Vural Bütün

Synthesis and aqueous solution properties of near-monodisperse tertiary amine methacrylate homopolymers and diblock copolymers

Group transfer polymerisation (GTP) of four tertiary amine methacrylates, 2-(dimethylamino)ethyl methacrylate (DMA), 2-(diethylamino)ethyl methacrylate (DEA), 2-(diisopropylamino)ethyl methacrylate (DPA) and 2-(N-morpholino)ethyl methacrylate (MEMA) produced a series of near-monodisperse homopolymers (Mw/Mn<1.15). Molecular weights were controlled by varying the monomer/initiator ratio. The DMA and MEMA homopolymers were both water-soluble at 20°C in acidic or neutral media. Inverse temperature solubility behaviour was observed at higher temperatures, with cloud-points ranging from 32 to 53°C at pH 8. The Cloud-points decreased monotonically with increasing degrees of polymerisation, as expected. The MEMA homopolymers were particularly sensitive to the added electrolyte, with ‘salting out’ occurring at 20°C on addition of 0.2–0.3 M Na2SO4. The more hydrophobic DEA and DPA homopolymers were both insoluble at 20°C and neutral pH but readily dissolved as cationic polyelectrolytes in acidic media due to protonation of the tertiary amine residues. In addition, DMA was block copolymerized in turn with each of the other three tertiary amine methacrylate comonomers. These diblock copolymers could be dissolved molecularly without co-solvents in aqueous media at 20°C, with micellization occurring reversibly on judicious adjustment of the solution pH, temperature or electrolyte concentration. In all three cases, stable block copolymer micelles were formed with DMA coronas and hydrodynamic diameters of 20–60 nm.

pH-Responsive polymers

In this review, we provide an analysis of some of the recent literature reports on the synthesis and applications of pH-responsive polymers. Depending on the solution pH, such copolymers can self-assemble and form various nanosized structures including core–shell micellar structures, micelles/reverse micelles, hollow spheres, vesicle structures, adsorbed species at the water–air interface, and more complex architectures. Their self-assembly behaviors open the door for the production of various novel nanostructures including shell/core cross-linked micelles, hollow spheres, hydrogels, microgels, layer-by-layer (LbL) nanofilms, controlled releasing systems, drug carrier systems, etc. The review consists of various major parts including types of pH-responsive polymers, synthetic methods for their synthesis and their solution behaviors, their nanostructures in aqueous media, applications as LbL nanofilms, delivery devices, controlled release systems, sensors, stabilizers, solubilizers, etc. In the last two decades, there have been great developments in synthetic methods and strategies for the preparation of novel pH-responsive polymers or polymeric materials providing possible materials for various applications including biotechnology, nanotechnology, colloid and surface science, materials science, etc.

Use of oxyanion-initiated polymerization for the synthesis of amine methacrylate-based homopolymers and block copolymers

Abstract A series of amine methacrylate homopolymers, diblock copolymers and triblock copolymers has been synthesized using oxyanion-initiated polymerization. The amine methacrylate monomers of interest were 2-(dimethylamino)ethyl methacrylate (DMA), 2-(diethylamino)ethyl methacrylate (DEA), 2-( N -morpholino)ethyl methacrylate (MEMA) and t -(butylamino)ethyl methacrylate (BAE). In most experiments potassium benzyl alcoholate was utilized as an initiator since this facilitated both UV GPC studies and end group analysis using 1 H NMR spectroscopy. For the homopolymerization of DMA, molecular weights increased linearly with conversion and polydispersities were reasonably narrow. Together with successful block copolymer formation, this constitutes good evidence for the “living” character of oxyanion-initiated polymerization. Most of the diblocks are novel copolymers and selected copolymers undergo reversible temperature-induced micellization in aqueous media. NMR studies confirmed that the DMA residues of a DMA–BAE diblock copolymer could be selectively quaternized using a stoichiometric amount of methyl iodide under mild conditions. Finally, shell cross-linked micelles could be prepared from ABC triblock copolymers. The C block formed the core, the B block contained cross-linkable residues and the A block acted as a steric stabilizer and prevented inter-micelle aggregation even when the cross-linking chemistry was carried out at high copolymer concentrations.

Selective betainisation of tertiary amine methacrylate blockcopolymers

2-(Dimethylamino)ethyl methacrylate (DMAEMA) was block copolymerised in turn with three other tertiary amine methacrylate comonomers using group transfer polymerisation; the DMAEMA residues of each of these diblock copolymers wereselectively betainised using propane-1,3-sultone under mild conditions to yield a series of novel water-soluble sulfobetaine block copolymers which exhibit reversible pH- and temperature-induced micellisation.

pH-responsive layer-by-layer films of zwitterionic block copolymer micelles

We report a strategy to incorporate micelles of poly[3-dimethyl (methacryloyloxyethyl) ammonium propane sulfonate]-block-poly[2-(diisopropylamino)ethyl methacrylate] (βPDMA-b-PDPA) into electrostatic layer-by-layer (LbL) films. We obtained micelles with pH-responsive PDPA-cores and zwitterionic βPDMA-coronae at pH 8.5 through pH-induced self-assembly of βPDMA-b-PDPA in aqueous solution. To incorporate βPDMA-b-PDPA micelles into LbL films, we first obtained a net electrical charge on βPDMA-coronae. Negative charges of the zwitterionic units were screened through complexation of βPDMA-b-PDPA micelles and poly(allylamine hydrochloride) (PAH). Positively charged micellar complexes were then self-assembled at the surface using poly(sodium 4-styrenesulfonate) (PSS). The pH-stability of the multilayers was examined by exposing the films to decreasing pH values. Despite the disintegration of micellar complexes below pH 7, no change in film thickness was recorded between pH 8.5 and 3.5. Only ∼20% of the film released at pH < 3.5. Moreover, we demonstrated that when multilayers were exposed to decreasing pH at a temperature below the upper critical solution temperature (UCST) of betainized coronal chains, the film thickness increased by 20% between pH 4.5 and 3. This is probably due to phase separation of the corona block and formation of voids within the film, probably entrapping water molecules within the multilayers. Decreasing temperature also shifted the critical disintegration pH (onset of multilayer dissolution) to a slightly lower pH. By taking advantage of the pH-responsive cores, we showed that multilayers were capable of releasing functional molecules under moderately acidic conditions. Important biological properties of polybetaines, higher loading capacity of zwitterionic block copolymer micelles than linear polybetaines and pH-response of the multilayers at physiologically related pH values make such films promising for biomedical applications.

Novel Multiresponsive Microgels: Synthesis and Characterization Studies

The dispersion polymerization of 2-(N-morpholino)ethyl methacrylate (MEMA) in the presence of ethylene glycol dimethylacrylate (EGDMA) cross-linker and diblock copolymer stabilizer in n-hexane afforded sterically stabilized multiresponsive PMEMA microgels. By changing the reaction parameters, a wide range of particle sizes (120-720 nm) was obtained. Both dynamic light scattering and electron microscopy studies confirmed monodisperse spherical morphologies. These microgels had a response to the solution pH, temperature, and ionic strength. As expected, PMEMA microgels acquired cationic character at low pH because of the protonation of all morpholino groups. Although PMEMA microgels are in a swollen state in both acidic media and at low temperatures, they are in a deswollen state in basic media at high temperatures and in the presence of electrolytes above pH 6. In addition to these multiresponsive behaviors, PMEMA microgels have the ability to swell in various organic solvents. They also interact very well with magnetic particles and gain responsiveness to the magnetic field. Multiresponsive behaviors of PMEMA microgels were investigated by using DLS, UV-vis spectrophotometry, and zeta potentiometry.

Novel zwitterionic ABA-type triblock copolymer for pH- and salt-controlled release of risperidone

ABSTRACT An ABA-type triblock copolymer was synthesized through group-transfer polymerization by using poly[2-(diethylamino) ethyl methacrylate] (PDEA) as A block and poly[2-(dimethylamino) ethyl methacrylate] (PDMA) as B block. By utilizing the 1,3-propane sultone to obtain polyzwitterionic triblock copolymer under moderate conditions, PDMA block of the triblock copolymer has been selectively betainized. The selectively betainized block copolymer and its precursor were molecularly dissolved in acidic aqueous media without any use of cosolvent at room temperature. In both cases, an increase in solution pH caused near monodisperse cationic or neutral flower-like micellization with hydrophobic PDEA-core at basic aqueous solution. However, at higher polymer concentrations where precursor triblock copolymer does not exhibit any gelling behavior (10% and higher), polyzwitterionic copolymer derivative can be gelated as a result of inter-chain integration of polyzwitterionic groups. Furthermore, the load of risperidone (RISP) into gel matrix and release studies have been successively realized. The results indicated that the betainized novel gel is appropriate for using as a pH- and salt-controlled risperidone-releasing system. GRAPHICAL ABSTRACT

Bacterial anti-adhesive and pH-induced antibacterial agent releasing ultra-thin films of zwitterionic copolymer micelles☆

UNLABELLED We report on preparation of substrates with dual function coatings, i.e. bacterial anti-adhesive and antibacterial agent releasing polymer films of zwitterionic block copolymer micelles (BCMs). BCMs were obtained by pH-induced self-assembly of poly[3-dimethyl (methacryloyloxyethyl) ammonium propane sulfonate-b-2-(diisopropylamino)ethyl methacrylate] (βPDMA-b-PDPA), resulting in BCMs with zwitterionic βPDMA-coronae and pH-responsive PDPA-core. These zwitterionic BCMs were then used as building blocks to construct mono- and multi-layer films. We found that the number of layers in the film was critical for the anti-adhesive property and 3-layer films were the most anti-adhesive against a model Gram-positive bacterium, Staphylococcus aureus. Antibacterial activity could be introduced to the films by loading Triclosan into βPDMA-b-PDPA micelles. Triclosan containing films were effective against Triclosan-sensitive Staphylococcus aureus specifically at moderately acidic conditions due to pH-induced disintegration of the micellar core blocks and release of Triclosan from the surface. Three-layer films also exhibited anti-adhesive property at physiological pH against a model Gram-negative bacterium, Escherichia coli. At moderately acidic pH, the coatings showed a contact antibacterial effect against an isolate of Escherichia coli with low sensitivity to Triclosan only when micellar cores were loaded with Triclosan. Such dual function films can be promising to combat biofouling at the non-homogeneous and/or defective parts of an anti-adhesive coating. Moreover, considering the moderately acidic conditions around an infection site, these multilayers can be advantageous due to their property of pH-induced antibacterial agent release. STATEMENT OF SIGNIFICANCE This study presents preparation of substrates with dual function ultra-thin coatings of zwitterionic block copolymer micelles which show bacterial anti-adhesive properties against a Gram-positive and a Gram-negative bacterium. Such coatings are also capable of releasing antibacterial compounds in response to pH changes. Films were prepared by self-assembly of polymers at the surface. Our findings showed that zwitterionic micellar coronae introduced bacterial anti-adhesive property to the films, whereas pH-responsive micellar cores enabled release of an antibacterial agent from the surface at acidic pH. Considering the moderately acidic conditions around an infection site, such multilayers can be promising for the coating of implants/medical devices.

Bacterial anti-adhesive properties of a monolayer of zwitterionic block copolymer micelles.

We report on bacterial anti-adhesive properties of a monolayer of block copolymer micelles (BCMs) with zwitterionic coronae and pH-responsive cores. BCMs were obtained by pH-induced self-assembly of selectively betainized poly[3-dimethyl (methacryloyloxyethyl) ammonium propane sulfonate-b-2-(diisopropylamino)ethyl methacrylate] (βPDMA-b-PDPA) in aqueous solution above neutral pH. Monolayer films were self-assembled at pH 7.5 when βPDMA-b-PDPA was in the micellar form. Bacterial anti-adhesive properties of the zwitterionic micellar coatings were examined against S. aureus through: i) a macroscopic test based on viable cell counting; ii) direct microscopic visualization of adherent bacteria by live/dead staining and iii) crystal violet staining to evaluate surface adherent biomass. 95% reduction in cell adhesion was observed by microscopy indicating the anti-adhesive properties of βPDMA-b-PDPA micellar monolayer. Results obtained from the viable cell count assay and crystal violet staining showed similar trends and were in good agreement with the microscopy results. Such coatings are promising to impart both anti-adhesive and antimicrobial properties to a surface due to bacterial anti-adhesive properties of zwitterionic coronae and the potential of pH-responsive cores to release antimicrobial agents.

Characterization of PDPA-b-PDMA-b-PDPA triblock copolymer Langmuir-Blodgett films for organic vapor sensing application

ABSTRACT This study reports the synthesis, characterization, and gas sensing applications of the PDPA-b-PDMA-b-PDPA triblock copolymer material using NMR, UV-visible spectroscopy, atomic force microscopy (AFM), quartz crystal microbalance (QCM), and Langmuir-Blodgett (LB) thin film deposition techniques. The thin film deposition conditions of the copolymer material, which are prepared by LB film technique, are characterized by UV-visible spectroscopy, AFM, and QCM system. In this study, the swelling behaviors of the PDPA-b-PDMA-b-PDPA triblock copolymer Langmuir-Blodgett (LB) films were investigated with respect to volatile organic compounds (VOCs) at room temperature. The sensing responses of the films against VOCs were measured by QCM method. The swelling processes could be investigated using the early-time Ficks law of diffusion.