Thesis
The design of fluorogenic platinum(IV) complexes and their potential applications in tumour hypoxia
- Abstract:
-
This thesis details the synthesis of various fluorogenic Pt(IV) complexes derived from FDA approved Pt-based chemotherapeutics and investigates their behaviour under hypoxic conditions.
Chapter 1 introduces the field of platinum chemistry and the application of Ptderived chemotherapeutics in medicine, with an emphasis on Pt(IV) pro-drugs and areas relevant to this thesis.
Chapter 2 explores the synthesis of fluorogenic Pt(IV) complexes derived from the three common FDA approved chemotherapeutics prescribed in clinic and assesses their behaviour under hypoxic conditions. A detailed investigation of an unprecedented Hypoxia Activated Platinum is discussed, elucidating critical structural design and reduction potential requirements to confer hypoxia selective toxicity for Pt(IV) pro-drugs.
Chapter 3 investigates analogues of the fluorogenic Pt(IV) complexes interrogated in Chapter 2, identifying an unexpected intramolecular photomediated pathway for reduction of fluorogenic Pt(IV) complexes, and explains a promising foundational scaffold for developing photochemotherapeutic agents that induce toxicity irrespective of oxygen concentrations.
Chapter 4 expands on the results of Chapter 2 to apply the foundational scaffold towards developing multi-action hypoxia-activated Pt(IV) pro-drugs. The first carboplatin-based aryl carbamate multi-action pro-drugs with unprecedented toxicity in breast cancer cell lines is discussed.
Chapter 5 summarises the conclusions of this thesis and explores potential next steps for future work.
Chapter 6 details all experimental procedures and methods used in this work and describes the characterization of compounds presented in Chapters 2 – 4.
Actions
Authors
Contributors
+ Faulkner, S
- Institution:
- University of Oxford
- Division:
- MPLS
- Department:
- Chemistry
- Sub department:
- Inorganic Chemistry
- Role:
- Supervisor
- ORCID:
- 0000-0003-1878-5857
+ Schofield, C
- Institution:
- University of Oxford
- Division:
- MPLS
- Department:
- Chemistry
- Sub department:
- Organic Chemistry
- Role:
- Supervisor
- ORCID:
- 0000-0002-0290-6565
+ Sedgwick, A
- Institution:
- University of Oxford
- Division:
- MPLS
- Department:
- Chemistry
- Sub department:
- Inorganic Chemistry
- Role:
- Supervisor
+ Rhodes Trust
More from this funder
- Funder identifier:
- https://ror.org/04v48nr57
- Funding agency for:
- Marsh, JW
- Programme:
- The Rhodes Scholarship
- DOI:
- Type of award:
- DPhil
- Level of award:
- Doctoral
- Awarding institution:
- University of Oxford
- Language:
-
English
- Keywords:
- Subjects:
- Deposit date:
-
2026-10-30
- ARK identifier:
Terms of use
- Copyright holder:
- Jevon W. Marsh
- Copyright date:
- 2025
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