4 Year GTA - Accessing deuterated amine-based pharmaceuticals through new approaches to hydrogen isotope exchange

About the Project

Open to UK applicants only

The School of Chemistry has fully-funded Graduate Teaching Assistant (GTA) studentships available for UK applicants, starting in September 2026.

The opportunities allow successful candidates to pursue their passion for research in the chemical sciences, alongside developing their skills as chemistry lecturers and educators of the future. This includes working toward gaining recognition as an Associate Fellow of the Higher Education Academy.

The GTA involves laboratory demonstrating and other teaching responsibilities in term time, with approximately 80% of your time dedicated to research across the calendar year. These are 4-year positions that include an annual stipend and salary package, full UK tuition fees, and a research and training grant.

Project Highlights

• Discovers efficient methodology with direct industrial applications in drug discovery.
• Utilises unexplored reactivity of boron-based catalysts.
• Boarders on the traditional realms of organic and inorganic and biological chemistry, as well as machine learning, and therefore provides a unique training opportunity suitable for careers in industry (e.g. pharmaceutical, agrochemical, fine chemicals, etc) and academia.

Description

Summary

An exciting PhD opportunity is available in the Pulis group that will push the boundaries of organic chemistry by interfacing organic and inorganic chemistry with biological chemistry/chemical biology and data science.

Background

Deuterium- and tritium-labelled organic compounds are essential throughout academic and industrial research. They are utilised in the investigation of reaction mechanisms, neutron scattering, and extensively in the drug discovery process, from target identification to clinical trials. For example:

(1) receptor binding studies rely on the use of tritium-labelled molecules;

(2) deuterium-labelled MS standards aid the identification of metabolites from animal and human studies;

(3) deuterium labels serve as simple bioisosteres for hydrogen and can alter ADME properties; and

(4) regulatory authorities often require radiolabelled (i.e. tritium) in vivo metabolism studies.

Approved deuterium-labelled drugs are increasing in prevalence, and deuterium derivatives offer opportunities for new chemical entities; however, no clear regulatory framework has yet been established. Therefore, methods that allow precise control of regio-, chemo-, and stereoselectivity in generating deuterium- and tritium-labelled organic compounds are of strategic importance.

In this project, we will develop a hydrogen isotope exchange platform that directly exchanges hydrogen for deuterium or tritium in complex molecules, avoiding the need for costly and time-consuming de novo approaches.

Project aims

The project will build on the Pulis group’s expertise and success in the application of main group element reactivity.^[1–3] It will exploit the unusual and unique ability of organoboranes to selectively activate α-amino C(sp³)−H bonds in the development of a new approach to late-stage deuterium- and tritium-labelling of amine-containing pharmaceutical compounds. he new methodology will be stereo- and regioselective and will deliver high levels of isotope incorporation suitable for a variety of industrial and academic research applications.

We have exciting preliminary results from which to launch this project. To ensure that the methodology developed is suitable for industrial applications, we will work closely with established partners from the pharmaceutical industry, including performing late-stage tritiation at an industrial site.

We will test deuterated amine-based pharmaceuticals with industrial and academic collaborators, leveraging partners who have interests in specific approved drugs (i.e. patent holders) and/or therapeutic areas. We will also use the methodology to develop a dataset from which to build machine learning models that can predict reaction success, experimental conditions, and regio- and stereoselectivity.

Methodology and approach

The project will involve organic and inorganic chemistry procedures, along with relevant analytical techniques (primarily NMR spectroscopy and mass spectrometry). Initially, the project will identify and optimise suitable sources of deuterium for hydrogen isotope exchange, including readily accessible deuterated organic molecules and deuterium gas as a surrogate for tritium gas. The substrate scope will be investigated using model molecules that feature functional groups and moieties important to drug discovery, including heterocycles and polar functional groups. The methodology will then be applied to the late-stage deuteration of approved amine-containing drug molecules, such as gefitinib (anticancer), fluopromazine (antipsychotic), donepezil (Alzheimer’s treatment), fluoxetine (antidepressant), cetirizine (antihistamine), and loperamide (antidiarrhoeal), to showcase the power of the methodology. We will utilise the unique stopped-flow NMR setup at the University of Leicester to investigate the reaction mechanism and use that knowledge to improve the methodology, including designing new catalysts.

With deuterated amine-based pharmaceuticals in hand, we will explore the effects of deuteration on biological activity with existing collaborators, including the second supervisor and industrial contacts throughout the UK. Finally, we will leverage the data generated to develop machine learning workflows. In collaboration with data scientists, we will featurise the data, select models for training, and evaluate performance, enabling predictions of hydrogen isotope exchange success, optimal experimental conditions, and regio- and stereoselectivity for given substrates.

Note this project is expansive and has scope to suit the interests of the candidate.

Project enquiries to Dr Alexander Pulis a.pulis@le.ac.uk

Application enquiries to Dr Richard Doveston r.g.doveston@leicester.ac.uk(Postgraduate Admissions tutor for the School of Chemistry)

To apply please refer to the application advice and use the application link at https://le.ac.uk/study/research-degrees/funded-opportunities/chemistry-gta

Start 21 September 2026

Funding Notes

GTA Studentships provide funding for 4 years to include:

• Tuition fees at UK rates
• A combined teaching and stipend payment (for 2026/7 this will be £21,805 per year, paid in monthly instalments)

References

[1] Alvarez-Montoya, Gillions, Winfrey, Hawker, Singh, Ortu, Fu, Li, Pulis, ACS Catal. 2024, 14, 4856.

[2] Basak, Alvarez-Montoya, Winfrey, Melen, Morrill, Pulis, ACS Catal. 2020, 10, 4835.

[3] Basak, Winfrey, Kustiana, Melen, Morrill, Pulis, Chem. Soc. Rev. 2021, 50, 3720.