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Synthetically straightforward conditions have been developed for the preparation of poly(bis 2,2,2-trifluoroethoxy)- phosphazene with low PDI (

Linear poly(ethylenimine) is a cationic polymer that is actively being progressed into clinical trials for gene therapy. The existing synthetic methodology produces a relatively broad distribution of molecular weights. We describe an improved method of polymerizing 2-alkyl-2-oxazolines as a route to linear poly(ethylenimine). By using an apolar noninterfering solvent (chlorobenzene) at low temperature (∼42 °C), the polymerization of 2-isopropyl-2-oxazoline proceeds much more rapidly than is observed in acetonitrile, and with far fewer side reactions. 1H NMR observations showed close ion pairing at the propagating center (vice free ions in acetonitrile) to form a propagating complex of greater reactivity than free oxazolinium ions. Our results indicate that uniform or near uniform (“monodisperse”) polymers can be synthesized with nominal deviation from the theoretically achievable Poisson distributions.

Poly(ethylene glycol) [1, PEG(similar to 4)(OH)2, M-n similar to 2001, glycerol ethoxylate [2, PEG(similar to 21)(OH)3, M-n similar to 1000] and pentaerythritol ethoxylate [3, PEG(similar to 15)(OH)(4), M-n similar to 797] react directly with phenyl-C-61-butyric acid methyl ester (PCBM), in the presence of dibutyltinoxide (DBTO) catalyst at 140 degrees C, to give a mixture of fullerene [C-60] end-capped PEGs via transesterification. Among these PEG linkers, only PEG(similar to 4)(OPCB)(2) (4a) (OPCB: ester oxygen linked phenyl-C-61-butyryl group) was successfully isolated from the crude product mixture in the fully end-capped form. Fully acylated PEG(similar to 21)(OPCB)(3) (5) and PEG(similar to 15)(OPCB)(4) (6) could not be separated chromatographically from incompletely reacted species due to the polydispersity in branch lengths. This purification challenge was overcome by using a monodisperse branched core, 1,3,5-tris-(Octagoloxymethyl)benzene [7, PEG(24)(OH)(3)] to give a monodisperse tris-fullerene homostar, PEG(24)(OPCB)(3) (8). The structures of the bis- and tris-fullerene products were confirmed by MALDI-TOF mass spectrometry and H-1 NMR spectroscopy with supporting FTIR and UV-vis spectroscopic analysis.

In order to develop inks suitable for roll-to-roll printing processes, which can be cured into in situ electrolyte filled high porosity macroporous polymer membranes, non-aqueous high internal phase emulsions (HIPEs) were prepared. The external phase of the formulated HIPEs consisted of lauryl methacrylate (LMA) and 1,14-tetradecanediol dimethacrylate (TDDMA) while a solution of bis(trifluoromethane)sulfonimide lithium salt (LiTFSI) in a mixture of ethylene (EC) and propylene carbonate (PC) served as the internal phase. The stability of these non-aqueous HIPEs was strongly affected by the surfactant and the LiTFSI concentration in the internal phase. HIPE templates could only be polymerised when the LiTFSI concentration varied between 0.06 and 0.8 mol l−1. Electrochemical, thermal properties as well as morphology of the resulting polyHIPEs are discussed with respect to HIPE composition. The ionic conductivity of the resulting polyHIPEs was measured to be in the range from 4.18 to 8.64 mS cm−1.

A series of methacrylate-crosslinked polymers were investigated as potential polymer electrolytes for energy storage application. Methacrylate ester crosslinkers (25–50 mol.%) with different spacer lengths and MMA as comonomer were polymerised into thin films. Mixtures of ethylene carbonate and propylene carbonate (EC/PC) or alternatively the ionic liquid 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide (EMIM TFSI), both doped with lithium bis(trifluoromethane)sulfonimide (LiTFSI), fulfilled the role of electrolyte and porogen simultaneously. Ionic conductivity increased with increasing porogen content, Li ion concentration, and decreasing amounts of crosslinker (maximum values: 0.5 mS/cm (EC/PC) and 4.5 mS/cm (EMIM TFSI)). Thin films with permanent porosity were obtained for both electrolyte systems. The flexibility of the films increased with a lower concentration of crosslinker or the choice of a crosslinker with a longer spacer. The relationship between pore size, pore morphology, glass transition temperature and ionic conductivity on the other hand was complex and did not exhibit distinct trends. High thermal stability, ionic conductivity and tunable mechanical properties make these polymer thin films attractive candidates as in situ filled Li ion battery separator films either preformed or directly printed.

A versatile method to prepare non-covalently crosslinked polyHIPEs hydrogels from oil-in-water high internal phase emulsions (HIPEs) whose aqueous phase contained thermo-responsive linear polymers is described. The interconnected pore structure of the polyHIPEs is maintained by reversible physical aggregation of thermo-responsive polymer chains in an aqueous environment. This method to prepare interconnected porous hydrogels using a thermal trigger in the guise of thermo-responsive polymers by emulsion templating requires no chemical reaction during solidification of the template. This particular feature could provide a safer route to injectable scaffolds as issues of polymerisation/crosslinking chemistry and residual initiator fragments or monomers do not arise.

Stable high internal phase emulsions (HIPEs) with the ionic liquid 1-ethyl-3-methylimidazolium bis(trifluoromethyl-sulfonyl)imide as dispersed phase were prepared and polymerised thermally into polyHIPEs. All polyHIPEs exhibited pore morphologies similar to that of polyHIPEs obtained with an aqueous dispersed phase. PolyHIPEs containing the dispersed phase possess a low T(g) and are thermally stable in excess of 200 °C, offering the potential for new porous materials where water as dispersed phase is chemically or physically undesirable.

In recent years genetic modification of cells has promised to revolutionize medicine by offering novel therapeutic approaches in a range of diseases. However, lack of effective means of delivery has so far limited therapeutic applications. Polymeric vectors have been a much-investigated area of non-viral gene delivery but until recently the focus has been on plasmid DNA (pDNA) delivery. Current research suggests that polymer-mediated siRNA delivery is gaining momentum. Previous work in our group has resulted in an effective non-cytotoxic alternative to PEI for pDNA delivery in the lungs, using the reductive environment of the cytoplasm as a means of triggering polymer degradation. Here we present a review covering delivery of either pDNA or siRNA to the lungs, using different polymers. We critically review the key structural polymer characteristics for efficient gene lung delivery. We conclude that for highly efficient pulmonary gene delivery, non-toxic, bioresponsive polymers are required transfer the nucleic acid and genetically modify the lung tissue.

Poly(vinyl ether) gels SLURPS (Superior Liquid Uptake Resin for Polymer-supported synthesis) with low cross-linking levels have been synthesized for the first time in beaded form using a non-aqueous inverse suspension polymerisation approach. The synthetic protocol was optimized with regards to several parameters including reactions conditions, type and concentration of suspension stabilizer and controlled low temperature addition of co-initiator. Particle size measurements confirm the production of beads with average diameters of 700e950 mm. Optimization of the monomer composition of the poly (vinyl ether) gels resulted in a novel beaded polymer support with considerably improved as well as unique swelling characteristics in solvents ranging from hexane to water. The synthetic utility of the new gel was confirmed by carrying out a set of transformations with complete conversion leading to a useful amino and hydroxy terminated solid-phase precursor resin. Reaction progress could be monitored easily by 1 H and 13C gel-phase NMR

Spiral-wound modules of solvent stable integrally skinned asymmetric nanofiltration membranes made from polyaniline (PANI) are reported. PANI membranes were made by phase inversion and crosslinked by chemical and thermal processes. In the chemical crosslinking process, PANI membrane cast on polypropylene non-woven backing was crosslinked using glutaraldehyde, and a 1.8 in. spiral-wound module was prepared. To crosslink membranes thermally, a 1.8 in. spiral-wound membrane module prepared from PANI membrane cast on polyester non-woven backing was heated at 180 °C for 2 h. The resultant membranes and modules were found to be stable in various organic solvents including acetone, tetrahydrofuran and N,N -dimethyl formamide. Filtrations carried out in acetone, tetrahydrofuran and dimethyl formamide gave stable permeate fluxes and good separation performances in the nanofiltration range. Molecular weight cut-off (MWCO) of the membranes was dependent on the nature of the solvent and temperature. MWCO of PANI membranes in different solvents was found to lie between 150 and 300 g mol −1 at 30 °C. The membranes were also found to be stable for operations at elevated temperatures up to 65 °C and possibly higher. These membranes retain their nanofiltration properties even after drying so the use of conditioning or preservative agents can be avoided.

A new family of functional materials is reported for organic solvent nanofiltration, with excellent chemical stability and high retention of solute molecules. Integrally skinned asymmetric polyaniline (PANI) membranes were fabricated from concentrated solutions of doped PANI by phase inversion. Doped PANI solutions were prepared by adding organic acids directly to PANI dissolved in a mixture of NMP and 4-methyl piperidine before casting. Among the organic acids investigated, maleic acid, phthalic acid, sulfosalicylic acid and camphorsulfonic acid were able to dope PANI without causing gelation. These acids acted as soft templates, creating nanoporosity in the thin skin layer of the asymmetric PANI film. Their removal by alkaline extraction created membranes through which small solvent molecules can pass. After extracting the organic acids, the membranes were thermally crosslinked which conferred excellent solvent stability. These membranes had a molecular weight cut-off (MWCO) in the range of 150–250 g mol−1 in methanol, making them the tightest OSN membranes reported to date. It was found that an increase in crosslinking temperature or time led to a decrease in solvent flux. PANI membranes were found to be resistant to a variety of organic solvents such as ethyl acetate, acetonitrile and acetone. These remarkable membranes have the potential to be used in OSN operations at high temperatures (up to 150 °C), and gave increasing fluxes with increasing temperature while maintaining a high solute rejection.

Solvent stable integrally skinned asymmetric nanofiltration membranes were prepared from polyaniline. These membranes were made by phase inversion and then crosslinked using two different chemical crosslinkers, α,α′-dichloro- p -xylene and glutaraldehyde. The resultant membranes were found to be stable in various organic solvents including acetone, methanol, ethyl acetate, tetrahydrofuran and N , N -dimethyl formamide. Nanofiltration experiments carried out in acetone and dimethyl formamide showed that the membranes gave stable permeate fluxes and good separation performances in the nanofiltration range. Molecular weight cut-off (MWCO) of the membranes was found to be between 150 and 250 g mol −1 . These membranes were also found to be stable for operations at elevated temperatures up to 70 °C and possibly higher. Furthermore, no fillers or preservative agents are required to maintain the membranes in a dry state thereby increasing the ease of handling.

Here we present the synthesis and characterization of pH responsive polyacrylamide microgels, synthesized via free radical polymerization of acrylamide and bis (acryloylcystamine) (BAC). The gels were made with ultralow amounts of thiol functional groups incorporated into the polymer. The resulting gel monoliths were mechanically chopped into microgel particles with size distributions ranging from 80 to 200 mum. The gels exhibit an interesting reversible pH-dependent rheological behavior which led to gelling of the colloidal suspension when the pH was increased, and a low-viscosity suspension was obtained when the pH was taken back to the original value. The viscosity of the colloidal system containing MBA crosslinked microgels remained insensitive to pH. This observation motivated further analysis; viscosity measurements of the highly viscous (gel-like) state of the BAC crosslinked microgel colloidal suspension were carried out to further understand the rheological behavior of the colloidal system. Electrophoretic mobility measurements as function of pH of the BAC and MBA crosslinked colloidal polyacrylamide microgel suspensions were performed. The swelling behavior of the microgels for both colloidal systems was also determined as function of pH using static light scattering. This swelling behavior was used to rationalize the observed rheological behavior. The work presented here demonstrates that free thiol groups present within a polymer gel matrix confer pH responsive behavior to the gel in solution. The viscosity of a BAC crosslinked microgel suspension was also measured under reducing conditions. The viscosity of the microgel suspension reduced with time, due to the breakage of the disulfide bonds in the crosslinkers.

A systematic study of the ruthenium-catalysed metathesis of alkenes containing hydrogen-bonding substituents (namely urea and thiourea groups) is presented. Under standard metathesis conditions, several of the substrates under study undergo alkene isomerisation instead of the targeted metathesis. However, in the course of these investigations it has been established that this unwanted isomerisation process can be suppressed by addition of phenylphosphoric acid to the reaction mixture. Some other potential isomerisation inhibitors (e.g. benzoic acid and salts of phosphoric acid) have been studied and their performance compared to that of phenylphosphoric acid. To extend the scope of phenylphosphoric acid, we also studied the metathesis of 1,3-diallylurea. Interestingly, not only did we observe the complete suppression of the isomerisation process, but also that it is possible to obtain instead of the ring-closing metathesis (RCM) product,ADMET oligomers resulting from the cross-metathesis of diallylurea at higher concentrations. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)

Multifunctional composites which can fulfil more than one role within a system have attracted considerable interest. This work focusses on structural supercapacitors which simultaneously carry mechanical load whilst storing/delivering electrical energy. Critical mechanical properties (in-plane shear and in-plane compression performance) of two monofunctional and four multifunctional materials were characterised, which gave an insight into the relationships between these properties, the microstructures and fracture processes. The reinforcements included baseline T300 fabric, which was then either grafted or sized with carbon nanotubes, whilst the baseline matrix was MTM57, which was blended with ionic liquid and lithium salt (two concentrations) to imbue multifunctionality. The resulting composites exhibited a high degree of matrix heterogeneity, with the ionic liquid phase preferentially forming at the fibres, resulting in poor matrix-dominated properties. However, fibre-dominated properties were not depressed. Thus, it was demonstrated that these materials can now offer weight savings over conventional monofunctional systems when under modest loading.

Multi-functional monomer induced hyperbranched PMMA production has been shown to be a relatively facile, one-step batch solution polymerisation reaction. Essentially, the reaction is a linear polymerisation doped with appropriate amounts of multi-functional monomer (MFM) and chain transfer agent (CTA). A theoretical model for the MFM reaction has been experimentally validated using conversion, number-average molecular weight, and branching data, by employing key reaction parameters from established linear PMMA kinetics. However, the kinetic model has been modified to account for the MFM and CTA contributions, which generate the branched architecture and inhibit the onset of gelation, respectively. An important outcome of this work is the development of a generic model for hyperbranched polymer synthesis, in which the manufacture of other free-radical hyperbranched polymers, of desired architecture or physical properties, can be guided using modelling and optimisation methods. © 2005 Elsevier Ltd. All rights reserved.

This study reports the syntheses of aliphatic polyethers, by cationic ring-opening photo polymerisation of oxetane functionalised polypropylene glycol (PPG), and the application of these polyethers in forming membranes for use in the membrane aromatic recovery system (MARS). The PPG was functionalised using 3-methyl-3-bromomethyl oxetane. The cationic ring-opening polymerisation of oxetane functionalised PPG was effected by UV light in the presence of onium salt photoinitiator to produce crosslinked gels. This is the first study reporting the photo-initiated cationic ring-opening polymerisation of PPG. The polyethers produced showed high affinity for phenol (partition coefficient of 58 between polyether and water) and proved chemically stable in 10 wt.% caustic solution. The membranes were prepared by impregnating the mixture of oxetane functionalised PPG and onium salt photoinitiator into the pores of a mesoporous polypropylene support and subsequently exposing them to UV light. The membrane prepared was then tested under MARS operating conditions for more than 2 months during which it was observed to be stable. The membrane exhibited mass transfer rates (3 × 10 −6 m s −1 ) 20 times higher than that of tubular silicone rubber membranes (1.5 × 10 −7 m s −1 ).

The free radical synthesis of hyperbranched polymer architectures using a thermally and photochemically labile styrenic Barton ester monomer of the AB type, designed to combine the functions of initiator, monomer, and branch unit, is described. Highly branched poly(styrene)s were obtained in one step by copolymerizing this monomer with styrene. Residual Barton ester functionality in the hyperbranched products enabled their use as macroinitiators in subsequent polymerizations. Linear PMMA was thus successfully grafted from the hyperbranched poly(styrene) cores. This approach is a versatile route for the synthesis of hyperbranched homopolymers and copolymers via free radical polymerization chemistry.

This study reports the stabilization of supported liquid membranes, through cross-linking the liquid membrane phase by using γ-radiation, and the performance of the resulting membranes under Membrane Aromatic Recovery System (MARS) operating conditions. The membranes were prepared by impregnating polypropylene glycol (PPG) into the pores of microporous flat sheet membranes [polyvinylidene fluoride (PVDF) or polypropylene (PP)] and subsequently exposing them to γ-radiation. The membranes prepared exhibited operational stability when investigated under MARS operating conditions for more than 1 month. The PP (0.05 mm) membrane provided the best combination of high phenol mass transfer rates and low water flux for the MARS process among the membranes tested in this study. The phenol mass transfer rate through this membrane (27 x 10 -7 m s -1 ) was 18 times higher than that of silicone rubber tubing (1.5 x 10 -7 m s -1 ). This study also reports the effect of radiation dose on the mass transfer rates and on the membrane support itself.

Conformational characteristics of poly(ethylene imine) (PEI) have been investigated by a rotational isomeric state (RIS) analysis of ab initio molecular orbital (MO) calculations and 1H and 13C NMR experiments for a monomeric model compound, N,N‘-dimethylethylenediamine (di-MEDA). From the MO and NMR data, it was shown that the C−C and C−N bonds of di-MEDA have high gauche (71−93%) and trans (64−86%) preferences, respectively. Conformational energies of PEI were determined from the MO calculations for di-MEDA at the MP2/6-311++G(3df, 3pd)//HF/6-31G(d) level. The high gauche stability in the C−C bond was indicated to stem from a moderate and a weak intramolecular N−H···N hydrogen bonds; the interaction energies were evaluated as −1.54 and −0.58 kcal mol-1, respectively. The RIS scheme including rotational and inversional isomerizations was developed and applied to PEI to evaluate the chain dimension and diad probabilities. With the conformational energies determined as above, the characteristic ratio and m...

Emulsion polymerizations of methyl methacrylate were carried out in a pilot-scale tubular reactor configured in a batch-loop mode. The tubular sections of the reactor were fitted with in-line static mixers to incite low-shear mixing. The reactor was used to investigate the influence of different recipes and operating conditions on reaction, particularly on the monomer conversion and the polymer particle-size distribution. Experimental data were compared to equivalent bench-scale studies using a conventional stirred flask. A mathematical model was also developed for predicting the temperature dynamics and the conversion of methyl methacrylate polymerization in the pilot-scale reactor. Conversions and particle-size distributions of the pilot-scale loop reactor were found to be very similar to that of the bench-scale studies. The results indicate that in-line static mixers can help to maintain emulsion stability and provide a means for good temperature control, without unduly influencing polymer particle-size distribution. © 2005 American Chemical Society.

The key factors that control the performance of perfluorinated sulfonic acid polymer electrolyte membranes cannot be deeply understood without a structural model of the material. Models of different complexity have been discussed in the literature. In this paper, we suggest a more detailed structural model of Nafion-type membranes, which results from a combined analysis of the ionomer molecular structure, data on swelling, small-angle diffraction, and conductivity as a function of water content. The analysis focuses on geometrical constraints on the self-organization of the polymer and possible patterns of phase segregation within it. The model identifies the percolation bottlenecks for proton transport and resolves controversies about the water-content dependence of the activation energy of proton mobility. It also suggests a new framework for molecular dynamics simulations of proton and water transport in such media.

Main chain and branched polyrotaxanes have been synthesized in which polymerization and rotaxane formation occur simultaneously, due to the presence of the catalytically active self-threading macrocycle cucurbit[6]uril. Using monomers that contain stopper groups to prevent the catalytic macrocycle from noncatalytic threading, it was possible to prepare polyrotaxanes in high yields with molecular weights up to 39000. These polyrotaxanes are structurally perfect in the sense that exactly two macrocycles are threaded onto each structural repeat unit. Investigations into the polymerization mechanism have demonstrated that the catalyst cucurbit[6]uril is highly sensitive toward the structure of the monomers employed and a poorly designed monomer may result in complete inactivity. Features of the mechanism are discussed in some detail.

A pilot-scale tubular reactor fitted with in-line static mixers is experimentally and theoretically evaluated for the polymerisation of methyl methacrylate (MMA). A non-isothermal and non-adiabatic axially dispersed plug-flow model is used to describe the flow characteristics of the reactor. The model is applied to the polymerisation of a concentrated MMA solution (up to 72% (v/v)). Key model parameters were attained through independent bench and pilot-scale experiments. Measured monomer conversions and polymer molecular weight were accurately predicted by model simulation. The presence of static mixers is shown to give near-ideal plug-flow operation for the experimental conditions of this study. Furthermore, an approximately four-fold increase in overall heat transfer coefficient is indicated due to the radial mixing incited by the mixers. Studies also demonstrated the importance of inhibitor kinetics on the dynamic and steady-state performance of the reactor.

Quantitative microbeam Rutherford backscattering (RBS) analysis with a 1.5 MeV 4 He+ beam has determined limits on the purity of copper deposited on glass with a novel inkjet process. A tetravinyl silane tetrakisCu(I) 1,1,1,5,5,5-hexafluoroacetylacetonate (TVST[Cu]hfac) complex was heated to 70 °C and jetted onto the glass substrate through a piezoelectric ceramic print head in droplets about 0.5 mm diameter. The substrate temperature was 150 °C. Solid well-formed deposits resulted which have a copper content greater than about 90% by weight. The RBS spectra were analysed objectively using the DataFurnace code, with the assumption that the deposit was CuOx, and the validity of different assumed values of x being tested. The assumptions and the errors of the analysis are critically evaluated.

A series of elastomers were investigated, by measuring their toluene permeability and acid resistance, for their potential for use in the extraction of organics from hydrochloric acid and other membrane processes utilising acidic aqueous phases. In this study, toluene was used as a solute in aqueous solution to measure permeabilities of the elastomers, and their acid resistance was assessed after immersion in 37 wt.% hydrochloric acid by tensile-strain tests. Silicone rubber has the highest permeability among the elastomers investigated in this study, but it has poor resistance to concentrated HCl. Polyoctenamer is the best membrane material in terms of permeability and acid resistance. Other olefin based materials such as poly(ethylene-co-propylene) and poly(ethylene-co-propylene-co-diene) (EPDM) are also good candidates. The permeability generally decreases with an increase in Tg for the elastomers investigated. However, for the EPDM materials with Tg values grouped around −60 °C, the relationship between Tg and permeabilities is not clear. A model derived from Flory–Huggins Theory and the Hildebrand and Scatchard equation was used to predict the partition coefficients of toluene between the elastomers and aqueous solution, and the predictive power found to depend critically on the value employed for the water solubility parameter. The diffusion coefficients of toluene in the elastomers can be explained by considering the polymer structure.

The piezoelectric ink jet (IJ) printing of an organic semiconducting ink, as applied to the fabrication of a thin film diode, has been demonstrated. IJ printed regioregular poly (3-hexylthiophene-2,5-diyl) [ rr -P3HT] semiconducting films were directly patterned on to gold thin film contact surfaces. The resulting metal–semiconductor–metal diode exhibited low leakage current and a good forward–reverse current ratio. IJ printing of the P3HT as directly patterned thin films represents a significant step toward the realisation of cheap, large area, organic microelectronic devices and transistor active matrix backplanes.

Reactions between tetraalkene silanes SiR4 (R = vinyl and allyl), copper(I) oxide, and 1,1,1,5,5,5-hexafluoroacetylacetonate (hfac) gave novel multicoordinated β-diketonate copper(I) Lewis base ligand complexes. The synthesis and spectroscopic data of tetravinylsilane biscopper(I)hfac complex (TVSB[Cu]hfac) (1), tetravinylsilane tetrakiscopper(I)hfac (TVST[Cu]hfac) (2), and tetrallylsilane triscopper(I)hfac complex (TASTri[Cu]hfac) (3) are presented, and the structural characterization of tetravinylsilane tetrakiscopper(I)hfac (TVST[Cu]hfac) (2) is reported.

Benzonorbornadiene substituted porphyrazines are homo- and copolymerised (ROMP) with norbornene using Cl 2 (Cy 3 P) 2 RuCHPh to provide dark-green and blue polymers. These novel materials have been characterised using GPC, UV-vis and EPR spectroscopy.

The self-association constant of 2-acrylamido pyridine (AAPY) and its temperature-dependence was determined by 2D-NOE-NMR spectroscopy. AAPY was shown to be a versatile polymerisable receptor for a variety of carboxylic acid derivatives. Preliminary results suggest that polymers of AAPY can be rendered main-chain chiral being potential candidates for novel sorbents.

Free-radical polymerization of trimethylolpropane trimethacrylate (TRIM) was carried out in the presence of a variety of porogens at room temperature, yielding transparent (macro)porous polymer monoliths. N2 BET and surface area and Hg intrusion porosimetry data from the resulting polymers showed a variety of different pore sizes and pore size distributions. In the latter, three distinct maxima at 13, 50−60, and ∼500 nm were found for small pores ( 500 nm) did not exhibit any regularity. Variation of initiator concentration, ratio of monomer to porogen, polymerization temperature, and cross-linker had no influence in obtaining transparent monoliths. Correlation of the transparency of the monoliths with the refractive index and solubility parameter of the corresponding porogens led to threshold values for the refractive index (1.42) above which, and for the total solubility parameter (∼20 (MPa)1/2) below which, a transparent polymer monolith i...

Establishing structure–activity relationships is vital if the efficacy of non-viral vectors is to match that of their viral counter-parts. Recently, we reported on the ability of a series of small molecule, cyclic polyamine disulfides to condense and cage plasmid DNA (pDNA) by a process of thermodynamically controlled templated polymerization, leading to a series of corresponding pDNA-polyplex nanoparticles able to mediate high levels of transfection with no associated cytotoxicities. The leading cyclic polyamine disulfide was shown to be the spermine tetra-amine disulfide ( TetraN-3,4,3 ). Herein we report on the significantly more challenging syntheses of cyclic disulfides with longer polyamine motifs. Two new cyclic polyamine disulfides, based on hexa- and octa-amine inserts, were prepared and their transfection efficacies and cytotoxicities compared with our previously reported cyclic tri- and tetra-amine disulfides. The new cyclic hexa- and octa-amine disulfides prove more effective at transfection in vitro , especially of lung epithelial A549 cell line. By contrast, our original cyclic tetra-amine disulfide remains the most efficient agent for the transfection of lung epithelial cells in vivo following intra-nasal administration. Hypothetical mechanistic reasons are presented to explain this outcome. Our data in toto support the concept of shorter cyclic polyamine disulfides as preferred agents for polycation-mediated controlled condensation and functional delivery of pDNA to lung epithelial cells in vivo .

Two types of porous materials derived from emulsion templates are described as potential scaffolds for tissue engineering. Novel oil-in-water particle stabilised, Pickering High Internal Phase Emulsions (HIPE) stabilised with hydroxyapatite (HAp) nanoparticles were prepared and polymerised to form stable polyHIPEs. By adding a water soluble glycidyl methacrylate (GMA) derivatised dextran as monomer to the continuous aqueous phase of the HIPEs, these Pickering-HIPEs stabilised by nontoxic biocompatible HAp nanoparticles, can be used as templates to manufacture interconnected high porosity macroporous hydrogels. A second type of emulsion templated “poly”HIPE was prepared without the need for covalent crosslinking chemistry which was replaced by a thermally-induced non-covalent scaffold forming process (thermoHIPE). These scaffolds form close to body temperature and potentially offer a new approach to the formation of injectable scaffolds for tissue engineering.

Nonviral gene therapy continues to require novel synthetic vectors to deliver therapeutic nucleic acids effectively and safely. The majority of synthetic nonviral vectors employed in clinical trials to date have been cationic liposomes; however, cationic polymers are attracting increasing attention. One of the few cationic polymers to enter clinical trials has been polyethylenimine (PEI); however, doubts remain over its cytotoxicity, and in addition it displays lower levels of transfection than viral systems. Herein, we report on the development of a series of small molecule analogues of PEI that are bioresponsive to the presence of pDNA, forming poly(disulfide)s that are capable of efficacious transfection with no associated toxicity. The most effective small molecule developed, a cyclic disulfide based upon a spermine backbone, is shown to form very well-defined polyplexes (100-200 nm in diameter) that mediate murine lung transfection in vivo to within an order of magnitude of in vivo jetPEI, and at the same time display a much improved cytotoxicity profile.

Novel non-PEG derived polyether resins, coined SLURPS (Superior Liquid Uptake Resins for Polymer-supported Synthesis), were studied for their performance in solid-phase synthesis. Novel amino functional resins, SLURPS-NH2, were prepared with a loading of up to 8.5 mmol/g and employed successfully in the solid-phase synthesis of Leu-Enkephalin. The peptide was obtained with the same purity when compared to its synthesis with commercial standard poly(dimethyl acrylamide) resins. Furthermore we show loading and cleavage of aromatic carboxylic acids in excellent yield. The advantageous solvent compatibility of our support was demonstrated through the biphasic dihydroxylation of alkenes with OsO4 in t-BuOH/water mixtures producing bound 1,2-diols and synthesis and removal of a bound oxime using ethanol/water mixtures both in excellent yields. Reactions were easily monitored by gel-phase NMR and FTIR. These results show that SLURPS are very well suited for organic transformations using highly polar solvent mixtures and reagents and at much higher loading levels than standard amphiphilic resins of similar solvent compatibility.

[Chemical reaction: see text] The reactions of a series of urea- and amide-substituted olefins with Grubbs' catalysts are presented. Depending on the substrate's nature, the formation of either cross-metathesis or isomerization products is observed. To favor the cross-metathesis products, the reactions have been carried out using a wide range of experimental conditions. Upon addition of monophenyl phosphoester to these reactions, the isomerization of the olefins is completely suppressed and the cross-metathesis products are obtained in up to 60% yield.

Uncontrolled cell proliferation is a hallmark of cancer and its inhibition is desired in cancer therapy. The most widely used radiotracer for proliferation is 18F-fluorothymidine (18F-FLT). To be retained in cells, 18F-FLT is phosphorylated to thymidylate (dTMP) by thymidine kinase 1 (TK1), the rate limiting step in the salvage pathway for DNA synthesis. We studied TK1 protein phosphorylation in mammalian cells, hypothesising that TK1 is subject to different phosphorylations through the cell cycle, which are responsible for the regulation of its activity, therefore modulating 18F-FLT uptake, particularly during G2/M. Using phos-tag™ acrylamide gels we isolated three forms of phosphorylated TK1, one of which was present throughout the cell cycle, but increased during S and G2/M phases, and two phosphorylated forms that appeared upon G2/M arrest. The implications of these phosphorylations on 18F-FLT uptake were tested by conducting FLT cell uptake studies after treating HCT116 human colon cancer cells with cell cycle-arresting drugs. A marked reduction of radiotracer uptake was observed in cells arrested in S phase (aphidicolin) or G2/M phase (nocodazole and paclitaxel), confirming previous findings regarding TK1 phosphorylation during G2/M being responsible of reduced enzymatic activity. Transient transfection of Ost TK1- cells with FLAG-pCMV vectors encoding WT, S13A, S13D or S231A TK1 suggested that S13 phosphorylation occurs throughout the cell cycle and increases upon G2/M arrest after treatment with nocodazole or paclitaxel. Substitution of S231 with alanine (S231A) was linked to G2/M-specific phosphorylation of TK1. Further experiments were performed to assess the role of the two serine phosphorylations on 18F-FLT cell uptake. There was a significant reduction in 18F-FLT uptake in S13A transfected cells compared to WT. S13D and S231A plasmids rescued 18F-FLT uptake almost to levels seen in WT cells, supporting the relevance of S13 and S231 phosphorylation for TK1 enzymatic activity. Nocodazole induced G2/M arrest further reduced 18F-FLT uptake, even in S231A transfection, implicating phosphorylation sites other than those studied here in the reduced TK1 activity. 18F-FLT-PET imaging of HCT116 tumour-bearing nude mice 24h after treatment with 40 mg/kg paclitaxel indicated a significant reduction in tumour 18F-FLT uptake, which correlates with the G2/M-induced reduction in TK1 activity as a result of TK1 phosphorylation. Our present study demonstrates the presence of at least three phosphorylated forms of TK1, which are responsible for the post-translational regulation of TK1 activity, and demonstrates the effect of these modifications on the uptake of 18F-FLT. Citation Format: Roberta Sala, Quang-De Nguyen, Chirag Patel, David Mann, Joachim H. G. Steinke, Ramon Vilar, Eric O. Aboagye. Regulation of 18F-fluorothymidine uptake by thymidine kinase 1 protein phosphorylation. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2660. doi:10.1158/1538-7445.AM2013-2660

Ion-responsive biocompatible macroporous hydrogels with a well-defined highly interconnected open porous structure were synthesised using oil-in-water (o/w) high internal phase emulsion (HIPE) templating. Methacrylate-modified alginate was crosslinked in the continuous minority water phase and the oil internal phase removed to produce macroporous hydrogel monoliths. The physical dimensions, pore and pore throat size as well as water uptake of the alginate polyHIPE hydrogel can be controllably tuned by ion-responsive behaviour towards Ca2+ ions. The ionic crosslinks formed are fully reversible and be dissolved using sodium citrate to remove Ca2+ ions through chelation. The polyHIPE hydrogels possess mechanical properties with storage moduli up to 20 kPa and are biocompatible as shown by cytotoxicity assays. The hydrogel can be extruded through a hypodermic needle causing it to break into small pieces (about 1 to 3 mm in diameter) while retaining the interconnected pore morphology after injection. Furthermore, these hydrogel fragments can be reformed into a coherent scaffold under mild conditions using an alginate solution containing Ca2+ ions.

In situ ionic liquid (IL) filled poly(merized) high internal phase emulsion monoliths and films were produced by polymerizing surfactant stabilized IL/monomer emulsion templates. The resulting in situ ionic liquid filled macroporous polymers have almost the ionic conductivity of the neat ionic liquid electrolyte. The effect of surfactant and lithium salt concentration, monomer to crosslinker ratio as well as internal phase volume ratio on the morphology and ionic conductivity were studied. It was found that the morphology of the resulting polyHIPEs affects significantly their ionic conductivity. PolyHIPEs with bigger pore throats have a higher ionic conductivity.

‘Structural electrolytes’ retain the desirable mechanical characteristics of structural (epoxy) resins whilst introducing sufficient ionic conductivity to operate as electrolytes in electrochemical devices. Here, a series of ionic liquid–epoxy resin composites were prepared to identify the optimum system microstructure required to achieve a high level of multifunctionality. The ionic conductivity, mechanical properties, thermal stability and morphology of the cured epoxy based structural electrolytes were studied as a function of phase composition for three fully formulated high performance structural epoxy systems. At only 30 wt% of structural resin and 70 wt% of ionic liquid based electrolyte, stiff monolithic plaques with thicknesses of 2–3 mm were obtained with a room temperature ionic conductivity of 0.8 mS cm−1 and a Young's modulus of 0.2 GPa. This promising performance can be attributed to a long characteristic length scale spinodal microstructure, suggesting routes to further optimisation in the future.

Commercially available hydroxyapatite (HAp) nanoparticles were used as sole emulsifiers to produce stable methyl myristate-in-water and soybean oil-in-water high internal phase emulsions (HIPEs). The droplet size in the Pickering inverse HIPEs (i-HIPEs) could be adjusted within a certain range by tailoring the energy input during emulsification and emulsifier concentrations. These HAp nanoparticle stabilised i-HIPEs were then used as templates to synthesise interconnected high porosity macroporous hydrogels by crosslinking glycidyl methacrylate (GMA) functionalised dextran, which was dissolved in the continuous aqueous phase of the i-HIPEs. The pore size of these polyPickering-HIPE hydrogels could be adjusted by the emulsifier concentration, oil type, emulsification conditions or ripening time of the i-HIPE templates.

Three different tetraazamacrocyclic ligands containing four amide substituents that feature groups (namely allyl, styryl and propargyl groups) suitable for polymerisation have been synthesised. Gadolinium(III) complexes of these three ligands have been prepared as potential monomers for the synthesis of polymeric MRI contrast agents. To assess the potential of these monomers as MRI contrast agents, their relaxation enhancement properties and cytotoxicity have been determined. A europium(III) complex of one of these ligands (with propargyl substituents) is also presented together with its PARACEST properties. In addition, to gain further insight into the coordination chemistry of the tetra-propargyl substituted ligand, the corresponding zinc(II) and cadmium(II) complexes have been prepared. The X-ray crystal structures of the tetra-propargyl ligand and its corresponding gadolinium(III), zinc(II) and cadmium(II) complexes are also presented.

Intrinsically-skinned asymmetric PANi hollow fibres, fabricated using a process of directly adding large organic acids to highly concentrated PANi solutions, show stability in a wide variety of organic solvents and have shown promising nanofiltration properties, giving high rejections of nanosolutes in acetone.

We report a new cationic poly(phenylene ethynylene) (PPE) derivative that exhibits strong amplified fluorescence quenching in the presence of electron-deficient species, yielding high Stern–Volmer coefficients of 4.7 × 107 M−1 in aqueous solutions. Importantly, with the addition of appropriate non-ionic surfactants, the polymer is found to retain its excellent sensitivity even when transferred to high ionic strength buffered media, which have previously been shown to suppress the amplified quenching effect in other polyelectrolyte systems. The cationic PPE derivative yields Stern–Volmer coefficients as high as 107 M−1 in 25 mM buffer solutions of both tris(hydroxymethyl) aminomethane (Tris) and sodium acetate containing 150 mM sodium chloride, the optimal conditions for many enzymes such as phosphatases. The ability to maintain high Stern–Volmer coefficients in high ionic strength buffered media extends the applicability of ionic conjugated polymers to high sensitivity detection in biological media, and thus greatly enhances their versatility as biological sensors.

Screened anionic copolymerisation of methyl methacrylate with the perfluoroalkyl methacrylates 2 affords well-defined AB block copolymers 4–6, which serve as effective surfactants in the dispersion polymerisation of methyl methacrylate in supercritical carbon dioxide.

NSF (1) verdrangt in [Mn(CO)5SO2]+[AsF6]− (3b) bzw. [CpCr-(NO)2SO2]+[AsF6]− (8) das komplexgebundene SO2 unter Bildung von [Mn(CO)5NSF]+[AsF6]− (7) bzw. [CpCr(NO)2-NSF]+[AsF6]− (9). Mit Hilfe von [Ag(NSF)]+[AsF6]− (13) last sich in Ubergangsmetallhalogeniden das Halogen durch 1 ersetzen; auf diesem Wege sind auch [CpFe(CO)2NSF]+[AsF6]− (11) und [Cp2Ti(NSF)2]2+[AsF]2 (16) zuganglich. AsF5 abstrahiert aus den metallorganischen NSF-Monokationen das Schwefel-gebundene Fluor; unter sehr milden Bedingungen werden Thionitrosyl-Dikationen, wie z. B. [Mn(CO)5NS]2+ (17) und [CpCr-(NO)2NS]2+ (18) erhalten. Organometallic Thiazyl Fluoride and Thionitrosyl Complexes NSF (1) displaces in [Mn(CO)5SO2]+[AsF6]− (3b) and [CpCr-(NO)2SO2]+[AsF6]− (8) the SO2 ligand under formation of [Mn(CO)5NSF]+[AsF6]− (7) and [CpCr(NO)2NSF]+[AsF6]− (9). With [Ag(NSF)]+[AsF6]− (13) in organometallic halides the halogen is exchanged by 1; by this route also [CpFe(CO)2NSF]+[AsF6]− (11) and [Cp2Ti(NSF)2]2+[AsF]2 (16) are obtained. From organometallic monocations AsF5 abstracts the sulfur-bonded fluorine; under mild conditions thionitrosyl dications are formed, e.g. [Mn(CO)5NS]2+ (17) and [CpCr(NO)2NS]2+ (18).