The synthesis and characterisation of Sn(IV) porphyrin derivatives and their potential application in anti-cancer and antimicrobial photodynamic therapy
- Authors: Dingiswayo, Somila
- Date: 2021-10
- Subjects: Porphyrins , Photochemotherapy , Cancer Photochemotherapy , Active oxygen Physiological effect , Aromaticity (Chemistry) , Tetrapyrroles , Magnetic circular dichroism , Corroles , Chlorins , Photodynamic antimicrobial chemotherapy (PACT)
- Language: English
- Type: Masters theses , text
- Identifier: http://hdl.handle.net/10962/188843 , 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. , Thesis (MSc) -- Faculty of Science, Chemistry, 2021
- Full Text:
- Date Issued: 2021-10
- Authors: Dingiswayo, Somila
- Date: 2021-10
- Subjects: Porphyrins , Photochemotherapy , Cancer Photochemotherapy , Active oxygen Physiological effect , Aromaticity (Chemistry) , Tetrapyrroles , Magnetic circular dichroism , Corroles , Chlorins , Photodynamic antimicrobial chemotherapy (PACT)
- Language: English
- Type: Masters theses , text
- Identifier: http://hdl.handle.net/10962/188843 , 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. , Thesis (MSc) -- Faculty of Science, Chemistry, 2021
- Full Text:
- Date Issued: 2021-10
Assessing South African Medical Interns’ Experience and Confidence in Managing Obstetric Emergencies
- Authors: Miller, Andrew
- Date: 2021-02
- Subjects: Obstetrical emergencies
- Language: English
- Type: Masters theses , text
- Identifier: http://hdl.handle.net/11260/6882 , vital:52352
- Description: Background: Medical doctors in South Africa are required to complete a two-year internship at training hospitals, including a four-month rotation in obstetrics and gynaecology. Following this, doctors are allocated to community service posts; many of which are at district and primary level facilities where supervision is limited. The latest triennial Saving Mothers Report identified district hospitals as the second leading site for maternal deaths of all causes. District hospital were also the leading site for maternal deaths secondary to obstetric haemorrhage and the most likely site for the lack of a skilled doctor to be identified as a factor in deaths associated with caesarean delivery. Methods: This cross-sectional descriptive study aimed to describe the self-perceived readiness of medical interns completing their training to independently manage obstetric emergencies, based on the ESMOE modules in the HPCSA internship logbook. The research assessed medical interns in the last three months of their training, using a self-administered online questionnaire, with data collection between October and December 2019. Cluster sampling of interns at training facilities throughout the country resulted in a total of 182 respondents from 17 hospitals in seven provinces in the country, with an overall response rate of 34.1%. Results: Most interns had experience with, and confidence in, the management of miscarriage and hypertension in pregnancy. However, gaps in labour ward management, pregnancy related sepsis and surgical skills were identified. Only 42.3% of respondents were confident in their ability to diagnose obstructed labour, 26.3% had performed an assisted delivery, 39.0% were confident in their knowledge of the indications and contraindications of assisted deliveries and 35.7% had been involved in the delivery of a baby with shoulder dystocia. Regarding pregnancy related sepsis, 54.4% had experience with managing a wound abscess and 29.7% were confident managing puerperal endometritis. While 78.0% felt confident to perform a caesarean section, only 28.6% had performed uterine compression sutures for uterine atony at caesarean section. Additionally, there was a statistically significant variation in scores between training hospitals. Conclusion: A gap exists between the shortcomings in district hospital obstetric services, the prioritisation of placement of community service doctors at primary care and district hospitals, and the self-perceived readiness of medical interns completing their training to safely manage obstetric emergencies. This highlights the importance of clinical support for junior doctors at district hospitals and standardisation of intern training at accredited facilities across the country. , Thesis (Masters) -- Faculty of Health Sciences, 2021
- Full Text:
- Date Issued: 2021-02
Assessing South African Medical Interns’ Experience and Confidence in Managing Obstetric Emergencies
- Authors: Miller, Andrew
- Date: 2021-02
- Subjects: Obstetrical emergencies
- Language: English
- Type: Masters theses , text
- Identifier: http://hdl.handle.net/11260/6882 , vital:52352
- Description: Background: Medical doctors in South Africa are required to complete a two-year internship at training hospitals, including a four-month rotation in obstetrics and gynaecology. Following this, doctors are allocated to community service posts; many of which are at district and primary level facilities where supervision is limited. The latest triennial Saving Mothers Report identified district hospitals as the second leading site for maternal deaths of all causes. District hospital were also the leading site for maternal deaths secondary to obstetric haemorrhage and the most likely site for the lack of a skilled doctor to be identified as a factor in deaths associated with caesarean delivery. Methods: This cross-sectional descriptive study aimed to describe the self-perceived readiness of medical interns completing their training to independently manage obstetric emergencies, based on the ESMOE modules in the HPCSA internship logbook. The research assessed medical interns in the last three months of their training, using a self-administered online questionnaire, with data collection between October and December 2019. Cluster sampling of interns at training facilities throughout the country resulted in a total of 182 respondents from 17 hospitals in seven provinces in the country, with an overall response rate of 34.1%. Results: Most interns had experience with, and confidence in, the management of miscarriage and hypertension in pregnancy. However, gaps in labour ward management, pregnancy related sepsis and surgical skills were identified. Only 42.3% of respondents were confident in their ability to diagnose obstructed labour, 26.3% had performed an assisted delivery, 39.0% were confident in their knowledge of the indications and contraindications of assisted deliveries and 35.7% had been involved in the delivery of a baby with shoulder dystocia. Regarding pregnancy related sepsis, 54.4% had experience with managing a wound abscess and 29.7% were confident managing puerperal endometritis. While 78.0% felt confident to perform a caesarean section, only 28.6% had performed uterine compression sutures for uterine atony at caesarean section. Additionally, there was a statistically significant variation in scores between training hospitals. Conclusion: A gap exists between the shortcomings in district hospital obstetric services, the prioritisation of placement of community service doctors at primary care and district hospitals, and the self-perceived readiness of medical interns completing their training to safely manage obstetric emergencies. This highlights the importance of clinical support for junior doctors at district hospitals and standardisation of intern training at accredited facilities across the country. , Thesis (Masters) -- Faculty of Health Sciences, 2021
- Full Text:
- Date Issued: 2021-02
Outcomes of Drug Resistant Tuberculosis in Two Rural District Hospitals, Eastern Cape Province, South Africa
- Authors: Lotz, John-D Knipe
- Date: 2021-02
- Subjects: Medicinal plants
- Language: English
- Type: Masters theses , text
- Identifier: http://hdl.handle.net/11260/6834 , vital:51018
- Description: Tuberculosis (TB) is still rampant in South Africa, and drug resistant tuberculosis (DR-TB) forms a significant part of this burden on both the health care system and economy. A number of interventions have recently been introduced to help curb the growing epidemic of DR-TB, including increasing access to novel and repurposed drugs, decentralisation of care, and a new shorter (9-11 month) treatment regimen recently endorsed by the World Health Organization (WHO). Significantly, this new regimen has now also become injectable-free (also known as an all-oral regimen). However, at the time of implementation in 2017, the shorter regimen was yet to be proven effective in a programmatic setting in South Africa. This is a retrospective cohort study to describe the outcomes in patients on short and long DR-TB treatment regimens, over five years, at two treatment sites in a rural setting in the Eastern Cape province of South Africa. It is the hope that elucidation of factors involved in affecting outcomes in DR-TB may direct future interventions in these two facilities, and the wider DR-TB program in South Africa , Thesis (Masters) -- Faculty of Health Sciences, 2021
- Full Text:
- Date Issued: 2021-02
- Authors: Lotz, John-D Knipe
- Date: 2021-02
- Subjects: Medicinal plants
- Language: English
- Type: Masters theses , text
- Identifier: http://hdl.handle.net/11260/6834 , vital:51018
- Description: Tuberculosis (TB) is still rampant in South Africa, and drug resistant tuberculosis (DR-TB) forms a significant part of this burden on both the health care system and economy. A number of interventions have recently been introduced to help curb the growing epidemic of DR-TB, including increasing access to novel and repurposed drugs, decentralisation of care, and a new shorter (9-11 month) treatment regimen recently endorsed by the World Health Organization (WHO). Significantly, this new regimen has now also become injectable-free (also known as an all-oral regimen). However, at the time of implementation in 2017, the shorter regimen was yet to be proven effective in a programmatic setting in South Africa. This is a retrospective cohort study to describe the outcomes in patients on short and long DR-TB treatment regimens, over five years, at two treatment sites in a rural setting in the Eastern Cape province of South Africa. It is the hope that elucidation of factors involved in affecting outcomes in DR-TB may direct future interventions in these two facilities, and the wider DR-TB program in South Africa , Thesis (Masters) -- Faculty of Health Sciences, 2021
- Full Text:
- Date Issued: 2021-02
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