David Valade

Cyclic polystyrene topologies via RAFT and CuAAC

Cyclic polymer have attracted interest due to their different self-assembly behavior and physical properties compared to their linear counterparts with the same molecular weight. There are only a few examples of using polymer made by RAFT to create cyclic polymers, and no reports of coupling these cyclic polymers together to form stars. In this work, we have demonstrated a novel approach to produce cyclic polymers by RAFT with the required functionality for further coupling to form 2- and 3-arm stars. Cyclization of a chemically modified linear RAFT polystyrene (PSTY) using the copper-catalyzed azide–alkyne cycloaddition (CuAAC) gave cyclic polystyrene (cPSTY) with a purity of 95% as determined by simulating the experimental molecular weight distribution using the log-normal distribution method. The –OH group on cPSTY was converted to an azide via a two step procedure, allowing the cyclic polymers to be coupled together using propargyl ether or tripropargylamine via the CuAAC reaction to form the 2- and 3-arm stars, respectively. When the conventional ligand complex and solvent was used (i.e. CuBr–PMDETA in toluene), the linkage between the cyclic arms degraded fully after 24 h due to base cleavage. We overcame this by changing the ligand to a triazole or carrying out the reaction in ligand-free conditions (i.e. CuBr in DMF). These latter experimental conditions gave ‘click’ efficiencies of greater than 82%. Our methodology for producing cyclic polymers by RAFT will not only extend the range of cyclic polymer by the ring closure method but allow one to utilize these cyclic polymers as building blocks in the formation of more complex polymer architectures.

Synthesis of siRNA Polyplexes Adopting a Combination of RAFT Polymerization and Thiol-ene Chemistry

Block copolymers of allyl methacrylate and N-(2-hydroxypropyl) methacrylamide (HPMA) with different block lengths have been synthesized by reversible additionfragmentation chain transfer polymerization. Allyl groups were modified with cysteamine, via a thiol-ene photoreaction, with a high efficiency (∼100%) as evidenced by NMR spectroscopy, yielding cationic copolymers of HPMA. Polyelectrolyte complexes of small interfering RNAs (siRNA) and the cationic block copolymers were then formed at an N/P ratio between 1 and 4 depending on the block length of the copolymers. Increasing the length of the hydrophilic block was found to decrease the efficiency of siRNA complexation. The hydrodynamic diameter of the polyplexes in 130 mM buffer solution was less than 100 nm.

Narrow molecular weight and particle size distributions of polystyrene 4-arm stars synthesized by RAFT-mediated miniemulsions

There are no reports of star polymers synthesized by reversible addition–fragmentation chain transfer (RAFT) polymerization in aqueous dispersions (e.g. emulsion, miniemulsions). In this work, we used two RAFT agents to produce linear and 4-arm star polymers in a well-controlled miniemulsion system using conventional surfactants (sodium dodecyl sulfate and hexadecane) and initiators (ammonium persulfate). The miniemulsions were formed through ultrasonication of the polymerization mixture to produce very small droplet sizes. Polymerization of styrene in these miniemulsions resulted in the formation of polymer nanoparticles of approximately 60 and 75 nm with narrow particle size distributions regardless of the targeted molecular weight. The rate of polymerization in these miniemulsions (100% conversion after 3.3 h) was significantly faster than in solution (60% conversion after 20 h). The reason for this fast rate was due to compartmentalization of the radicals within the growing particles. In addition, narrow MWDs were produced with polydispersity (PDIMWD) values below 1.22 for the linear and below 1.09 for the 4-arm star polymers. The particle size distributions were found to be narrow, less than 0.055 for the linear and less than 0.113 for the 4-arm star polymers. This is the first successful miniemulsion, to our knowledge, of 4-arm stars by RAFT to create both narrow molecular weight and narrow particle size distributions. The properties of such polymer latex particles are yet to be explored but they should have vastly different properties compared to latex particles with linear polymers. Our work opens a synthetic route to this class of latex particles previously unobtainable using conventional reagents, and providing exciting opportunities for various applications.

Nanoparticles of Well-Defined 4-Arm Stars made using Nanoreactors in Water

In this work, the use of a nanoreactor is demonstrated to rapidly prepare monodisperse polymer nanoparticles in water-based dispersion consisting of 4-arm star polymer via the R-group RAFT approach. It is shown that by heating a nanoparticle assembler above its lower critical solution temperature (LCST), stabilized nanoparticles are formed that act as a template for the 4-arm star RAFT-mediated polymerization of styrene. Monodisperse nanoparticles of size (between 40 and 90 nm) containing monodisperse polymer of desired molecular weight (30-95 k) are obtained with little star-star coupling due to compartmentalization. The nanoreactor technique allows independent control over the size and molecular weight with a 4-arm star topology.

Heck Reactions in Aqueous Miniemulsions

Carrying out organic reactions in water-based nanoreactors represents a ‘green’ method for the preparation of organic compounds. This process eliminates the need for solvents, thus reducing the effect of high volumes of solvent on the environment. In this work, we demonstrate a successful Heck cross-coupling reaction, one of the most used approaches to form C–C bonds using a palladium catalyst, in a miniemulsion. The miniemulsion droplet sizes were small (25 to 42 nm), and the reactions resulted in high conversions of three different products with high trans stereoisomers.

Precise control of drug loading and release of an NSAID–polymer conjugate for long term osteoarthritis intra-articular drug delivery

A facile synthesis method of polymer diclofenac conjugates (PDCs) based on biocompatible polyurethane chemistry that provides a high drug loading and offers a high degree of control over diclofenac (DCF) release kinetics is described. DCF incorporating monomer was reacted with ethyl-l-lysine diisocyanate (ELDI) and different amounts of polyethylene glycol (PEG) in a one-step synthesis to yield polymers with pendent diclofenac distributed along the backbone. By adjusting the co-monomers feed ratio, the drug loading could be tailored accordingly to give DCF loading of up to 38 w/w%. The release rate could also be controlled easily by changing the amount of PEG in the backbone. Above 10 w/w% of PEG, the in vitro DCF release studies in physiological conditions showed an apparent zero-order profile without an initial burst effect for up to 120 days. The PDCs described may be suitable for long-term intra-articular (IA) delivery for the treatment of osteoarthritis (OA).

Selective catalytic reduction of NO by NH3 on Fe-ZSM-5 elaborated from different methods

Abstract Different methods of preparation have been used to introduce iron species in the zeolite ZSM-5. Special consideration has been devoted to the FeCl3 sublimation method. The various samples have been characterised by XRD and temperature programmed reduction. Two general types of species have been identified: iron oxide aggregates and iron cationic species. In the SCR of NO by NH3, Fe-ZSM-5 prepared from sublimation of FeCl3 displays the highest activity which is assumed to be related to the formation of iron-oxo complexes. The formation of these species is enhanced by a rapid washing of the preparation after the sublimation of FeCl3 following by a calcination with 5–10%O2 atmosphere. The SCR activity has been correlated with the activity in oxidising NO to NO2.

Embedded top-coat for reducing the effect out of band radiation in EUV lithography

Out of band (OOB) radiation from the EUV source has significant implications for the performance of EUVL photoresists. Here we introduce a surface-active polymer additive, capable of partitioning to the top of the resist film during casting and annealing, to protect the underlying photoresist from OOB radiation. Copolymers were prepared using reversible addition-fragmentation chain transfer (RAFT) polymerization, and rendered surface active by chain extension with a block of fluoro-monomer. Films were prepared from the EUV resist with added surface-active Embedded Barrier Layer (EBL), and characterized using measurements of contact angles and spectroscopic ellipsometry. Finally, the lithographic performance of the resist containing the EBL was evaluated using Electron Beam Lithography exposure

Systematic investigation of the synthesis, characterization and switching mechanism of metal oxide nanoparticle resists

Metal oxide nanoparticle resists have recently emerged as next generation photoresist materials which exhibit promising performance for extreme ultraviolet lithography. In this present work, we are able to show our ability to synthesize and well characterize small uniform metal oxide nanoparticles, to present stability study of the nanoparticles in the resist solvent over time, to pattern ~20 nm features by electron beam lithography, and to provide an insight into the insolubilization mechanism of the resist system.