Polythiophenes with PMMA and Polystyrene

A simple and efficient approach for the preparation of rod‐coil block copolymers comprising oligo‐ and polythiophenes blocks together with PMMA or PS blocks is described. The block copolymers were prepared using a two‐step procedure. α,ω‐dicarboxy‐terminated oligothiophenes and carboxy terminated poly(3‐hexylthiophene) were first prepared. These were then reacted with P₄S₁₀ in a second step to generate the α,ω‐thioester terminated oligothiophenes and poly(3‐hexylthiophene)s which were subsequently used in a one‐pot reaction as RAFT polymerization agents with methylmethacrylate and styrene. The di‐ and tri‐block copolymers hence obtained were fully characterized, both in solution and as thin films.

     

Synthesis of Amphiphilic and Double‐Hydrophilic Block Copolymers Containing Poly(vinyl amine) Segments by RAFT Polymerization of N‐Vinylphthalimide

We report on the controlled synthesis of amphiphilic and double‐hydrophilic block copolymers having poly(vinyl amine) segments by the reversible addition–fragmentation chain transfer (RAFT) polymerization of N‐vinylphthalimide (NVPI), followed by deprotection. The block copolymer poly(NVPI)‐b‐poly(N‐isopropylacrylamide) with a controlled molecular weight and low molecular mass distribution was obtained by the polymerization of N‐isopropylacrylamide (NIPAAm) using dithiocarbamate‐terminated poly(NVPI). The chain extension from the dithiocarbamate‐terminated polystyrene to NVPI could be controlled well under suitable conditions, and provided the block copolymer, polystyrene‐b‐poly(NVPI). We also investigated the thermoresponsive and optoelectronic properties and the aggregation behavior of double hydrophilic and amphiphilic block copolymers obtained after deprotection.

     

Controlled Synthesis of Alternating Copolymers by RAFT Copolymerization of N‐Vinylphthalimide with N‐Isopropylacrylamide

A nonconjugated N‐vinyl monomer, N‐vinylphthalimide (NVPI), was copolymerized with various comonomers via reversible addition‐fragmentation chain transfer (RAFT) process. Two different chain transfer agents (CTAs), O‐ethyl‐S‐(1‐ethoxycarbonyl) ethyldithiocarbonate (CTA 1) and benzyl 1‐pyrrolecarbodithioate (CTA 2), were compared for these copolymerizations with 2,2′‐azobis(isobutyronitrile) as an initiator. The effects of the nature of CTA, the comonomer structure, and solvent on the copolymerization were investigated in terms of the controlled character of the copolymerization and alternating structure. The copolymerization of NVPI and N‐isopropylacrylamide using CTA 2 in DMF or MeOH afforded well‐defined copolymers with predominantly alternating structure, controlled molecular weights, and low molecular mass distributions.

     

Synthesis and Characterization of PDMS‐, PVP‐, and PS‐Containing ABCBA Pentablock Copolymers

Amphiphilic ABCBA pentablock copolymers based on PVP, PS, and PDMS were synthesized using a combination of ATRP and RAFT polymerizations. The PVP‐block‐PS‐block‐PDMS‐block‐PS‐block‐PVP pentablock copolymer was characterized using a variety of chromatography and spectroscopic methods which showed that a high degree of end group and molecular weight control can be achieved. Preliminary analysis of the aqueous solution behavior of the pentablock copolymer showed that it self‐assembles in water in order to shield the PDMS and PS segments from the water.

     

Synthesis,Assembled Structures,and Optoelectronic Properties of Amphiphilic Block Copolymers Containing Anthracene Units in the Main Chain

Novel amphiphilic block copolymers containing the anthracene unit in the main chain are synthesized by reversible addition‐fragmentation chain transfer (RAFT) polymerization of a cyclic monomer, 10‐methylene‐9,10‐dihydroanthryl‐9‐spirophenylcyclopropane (MDS). A hydrophilic macro‐chain transfer agent is prepared by RAFT polymerization of 2‐hydroxyethyl acrylate (HEA). The polymerizations of MDS using the poly(HEA) afford amphiphilic block copolymers, in which the hydrophobic poly(MDS) segment has a perfectly alternating structure composed of an anthracene unit and a styrene unit, owing to the ring‐opening polymerization system. Characteristic assembled structures and optoelectronic properties of the amphiphilic block copolymers are investigated in various selective solvents.     

Miscibility of Carboxy‐Terminated Polystyrene/Poly[2‐(N,N‐dimethylamino)ethyl methacrylate] Blends

The miscibility/immiscibility behavior of CPS/PDMAEMA binary blends were investigated by means of DSC and optical microscopy. CPS was prepared by RAFT polymerization. CPS in a molecular weight range of 5 200–14 400 g · mol^?1 was found to be miscible with PDMAEMA as shown by the existence of a single glass transition, whereas benzyl‐terminated polystyrene with a similar molecular weight was immiscible with PDMAEMA. DSC results suggested that the carboxylic acid terminal groups effectively operated as miscibility enhancers in polystyrene/PDMAEMA blends. Moreover, it was observed that this effect depended on the molecular weight of CPS and the hydrogen bonding function of solvents.

     

Synthesis of Symmetrical Triblock Copolymers of Styrene and N‐isopropylacrylamide Using Bifunctional Bis(trithiocarbonate)s as RAFT Agents

Six new bifunctional bis(trithiocarbonate)s were explored as RAFT agents for synthesizing amphiphilic triblock copolymers ABA and BAB, with hydrophilic “A” blocks made from N‐isopropylacrylamide and hydrophobic “B” blocks made from styrene. Whereas the extension of poly(N‐isopropylacrylamide) by styrene was not effective, polystyrene macroRAFT agents provided the block copolymers efficiently. End group analysis by ¹H NMR spectroscopy supported molar mass analysis and revealed an unexpected side reaction for certain bis(trithiocarbonate)s, namely a fragmentation to simple trithiocarbonates while extruding ethylenetrithiocarbonate. The amphiphilic block copolymers with short polystyrene blocks are directly soluble in water and self‐organize into thermoresponsive micellar aggregates.

     

Structures and Chiroptical Properties of Thermoresponsive Block Copolymers Containing L‐Proline Moieties

Amino acid‐based block copolymers containing poly(A‐Pro‐OMe) have been synthesized by RAFT polymerization using the dithioester‐terminated poly(DMA) as a macro‐CTA. An amphiphilic block copolymer composed of polystyrene as a hydrophobic segment and poly(A‐Pro‐OMe) as a hydrophilic segment was also prepared using polystyrene as the macro‐CTA. The chiroptical properties of the block copolymer, poly(DMA)‐block‐poly(A‐Pro‐OMe), was evaluated by specific rotation, CD, and UV‐vis spectroscopy. The assembled structure of the block copolymer on a mica surface was characterized by SFM. Thermally induced phase separations of the random and block copolymers were also studied in aqueous solution.

     

One‐Pot Synthesis of Micelles with a Cross‐Linked Poly(acrylic acid) Core

Summary: Stable micelles with polystyrene (PS) as a shell and cross‐linked poly[(acrylic acid)‐co‐(ethylene glycol diacrylate)] as a core have been successfully prepared by reversible addition fragmentation chain transfer (RAFT) copolymerization of acrylic acid and ethylene glycol diacrylate in a selective solvent with PS‐SC(S)Ph as a RAFT agent. For the preparation of stable micelles, the RAFT polymerizations are carried out in different solvents: benzene, cyclohexane, and mixtures of tetrahydrofuran and cyclohexane. The monomer/PS‐SC(S)Ph molar ratio and molecular weight of the macro‐RAFT agent, PS‐SC(S)Ph, influence the RAFT polymerization and the formation of micelles.

Block copolymerization in selective solvent with the RAFT agent.     

Synthesis of Well‐Defined Statistical and Diblock Copolymers of Acrylamide and Acrylic Acid by Inverse Miniemulsion Raft Polymerization

Well‐defined statistical and diblock copolymers with acrylamide and acrylic acid were synthesized by inverse miniemulsion RAFT polymerization. Statistical copolymers with various composition ratios were synthesized. Compositional drift was observed during polymerization. Acrylamide was polymerized with a water‐soluble initiator (VA‐044) at 60 °C to give the RAFT‐agent‐containing acrylamide homopolymer with a narrow molecular‐weight distribution (PDI < 1.3), which was then chain‐extended with acrylic acid to obtain the diblock copolymer.

     

Synthesis of Double‐Hydrophilic BAB Triblock Copolymers via RAFT Polymerisation and their Thermoresponsive Self‐Assembly in Water

Triblock copolymers of poly(N‐isopropylacrylamide)‐block‐poly(N,N‐dimethylacrylamide)‐block‐poly(N‐isopropylacrylamide) were synthesised via RAFT polymerisation using a symmetrical bistrithiocarbonate. Keeping the block length of the permanently hydrophilic middle block constant, the length of the poly(N‐isopropylacrylamide) block was varied broadly. The thermoresponsive aggregation of the polymers in water was studied by ¹H NMR, turbidimetry, and dynamic light scattering. The complex aggregation behaviour was block length dependent and occurred under kinetic control. Importantly, different information on the hydrophilic‐hydrophobic transition of the poly(N‐isopropylacrylamide) block was obtained using the various analytical methods and could not be directly correlated.

     

RAFT Synthesis and Solution Properties of pH‐Responsive Styrenic‐Based AB Diblock Copolymers of 4‐Vinylbenzyltrimethylphosphonium Chloride with N,N‐Dimethylbenzylvinylamine

The RAFT synthesis and solution properties of AB block copolymers of 4‐vinylbenzyltrimethylphosphonium chloride (TMP) and N,N‐dimethylbenzylvinylamine (DMBVA) is described. The pH‐dependent self‐assembly properties of the AB diblock copolymers were examined using of ¹H NMR, DLS, and fluorescence spectroscopy. The size of the polymeric aggregates depends on the block copolymer composition/molecular mass. The self assembly is completely reversible, as predicted from the tunable hydrophilicity/hydrophobicity of the DMBVA residues. The AB diblock copolymers can be effectively locked in the self‐assembled state using a straightforward core crosslinking reaction between the tertiary amine residues of DMBVA and difunctional 1,4‐bis(bromomethyl)benzene.

     

Polymerization Rate Considerations for High Molecular Weight Polyisoprene‐b‐Polystyrene‐b‐Poly(N,N‐dimethylacrylamide) Triblock Polymers Synthesized Via Sequential Reversible Addition‐Fragmentation Chain Transfer (RAFT) Reactions

The reversible addition‐fragmentation chain transfer (RAFT) polymerization mechanism is a powerful technique for synthesizing functional block polymers for myriad applications. Most kinetic studies regarding the RAFT mechanism have focused on low molecular weight homopolymer and block polymer syntheses using a dithiobenzoate chain transfer agent (CTA). Here, the polymerization kinetics are evaluated for a high molecular weight A‐B‐C triblock polymer system, polyisoprene‐b‐polystyrene‐b‐poly(N,N‐dimethylacrylamide) (PI‐PS‐PDMA), using a trithiocarbonate agent for application of these types of polymers. Importantly, it is demonstrated that the polymerization of polyisoprene is the step that generates the block with the largest dispersity for high molecular weight PI‐PS‐PDMA polymers. As such, the kinetics of isoprene polymerization must be altered systematically for desired nanostructures to be formed. In addition, it is established that the PS and PDMA block additions exhibit polymerization rate retardation, which is due to slow chain fragmentation of the CTA, as demonstrated by the magnitudes of the equilibrium constants for both the styrene and N,N‐dimethylacrylamide reactions, and as calculated using ab initio modeling. This elucidation of the nature of the controlled RAFT mechanism provides a critical handle for the more precise design and control of other next‐generation high molecular weight block polymer systems that are polymerized using the RAFT mechanism.

     

Synthesis of Triazole‐Based Amphiphilic Block Copolymers Containing Carbazole Moiety By RAFT Polymerization

N‐Vinyl‐1,2,4‐triazole (NVTri), which is a nonconjugated N‐vinyl monomer having a basic aromatic heterocycle, was polymerized by reversible addition–fragmentation chain transfer (RAFT) polymerization. With the xanthate‐type chain transfer agent (CTA), reasonable control of the polymerization of NVTri was confirmed by the formation of the relatively low polydispersity products, linear increase in the molecular weight with the conversion, feasibility to control molecular weight, and chain extension experiment. Chain extension from poly(NVTri) to N‐vinyl carbazole (NVC) could be well controlled under suitable conditions and provided novel amphiphilic block copolymers. We investigated assembled structures and basic optoelectronic properties of the block copolymers.     

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.