- Title
- The synthesis and characterisation of Sn(IV) porphyrin derivatives and their potential application in anti-cancer and antimicrobial photodynamic therapy
- Creator
- Dingiswayo, Somila
- ThesisAdvisor
- Mack, John, 1966-
- ThesisAdvisor
- Nyokong, T
- Subject
- Porphyrins
- Subject
- Photochemotherapy
- Subject
- Cancer Photochemotherapy
- Subject
- Active oxygen Physiological effect
- Subject
- Aromaticity (Chemistry)
- Subject
- Tetrapyrroles
- Subject
- Magnetic circular dichroism
- Subject
- Corroles
- Subject
- Chlorins
- Subject
- Photodynamic antimicrobial chemotherapy (PACT)
- Date
- 2021-10
- Type
- Masters theses
- Type
- text
- Identifier
- http://hdl.handle.net/10962/188843
- Identifier
- vital:44791
- Description
- In photodynamic therapy (PDT), the activation of light-sensitive drugs in tumour cells produces reactive singlet oxygen species, which cause tumour destruction through a cascade of biochemical reactions. Over the years, the wavelength of activation has been shown to be a critical factor in the penetration of light. Hence the properties of photosensitiser dyes in this context shape their ability to treat deep-seated tumours. In this study, the synthesis, structural characterisation and photophysicochemical properties of a series of Sn(IV) porphyrins with meso-methylthiophenyl rings that have been prepared to study their PDT and photodynamic antimicrobial chemotherapy (PACT) activity properties are reported. The series of Sn(IV) complexes is comprised of a porphyrin (1-Sn), a corrole (2-Sn), a chlorin (3-Sn) and an N-confused porphyrin (4-Sn). Herein, the low symmetry Sn(IV) porphyrin derivatives are shown to have excellent singlet oxygen generation capabilities, and lifetimes of the triplet excited states were in the microsecond range. For example, 4-Sn had a singlet oxygen quantum yield (ФΔ) and an excited triplet state lifetime (τT) of 0.88 and 27 μs, respectively. The complexes were studied using UV-visible and magnetic circular dichroism (MCD) spectroscopies. Interestingly, the positive-to-negative sign sequences of the Faraday B0 terms of 2-Sn and 3-Sn reveal that the structural modifications involved break the degeneracy of the MOs derived from the 1eg* LUMO of the porphyrin 1-Sn. In contrast, a conventional negative-to-positive sign sequence is observed for 4-Sn, since the confusion of a pyrrole moiety also results in a large separation of the 1a1u and 1a2u MOs of the porphyrin 1-Sn that are derived from the HOMO of a C16H162−parent hydrocarbon perimeter. The trends in the electronic structures of the Sn(IV) complexes were further investigated through a series of time-dependent density functional theory calculations, so that the suitability of the different types of complex for use in singlet oxygen applications could be further explored. During in vitro photodynamic antimicrobial chemotherapy (PACT) studies, chlorin derivative 3-Sn had the highest activity towards S. aureus and E. coli with log10 reductions of 10.5 and 8.74, respectively. The unusually high activity of 3-Sn against E.coli suggests that the interaction of neutral photosensitisers with gram-negativebacteria is more complex than previously understood. Anti-cancer PDT studies demonstrated that the photosensitisers had negligible dark cytotoxicity. Upon photoirradiation, the Sn(IV) complexes consistently exhibited IC50 values lower than 15 μM against MCF-7 adenocarcinoma cells. An IC50 value of 1.4 μM for 4-Sn after activation at the deep-red region of the spectrum demonstrates that complexes of this type merit further in-depth investigation. The results provide evidence that the low-symmetry Sn(IV) chlorins and N-confused porphyrins merit further in-depth study for use in singlet oxygen applications.
- Description
- Thesis (MSc) -- Faculty of Science, Chemistry, 2021
- Format
- computer, online resource, application/pdf, 1 online resource (125 pages), pdf
- Publisher
- Rhodes University, Faculty of Science, Chemistry
- Language
- English
- Rights
- Dingiswayo, Somila
- Rights
- Attribution 4.0 International (CC BY 4.0)
- Rights
- Open Access
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| Thumbnail | File | Description | Size | Format | |||
|---|---|---|---|---|---|---|---|
| View Details Download | SOURCE1 | DINGISWAYO-MSC-TR21-152.pdf | 3 MB | Adobe Acrobat PDF | View Details Download |