Neil Cameron

The preparation of PolyHIPE foams containing poly(epsilon-caprolactone) from macromonomers by free radical homo- or copolymerization is described. The macromonomers are synthesized from PCL diols and are polymerized in the continuous phase of high internal phase emulsions (HIPEs). Subsequent drying yields low-density foams with cell diameters of 5-100 microm. Foam morphology, as determined by scanning electron microscopy, depends on the type of diluent (styrene, methyl methacrylate, or toluene) added to the emulsion organic phase and on the PCL content. Increasing the latter increases the continuous phase viscosity to a point where emulsion formation is impeded. Foam swelling in toluene, 2-propanol, and water was investigated by solvent imbibition and increased with increasing solvent hydrophobicity. Furthermore, it was found generally to decrease with increasing PCL content, due to increasing cross-link density. Swelling generally increased when higher molar mass PCL macromonomer was used due to the formation of a less tightly cross-linked network. One type of foam sample was shown to support the growth of human fibroblasts over a period of 2.5 days.

Poly(ionic liquid)s (P(IL)s) of different degrees of polymerisation (10, 50 and 100) were prepared via RAFT polymerisation using an alkyne-terminated xanthate as transfer agent, with a monomer conversion of up to ~80% and a ƉM of 1.5 for P(IL)100. Subsequently, P(IL) chains were coupled to 15N-labelled azido-functionalized HEC, forming graft copolymers of HEC with different chain length and graft densities which were characterised using (13C and 15N) CP-MAS NMR and FT-IR spectroscopies. The antibacterial activities of HEC-g-P(IL)s were tested against E. coli and S. aureus and were comparable to ampicillin, a well-known antibiotic, demonstrating efficient activity of the graft copolymers against bacteria. Moreover, HEC-g-P(IL)s were slightly more effective against E. coli than S. aureus. A decrease in graft density of P(IL)10 on the HEC backbone decreased the activity of the graft copolymers against both bacteria. These findings suggest that HEC-g-P(IL) could find applications as an ...

immunofluorescence. Aims. Refine and extend analysis of cell grafts using fluorescence in-situ hybridisation (FISH) targeting specific DNA repeat sequences, in combination with multiple labelling immunofluorescence for a range of marker proteins. Background. Cell transplantation into animal models is a valuable research tool in a broad spectrum of research areas, with a critical aspect of these studies being the identification of implanted cells. A variety of methods including retroviral transfection of DNA sequences expressing fluorescent-proteins, incorporation of traceable particles and membrane permeant fluorescent tracers are used for detecting implanted cells. The analysis of cell grafts becomes challenging where large numbers of grafted cells need to be detected and characterised following proliferation and/or differentiation in host tissue. Further, in grafts of long duration reporter genes may cease being expressed or cell tracers may be lost or dispersed. Rationale. Automa...

ABSTRACT Highly porous polymers (polyHIPEs) have been prepared by the photopolymerization of high internal phase emulsions (HIPEs) with varying ratios of thiol and acrylate monomers. The resulting polymers have a nominal porosity of 80%, and are seen to have a well-defined, interconnected pore morphology, with average pore diameters ranging from 30 to 60 μm. The polyHIPE polymers have been shown using a colourimetric (Ellman's) assay to contain residual thiols which are reactive towards a range of (meth)acrylates (hexafluoroisopropyl acrylate, fluorescein O-acrylate and poly(ethylene glycol) methyl ether methacrylate). Functionalization was explored using thermally- and UV-initiated radical-mediated “click” reactions and an amine-catalysed Michael addition reaction. The extent of functionalization was investigated qualitatively and quantitatively using a range of techniques (solid state NMR spectroscopy; FTIR spectroscopy; X-ray photoelectron spectroscopy (XPS); observation of fluorescence); high levels of conversion (up to 90–95%) were observed for the thermally-initiated radical reaction and the Michael reaction.

ABSTRACT We demonstrate how 15N labelling can be used to probe the success of ‘grafting to’ processes, through the preparation of well-defined graft copolymers of hydroxyethyl cellulose by combining RAFT polymerisation and copper-catalysed azide-alkyne cycloaddition (CuAAC). Using synthesised alkyne-functionalised chain transfer agents, short-chain (DP=10) poly(N-vinylpyrrolidone) (PVP) and poly(N-isopropyl acrylamide) (PNIPAAM) were prepared in high conversion in a controlled manner (ƉM of ~1.4 and 1.2 respectively). Separately, partially 15N-labelled N3-HEC was synthesised and characterised using solid state 13C, 15N CP-MAS NMR and FTIR spectroscopies. Alkyne-terminated PVP and PNIPAAM were grafted at different graft densities onto partially 15N-labelled N3-HEC using the click reaction. The hybrid HEC-g-polymer materials were fully characterised using solid state 13C and 15N CP-MAS NMR and FTIR spectroscopies. While 13C and FTIR spectroscopies gave indirect or weak evidence of CuAAC coupling, the cycloaddition of the alkyne-terminated polymers with N3-HEC was proven unambiguously by 15N solid state NMR spectroscopy. This indicates the utility of 15N labelling for probing the coupling efficiency of CuAAC reactions when employed in ‘grafting to’ processes with cellulosic substrates.

ABSTRACT We describe the preparation of porous polymeric scaffolds via polymerization of the oil phase in high internal phase water-in-oil-emulsions using amphiphilic block copolymers polystyrene-b-poly(ethylene oxide), polystyrene-b-poly(acrylic acid), poly(1,4-butadiene)-b-poly(ethylene oxide), and poly(1,4-butadiene)-b-poly(acrylic acid) as surfactants. We show that the block copolymers anchor to the polymerized oil phase via the lipophilic block, which can occur by chemical and/or physical entanglement and consequent presentation of the hydrophilic block on the pore surfaces. The in situ polymerization enables the full surface functionalization of the porous materials with the final surface chemistry dictated by the hydrophilic block. Furthermore, the foam physical architecture may be tailored through controlling emulsion parameters such as the initiator, shear rate, and aqueous phase volume fraction.

ABSTRACT Use of Styryl-TITNO (the styrene alkoxyamine of 2,2,5-trimethyl-4-tert-butyl-3-azahexane-3-oxyl) as mediator for nitroxide-mediated polymerization (NMP) of n-butyl acrylate (BA) and styrene has been investigated at temperatures ≤110 °C. Very good control of molecular weight and molecular weight dispersity with no measurable loss of active chains, and no evidence of tails in the molecular weight distribution as conversion increases, was observed at 90 °C for BA and at 70 °C for styrene. The alkoxyamine dissociation equilibrium constant values determined for polyBA-TITNO (8.5 × 10−11 mol L−1 at 90 °C) and polystyrene-TITNO (3.1 × 10−9 mol L−1 at 70 °C) are consistent with those required for control when using more established nitroxides that require higher temperatures to achieve these values. The lower optimum polymerization temperatures with Styryl-TITNO as mediator provide new opportunities for NMP and are especially significant for styrene since this appears to eliminate completely the complications from thermal initiation.

ABSTRACT Factors underlying design of a new nitroxide, 2,2,5-trimethyl-4-tert-butyl-3-azahexane-3-oxyl (TITNO), and its styrene alkoxyamine (Styryl-TITNO) for effecting nitroxide-mediated polymerization (NMP) at temperatures ≤90 °C are described. The rate coefficient, kd, for thermal dissociation of Styryl-TITNO was determined in the range 70–100 °C, giving Arrhenius parameters Ad = 2.9 × 1012 s–1 and Ed = 104.1 kJ mol–1. Due to the low value of Ed, values of kd and the activation–deactivation equilibrium constant for NMP of n-butyl acrylate (BA) and styrene are much lower at any given temperature than for alkoxyamines of more established nitroxides. Good control of molecular weight and dispersity, with negligible contributions from termination, is achieved at 90 °C for BA and at 70 °C for styrene, thus, eliminating the complicating contributions from styrene thermal initiation. Hence, TITNO and Styryl-TITNO offer new opportunities for controlled NMP at temperatures much lower than has previously been attainable.

ABSTRACT Highly porous polymers (polyHIPEs) incorporating activated esters have been prepared by photopolymerisation of high internal phase emulsions (HIPEs) containing pentafluorophenyl acrylate (PFPA) in the monomer phase. The resulting materials have nominal porosity of 80% and a well-defined, interconnected pore morphology with average pore diameters ranging from 30 to 50 μm. PFPA could be added at up to 50 wt% of the monomer phase without destabilising the HIPE noticeably, however analysis of the polyHIPE materials revealed that only around half of this was incorporated into the final porous materials. The pentafluorophenyl groups were shown to be reactive towards a range of amines (tris-(2-aminoethyl)amine, benzylamine and Rhodamine 123), giving near complete loss of fluorine over the period of the reaction. The extent of functionalisation was however determined to be around 50% by elemental analysis, suggesting some loss of fluorine by hydrolysis of activated esters. We believe that this represents a facile method for the preparation of a variety of well-defined functional porous polymers by a post-polymerisation functionalisation route.

ABSTRACT Three end-capped oligomers 35, 41 and 45 related to poly(ethyleneglycol terephthalate) have been prepared starting from t-butylthioterephthalic acid 21 and its ethyleneglycol monoterephthalate derivative 25 terminally protected on the glycol moiety (by the tetrahydropyranyl group) and on the carboxylic acid moiety [by the 2-(2-pyridyl)-group].

In this comprehensive review, we report on the preparation of graft-copolymers of cellulose and cellulose derivatives using atom transfer radical polymerization (ATRP) under homogeneous conditions. The review is divided into four sections according to the cellulosic material that is graft-copolymerised; (i) cellulose, (ii) ethyl cellulose, (iii) hydroxypropyl cellulose and (iv) other cellulose derivatives. In each section, the grafted synthetic polymers are described as well as the methods used for ATRP macro-initiator formation and graft-copolymerisation. The physical properties of the graft-copolymers including their self-assembly in solution into nanostructures and their stimuli responsive behaviour are described. Potential applications of the self-assembled graft copolymers in areas such as nanocontainers for drug delivery are outlined.

ABSTRACT During the last decade, research and development in microfluidic devices have grown significantly due to their wide variety of applications in physics, chemistry and biology. A specific category of microfluidic devices focuses on the generation of micro-emulsions that can be used, for example, as chemical and biological reactors to synthesize new materials and perform assays. However, the traditional fabrication process of such microfluidic devices involves the use of special instrumentations and clean room facilities. These steps are generally expensive, time consuming and require specific levels of expertise. In this article, an alternative method to fabricate robust microfluidic devices using conventional components and a new commercially available self-setting rubber is presented. Using this method, a cheap, reproducible and easy to manufacture microfluidic device has been developed for generating single and double emulsions in the range of 100s of µm with high throughput. One possible application of this device is demonstrated with the synthesis of highly porous polymer beads from a High Internal Phase Emulsion (HIPE). The fabricated microbeads could find potential application in 3D cell culture due to their high porosity (up to 95%) and pore size (from 5 to 30 µm). The process here presented offers great opportunities for chemists and biologists interested in synthesising new materials while minimizing time, costs and expertise in the development of microfluidic systems.

ABSTRACT Since the past decade, the interest towards microfluidic devices has sensibly grown due to the wide variety of multidisciplinary applications. One branch of the microfluidic domain consists in the synthesis of various types of emulsions requested by cosmetic, food and biotechnological industries In particular, monodisperse water-in-oil microemulsion synthetised in microfluidic devices are quickly becoming the new generation of emulsions for precise bead control and high surface area. These microemulsions are generally aqueous bioreactors in the form of droplets from 500 nm to 10 μm in diameter, enclosed in an oil environment. An increasing demand for bigger emulsions has led us to investigate new techniques for fabricating fluidic devices allowing a better control over the final size of the droplets. An easy, cheap, reproducible and fast technology for generating emulsions in the range of 100s μm with high throughout (up to mL/h) is reported. Simply using pipette tips and tubing, an innovative microfluidic device was fabricated, able to synthetise water-in-oil emulsions within the range 50 - 500 _μm and double emulsions. These new emulsions are currently used for the synthesis of highly porous polymers beads from High Internal Phase Emulsion (HIPE). These beads will find high potential in 3D cell culture due to their high porosity (up to 90%) and pore size (from 5 to 30μm).

Self-assembling block copolypeptides were prepared by sequential ring-opening polymerization of N-carboxyanhydride (NCA) derivatives of γ-benzyl-L-glutamic acid and ε-carbobenzyloxy-L-lysine, followed by selective deprotection of the benzyl glutamate block. The synthesized polymers had number average molecular weights close to theoretical values, and had low dispersities (ĐM  = 1.15-1.28). Self-assembly of the amphiphilic block copolymers into nanoparticles was achieved using the "solvent-switch" method, whereby the polymer was dissolved in THF and water and the organic solvent removed by rotary evaporation. The type of nanostructures formed varied from spherical micelles to a mixture of spherical and worm-like micelles, depending on copolymer composition. The spherical micelles had an average diameter of 43 nm by dynamic light scattering, while the apparent diameter of the mixed phase system was around 200nm. Reproducibility of nanoparticle preparation was demonstrated to...

ABSTRACT Emulsion templating has been used to prepare highly porous polyHIPE materials by thiol–ene photoinitiated network formation. Commercially available multifunctional thiols and acrylates were formulated into water-in-oil high internal phase emulsions (HIPEs) using an appropriate surfactant, and the HIPEs were photo-cured. The temperature of the HIPE aqueous phase was found to influence the morphology of the resulting materials. In agreement with previous work, a higher aqueous phase temperature (80 °C) gave rise to a larger mean void and interconnect diameter. The influence of temperature on morphology was found to be reduced at higher porosity, but still significant. The Young's modulus of the porous materials was shown to be related to the functionality of the acrylate comonomer used. A mixture of penta- and hexa-acrylate gave rise to a 100-fold increase in modulus, compared to an analogous tri-functional acrylate. The materials could be functionalised conveniently by addition of mono-acrylates or thiols to the organic phase of the precursor HIPE. Degradation was observed to occur at a rate depending on the degradation conditions. Under cell culture conditions at 37 °C, 19% mass loss occurred over 15 weeks. The scaffolds were found to be capable of supporting the growth of keratinocytic cells (HaCaTs) over 11 days in culture. Some penetrative in-growth of the cells into the scaffold was observed.

ABSTRACT Highly porous and interconnected methacrylate-based porous materials were prepared by photopolymerisation of the continuous phase of high internal phase emulsion (HIPE) templates. The rapid cure afforded by photopolymerisation effectively ‘locks’ the emulsion morphology prior to emulsion destabilisation, in comparison to thermally-initiated HIPEs of similar compositions. Contrary to expectation, it was observed that fully cured photopolymerised polyHIPEs could be prepared with a thickness of up to 35 mm, despite the severe opacity of the parent emulsions. This is attributed to a photofrontal polymerisation process, where radicals generated on the surface propagate rapidly through the bulk of the emulsion. Homogeneous, well-defined polyHIPE materials of up to 95% nominal porosity were obtained by photopolymerisation of HIPEs containing up to 30 vol.% glycidyl methacrylate (GMA) in the monomer phase (the remaining monomers and crosslinker are acrylates). Surprisingly, poly(ethylene glycol) methacrylate (PEG-MA), a nonionic monomer that is miscible with both emulsion phases, could be added to such HIPEs after preparation. On polymerisation, hydrophilic, water-wettable porous materials were obtained. Finally, it was also demonstrated that all-methacrylate HIPEs could be prepared and cured to yield GMA-containing polyHIPEs. These findings demonstrate the versatility of photopolymerisation for the preparation of emulsion templated porous polymers.

ABSTRACT Foams containing poly(lactic acid) (PLA) have been prepared from the corresponding macromonomers using high internal phase emulsions (HIPEs) as templates to create the porous structure. The resulting PolyHIPE foams have been investigated by scanning electron microscopy and the influence of diluent type, either reactive (styrene or methyl methacrylate (MMA)) or unreactive (toluene), on foam morphology has been determined. The morphology was found to depend on the type of diluent: styrene resulted in cellular materials at low PLA levels but tended to give structures characteristic of phase separation at higher PLA content; MMA yielded porous cellular materials at all levels of PLA; toluene tended to give soft materials that collapsed on drying. The swelling of the foam materials in toluene, isopropyl alcohol (IPA) and water was also investigated. It was found that most of the foams swelled to a relatively low extent in all solvents, apart from that of low PLA content made with toluene. This was ascribed to a low crosslinking level and high porosity of this material. Cell and tissue growth studies on the resulting foams, as well as analogues prepared from poly(ε-caprolactone) (PCL) macromonomers, using whole chicken embryo explants, rat skin explants or individual human skin cells, indicated excellent biocompatibility of all foams over the length of each experiment (maximum length 6 days). Comparative studies indicated that cells adhered to PCL-based materials more rapidly than their PLA-containing counterparts.© 2002 Society of Chemical Industry

ABSTRACT Recent years have seen a dramatic increase in interest in the use of ring-opening polymerization of N-carboxyanhydride (NCA) monomers as a method to prepare well-defined polypeptides and peptide-hybrid materials. The resulting molecules are often capable of assembling into a variety of different structures, including micelles, vesicles, nanoparticles and hydrogels, and therefore have been explored as novel drug delivery systems. Peptides are attractive in this regard due to their rich chemical functionality and ability to assemble through the formation of secondary structures (for example α-helices and β-sheets). In addition, they are inherently biodegradable and biocompatible. This review describes recent advances in the field, covering aspects such as improved methods with which to prepare better-defined polypeptides, crosslinking of assemblies to enhance biostability, the preparation of materials that respond to a variety of stimuli (including light and intra- or extracellular redox conditions), functionalization with targeting ligands to enhance cellular uptake, assemblies for siRNA delivery and approaches to theranostic systems.

ABSTRACT Glycidyl methacrylate (GMA) emulsion-templated porous polymers (polyHIPEs) were prepared by thermal and photopolymerisation and derivatised with morpholine, tris(2-aminoethylamine) and a bisamino-PEG homobifunctional molecule. The extent of the functionalization reactions was investigated by a range of qualitative and quantitative techniques (FTIR, CHN analysis, titration, XPS, HR-MAS NMR spectroscopy, ninhydrin assay and Fmoc number determination) and was found to be excellent for small molecule amines (up to 89% conversion) but low for the reaction with PEG (2% conversion). This was ascribed to the high exclusion volume of the PEG chains in solution. Proteinase K (Pro K) was subsequently immobilized covalently onto the GMA polyHIPE material, both directly via reaction with surface epoxy groups and indirectly by activation of the pendent amine groups of PEGylated polyHIPE with glutaraldehyde then reductive amination with the enzyme. The activity of the supported enzymes was determined by a continuous electrochemical assay involving the hydrolysis of N-acetyl-L-tyrosine ethyl ester. The directly immobilized Pro K was found to have an activity of only 3.6 U/g whereas the activity of the enzyme immobilized via the PEG linker was much higher (up to 78 U/g).

ABSTRACT This paper describes the fabrication and performance of a novel device based on liquid crystals dispersed in a polymer matrix. A low molecular weight liquid crystal material is introduced into a pre-formed, thin, porous, low density polymer film. Application of an electric field across the thin film produces a change in the transmission of the film just as in conventional Polymer Dispersed Liquid Crystals (PDLC) due to the reorientation of the liquid crystal director. Thus the device acts as a shutter. One significant advantage of this type of device over conventional PDLC is that there is no intermixing of the liquid crystal and monomeric material. Also compressible porous polymer matrices can be formed giving the potential for controllably distorting the pores in a given direction. The formation and switching characteristics of a device using a porous polymer based on styrene and divinylbenzene is described.

ABSTRACT This work describes the synthesis of new hydrophobic acyclic nitroxides [derived from 2,2,5-trimethyl-4-phenyl-3-azahexane-3-nitroxide (TIPNO)] designed to be employed in radical miniemulsion polymerization. We present the synthetic strategies employed to obtain these different nitroxides and the determination of certain important parameters, such as the dissociation rate constant, the combination rate constant, and the decomposition rate constant, of the corresponding alkoxyamines. All these new nitroxides give good control of the bulk radical polymerization of styrene in comparison with the parent TIPNO. The molecular structure of some nitroxides presented herein has been elucidated by single-crystal X-ray diffraction, and their structural determination helps us to understand better the influence of the nitroxide structure on the activation energy. A molecular modeling study has also been conducted on these new nitroxides, and a good linear correlation between the activation energy and the CNC bond angle for a series of nitroxides with the same type of leaving radical has been found. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 1926–1940, 2006

ABSTRACT A novel type of highly porous polymeric monolith called PolyHipe has been applied as a support for an immobilized catalyst (sulfonic acid). Somewhat differently from a conventional packed bed where the reaction mixture flows around the porous catalytic particles, here, the reaction mixture is forced through the pores of the monolith. The kinetics of the liquid-phase hydration were measured both in a three-phase system consisting of an aqueous, an organic, and the polymer resin phase and in a two-phase system consisting of a solution of cyclohexene in aqueous sulfolane (90 mol % sulfolane) and the polymer resin phase, at a pressure of 2 MPa and temperatures between 343 and 368 K. In the three-phase system the observed conversion rates were analyzed by a three-phase reaction model with mass transfer and reaction based on the rate equation RA = k1psCA − k-1CP (with k1ps = k1*σρPH (with k1ps being the pseudo-first-order reaction rate constant of the forward reaction, k1* the idem, but applied per equivalent acid, σ the acid capacity, ρPH the apparent density of the PolyHipe, k-1 the first-order reaction rate constant of the backward reaction, and CA and CP the cyclohexene and cyclohexanol concentrations in the water phase, respectively), giving k1,aq* = 7.09 × 105 exp(−(87.01 ± 6.94) × 103/(RT)) maq3 equiv-1 s-1, where k1,aq* is the initial reaction rate constant of the reaction, R is the ideal gas constant, T is the temperature, and the subscript “aq” is the aqueous phase. In the two-phase system the observed initial rate equation could be described according to k1,s* = 4.1 × 10-4 exp(−(33.0 ± 47.9) × 103/(RT)) ms3 equiv-1 s-1, where the subscript “s” is the aqueous sulfolane phase. The value of k1,aq* agrees with the literature values of the initial rate constant measured in conventional ionic exchange beads (Amberlite XE307). k1,s* is an order of magnitude smaller than that in Amberlite XE307.