Dr James Bruce

While there has been considerable effort in developing processes and materials to make plastics recyclable and reusable, some plastics and polymeric materials remain difficult to recycle and typically end up in landfill. These materials are usually based on hard polystyrenes, epoxy resins and acrylates which are attractive to industries which require hard-wearing products, such as road marking and coatings. Furthermore, many of the current methods to make plastics recyclable or decomposable diminish their mechanical properties such as hardness and durability required for surface coatings. We have been piloting some approaches for polystyrene road studs to address this issue. These are temporary studs glued to the road to provide lane guidance during roadworks. They are currently deposited in landfill after a single use. The pilot approach used a range of surfactants and varying critical micelle concentrations to determine the optimum conditions (composition of surfactant, temperature, and time) to remove the adhesive that bonds the studs to the road. The recovered polystyrene studs will be ground and remolded and their mechanical and physical properties (e.g. hardness, hydrophobicity, glass and melting temperatures) examined and compared with newly manufactured studs. A second approach is based on current thermoplastics technologies using resins such as renewable rosin esters. These are interesting as the ester functionality is a point where additional functionality can be attached. The aim is to improve the wet weather performance of the material allowing it to be laid in wet conditions (so extending operation throughout the year), as well as lowering its application temperature from 250 °C. Other examples of additional desirable functionality are light emitting chromophores that improve the visibility of the markings in adverse conditions. The contribution to the material properties from these functionalities will be analysed using techniques such as Raman, SEM/TEM, adhesion, XRD, DSC and hardness testing. The final approach focuses on synthetic polymer chemistry and builds on pilot work we have done in preparing polymers with chemically cleavable bonds. This allows a polymer to be decomposed or decured and potentially makes it easier to remove and recover from the environment. Acrylates are increasingly being used as alternatives to thermoplastics in the road marking industry and this work will use light induced processes such as Photoinduced Electron Transfer (PET) to control the polymerisation of acrylates. This will build on the synthetic chemistry skills developed in the work with rosin esters above as well as the characterization techniques such as NMR and Fluorescence spectroscopy.

Extension for a further 2 months to the existing 6 month research fellowship to define a method development protocol for reversed-phase separations of pharmaceutical peptides and their related impurities. The idea is to select a smaller number of columns and mobile phases that provide large differences in selectivity based on a recent PhD project [Characterisation of Reversed Phase Chromatography Peptide Separation Systems, Strathclyde Institute of Pharmacy and Biomedical Sciences, Jennifer Kathryn Field, Year of Submission 2019) 201670008]. These mobile phases will subsequently be optimised to provide not only large differences in selectivity but also acceptable limit of quantitation and peak shape as well as horizontal UV baselines. Some of the mobile phases are potentially corrosive and thus also a corrosion study will be included in the work. Finally, based on these studies, a flow scheme for rational method development will be proposed and evaluated using a series of degraded peptides. Besides automated screening this strategy also involves retention modelling in order to define optimal gradient shape and column temperature. The ambition is to publish and article as well as disseminating the results at conferences.

The purpose of this 6 month research fellowship is to define a method development protocol for reversed-phase separations of pharmaceutical peptides and their related impurities. The idea is to select a smaller number of columns and mobile phases that provide large differences in selectivity based on a recent PhD project [Characterisation of Reversed Phase Chromatography Peptide Separation Systems, Strathclyde Institute of Pharmacy and Biomedical Sciences, Jennifer Kathryn Field, Year of Submission 2019) 201670008]. These mobile phases will subsequently be optimised to provide not only large differences in selectivity but also acceptable limit of quantitation and peak shape as well as horizontal UV baselines. Some of the mobile phases are potentially corrosive and thus also a corrosion study will be included in the work. Finally, based on these studies, a flow scheme for rational method development will be proposed and evaluated using a series of degraded peptides. Besides automated screening this strategy also involves retention modelling in order to define optimal gradient shape and column temperature. The ambition is to publish and article as well as disseminating the results at conferences.

This was to fund an undergraduate student, Kirsten Hawkins, who has approached the department for a summer placement.New approaches that localise radiosensitivity within tumours have the potential to improve the effectiveness of radiotherapy and reduce side effects for patients. Here we developed compounds, known as radiosensitisers, containing heavier elements such as metals that produce electrons upon radiotherapy. These electrons promote localised DNA damage in cancer cells leading to their death. Careful design of the complexes aimed to promote their localisation in the DNA of cancer cells so that those that these are most damaged upon radiotherapy. It is significant that we developed one copper containing compound that exhibited a comparatively low cytotoxicity in HEK293T cells (human embryonic kidney cells) over 24 h, for example it was approximately 45 times less cytotoxic to these cells in comparison to the anticancer drug cis-platin. This suggests its further study in targeted radiotherapy where the cytotoxicity in cancer cells would be turned on by the application of the radiotherapy. It is significant that we developed one copper containing compound that exhibited a comparatively low cytotoxicity in HEK293T cells (human embryonic kidney cells) over 24 h, for example it was approximately 45 times less cytotoxic to these cells in comparison to the anticancer drug cis-platin. This suggests its further study in targeted radiotherapy where the cytotoxicity in cancer cells would be turned on by the application of the radiotherapy. Abi Barbour, an A-S level student, also worked on this project under the Nuffield Research Placement scheme and as a result achieved her Gold Crest award.

The project will last for 6 weeks and will provide an OU student with the opportunity to carry out research work in our laboratories.

The proposed PhD will focus on the development of novel in-situ reporter agents and their application to in-vitro/in-vivo studies of drug induced toxicity. These studies will take the form of in-vitro screening studies and in vitro/in vivo mechanistic studies. The project may be considered as a series of phases or workpackages: • Phase 1: Identification of molecules to act as key determinants in the processes under study. • Phase 2: Design and synthesis of Lanthanide-based reporter agents to optimise selectivity and imaging characteristics. • Phase 3: In-vitro testing of novel reporter agent(s). This phase will include non-cellular in-vitro testing to determine the response of the agent to the marker understudy and cross-reactivity with similar target entities. • Phase 4: In-vivo testing of the reporter agent(s). In addition to studies utilising the action of the reporter, studies will be conducted to confirm the safety of the reporter agent so as to determine the utility within in vivo studies. (At GSK)