Chemistry

DESIGN OF FLUORESCENT TRANSITION METAL COMPLEXES FOR THE TREATMENT OF CANCER (LORDR_U21SF)

Applications are welcome for a self-funded PhD project within the School of Chemistry of the University of East Anglia to work in the research group of Dr Rianne Lord.

This project will be focused on the synthesis and characterisation of new transition metal complexes including both coordination and organometallic complexes (see attached references). The work will involve the organic synthesis of new ligands which will incorporation extended aromatic systems and fluorescent properties, and then their complexation reactions to a range of transition metals centres. All new metal complexes will be screened using 2D cell culture techniques to determine their cytotoxicity and then live-cell imaging, fluor9,5escence/confocal microscopy and whole-cell ICP-MS will be used to determine cellular uptake and distribution. These results will help us to determine additional assays to probe the complexes intracellular modes of action, e.g. DNA damage, mitochondrial dysfunction, apoptosis and cell cycle arrest. Any complexes showing promising cytotoxicity results and selectivity towards cancerous cells lines will then be screened using new 3D cell culture assays, in collaboration with Dr Christopher Morris (PHA at UEA). The applicant will not only gain experience in chemical synthesis and analytical techniques, but they will be fully trained in all start-of-the-art biological assays, giving them a significant amount of experience towards future careers in drug design and medicinal chemistry.

Applicants must have at least a 2:1 in Chemistry or related discipline or a good Masters degree in Chemistry.

Entry Requirements

Acceptable first degree in Chemistry or related discipline or a good Master's degree in Chemistry.

Funding

This PhD project is offered on a self-funding basis. It is open to applicants with funding or those applying to funding sources. Details of tuition fees can be found within our Finance pages.

A bench fee is also payable on top of the tuition fee to cover specialist equipment or laboratory costs required for the research. Applicants should contact the primary supervisor for further information about the fee associated with the project.

References

i) Bis-picolinamide Ruthenium(III) Dihalide Complexes: Dichloride-to-Diiodide Exchange Generates Single trans Isomers with High Potency and Cancer Cell Selectivity, A. M. Basri, R. M. Lord, S. J. Allison, A. Rodriguez-Barzano, S. J. Lucas, F. D. Janeway, H. J. Shepherd, C. M. Pask, R. M. Phillips and P. C. McGowan, Chem. Eur. J. 2017, 23(26), 6341-6356.
ii) Fast, Facile and Solvent-Free Dry-Melt Synthesis of Oxovanadium(IV) Complexes: Simple Design with High Potency towards Cancerous Cells, M. Zegke, H. L. M. Spencer and R. M. Lord, Chem. Eur. J. 2019, 25(53), 12275-12280.
iii) Hypoxia-Sensitive Metal β-Ketoiminato Complexes Showing Induced Single-Strand DNA Breaks and Cancer Cell Death by Apoptosis, R. M. Lord, A. J. Hebden, C. M. Pask, I. R. Henderson, S. J. Allison, S. L. Shepherd, R. M. Phillips, and P. C. McGowan, J. Med. Chem. 2015, 58, 12, 4940–4953.
iv) β-Ketoiminato Iridium(III) Organometallic Complexes: Selective Cytotoxicity towards Colorectal Cancer Cells HCT116 p53-/-, R. M. Lord, M. Zegke, I. R. Henderson, C. M. Pask, H. J. Shepherd and P. C. McGowan, Chem. Eur. J. 2019, 25(2), 495-500.
v) Enhanced selectivity, cellular uptake, and in vitro activity of an intrinsically fluorescent copper-tirapazamine nanocomplex for hypoxia targeted therapy in prostate cancer, V. L. Silva, A. Kaassis, A. Dehsorkhi, C. R. Koffi, M. Severic, M. Abdelhamid, D. Nyimanu, C. J. Morris and W’T. Al-Jamal, Biomater. Sci. 2020, 8, 2420-2433.

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