The development of amine-functionalised polymeric stars as dual-functional catalysts for polyurethane foam.

This Thesis explores the synthesis of amine-functionalised polymeric stars synthesised using Reversible Addition-Fragmentation Chain Transfer (RAFT) polymerisation, and their applicability as dual functional catalysts for both the catalysis of polyurethane foam production, and for the deblocking of blocked isocyanates. Chapter 1 introduces polyurethane chemistry, and provides an in-depth summary of blocked isocyanates. Additionally, it introduces the RAFT polymerisation chemistry utilised for catalyst synthesis within this thesis. Chapter 2 investigates the use of RAFT polymerisation for the production of non-responsive crosslinked methacrylate polymeric stars. Evaluation of polymeric stars with different structural properties in the polyurethane foam formulation was carried out to assess the protection afforded to the catalytic amine when tethered within the star polymer. Chapter 3 utilises the RAFT synthesis of analogous acrylate based polymeric stars, the hydrolytic susceptibility of which is able to act as a model to those introduced in Chapter 2. Evaluation of the hydrolytic behaviour allowed for further probing of the effect of structural parameters on the protection of the amine. Chapter 4 describes the incorporation of responsive crosslinkers to produce stimuli responsive polymeric stars, including the incorporation of a furan-maleimide thermoresponsive crosslinker utilising Diels-Alder chemistry, in addition to a disulphide based crosslinker which is redox responsive. Chapter 5 explores the incorporation of a diisocyanate based crosslinker with a view towards the production of thermoresponsive polymeric stars using blocked isocyanate chemistries, and therefore minimising the addition of contaminants (e.g. other crosslinkers) to the polyurethane formulation. Chapter 6 discusses the determination of the deblocking temperature of isocyanates in order to understand any trends in the deblocking of both externally and internally blocked isocyanates, as well probing the effect of amines on the deblocking temperature. In the final Chapter, a summary of the work reported in Chapters 2- 6 is provided, with an outlook towards further applications of the polymeric stars reported in this thesis

Blocked isocyanates:from analytical and experimental considerations to non-polyurethane applications

In this review we aim to provide an introductory guide to blocked isocyanates, through discussion on different examples of blocking groups, along with experimental considerations for their application. The review brings together updated examples of functionalities used and places specific emphasis on the analytical techniques used for the determination of deblocking temperature, updating previous reviews with the newly applied technique of X-ray photoelectron spectroscopy (XPS). Additionally, we put forward a brief update on the use of blocked isocyanates for other non-traditional polyurethane based polymer applications. We also highlight the importance of matching the analytical technique to the application of the blocked isocyanate, with differences in material state and experimental parameters having a great impact on the deblocking temperature reported

The hydrolytic behavior of N,N’-(dimethylamino) ethyl acrylate-functionalized polymeric stars

YesWell-defined N,N’-(dimethylamino)ethyl acrylate (DMAEA) functionalized polymeric stars have been synthesized via an arm-first approach. Utilizing reversible addition–fragmentation chain transfer polymerization, linear homopolymers (PEGA, PHEA) were chain extended with DMAEA and a divinyl crosslinker to produce a series of crosslinked polymeric stars. These stars were characterized using a range of techniques including NMR, SEC, DLS and TEM analysis. The hydrolytic behavior of the DMAEA when tethered within a micellar core was investigated by1 H NMR spectroscopy and was found to be strongly dependent on temperature. At elevated temperatures either a higher crosslinking density or a longer arm length was found to offer greater protection to the amine resulting in slower hydrolysis, with hydrolysis found to level off at a lower final percentage hydrolysis. In contrast, the composition and nature of the arm was found to have little impact on the hydrolysis, with the same trends relating to the effect of temperature and crosslinking density observed with a linear (HEA) and a brush (PEGA) arm. Additionally, the release of DMAE from the polymeric stars was successfully confirmed through the use of an enzymatic assay, producing a concentration of DMAE in good agreement with the theoretical concentration based on the 1H NMR spectroscopic analysis.Atomic Weapons Establishment (AWE), EPSR

Use of complementary nucleobase-containing synthetic polymers to prepare complex self-assembled morphologies in water

YesAmphiphilic nucleobase-containing block copolymers with poly(oligo(ethylene glycol) methyl ether methacrylate) as the hydrophilic block and nucleobase-containing blocks as the hydrophobic segments were successfully synthesized using RAFT polymerization and then self-assembled via solvent switch in aqueous solutions. Effects of the common solvent on the resultant morphologies of the adenine (A) and thymine (T) homopolymers, and A/T copolymer blocks and blends were investigated. These studies highlighted that depending on the identity of the common solvent, DMF or DMSO, spherical micelles or bicontinuous micelles were obtained. We propose that this is due to the presence of A–T interactions playing a key role in the morphology and stability of the resultant nanoparticles, which resulted in a distinct system compared to individual adenine or thymine polymers. Finally, the effects of annealing on the self-assemblies were explored. It was found that annealing could lead to better-defined spherical micelles and induce a morphology transition from bicontinuous micelles to onion-like vesicles, which was considered to occur due to a structural rearrangement of complementary nucleobase interactions resulting from the annealing process.European Research Council (ERC), University of Warwick, Engineering and Physical Sciences Research Council (EPSRC), National Science Foundation (U.S.) (NSF

The development and validation of a scoring tool to predict the operative duration of elective laparoscopic cholecystectomy

Background: The ability to accurately predict operative duration has the potential to optimise theatre efficiency and utilisation, thus reducing costs and increasing staff and patient satisfaction. With laparoscopic cholecystectomy being one of the most commonly performed procedures worldwide, a tool to predict operative duration could be extremely beneficial to healthcare organisations. Methods: Data collected from the CholeS study on patients undergoing cholecystectomy in UK and Irish hospitals between 04/2014 and 05/2014 were used to study operative duration. A multivariable binary logistic regression model was produced in order to identify significant independent predictors of long (> 90 min) operations. The resulting model was converted to a risk score, which was subsequently validated on second cohort of patients using ROC curves. Results: After exclusions, data were available for 7227 patients in the derivation (CholeS) cohort. The median operative duration was 60 min (interquartile range 45–85), with 17.7% of operations lasting longer than 90 min. Ten factors were found to be significant independent predictors of operative durations > 90 min, including ASA, age, previous surgical admissions, BMI, gallbladder wall thickness and CBD diameter. A risk score was then produced from these factors, and applied to a cohort of 2405 patients from a tertiary centre for external validation. This returned an area under the ROC curve of 0.708 (SE = 0.013, p  90 min increasing more than eightfold from 5.1 to 41.8% in the extremes of the score. Conclusion: The scoring tool produced in this study was found to be significantly predictive of long operative durations on validation in an external cohort. As such, the tool may have the potential to enable organisations to better organise theatre lists and deliver greater efficiencies in care

The ARID1B spectrum in 143 patients: from nonsyndromic intellectual disability to Coffin–Siris syndrome

Purpose: Pathogenic variants in ARID1B are one of the most frequent causes of intellectual disability (ID) as determined by large-scale exome sequencing studies. Most studies published thus far describe clinically diagnosed Coffin–Siris patients (ARID1B-CSS) and it is unclear whether these data are representative for patients identified through sequencing of unbiased ID cohorts (ARID1B-ID). We therefore sought to determine genotypic and phenotypic differences between ARID1B-ID and ARID1B-CSS. In parallel, we investigated the effect of different methods of phenotype reporting. Methods: Clinicians entered clinical data in an extensive web-based survey. Results: 79 ARID1B-CSS and 64 ARID1B-ID patients were included. CSS-associated dysmorphic features, such as thick eyebrows, long eyelashes, thick alae nasi, long and/or broad philtrum, small nails and small or absent fifth distal phalanx and hypertrichosis, were observed significantly more often (p < 0.001) in ARID1B-CSS patients. No other significant differences were identified. Conclusion: There are only minor differences between ARID1B-ID and ARID1B-CSS patients. ARID1B-related disorders seem to consist of a spectrum, and patients should be managed similarly. We demonstrated that data collection methods without an explicit option to report the absence of a feature (such as most Human Phenotype Ontology-based methods) tended to underestimate gene-related features

The application of blocked isocyanate chemistry in the development of tunable thermoresponsive crosslinkers

The synthesis of a novel monomer, methacryloyl pyrazole, and its subsequent reaction with diisocyanates to produce thermoresponsive crosslinkers is reported.</p