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.     

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.     

Migration of Additives in Polymer Coatings: Phosphonated Additives and Poly(vinylidene chloride)‐Based Matrix

Summary: The living radical terpolymerization of vinylidene chloride (VC₂), methyl acrylate (MA), and dimethyl‐2‐methacryloxyethylphosphonate (MAPHOS) was performed at 70 °C in benzene by a reversible addition fragmentation chain transfer (RAFT) process to yield a gradient terpolymer of controlled molecular weight ( = 5 800 g · mol⁻¹, I_p = 1.53) with a molar composition of 75:14:11 (VC₂/MA/MAPHOS). Such terpolymers, hydrolyzed (phosphonic acid groups) or not, were used as polymeric additives in coating formulations based on a poly(VC₂‐co‐MA) copolymer matrix ( = 63 300 g · mol⁻¹, I_p = 1.99, VC₂/MA = 80:20 molar ratio). The formulations were spun cast on stainless steel surfaces and the coatings were observed by scanning electron microscopy (SEM) coupled with X‐ray analyses (EDX). The hydrolyzed additive was shown to both segregate and migrate towards the metal interface, leading to a preferential organization of the coating. Hence, the matrix at the air surface acts as a barrier to gas while the additive ensures adhesion at the polymer/metal interface.

SEM photograph of a section of the coating with formulation 4 [poly(VC₂‐co‐MA‐co‐MAPHOS(OH)₂) (75:14:11)].     

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.     

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.

     

Characterization of New Amphiphilic Block Copolymers of N‐Vinylpyrrolidone and Vinyl Acetate, 2 ‐ Chromatographic Separation and Analysis by MALDI‐TOF and FT‐IR Coupling

PVP‐block‐PVAc block copolymers were synthesized by controlled radical polymerization applying a RAFT/MADIX system and were investigated by HPLC and by coupling of chromatography to FT‐IR spectroscopy and MALDI‐TOF MS. Chromatographic methods (LACCC and gradient techniques) were developed that allowed a separation of block copolymers according to their repeating units. The results of the spectroscopic and spectrometric analysis clearly showed transfer between radicals and process solvent. With the use of hyphenated techniques differences between main and side products were detected. In agreement with previously published results, obtained by NMR, SEC, static light scattering and MALDI‐TOF MS, our data proved a non‐ideal RAFT polymerization.

     

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.

     

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.

     

Controlled RAFT Polymerization of N‐Vinylphthalimide and its Hydrazinolysis to Poly(vinyl amine)

Polymerization of NVPI was carried out by a RAFT process using five xanthate‐type, a dithiocarbamate‐type, and a dithioester‐type CTA. The xanthate‐type [O‐ethyl‐S‐(1‐ethoxy carbonyl) ethyl dithiocarbonate and O‐ethyl‐S‐(1‐ethoxycarbonyl‐1‐methyl)ethyl dithiocarbonate] and the dithiocarbamate‐type CTA (benzyl‐1‐pyrrolecarbodithioate) were the most efficient to obtain poly(NVPI) with controlled molecular weights ( = 4 100–13 000) and low polydispersities ( = 1.29–1.38). The effects of parameters such as solvent, temperature, and CTA‐to‐initiator molar ratio, were examined in order to determine the conditions leading to optimal control of the polymerization.

     

Visible Light Induced RAFT Polymerization of 2‐Vinylpyridine without Exogenous Initiators or Photocatalysts

The controlled radical polymerization of 2‐vinylpyridine is reported using commercial blue light‐emitting diodes as visible light source in the presence of S‐1‐dodecyl‐S′‐(α,α′‐dimethyl‐α″‐aceticacid) trithiocarbonate without exogenous initiators or photocatalysts. With this system, poly(2‐vinylpyridine) with well‐regulated molecular weight and narrow dispersity (?) (? = 1.13) and a conversion efficiency of 84.9% is obtained after 9 h irradiation. The polymerization can be instantly switch “on” or “off” in response to visible light while maintaining a linear increase in molecular weight with conversion and first order kinetics. These results demonstrate the simplicity and efficiency of the photocatalysts‐free, visible light mediated reversible addition fragmentation chain transfer polymerization as a platform to achieve well‐defined poly(2‐vinylpyridine) under mild conditions.

     

Kinetic Investigations of Quaternization Reactions of Poly[2‐(dimethylamino)ethyl methacrylate] with Diverse Alkyl Halides

Kinetic investigations of the quaternization reactions of poly[2‐(dimethylamino)ethyl methacrylate] (PDMAEMA) with alkyl halides (1‐iodobutane, 1‐iodoheptane, and 1‐iododecane) are carried out at different temperatures. For this purpose, a PDMAEMA (M_n = 17.8 kDa, Ð = 1.35) synthesized via reversible addition fragmentation chain transfer polymerization is utilized. The progress of the quaternization reactions is followed by proton nuclear magnetic resonance. As expected, the rate of quaternization is higher with increasing temperature. The experimental data are used to determine the following kinetic parameters: order of the reaction, Arrhenius' pre‐exponential factor, and activation energy. To the best of knowledge, this is the first contribution that provides detailed kinetic data of the quaternization reactions on PDMAEMA.     

Synthesis of α,ω‐Isocyanate–Telechelic Poly(methyl methacrylate)

The preparation of α,ω‐isocyanate–telechelic poly(methyl methacrylate) using RAFT polymerization and two postpolymerization modification steps is presented. The synthetic strategy includes the RAFT polymerization of methyl methacrylate, which results in a hetero telechelic polymer. In the first modification step by radical exchange, a carboxylic acid homo telechelic PMMA was successfully prepared. Second, the carboxylic acid end groups are reacted with hexamethylene diisocyanate in excess and magnesium chloride as a catalyst. Under mild reaction conditions (80 °C, 4 h), the isocyanate homo telechelic PMMA is obtained. A conversion of 86% of the carboxylic acid end groups was achieved.     

Synthesis and Characterization of Four‐Arm Star Polystyrene Based on a Novel Tetrafunctional RAFT Agent

Reversible addition fragmentation chain transfer polymerization (RAFT) is a very versatile polymerization technique whereby the topology of the final polymer can be tailored using specific RAFT agents. The tetrafunctional RAFT agent, tetrabenzyl(1,3‐dithietane‐2,2,4,4‐tetrayl)­tetracarbanotrithioate, has not previously been used to synthesize polymers. Poly­styrene (PS) is synthesized using this tetrafunctional RAFT agent and advanced characterization is performed using spectroscopic and separation methods. In situ ¹H nuclear magnetic resonance spectroscopy (NMR) and size‐exclusion chromatography (SEC) are used to determine the topology of the resultant PS. The polymerization is followed by in situ ¹H NMR, using styrene‐d₈ rather than hydrogenous styrene. In situ ¹H NMR spectra show that the RAFT agent is incorporated into the polymer as a terminal group. Aminolysis of the star‐shaped PS is performed and the SEC and NMR results before and after aminolysis are compared. These results indicate that the expected star‐shaped topology of the polymer is achieved.

     

Xanthate‐Mediated Controlled Radical Polymerization of N‐Vinylcarbazole

Summary: Well‐defined poly(N‐vinylcarbazole) [poly(NVC)] was synthesized by macromolecular design via interchange of the xanthates (MADIX)/reversible addition‐fragmentation chain transfer (RAFT) polymerization. The homopolymers with controlled molecular weights ( = 3 000–48 000) and low polydispersities indices ( = 1.15–1.20) were obtained by the polymerization of NVC with AIBN in the presence of O‐ethyl‐S‐(1‐phenylethyl) dithiocarbonate as a xanthate‐type chain transfer agent (CTA). Good control of the polymerization was confirmed by the linear first‐order kinetic plot, the molecular weight controlled by the monomer/CTA molar ratio, linear increase in the molecular weight with the conversion, and the ability to extend the chains by the second addition of the monomer.

Radical polymerization of NVC in the presence of CTA and plot of number‐average molecular weight (circles) and polydispersity (squares) as a function of conversion.     

Miscibility and Intermolecular Specific Interactions in Blends of Poly(hydroxyether sulfone) and Poly(N‐vinylpyrrolidone)

Summary: The blends of poly(hydroxyether sulfone) (PHES) with poly(N‐vinylpyrrolidone) (PVPy) were investigated by means of differential scanning calorimetry (DSC) and FTIR spectroscopy. The miscibility of the blend system was established on the basis of the thermal analysis results. DSC showed that the PHES/PVPy blends prepared by casting from N,N‐dimethylformamide (DMF) possessed single, composition‐dependent glass transition temperatures, indicating that the blends are miscible in the entire composition. The experimental glass transition temperatures have higher values than those calculated on the basis of additive behavior; the variation of the glass transition temperatures of the blends was accounted for by the Kwei equation. FTIR studies indicate that competitive hydrogen bonding interactions exist upon addition of PVPy to the system, which were involved in the self‐ and cross‐association, i.e., ? OH···O?S, ? OH···OH of PHES and ? OH···O?C< of PVPy. The FTIR spectra in the range of the sulfonyl stretching vibrations showed that the hydroxyl‐associated sulfonyl groups are partially “set free” upon addition of PVPy to the system. The IR spectroscopic investigation of both the model compounds and the PHES/PVPy blends suggests that the strength of the hydrogen bonding interactions in the blend system increases in the following order: ? OH···O?S, ? OH···OH and ? OH···O?C<.

Plot of glass transition temperature for PHES/PVPy blends as a function of weight fraction of PVPy. The prediction of the Kwei equation yields the values of k = 1 and q = 122.     

Benzoyl Peroxide/2‐Vinylpyridine Synergy in RAFT Polymerization: Synthesis of Poly(2‐vinylpyridine) with Low Dispersity at Ambient Temperature

Redox‐initiated reversible addition fragmentation chain transfer polymerization of 2‐vinylpyridine at room temperature without a conventional reducing agent has been realized in the presence of an oxidizing agent only, i.e., benzoyl peroxide. Well‐defined poly(2‐vinylpyridine) is obtained with a low dispersity (dispersity = M_w/M_n = 1.11) and a conversion efficiency of 41.4% after 24 h at 25 °C. The kinetics, number‐average molecular weight, and dispersities for the polymerization of 2‐vinylpyridine are investigated. The results indicate that the number‐average molecular weight of the poly(2‐vinylpyridine) increases with the monomer conversion while retaining relatively low dispersity (M_w/M_n < 1.20).

     

Synthesis of High‐Molecular‐Weight Brush Polymers via RAFT Polymerization within the Micellar Nanoreactor of a PEG‐Based Macromonomer

The RAFT polymerization of an amphipathic PEG‐based macromonomer (mPEG‐g‐S) in water is performed. It is found that the polymerization proceeds via a micellar polymerization process. The polymerization kinetics, polymer chain extension, and polymer particle evolution of RAFT micellar polymerization are evaluated. It is demonstrated that the polymerization possesses a fast rate and high monomer conversion due to locally concentrating and orienting the hydrophobic polymerizing groups within the micellar nanoreactor. Moreover, the RAFT micellar polymerization is under good control since the polydispersity index (PDI) value of the synthesized brush copolymer is below 1.3 in most cases, even under polymerization conditions with the ratio of RAFT agent to macromonomer at 1:400. Polymerization leads to the formation of a completely grafted brush copolymer, and the as‐synthesized brush copolymer will self‐assemble into spherical particles during the polymerization process. This strategy is anticipated to be an efficient way for the controlled synthesis of completely grafted brush polymers with high molecular weights and their corresponding self‐assembled particles.

     

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.

     

Aqueous Solutions of Poly[2‐(N‐morpholino)ethyl methacrylate]: Learning about Macromolecular Aggregation Processes from a Peculiar Three‐Step Thermoresponsive Behavior

Aqueous solutions of narrowly distributed poly[2‐(N‐morpholino)ethyl methacrylate], a biocompatible multiple stimuli‐responsive polymer, show a peculiar three‐step aggregation behavior upon heating, an effect which has hitherto barely been reported for other polymers. The phenomenon is discussed in terms of mesoglobule formation (first step) as well as by an unusual distinct disruption of hydrophobic hydration (second step) and hydrogen bonding to the hydrophilic aggregate surface (third step). Macroscopic precipitation only takes place after the third step, a behavior which resembles the denaturation and limited aggregation of proteins. Furthermore, the influence of different anions along the Hofmeister series is investigated, identifying salting‐out (kosmotropic) and salting‐in (chaotropic) effects. As an experimental tool to monitor the thermally induced aggregate growth, dynamic light scattering is used. The reported findings might lead to a more detailed understanding of both aggregation behavior of (biological) macromolecules and mechanistic processes involved in thermoresponsivity and salt‐responsivity of water soluble polymers.

     

Characterization and Properties of Poly[N‐(2‐cyanoethyl)pyrrole]

PNCPy was prepared by anodic polymerization and its properties in both doped and undoped state were characterized. The doping level of the oxidized material has been found to be larger than that of other conducting polymers; the more relevant electrochemical properties of the doped material were retained after undoping. SEM and AFM data are consistent with a lumpy surface and a multidirectional growing of the polymer chains. Finally, PNCPy has been combined with PEDOT to prepare three‐layer systems with enhanced electroactivity and electrostability. Results suggest that PNCPy is a potential candidate for the fabrication of electric circuit components that are able to block the current flow below a given potential.