Photodynamic anticancer and antimicrobial activities of aza-BODIPY and porphyrinbased photosensitisers and their non-linear properties
- Authors: Molupe, Nthabeleng Regina
- Date: 2024-10-11
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/466603 , vital:76758 , DOI https://doi.org/10.21504/10962/466603
- Description: New aza-BODIPY dyes and porphyrins were synthesised and characterised so that photodynamic therapy (PDT) and photodynamic antimicrobial chemotherapy (PACT) activity studies could be performed. Several strategies were explored to achieve targeted nanoplatforms or biocompatible nanoplatforms to enhance the suitability of these compounds for use in PDT. Following earlier MSc research on the encapsulation of halogenated boron dipyrromethene (BODIPY) dyes into Pluronic® micelles, similar nanomicelles were prepared to encapsulate halogenated boron aza-dipyrromethene (aza-BODPY) dyes to enhance their aqueous solubility. However, the 1,7-dimethylthiophenyl- 2,6-diiodo-3,5-diphenyl (1) and 1,7-di-methylthiophenyl-2,6-diiodo- 3,5-dithien-3-yl (2) aza-BODIPY dyes that were prepared in this context were found to degrade when encapsulated. A different strategy was then followed in which gold nanoparticles (AuNPs) were conjugated to 1 and 2 via Au-S interactions to form biocompatible aza-BODIPY-AuNP conjugates (1-AuNP and 2-AuNP). This strategy was successful, and favourable IC50 values of 3.60 and 10.0 μM for 1-AuNP and 2- AuNP were obtained during in vitro PDT activity studies against MCF-7 human breast cancer cells, respectively, while values of 11.0 and 12.8 μM were obtained for 1 and 2. To further explore the preparation of better-targeted aza-BODIPY photosensitiser dyes, folic acid (FA) was conjugated to 1,7-dihydroxyphenyl-2,6-diiodo-3,5-di-4- bromophenyl (3) and 1,7-di-4-bromo-2,6-diiodo-3,5-dihydroxyphenylphenyl (4) aza- BODIPYs via ester bonds. Not only was the conjugation to form 3-FA and 4-FA successful, but the conjugated dyes are water-soluble, which is advantageous for drug transport in the context of PDT. These conjugates were applied in vitro against MCF-7 cancer cells and were found to have relatively high activities with IC50 values of 0.91 and 7.48 μM for 3-FA and 4-FA, respectively, while values of 11.3 and 13.0 μM were obtained for the non-conjugated 3 and 4 dyes. In a similar manner, tin (IV) and indium (III) tetrapyridylporphyrins (5 and 6) were axially conjugated to folic acid via ester bonds (5-FA and 6-FA). The conjugation was successful and enhanced the PDT activities of the dyes MCF-7 cancer cells in vitro from 48.2 to 29.6 μM for 5 and 5-FA, and from 43.9 to 13.3 μM for 6 and 6-FA. Relatively high dark toxicity was observed for 6-FA of 26.1 μM. When the nitrogen atoms of the meso-pyridyl rings were quaternized (5-FAQ and 6-FAQ) to further enhance the aqueous solubility of the complexes, it was not possible to calculate an IC50 value. When octanol-water partition coefficients (Log P) were calculated by the shake flask method, values of −0.70 and −1.70 were obtained for 5-FAQ and 6-FAQ, respectively. This provides evidence that the dyes are too water-soluble and not sufficiently lipophilic. The PACT activity properties of the synthesised diiodinated aza-BODIPYs were studied against Staphylococcus aureus (S. aureus) through photoirradiation for 60 min with Thorlabs M660L4 (280 mW.cm−2) and M730L4 (160 mW.cm−2) light emitting diodes (LEDs) mounted on the illumination chamber of Modulight® 7710-680 medical laser system providing doses at the well-plate of 100 and 57 J.cm−2.min−1. Aza- BODIPYs 2, 3 and 4 all inhibited the growth of S. aureus but with relatively low Log10 reductions of 1.37, 1.20 and 0.20. In contrast, aza-BODIPY 1 was found to have a Log10 reduction of 7.82. The PACT activities of free base and Sn(IV) 5-[4-(3- bromoethylcarboxyamidyl)phenyl]-10,15,20-triphenylporphyrins (7 and 8) prepared by Dr Balaji Babu (New Journal of Chemistry 2022, 46, 5288-5295) were tested against S. aureus to determine whether adding a triphenylphosphonium moiety to form free base and Sn(IV) 5-[4-(triphenylphosphonium)ethylcarboxyamidyl)phenyl]-10,15,20- triphenylporphyrin (18 and 19) enhances the photo-induced antibacterial activity, in addition to optimising the PDT properties due to its mitochondria-targeting properties. The PACT activities obtained against S. aureus were not favourable, but 18 exhibited enhanced activity across the studied concentration range. The potential utility of aza-BODIPY dyes 1-4 and their non-iodinated analogues (1a- 4a) for optical limiting applications was analysed by carrying out a series of Z-scan measurements, since dyes of this type have large ground state dipole moments, and this can enhance the non-linear optical limiting response. All the aza-BODIPY dyes under investigation exhibited intense non-linear absorption (NLA) behaviour with Zscan profiles that contain significant reverse saturable absorption (RSA) responses. Aza-BODIPYs 1, 2a, 2, 3, 4a, and 4 decreased the transmitted intensity of the strong laser beam to less than 50% of the linear response in organic solutions with a fixed absorbance of 1.8 for the main aza-BODIPY spectral band and a laser pulse input energy of 42 μJ. Higher second-order hyperpolarizability (γ) values were obtained for iodinated dyes 1, 2, 3 and 4. The highest value of 3.15×10−29 esu was obtained for 1. A comparative study involving the four non-iodinated dyes 1, 2, 3 and 4 and seven 1,3,5,7-tetraaryl aza-BODIPY dyes reported previously in the PhD thesis of Gugu Kubheka at Rhodes University demonstrated that there was no clear trend correlation between the γ values calculated from the Z-scan measurements and calculated dipole moments. , Thesis (PhD) -- Faculty of Science, Chemistry, 2024
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- Date Issued: 2024-10-11
A critical analysis of how the potential of Dynamic Geometry Software as a visualisation tool may enhance the teaching of Mathematics
- Authors: Mavani, Beena Deepak
- Date: 2021-04
- Subjects: Mathematics -- Computer-assisted instruction , Geometry -- Study and teaching (Secondary) -- South Africa -- Mthatha , Manipulatives (Education) -- South Africa -- Mthatha , Information visualization , Mathematics teachers -- Training of -- South Africa -- Mthatha , GeoGebra Literacy Initiative Project (GLIP) , Dynamic Geometry Software (DGS)
- Language: English
- Type: thesis , text , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/177192 , vital:42798 , 10.21504/10962/177192
- Description: Visualisation in the mathematics classroom has its own pedagogical value and plays a significant role in developing mathematical intuition, thought and ideas. Dynamic visualisation possibilities of current digital technologies afford new ways of teaching and learning mathematics. The freely available GeoGebra software package is highly interactive and makes use of powerful features to create objects that are dynamic, and which can be moved around on the computer screen for mathematical exploration. This research study was conceptualised within the GeoGebra Literacy Initiative Project (GLIP) – an ICT teacher development project in Mthatha in the Eastern Cape, South Africa. The focus of this study was on how GeoGebra could be used as a teaching tool by harnessing its powerful visualisation capacity. In the study, selected GLIP teachers collaboratively developed GeoGebra applets, then implemented and evaluated them. The research methodology took the form of action research cycles in which the design, implementation and evaluation of successive applets determined the data gathering and analysis process. My data consisted mainly of recorded observations and reflective interviews. The underlying theoretical foundation of this study lies in constructivism, which aligned well with the conceptual and analytical framework of Kilpatrick et al.’s (2001) description of teaching proficiency. An in-depth analysis of my classroom observations resulted in multiple narratives that illuminated how teachers harnessed the visualisation capabilities inherent in the software. My findings showed that dynamic visualisation and interactivity afforded by the use of technology are key enabling factors for teachers to enhance the visualisation of mathematical concepts. My analysis across participants also showed that technical difficulties often compromised the use of technology in the teaching of mathematics. The significance of this research is its contribution to the ongoing deliberations of visualisation and utilisation of technological resources, particularly through the empowerment of a community of teachers. The findings recognised that the integration of technology required appropriate training, proper planning and continuous support and resources for the teaching of mathematics. This action research provided insightful information on integrating Dynamic Geometry Software (DGS) tools in mathematics classrooms that could be useful to teachers and curriculum planners. , Thesis (PhD) -- Education, Education, 2021
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- Date Issued: 2021-04
Teachers’ views of pragmatic strategies to enhance leadership potential for female learners in primary schools at Amathole East Education District
- Authors: Bubulu, Thandiwe
- Date: 2020-09
- Subjects: Educational leadership , School improvement programs
- Language: English
- Type: Doctoral theses , text
- Identifier: http://hdl.handle.net/10353/20024 , vital:44949
- Description: This study examined how the establishment of leadership development programme targeted at female learners in primary schools could promote female learner leaders and motivate more women to take up leadership positions to address concerns of gender and to prepare females for the challenges they may face when assuming leadership roles in future.Whereas adolescent girls may be the future representation of women leaders in society, leadership development of female learners in primary schools has been neglected. Currently, a review of literature on the problem of gender imbalance at leadership level reveals a dearth of research among the youth, less so, among young women. Yet, globally, in Africa and in South Africa, particularly, there is an inequitable balance of leadership positions in society when comparing men and women. The researcher has identified this gap and has decided to dedicated research efforts in adolescent leadership development to enrich the scant existing knowledge on the born-global phenomenon. Because schools play an important role in student development and schools are a key resource for achieving equity goals, understanding how leadership is promoted by school teachers is an important step toward growing the literature on female learners’ leadership development. The study was based on five primary schools in the Amathole District in the Eastern Cape Province, South Africa. The study followed a qualitative research approach where interviews were employed to elicit data from the study’s participants and to help in understanding the phenomenon under study. A non-probability, purposive sampling technique was used where ten participants were selected. The study’s participants were five (5) principals, two (2) HoDs, two (2) post level 1 teachers and one (1) Learner Support Assistant (LSA). The study found that a paradigm shift from the traditional view of leadership, where young people are not given leadership positions because they are regarded as young or quiet is a patriarchal belief system that should be done away with. Instead, role-players should embrace and encourage female children to be transformational and servant leaders. There is need for a change of mind-set from all role-players in South Africa to accept learners as equal participants in school leadership and to prioritise the training and development of female learner leaders. Female learners need to be taught a broader understanding of leadership as a concept including differing leadership theories and styles. Leadership as a concept needs to be taught early in primary school and to all learners. The study recommended leadership development seminars, camps, workshops and guest speakers that could aid in the development of leadership at primary school, and to be prioritised. The study concluded that continuous leadership training from a young age, for all learners in primary schools should be encouraged to ensure that learners chosen to lead assume leadership roles with confidence, skills and experience. Government schools need to allocate budget for leadership development of learners, with special funding for the relatively disadvantaged gender. , Thesis (DPhil) -- Faculty of Education, 2020
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- Date Issued: 2020-09