A sequential native chemical ligation – thiol-Michael addition strategy for polymer–polymer ligation

Native Chemical Ligation (NCL) between cysteine-terminated polymers and functional thioesters has been employed to prepare functional (co)polymers. The retained thiol functionality at the NCL junction can be exploited for thiol-Michael addition

Polyurea microcapsules from isocyanatoethyl methacrylate copolymers

The synthesis of two types of isocyanate side chain containing copolymers, poly(methyl methacrylate-co-isocyanatoethyl methacrylate) (P(MMA-co-IEM)) and poly(benzyl methacrylate-co-isocyanatoethyl methacrylate) (P(BnMA-co-IEM)), which were synthesized by Cu(0)-mediated radical polymerization, is reported. Polymerization proceeded to high conversion giving polymers of relatively narrow molar mass distributions. The incorporation of the bulky aromatic groups in the latter copolymer rendered it sufficiently stable toward hydrolysis and enabled the isolation of the product and its characterization by 1 H and 13C NMR, and FTIR spectroscopy and SEC. Both P(MMA-co-IEM) and P(BnMA-co-IEM) were functionalized with dibutylamine, octylamine, and (R)-(1)-a-methylbenzyl-amine, which further proved the successful incorporation of the isocyanate groups. Furthermore, P(BnMA-co-IEM) was used for the fabrication of liquid core microcapsules via oil-in-water interfacial polymerization with diethylenetriamine as crosslinker. The particles obtained were in the size range of 10–90 mm in diameter independent of the composition of copolyme

Polymerisation of 2-acrylamido-2-methylpropane sulfonic acid sodium salt (NaAMPS) and acryloyl phosphatidylcholine (APC) via aqueous Cu(0)-mediated radical polymerisation

The scope of aqueous Cu(0)-mediated living radical polymerisation has been expanded with the preparation of poly(2-acrylamido-2-methylpropane sulfonic acid sodium salt (P(NaAMPS)) and poly(acryloyl phosphatidycholine) (PAPC). Manipulation of the reaction conditions furnishes polymers capable of undergoing chain extension and supporting the synthesis of block copolymers at 0 °C

Unraveling the spontaneous zwitterionic copolymerization mechanism of cyclic imino ethers and acrylic acid

We report a high-resolution electrospray ionization mass spectrometric (HR ESI MS) access route leading to in-depths insight into the spontaneous zwitterionic copolymerization mechanism between cyclic imino ethers (i.e. 2-methyl-2-oxazoline (MeOx), 2-ethyl-2-oxazoline (EtOx) or 2-ethyl-2-oxazine (EtOz)) with acrylic acid (AA), exploiting the characteristic species accumulating during the copolymerization as well as tandem mass spectrometry (MS/MS). We demonstrate preferences in α,ω-end group formation by screening various feed ratios of cyclic imino ethers and acrylic acid (e.g. MeOx:AA = 1:1; MeOx:AA = 2:1; MeOx:AA = 1:2). Critically, a calibration curve – based on AA-MeOx-AA dimer – was established allowing for semi-quantitative determination of the end group ratios with different feed ratios of acrylic acid. The formation of, previously suggested, alternating copolymers was confirmed by MS/MS experiments. Deviations from an ideal alternating composition were found to decrease from MeOx to EtOx to EtOz. The results of (semi-quantitative) HR ESI MS and MS/MS measurements suggest, for the first time presented in such precision, a polymerization mechanism for the spontaneous zwitterionic (alternating) copolymerization indicating optimal monomer ratios and pairings

Thermal study on polyester networks based on the renewable monomers citric acid and gluconolactone

A detailed thermal study is presented of the melt polycondensation between the renewable monomers citric acid and d-glucono-δ-lactone. It was found that the polyester networks formed have glass transition temperature ranges that increase with increasing reaction temperature and time, corresponding to an increase in molecular weight. The minimum reaction temperature was investigated and found to be 130 °C for a 1/1 system. Moreover, the monomers show eutectic melt behaviour, with a eutectic melting temperature of 125 °C. A range of additional co-monomers were evaluated, revealing that aliphatic and aromatic bifunctional co-monomers result in lower glass transition temperatures. When polyfunctional co-monomers were employed it was found that the chain flexibility influenced the resulting thermal properties. Moreover, it is shown that the ring structure of d-glucono-δ-lactone plays a key role in the thermal properties of the resulting polyesters. © 2016 Society of Chemical Industr

Well-defined PDMAEA stars via Cu(0)-mediated reversible deactivation radical polymerisation

The Cu(0)-mediated reversible deactivation radical polymerisation of N,N’-dimethylaminoethyl acrylate in DMSO and IPA at ambient temperature using Cu(0) wire is investigated. Tetra-functional and octa-functional initiators were utilised to facilitate the synthesis of well-defined PDMAEA star homo and block copolymers with a range of molecular weights (Mn ~ 5000-41000 g mol-1). Both solvents demonstrated to be excellent media for the controlled polymerisation of DMAEA yielding narrow molecular weight distributions (Ð ~ 1.1) when the reactions were ceased at ~ 40% conversion. Interestingly, at high conversions (typically > 55%) high and low molecular weight shoulders were evident by SEC when DMSO and IPA were used respectively, suggesting large extent of termination and/or side reactions at prolonged reaction times. Nevertheless, high end group fidelity could be maintained when immediate precipitation of the polymers (at lower conversion) was performed yielding low dispersed P(DMAEA-b-MA) star block copolymers (Ð < 1.19, Mn ~ 20000 g mol-1). Importantly, guidelines on how to prevent hydrolysis, termination and side reactions of PDMAEA as well as how to purify and store such materials are also provided and discussed

Synthesis of well-defined catechol polymers for surface functionalization of magnetic nanoparticles

In order to obtain dual-modal fluorescent magnetic nanoparticles, well-defined fluorescent functional polymers with terminal catechol groups were synthesized by single electron transfer living radical polymerization (SET-LRP) under aqueous conditions for “grafting to” modification of iron oxide nanoparticles. Acrylamide, N-isopropylacrylamide, poly(ethylene glycol) methyl ether acrylate, 2-hydroxyethyl acrylate, glycomonomer and rhodamine B piperazine acrylamide were homo-polymerized or block-copolymerized directly from an unprotected dopamine-functionalized initiator in an ice-water bath. The Cu-LRP tolerated the presence of catechol groups leading to polymers with narrow molecular weight distributions (Mw/Mn < 1.2) and high or full conversion obtained in a few minutes. Subsequent immobilization of dopamine-terminal copolymers on an iron oxide surface were successful as demonstrated by Fourier transform infrared spectroscopy (FTIR), dynamic light scattering (DLS), transition electron microscopy (TEM) and thermogravimetric analysis (TGA), generating stable polymer-coated fluorescent magnetic nanoparticles. The nanoparticles coated with hydrophilic polymers showed no significant cytotoxicity when compared with unmodified particles and the cellular-uptake of fluorescent nanoparticles by A549 cells was very efficient, which also indicated the potential application of these advanced nano materials for bio-imaging

Stability enhancing N-Terminal PEGylation of oxytocin exploiting different polymer architectures and conjugation approaches

Oxytocin, a cyclic nine amino acid neurohypophyseal hormone therapeutic, is effectively used in the control of postpartum hemorrhaging (PPH) and is on the WHO List of Essential Medicines. However, oxytocin has limited shelf life stability in aqueous solutions, particularly at temperatures in excess of 25 °C and injectable aqueous oxytocin formulations require refrigeration (<8 °C). This is particularly problematic in the hot climates often found in many developing countries where daytime temperatures can exceed 40 °C and where reliable cold-chain storage is not always achievable. The purpose of this study was to develop N-terminal amine targeted PEGylation strategies utilizing both linear PEG and polyPEG “comb” polymers as an effective method for stabilizing solution formulations of this peptide for prolonged storage in the absence of efficient cold-chain storage. The conjugation chemistries investigated herein include irreversible amine targeted conjugation methods utilizing NHS ester and aldehyde reductive amination chemistry. Additionally, one reversible conjugation method using a Schiff base approach was explored to allow for the release of the native peptide, thus, ensuring that biological activity remains unaffected. The reversibility of this approach was investigated for the different polymer architectures, alongside a nonpolymer oxytocin analogue to monitor how pH can tune native peptide release. Elevated temperature degradation studies of the polymer conjugates were evaluated to assess the stability of the PEGylated analogues in comparison to the native peptide in aqueous formulations to mimic storage conditions in developing nations and regions where storage under appropriate conditions is challenging

Engineered hydrogen-bonded glycopolymer capsules and their interactions with antigen presenting cells

Hollow glycopolymer microcapsules were fabricated by hydrogen-bonded layer-by-layer (LbL) assembly, and their interactions with a set of antigen presenting cells (APCs), including dendritic cells (DCs), macrophages (MACs), and myeloid derived suppressor cells (MDSCs), were investigated. The glycopolymers were obtained by cascade postpolymerization modifications of poly(oligo(2-ethyl-2-oxazoline methacrylate)-stat-glycidyl methacrylate) involving the modification of the glycidyl groups with propargylamine and the subsequent attachment of mannose azide by copper(I)-catalyzed azide–alkyne cycloaddition (CuAAC). Multilayer assembly of the hydrogen-bonding pair (glycopolymer/poly(methacrylic acid) (PMA)) onto planar and particulate supports (SiO2 particles, d = 1.16 μm) yielded stable glycopolymer films upon cross-linking by CuAAC. The silica (SiO2) particle templates were removed yielding hollow monodisperse capsules, as demonstrated by fluorescence and scanning electron microscopy. Cellular uptake studies using flow cytometry revealed the preferential uptake of the capsules by DCs when compared to MACs or MDSCs. Mannosylated capsules showed a cytokine independent cis-upregulation of CD80 specifically on DCs and a trans-downregulation of PDL-1 on MDSCs. Thus, the glycopolymer capsules may have potential as vaccine carriers, as they are able to upregulate costimulatory molecules for immune cell stimulation on DCs and at the same time downregulate immune inhibitory receptors on suppressor APC such as MDSCs

Controlled aqueous polymerization of acrylamides and acrylates and “in situ” depolymerization in the presence of dissolved CO2

Aqueous copper-mediated radical polymerization of acrylamides and acrylates in carbonated water resulted in high monomer conversions (t t > 10 min). The regenerated monomer was characterized and repolymerized following deoxygenation of the resulting solutions to reyield polymers in high conversions that exhibit low dispersities