Synthesis and biological evaluation of new titanium (IV) complexes and their use in anti-cancer treatment
This thesis considers the synthesis, and characterisation of new fulvene ligands and titanium(IV) complexes and evaluation of their potential as anti-cancer agents. It contains the in vitro cell results from different techniques used to investigate their biological mechanisms of action and their act...
| Main Author: | |
|---|---|
| Format: | Thesis (University of Nottingham only) |
| Language: | English |
| Published: |
2021
|
| Subjects: | |
| Online Access: | https://eprints.nottingham.ac.uk/64686/ |
| _version_ | 1848800154362052608 |
|---|---|
| author | ABID, Mohammed Adnan |
| author_facet | ABID, Mohammed Adnan |
| author_sort | ABID, Mohammed Adnan |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | This thesis considers the synthesis, and characterisation of new fulvene ligands and titanium(IV) complexes and evaluation of their potential as anti-cancer agents. It contains the in vitro cell results from different techniques used to investigate their biological mechanisms of action and their activity against human cancer cell lines.
Chapter One covers an introduction to the PhD project, including a literature search focusing on previously synthesised titanium anti-cancer compounds (1979-2020), and a description of the aims of the thesis.
Chapter Two discusses the synthesis and characterisation of novel (R)-3- (cyclopenta-2,4-dien-1-ylidene)-2,3-dihydro-1H-inden-1-ol ligand precursors (two X-ray structures reported) attained via iminium-based organo catalysis in 53-78% yield (> 99% er). Unsuccessful attempts to form new titanocene complexes from these ligands are also discussed.
Chapter Three discusses the synthesis and characterisation of novel titanium(IV) complexes, using [ONO] donor atom sets from underutilised 2,2’-((methylazanedyl) bis(methylene)diphenol ligands. Complexes featuring different substituents (e.g. Cl, Me, OMe) ortho and para to the phenolic donors can be prepared in good yield (66- 89%, eight examples). The structures of these complexes were proved by X-ray crystallography in four cases and studies of their hydrolysis in DMSO/water mixtures have conducted by 1H NMR spectroscopy and LCMS. In one case a [(ONOligand)Ti (OH)(OH2)]+ intermediate can be detected. Biological studies, including MTT and clonogenic techniques, show high anti-cancer activity for these species (GI50 values down to 1 µM for the MCF-7 cell line). The mode of action of these agents was studied by annexine-V, cell cycle analysis, γ-H2AX, and caspase techniques. The antiproliferative activity of the new [ONO] donor atom titanium complexes compares favourably or outperforms cisplatin, in five carcinoma cell lines: HCT-116 (colorectal cancer) MCF-7 (breast cancer), MDA-MB-468 (breast cancer), PANC-1 (pancreatic cancer), and HT-29 (colon cancer). Thus, the new [ONO] donor atom complexes developed herein are some of the most active anticancer titanium species presently known.
Chapter Four presents the experimental details and characterisation data for all compounds described in Chapters Two and Three. It also provides protocols for all biological studies. Appendix introduces additional figures relating to Chapter Three and a summary of crystallographic data for the X-ray structures obtained within this work. |
| first_indexed | 2025-11-14T20:47:03Z |
| format | Thesis (University of Nottingham only) |
| id | nottingham-64686 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| language | English |
| last_indexed | 2025-11-14T20:47:03Z |
| publishDate | 2021 |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-646862025-02-28T15:11:29Z https://eprints.nottingham.ac.uk/64686/ Synthesis and biological evaluation of new titanium (IV) complexes and their use in anti-cancer treatment ABID, Mohammed Adnan This thesis considers the synthesis, and characterisation of new fulvene ligands and titanium(IV) complexes and evaluation of their potential as anti-cancer agents. It contains the in vitro cell results from different techniques used to investigate their biological mechanisms of action and their activity against human cancer cell lines. Chapter One covers an introduction to the PhD project, including a literature search focusing on previously synthesised titanium anti-cancer compounds (1979-2020), and a description of the aims of the thesis. Chapter Two discusses the synthesis and characterisation of novel (R)-3- (cyclopenta-2,4-dien-1-ylidene)-2,3-dihydro-1H-inden-1-ol ligand precursors (two X-ray structures reported) attained via iminium-based organo catalysis in 53-78% yield (> 99% er). Unsuccessful attempts to form new titanocene complexes from these ligands are also discussed. Chapter Three discusses the synthesis and characterisation of novel titanium(IV) complexes, using [ONO] donor atom sets from underutilised 2,2’-((methylazanedyl) bis(methylene)diphenol ligands. Complexes featuring different substituents (e.g. Cl, Me, OMe) ortho and para to the phenolic donors can be prepared in good yield (66- 89%, eight examples). The structures of these complexes were proved by X-ray crystallography in four cases and studies of their hydrolysis in DMSO/water mixtures have conducted by 1H NMR spectroscopy and LCMS. In one case a [(ONOligand)Ti (OH)(OH2)]+ intermediate can be detected. Biological studies, including MTT and clonogenic techniques, show high anti-cancer activity for these species (GI50 values down to 1 µM for the MCF-7 cell line). The mode of action of these agents was studied by annexine-V, cell cycle analysis, γ-H2AX, and caspase techniques. The antiproliferative activity of the new [ONO] donor atom titanium complexes compares favourably or outperforms cisplatin, in five carcinoma cell lines: HCT-116 (colorectal cancer) MCF-7 (breast cancer), MDA-MB-468 (breast cancer), PANC-1 (pancreatic cancer), and HT-29 (colon cancer). Thus, the new [ONO] donor atom complexes developed herein are some of the most active anticancer titanium species presently known. Chapter Four presents the experimental details and characterisation data for all compounds described in Chapters Two and Three. It also provides protocols for all biological studies. Appendix introduces additional figures relating to Chapter Three and a summary of crystallographic data for the X-ray structures obtained within this work. 2021-07-31 Thesis (University of Nottingham only) NonPeerReviewed application/pdf en arr https://eprints.nottingham.ac.uk/64686/1/Mohammed%20Adnan%20ABID%20Thesis%20Final%20Draft.pdf ABID, Mohammed Adnan (2021) Synthesis and biological evaluation of new titanium (IV) complexes and their use in anti-cancer treatment. PhD thesis, University of Nottingham. Synthesis Biological evaluation New titanium (IV) complexes Anti-cancer treatment |
| spellingShingle | Synthesis Biological evaluation New titanium (IV) complexes Anti-cancer treatment ABID, Mohammed Adnan Synthesis and biological evaluation of new titanium (IV) complexes and their use in anti-cancer treatment |
| title | Synthesis and biological evaluation of new titanium (IV) complexes and their use in anti-cancer treatment |
| title_full | Synthesis and biological evaluation of new titanium (IV) complexes and their use in anti-cancer treatment |
| title_fullStr | Synthesis and biological evaluation of new titanium (IV) complexes and their use in anti-cancer treatment |
| title_full_unstemmed | Synthesis and biological evaluation of new titanium (IV) complexes and their use in anti-cancer treatment |
| title_short | Synthesis and biological evaluation of new titanium (IV) complexes and their use in anti-cancer treatment |
| title_sort | synthesis and biological evaluation of new titanium (iv) complexes and their use in anti-cancer treatment |
| topic | Synthesis Biological evaluation New titanium (IV) complexes Anti-cancer treatment |
| url | https://eprints.nottingham.ac.uk/64686/ |