The Role of Inorganic Photosensitisers in Radiation Sensitive Films for Cancer Treatment

The commercially important diacetylenes are used to provide a colourimetric change in practical chemosensors, biosensors, and dosimeters. Of particular importance are radiology and radiotherapy films such as Gafchromic which are used, for example, to monitor radiation targeting and dosage during cancer radiotherapy. Gafchromic films can also be utilized in non-destructive testing (NDT) applications where rapid X-ray inspection of articles (e.g. pipes, boxes etc.) can be essential. Gafchromic films are based on radiation-induced photopolymerization of a lipophilic diacetylene as part of a complex photoactive layer coated on a polyester base. Tuning of the photoresponse of the active ingredient and its dosage dependent conversion is of considerable interest for radiation dosimetry applications. In particular, the role of inorganic photosensitizers within the film is poorly understood both in terms of mode of action and chemical speciation. Existing film components such as bismuth and aluminium oxides seem to play a key role in activating and controlling film response but the way in which they interact with the diacetylene is unknown. This project aims to derive a bottom-up understanding of the in-film coordination chemistry of bismuth and aluminium oxides and the role these inorganic additives have in organizing the solid state structure of diacetylenes in order to promote radiation absorption and result in controlled, well-understood topotactic photopolymerization. The project will involve the synthesis and structural characterization of diacetylene carboxylate complexes of bismuth and aluminium, study of the chemical speciation of this system in films, dependence on factors such as local pH and derivation of structure-sensitivity relationships guided by the topochemical parameters governing solid state dialkyne photopolymerization. The project will also explore new photosensitisers such as bismuth vanadium oxides and chart the structure-property relationships arising from vanadium coordination. The project will rely heavily on single crystal and powder X-ray diffraction methods and in previous work it has been surprisingly possible to undertake detailed X-ray structural work on these types of diacetylenes despite their surfactant-like nature. the student will be exposed to synthetic coordination chemistry as well as multiple crystallization approaches. The student will learn to use a broad range of analytical techniques such as X-ray powder diffraction, single crystal diffraction, thermal analysis of crystalline & amorphous materials, NMR spectroscopy (particularly solid state NMR), and approaches to understand crystal packing and structure-property relationships. The student will also use hot stage polarized optical microscopy, SEM and TEM in analysing particle shape and thermal behaviour. The student will benefit from monthly meetings and presentations with the industrial supervisory team led by Dr. Osama Musa (Chief Technology Officer) and Dr. David Hood at Ashland. They will be exposed to product development workflows and approaches taken in industry to understand solid forms, complex formulations and photoreactivity. They will prepare regular technical reports and slide packs to present and so will learn softer communication skills, presenting with impact and reaching out to a wider audience beyond chemical scientists to demonstrate the value of their research. They will take part in national training courses such as the BCA Crystallography and Powder Diffraction Schools and will present their work at Conferences such as the RSC MASC.

1. PEOPLE. The SOFI2 CDT will have varied economic and societal impacts, the greatest of which will be the students themselves. They will graduate with a broad and deep scientific education as well as an entrepreneurial mind-set combined with business awareness and communication skills. The training programme reflects the knowledge and skills identified by industry partners, the EPSRC, recent graduates and national strategies. Partners will facilitate impact through their engagement in the extensive training programme and through the co-supervision of PhD projects. Responsible Innovation is embedded throughout the training programme to instil an attitude towards research and innovation in which societal concerns and environmental impact are always to the fore. The team-working and leadership skills developed in SOFI2 (including an appreciation of the benefits that diversity brings to an organisation and how to foster an atmosphere of equality and inclusion) will enable our graduates to take on leadership roles in industry where they can, in turn, influence the thinking of their teams.

2. PROJECTS. The PhD research projects themselves are impact pathways. Approximately half the projects will be co-sponsored by external partners and will be aligned to scientific challenges faced by the partner. Even projects funded entirely by the EPSRC/Universities will have an industrial co-supervisor who can provide advice on development of impact. The impact workshops and Entrepreneur in Residence will additionally help students to develop impact from their research, while at the same time developing the mind-set that sees innovation in invention.

3. PUBLIC. The public benefits from innovation that comes from the research in the CDT. It also benefits from the training of a generation of researchers trained in RI who seek out the input of stakeholders in the development of products and processes. The public benefits from the outreach activities that enable them to understand better the science behind contemporary technological developments - and hence to make more informed decisions about how they lead their lives. The younger generations benefit from the excitement of science that might attract them to higher education and careers in STEM subjects.

4. PARTNERSHIPS. SOFI2 involves collaborative research with >25 external partners from large multinationals to small start-ups. In addition to the results of sponsored projects and the possibility of recruiting SOFI2 students, companies benefit from access to training resources, sharing of best practice in RI and EDI, access to the knowledge of the SOFI2 academics and sharing of expertise with other partners in the SOFI2 network. This networking is of particular benefit to SMEs and we have an SME strategy to facilitate engagement of SMEs with SOFI2. SME representation on the Management and Strategic Advisory Boards will support the SME strategy.

CPI/NFC is a key partner both for delivery of training and to connect SOFI2 research, students and staff to a wide network of companies in the formulated products sector.

The unusual partnership with the Leverhulme Research Centre on Forensic Science may lead to a stronger scientific underpinning of forensic evidence with positive impacts on the legal process and the pursuit of justice.

5. PRODUCTS. Partner companies identify areas of fundamental and applied science of interest to them with the knowledge that advances in these areas will help them to overcome technological challenges that will lead to better products or new markets. It is an expectation that scientific discoveries made within the CDT will drive new products, new markets and potentially new companies. SOFI2 CDT seeks also to develop innovative training materials, for example, in RI and in data analytics and AI (in collaboration with the Alan Turing Institute), from which other CDTs and training organisations can benefit.