Bryn D. Monnery

Photoiniferter (PI)-RAFT polymerization is a promising approach to synthesise a broad range of (meth)acrylic and styrenic polymers because of its highly ‘living’ nature. The lack of an imbalance between initiating and chain-transfer fragments minimises the inherent bimolecular termination of conventional RAFT. Poly(poly(ethylene glycol) methyl ether methacrylate) (P(PEGMA)) is a potential biocompatible material for biomedical applications, but the highly reactive free radical of PEGMA makes control of its polymerisation challenging. In this study, we investigated the synthesis of P(PEGMA) through PI-RAFT. Current studies on the PI-RAFT mechanisms are limited and the effect of solvents on kinetics has not been reported. We varied several reaction conditions: excitation wavelengths, monomer concentrations, temperatures, and solvents. The propagation constant (k_p) values were affected by the RAFT main equilibrium. We calculated the Arrhenius parameters, enthalpy of activation (ΔH^‡), and entropy of activation (ΔS^‡) for polymerization in various solvents. Regression analysis was conducted to fit the results with extinction coefficients of CTA in seven common solvents, solvent physical properties, and solvatochromic scales. The effective collision factor A had a good fitting with an exponential regression model of the extinction coefficients, indicating a strong relationship between the reaction rate and excitation of the CTA. Solvent polarity scales, such as Kalmet–Abraham–Taft (KAT) and Catalan parameters, failed to predict k_p, Arrhenius parameters, ΔH^‡, and ΔS^‡. A chain transfer constant C_tr > 1 for all syntheses indicated relatively good control over the polymerization through degenerative chain transfer with CTA radicals. In general, C_tr decreased with increasing temperatures, a result of the rate of excitation by photon absorption being constant, but the k_p being increased by the temperature. Anisole was the best solvent, able to keep Đ = 1.30 even at 40 °C.

Diffusion ordered ¹H-NMR spectroscopy (DOSY) is a useful, non-destructive technique for analysing polymer hydrodynamic size and in solution viscosity.

This content was removed because it was posted without all parties' consent.

Segmented thermoplastic copolyether esters (TPEE's) with a partially renewable hard block containing isosorbide (ISB) and poly(ethylene glycol) (PEG) soft blocks were prepared by melt polycondensation. A range of compositions was accessible despite the relatively low reactivity of the sterically and electronically hindered ISB monomer. The small‐scale reactions performed in the melt were limited in terms of achievable molar mass. This is attributed to the challenge of attaining stoichiometric balance in the feed and maintaining this balance throughout the high temperature (>200°C) reactions. Nevertheless, products were isolated that could be manipulated and melt‐pressed into specimen for tensile testing. Varying the feed compositions gave rise to copolymers exhibiting a broad range of mechanical properties (elastic modulus from 1–66 MPa). These characteristics are consistent with a segmented polymer architecture with morphological features similar to commercially available TPEE counterparts. These results pave the way for more responsibly sourced building blocks being incorporated into materials with high market value potential.

Polyplex-mediated gene transfection is now in its’ fourth decade of serious research, but the promise of polyplex-mediated gene therapy has yet to fully materialize. Only approximately one in a million applied plasmids actually expresses. A large part of this is due to an incomplete understanding of the mechanism of polyplex transfection. There is an assumption that internalization must follow a canonical mechanism of receptor mediated endocytosis. Herein, we present arguments that untargeted (and most targeted) polyplexes do not utilize these routes. By incorporating knowledge of syndecan-polyplex interactions, we can show that syndecans are the “target” for polyplexes. Further, it is known that free polycations (which disrupt cell-membranes by acid-catalyzed hydrolysis of phospholipid esters) are necessary for (untargeted) endocytosis. This can be incorporated into the model to produce a novel mechanism of endocytosis, which fits the observed phenomenology. After membrane translocation, polyplex containing vesicles reach the endosome after diffusing through the actin mesh below the cell membrane. From there, they are acidified and trafficked toward the lysosome. Some polyplexes are capable of escaping the endosome and unpacking, while others are not. Herein, it is argued that for some polycations, as acidification proceeds the polyplexes excluding free polycations, which disrupt the endosomal membrane by acid-catalyzed hydrolysis, allowing the polyplex to escape. The polyplex’s internal charge ratio is now insufficient for stability and it releases plasmids which diffuse to the nucleus. A small proportion of these plasmids diffuse through the nuclear pore complex (NPC), with aggregation being the major cause of loss. Those plasmids that have diffused through the NPC will also aggregate, and this appears to be the reason such a small proportion of nuclear plasmids express mRNA. Thus, the structural features which promote unpacking in the endosome and allow for endosomal escape can be determined, and better polycations can be designed.

Addressing the polymerization of 2-ethyl-2-oxazoline (EtOx) in ethyl acetate to replace the current state-of-the-art solvents. The switch to ethyl acetate is important towards pharmaceutical compliance/compatibility of PEtOx, besides low environmental burden.

Hydrogels are useful materials for drug delivery and tissue engineering. A subset of these are responsive hydrogelators that are liquids until a stimulus triggers their gelation. Poly(2-oxazoline)s with moderately hydrophobic side chains, such as ethyl and propyl, are inherently thermoresponsive exhibiting lower critical solution temperature behavior. However, previous attempts to make thermoresponsive poly(2-oxazoline) block copolymer hydrogelators have all failed. In this work we report the first working thermoresponsive poly(2-oxazoline) hydrogelator based on ABA triblock copolymers with thermoresponsive outer blocks composed of poly(2-n-propyl-2-oxazoline) and a more hydrophilic poly(2-ethyl-2-oxazoline) inner block that can form hydrogels upon heating an aqueous solution. It was found that thermoresponsive hydrogels are only formed if the block size is tuned to adjust the cloud point temperature and, presumably, to allow sufficient flexibility to non-covalently crosslink the flower-like micelles that these materials form. These triblocks copoly(2-oxazoline)s formed relatively soft thermoresponsive hydrogels that could be suitable for drug release and cell culture applications.

In this communication, we report for the first time the synthesis of defined high molar mass poly(2-methyl-2-oxazoline) (PMeOx), a water-soluble polymer with excellent anti-fouling properties. So far, there has been no report on low dispersity (Đ < 1.2) PMeOx longer than 10 kg mol⁻¹. Higher molar mass would be beneficial for synthesis of polymer–drug conjugates, excipients as well as for other biomedical applications. We report our attempts to prepare defined high molar mass PMeOx via living cationic ring-opening polymerization (CROP) of its monomer using our optimized method that failed due to extensive chain transfer and chain coupling side reactions. Therefore, we proposed an alternative strategy to high molar mass PMeOx based on acetylation of well-defined linear polyethyleneimine (PEI) prepared by controlled side-chain hydrolysis of defined high molar mass PEtOx. This method allowed us to synthesize a series of low-dispersity PMeOx up to 58 kg mol⁻¹ (Đ = 1.07). Considering the biomedical potential of PMeOx, the synthesis of such polymers might open a way to a new class of effective polymer-based therapeutics.

Poly(2‐alkyl‐2‐oxazoline)s (PAOx) are regaining interest for biomedical applications. However, their full potential is hampered by the inability to synthesise uniform high‐molar mass PAOx. In this work, we proposed alternative intrinsic chain transfer mechanisms based on 2‐oxazoline and oxazolinium chain‐end tautomerisation and derived improved polymerization conditions to suppress chain transfer, allowing the synthesis of highly defined poly(2‐ethyl‐2‐oxazoline)s up to ca. 50 kDa (dispersity (Ð) Ð<1.2). The determination of the chain transfer constants for the polymerisations hinted towards the tautomerisation of the oxazolinium chain end as most plausible cause for chain transfer. Finally, the method was applied for the preparation of up to 60 kDa molar mass copolymers of 2‐ethyl‐2‐oxazoline and 2‐methoxycarbonylethyl‐2‐oxazoline.