Design and synthesis of L-proline containing polymer assemblies with tuneable catalytic activity

The general concepts of the thesis are introduced in Chapter 1, including polymerization techniques employed to synthesize our catalytic nanoreactors and our motivations behind the work in this thesis. In Chapter 2 the catalytic activity of the amino acid L-proline after functionalization onto a polymer backbone was investigated. This was achieved using reversible addition fragmentation chain transfer (RAFT) polymerization yielding copolymers with predictable molecular weights and catalyst incorporation. Chapter 3 discusses the synthesis and self-assembly of block copolymers to yield polymer micelles with the catalytic motif contained within the hydrophobic micelle core. The application of polymer micelles as nanoreactors in water was assessed and the influence of core hydrophobicity on catalytic activity investigated. The effect of tethering the catalytic moiety to the micelle shell was also examined. In Chapter 4 the catalytic motif is incorporated into cross-linked nanogels and the property of the scaffold was investigated more in depth, such as the effect of crosslinking density and degree of functionalization on catalytic activity and selectivity. The hydrophobic nature of the nanogel and its importance in maintaining high selectivity was further examined. Chapter 5 reviews the possibility of using core-shell nanogels as recyclable nanoreactors. A thermo-responsive shell was introduced and the catalytic dependency of the core-shell nanostructures on temperature was investigated. The morphology of the shell was found to have a significant effect on the catalytic efficiency of the nanostructrues

One-pot synthesis of responsive sulfobetaine nanoparticles by RAFT polymerisation: the effect of branching on the UCST cloud point

We describe the one-pot synthesis of temperature-responsive branched polymer nanoparticles. Reversible addition–fragmentation chain transfer (RAFT) polymerisation has been utilised to synthesise ultra-high molecular weight sulfobetaine polymers (up to ca. 500 kDa) with good control over molecular weight (Mn) and dispersity (Mw/Mn). The UCST cloud points of these linear polymers were found to increase with both Mn and concentration, and represent one of the few recent descriptions of polymers exhibiting UCST behaviour in aqueous solution. The incorporation of difunctional monomers results in branched polymers which display vastly reduced transition temperatures compared to their linear counterparts. Furthermore, the incorporation of a permanently hydrophilic monomer results in the formation of stable core–shell particles which no longer exhibit a cloud point in water, even at very high concentrations (ca. 50 mg mL−1). The branched polymers are shown to form discrete well-defined nanoparticles in aqueous solution, and these have been characterised by DLS, SLS, TEM and DOSY. Their reversible swelling behaviour in response to temperature is also demonstrated

Complementary light scattering and synchrotron small-angle X-ray scattering studies of the micelle-to-unimer transition of polysulfobetaines

YesAB and ABA di- and triblock copolymers where A is the hydrophilic poly(oligoethylene glycol methacrylate) (POEGMA) block and B is a thermo-responsive sulfobetaine block [2-(methacryloyloxy) ethyl] dimethyl-(3-sulfopropyl) ammonium hydroxide (PDMAPS) were synthesised by aqueous RAFT polymerisation with narrow dispersity (ĐM ≤ 1.22), as judged by aqueous SEC analysis. The di- and triblock copolymers self-assembled in salt-free water to form micelles with a PDMAPS core and the self-assembly of these polymers was explored by SLS and TEM analysis. The micelles were shown, by DLS analysis, to undergo a micelle-to-unimer transition at a critical temperature, which was dependent upon the length of the POEGMA block. Increasing the length of the third, POEGMA, block decreased the temperature at which the micelle-to-unimer transition occurred as a result of the increased hydrophilicity of the polymer. The dissociation of the micelles was further studied by SLS and synchrotron SAXS. SAXS analysis revealed that the micelle dissociation began at temperatures below that indicated by DLS analysis and that both micelles and unimers coexist. This highlights the importance of using multiple complementary techniques in the analysis of self-assembled structures. In addition the micelle-to-unimer morphology transition was employed to encapsulate and release a hydrophobic dye, Nile Red, as shown by fluorescence spectroscopy.Engineering and Physical Sciences Research Council (EPSRC), University of Warwic

Advances in nanoreactor technology using polymeric nanostructures

Site isolation, compartmentalization and substrate specificity are a few of the characteristics responsible for the catalytic efficiency demonstrated by enzymes in natural systems. In efforts to mimic these highly efficient systems, research has been directed towards macromolecular chemistry. Robust polymer assemblies can create a favorable and isolated environment around the catalytic site allowing specific and sometimes incompatible reactions to take place within this protected reaction pocket. Further exploring the use of ‘smart’ polymers, control over both the catalytic activity and substrate specificity is achieved. In addition, polymeric systems provide the opportunity for recycling of the active catalysts, further enhancing the advantages of polymer supported catalytic systems

The effect of polymer nanostructure on diffusion of small molecules using tryptophan as a FRET probe

The amino acid L-tryptophan has been converted into a polymerizable monomer which has been incorporated into a range of cross-linked polymeric nanogels prepared by emulsion polymerization. By using time-lapse fluorescence spectroscopy the diffusion time of a small molecule Forster resonance energy transfer (FRET) pair, dansyl amide, into the central nanogel domain has been monitored through the decreased emission of the L-tryptophan FRET donor. In this initial study it has been found that diffusion of the small molecule into the nanogels is affected by altering the synthetic parameters (cross-linking density and co-monomer hydrophobicity). When increasing the cross-linking density of the nanogels the uptake diffusion time increased, while increasing the hydrophobicity of the co-monomer (and consequently lowering the glass-transition temperature (Tg)) caused a decrease in the diffusion time

Studying the activity of the MacMillan catalyst embedded within hydrophobic cross-linked polymeric nanostructures

The immobilization of the MacMillan catalyst within a unique hydrophobic environment created by a lightly cross-linked nanogel structure and its resulting catalytic activity is reported. The catalytic activity and selectivity of the catalyst were evaluated using the Diels–Alder (DA) reaction between cyclopentadiene and cinnamaldehyde. The relatively easy synthetic route applied allowed for the synthesis of a collection of nanogels with catalyst incorporations ranging from 0.5 to 25 wt%. In addition, core–shell type nanogels were synthesized to evaluate potential recovery and reuse of the catalytic system. The influence of the concentrator effect and possible partition coefficient on the catalyst activity was investigated. The results indicate catalyst loading/concentration can be more significantly reduced when the catalyst is embedded within the polymeric nanostructures compared to the small molecule equivalent

Functionalized organocatalytic nanoreactors : hydrophobic pockets for acylation reactions in water

The effect of covalently attaching 4-(dimethylamino)pyridine (DMAP) functionality to the hydrophobic core of a polymeric micelle in water has been investigated in the context of acylation reactions employing non-water-soluble substrates. For this purpose a novel temperature-responsive polymeric micelle has been synthesized using reversible addition-fragmentation chain transfer (RAFT) polymerization techniques. The reactivity of the tethered organocatalyst within the nanostructure was found to be extremely high, improving in some cases the acylation rates up to 100 times compared to those for unsupported DMAP in organic solvents. Moreover, the catalytic nanoreactors have been demonstrated to be capable of reuse up to 6 times while maintaining high activity. © 2012 American Chemical Society

Organocatalytic tunable amino acid polymers prepared by controlled radical polymerization

Two families of organocatalytically active polystyrene-based copolymers with tunable incorporations of 4-hydroxyproline have been synthesized using two different controlled radical polymerization technologies: nitroxide-mediated polymerization (NMP) and reversible addition-fragmentation chain transfer (RAFT) polymerization. Both of these methodologies allow ready access to a number of polymeric species with controllable molecular weights, narrow molecular weight distributions (ca. 1.2), and reliable functionality incorporations (between 3 and 26%). The organocatalytic activity and selectivity of the NMP-derived family of copolymers with variable incorporations of L-proline have been investigated using the aldol reaction, which provided high conversion to products ( > 95%) with very good diastereo- and enantioselectivities. We propose that these materials have potential as highly efficient recoverable organocatalyst supports whose solubility and loading can be readily tailored to the desired application

Effect of complementary nucleobase interactions on the copolymer composition of RAFT copolymerizations

Methacryloyl-type monomers containing adenine and thymine have been successfully synthesized with good yields. The homopolymerization and copolymerization of these two new functional monomers were carried out using RAFT polymerization. The reactivity ratios of monomer pairs were measured and calculated using a nonlinear least-squares (NLLS) method, and the results confirmed that the monomer reactivities were dependent on the solvent used for polymerization. The presence and absence of hydrogen bonding affected the resultant copolymer composition where moderate alternating copolymers had a tendency to be formed in CHCl3, while in DMF, statistical copolymers were formed. Furthermore, the glass transition temperatures of the copolymers were investigated, and the self-assembly of block copolymers made in solvents with different polarity were studied