Catalytic labelling methods for the deuteration and fluorination of drug targets
- Closing Date
- Wednesday, 10th March 2021
About the Project
Application deadline: Open until filled
Supervisor: Dr Miriam O’Duill (https://www.nottingham.ac.uk/chemistry/people/miriam.oduill )
Start date: flexible, Apr 2021 or no later than Oct 2021
Funded PhD project (European/UK students only)
The incorporation of isotopes such as deuterium, tritium or fluorine-18 into molecules is instrumental in medicinal chemistry: Deuterium and tritium labelling is required for preclinical ADME studies and clinical trials,1 deuteration can improve the metabolic stability, pharmacokinetics and toxicity profile of drugs,2 and fluorine-18 is the isotope of choice for positron emission tomography (PET) – an in vivo imaging technique that is used both for diagnostics and in the drug development process.3 Developing new, selective functionalisation reactions that allow for the incorporation of these isotopes at a late stage in the synthesis is therefore of utmost importance and interest.
The aim of this PhD project is to address this challenge and develop reactions for the late-stage deuteration, tritiation and fluorination of drug-like molecules using transition-metal catalysed and metal-free, organocatalytic methods. The specific focus of the project will be defined in collaboration with the successful applicant.
Based in the School of Chemistry, University of Nottingham, this project will provide extensive training in organic synthesis and catalysis, reaction screening for methodology development and analytical techniques (NMR, MS, X-ray).
Candidates will have a chemistry degree with a strong interest in catalysis and methodology development. The starting date for the project is flexible: ideally Apr 2021 or, at the latest, Oct 2021. Prospective applicants are encouraged to contact Dr Miriam O’Duill (firstname.lastname@example.org) for more details or enquires about the project. More information about the research group is available at https://oduillgroup.com/
Formal applications should be made online through the University of Nottingham’s online application system: http://www.nottingham.ac.uk/pgstudy/how-to-apply/apply-online.aspx. Please also send a cover letter and CV to email@example.com detailing your previous research experience and current research interests. Applications are open until a suitable candidate has been found and early applications are encouraged.
Fully funded studentship to commence before Oct 2021 (preferred starting date Apr 2021). UK students – tuition fees paid and full stipend, tax-free, for 42 months at the RCUK rate (currently £15,285 per annum). EU students eligible and considered as UK students if available to start by Aug 2021, please get in touch for further details.
Applicants should have, or expected to achieve, a First Class or good 2:1 Honours degree (or equivalent) in chemistry and an interest in catalysis. Substantial research experience will be advantageous.
If English is not the candidate’s first language, they must provide evidence before the beginning of the studentship that they meet the University minimum English Language requirements (IELTS 6.0 with at least 5.5 in each element).
1. Atzrodt, J.; Derdau, V.; Kerr, W. J.; Reid, M. Deuterium‐ and Tritium‐Labelled Compounds: Applications in the Life Sciences, Angew. Chem. Int. Ed. 2018, 57, 1758–1887.
2. Lowe, D. In The Pipeline, https://blogs.sciencemag.org/pipeline/archives/2017/04/04/the-first-deuterated-drug-arrives (accessed 6.12.2020)
3. S. Purser, P. R. Moore, S. Swallow, V. Gouverneur, Fluorine in medicinal chemistry Chemical Society Reviews 2008, 2008, 320-330.